Sample records for tablets enteric-coated

  1. The Preparation of Capsaicin-Chitosan Microspheres (CCMS) Enteric Coated Tablets

    PubMed Central

    Chen, Jian; Huang, Gui-Dong; Tan, Si-Rong; Guo, Jiao; Su, Zheng-Quan

    2013-01-01

    This study aimed to research the preparation and content determination of capsaicin-chitosan microspheres (CCMS) enteric coated tablets. The core tablets were prepared with the method of wet granulation. Nine formulae were designed to determine the optimal formula of the core tablet. Eudragit L100 was used to prepare the CCMS enteric-coated tablets. The effect of enteric coated formulation variables such as content of talc (10%, 25% and 40%), plasticisers (TEC and DBS), dosage of plasticiser (10%, 20% and 30%) and coating weight (2%, 3% and 5%) were evaluated for drug release characteristics. The in vitro release was studied using 0.1 N HCl and pH 6.8 phosphate buffer. Enteric coated tablets without ruptures or swelling behaviour over 2 h in 0.1 N HCl indicated that these tablets showed acid resistance. The accumulated release rate in phosphate buffer (pH 6.8) revealed that the prepared tablets were able to sustain drug release into the intestine and a first-order release was obtained for capsaicin. This research is the first report of the preparation and content determination of CCMS enteric coated tablets. The sustained release behavior of enteric coated formulations in pH 6.8 phosphate buffer demonstrated that it would be a potential drug delivery platform for sustained delivery of gastric irritant drugs. PMID:24351818

  2. Design and evaluation of enteric-coated tablets for rifampicin and isoniazid combinations.

    PubMed

    Wang, Yongjun; Liu, Hongzhuo; Liu, Kai; Sun, Jin; He, Zhonggui

    2013-01-01

    In order to improve the bioavailability of rifampicin (RIF) from rifampicin and isoniazid (INH) combination formulations, the physicochemical characteristics of RIF, stability of RIF in different pH buffers in the presence of INH, as well as the effect of particle size of RIF materials on the dissolution rate were investigated. On the basis of the above examinations, enteric-coated tablets for RIF and INH combinations were designed and prepared. RIF showed low solubility and high apparent distribution coefficient in the intestinal pH (pH 4.0-7.4). With the decrease in pH, the degradation of RIF increase and the presence of INH deepen the degradation. Enteric-coated tablets were prepared after grinding the RIF materials by dry granulation technique. The pharmacokinetics of RIF and INH of self-made enteric-coated tablets in dogs were studied by comparing with the reference tablets. The AUC(0-48) of RIF in both reference and test tablets were 304.77 ± 42.27 and 353.79 ± 31.63 µg·h·mL(-1), respectively. The AUC(0-48) of INH in both reference and test tablets were 17.14 ± 8.59 and 19.62 ± 10.57 µg·h·mL(-1), respectively. Enteric-coated tablets may minimize the decomposition of RIF in gastrointestinal tract and improve the bioavailability.

  3. Gastric emptying of enteric-coated tablets

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Park, H.M.; Chernish, S.M.; Rosenek, B.D.

    1984-03-01

    To evaluate the gastric emptying time of pharmaceutical dosage forms in a clinical setting, a relatively simple dual-radionuclide technique was developed. Placebo tablets of six different combinations of shape and size were labeled with indium-111 DTPA and enteric coated. Six volunteers participated in a single-blind and crossover study. Tablets were given in the morning of a fasting stomach with 6 oz of water containing /sup 99m/Tc pertechnetate and continuously observed with a gamma camera. A scintigraph was obtained each minute. The results suggested that the size, shape, or volume of the tablet used in this study had no significant effectmore » in the rate of gastric emptying. The tablets emptied erratically and unpredictably, depending upon their time of arrival in the stomach in relation to the occurrence of interdigestive myoelectric contractions. The method described is a relatively simple and accurate technique to allow one to follow the gastric emptying of tablets.« less

  4. Preparation and evaluation of enteric coated tablets of hot melt extruded lansoprazole

    PubMed Central

    Alsulays, Bader B.; Kulkarni, Vijay; Alshehri, Sultan M.; Almutairy, Bjad K.; Ashour, Eman A.; Morott, Joseph T.; Alshetaili, Abdullah S.; Park, Jun-Bom; Tiwari, Roshan V.; Repka, Michael A.

    2017-01-01

    The objective of this work was to use hot-melt extrusion (HME) technology to improve the physiochemical properties of lansoprazole (LNS) to prepare stable enteric coated LNS tablets. For the extrusion process, we chose Kollidon® 12 PF (K12) polymeric matrix. Lutrol® F 68 was selected as the plasticizer and magnesium oxide (MgO) as the alkalizer. With or without the alkalizer, LNS at 10% drug load was extruded with K12 and F68. LNS changed to the amorphous phase and showed better release compared to that of the pure crystalline drug. Inclusion of MgO improved LNS extrudability and release and resulted in over 80% drug release in the buffer stage. Hot-melt extruded LNS was physically and chemically stable after 12 months of storage. Both formulations were studied for compatibility with Eudragit® L 100-55. The optimized formulation was compressed into a tablet followed by coating process utilizing a pan coater using L 100-55 as an enteric coating polymer. In a two-step dissolution study, the release profile of the enteric coated LNS tablets in the acidic stage was less than 10% of the LNS, while that in the buffer stage was more than 80%. Drug content analysis revealed the LNS content to be 97%, indicating the chemical stability of the enteric coated tablet after storage for 6 months. HME, which has not been previously used for LNS, is a valuable technique to reduce processing time in the manufacture of enteric coated formulations of an acid-sensitive active pharmaceutical ingredient as compared to the existing methods. PMID:27486807

  5. Application of a radiotelemetric system to evaluate the performance of enteric coated and plain aspirin tablets.

    PubMed

    Lui, C Y; Oberle, R; Fleisher, D; Amidon, G L

    1986-05-01

    The bioavailability of enteric coated and plain aspirin tablets was studied in four beagle dogs. Blood sampling for enteric coated tablets was planned with the aid of a radiotelemetric system. The release of aspirin from its dosage form was detected by monitoring the change in intestinal pH. Aspirin and salicylic acid levels in plasma obtained from the enteric coated dosage form exhibited familiar concentration versus time absorption profiles. Variation in the plasma concentrations of these two compounds within each dog studied (four runs each) was relatively small when time zero was adjusted to the commencement of tablet dissolution. The plasma levels obtained from plain aspirin (three runs each), however, show atypical absorption. The estimated absolute bioavailability was 0.432 +/- 0.0213 and 0.527 +/- 0.0260 for enteric coated and plain aspirin, respectively. Other pharmacokinetic parameters for these two dosage forms such as the highest observed plasma concentration (Cmax) (10.9 +/- 0.535 microgram/mL versus 13.6 +/- 1.88 micrograms/mL) and the time to reach Cmax (tmax) (26.6 +/- 1.94 min versus 31.0 +/- 7.04 min) agree well. The mean values for gastric emptying time, in vivo coating dissolution time, and in vivo disintegration/dissolution time of the tablet core for enteric coated aspirin are 48.7 +/- 7.23 min, 44.3 +/- 3.80 min, and 34.7 +/- 2.04 min, respectively.

  6. Use of bicarbonate buffer systems for dissolution characterization of enteric-coated proton pump inhibitor tablets.

    PubMed

    Shibata, Hiroko; Yoshida, Hiroyuki; Izutsu, Ken-Ichi; Goda, Yukihiro

    2016-04-01

    The aim of this study was to assess the effects of buffer systems (bicarbonate or phosphate at different concentrations) on the in vitro dissolution profiles of commercially available enteric-coated tablets. In vitro dissolution tests were conducted using an USP apparatus II on 12 enteric-coated omeprazole and rabeprazole tablets, including innovator and generic formulations in phosphate buffers, bicarbonate buffers and a media modified Hanks (mHanks) buffer. Both omeprazole and rabeprazole tablets showed similar dissolution profiles among products in the compendial phosphate buffer system. However, there were large differences between products in dissolution lag time in mHanks buffer and bicarbonate buffers. All formulations showed longer dissolution lag times at lower concentrations of bicarbonate or phosphate buffers. The dissolution rank order of each formulation differed between mHanks buffer and bicarbonate buffers. A rabeprazole formulation coated with a methacrylic acid copolymer showed the shortest lag time in the high concentration bicarbonate buffer, suggesting varied responses depending on the coating layer and buffer components. Use of multiple dissolution media during in vitro testing, including high concentration bicarbonate buffer, would contribute to the efficient design of enteric-coated drug formulations. © 2016 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology.

  7. In-vitro evaluation of enteric coated insulin tablets containing absorption enhancer and enzyme inhibitor.

    PubMed

    Wong, Chun Y; Martinez, Jorge; Carnagarin, Revathy; Dass, Crispin R

    2017-03-01

    The aim of this study was to develop an enteric coated insulin tablet formulation using polymers, absorption enhancer and enzyme inhibitor, which protect the tablets in acidic pH and enhance systemic bioavailability. In this study, the influence of coating by cellulose acetate hydrogen phthalate solution and chosen excipients on Glut-4 transporter translocation in C2C12 skeletal muscle cells was examined. Following the determination of optimum number of coating layers, two dissolution buffers such as 0.01 m hydrochloric acid, pH 2, and 50 mm phosphate, pH 7.4, were employed to determine the in-vitro release of insulin. Insulin was protected by the coating during the dissolution process. Five (5-CL) coating layers and eight (8-CL) coating layers had minimal insulin release in hydrochloric acid, but not three (3-CL) coating layers. Glut-4 translocation in C2C12 cells was promoted by the chosen excipients. No detrimental metabolic effects were observed in these cells. To date, limited studies combine the overall effectiveness of multiple excipients. Our study showed that the coated tablets have an immediate release effect in phosphate buffer. In Glut-4 translocation assay, insulin was still functional after releasing from the tablet. Such tablet formulation can be potentially beneficial to type 1 diabetes patients. © 2017 Royal Pharmaceutical Society.

  8. Preparation of enteric coated timed-release press-coated tablets and evaluation of their function by in vitro and in vivo tests for colon targeting.

    PubMed

    Fukui, E; Miyamura, N; Uemura, K; Kobayashi, M

    2000-08-25

    As a new oral drug delivery system for colon targeting, enteric coated timed-release press-coated tablets (ETP tablets) were developed by coating enteric polymer on timed-release press-coated tablets composed of an outer shell of hydroxypropylcellulose and core tablet containing diltiazem hydrochloride (DIL) as a model drug. The results of the in vitro dissolution tests in JP 1st fluid (pH 1.2) and JP 2nd fluid (pH 6.8) indicated that these tablets showed both acid resistance and timed-release. To clarify whether ETP tablets could have been of use in the gastrointestinal tract, ETP tablets with a layer of phenylpropanolamine hydrochloride (PPA) (a marker of gastric emptying) between the enteric coating layer and outer shell were prepared, and were administered to beagle dogs. The gastric emptying time and lag time after gastric emptying were evaluated by determining the times at which PPA and DIL first appeared in the plasma (TFA(PPA) and TFA(DIL), respectively). TFA(PPA) and TFA(DIL) were about 4 and 7 h, respectively. This value of TFA(PPA) indicated that ETP tablets displayed acid resistance in the stomach as well as in JP Ist fluid. Subtraction of TFA(PPA) from TFA(DIL) gave a value of about 3 h which agreed well with the lag time determined by in vitro dissolution test in JP 2nd fluid. Also, the results seemed to be in accordance with the time at which the tablets reached the colon after gastric emptying. Therefore, ETP tablets seemed to be an effective tool for oral site-specific delivery including targeting of the colon.

  9. Novel method for screening of enteric film coatings properties with magnetic resonance imaging.

    PubMed

    Dorożyński, Przemysław; Jamróz, Witold; Niwiński, Krzysztof; Kurek, Mateusz; Węglarz, Władysław P; Jachowicz, Renata; Kulinowski, Piotr

    2013-11-18

    The aim of the study is to present the concept of novel method for fast screening of enteric coating compositions properties without the need of preparation of tablets batches for fluid bed coating. Proposed method involves evaluation of enteric coated model tablets in specially designed testing cell with application of MRI technique. The results obtained in the testing cell were compared with results of dissolution studies of mini-tablets coated in fluid bed apparatus. The method could be useful in early stage of formulation development for screening of film coating properties that will shorten and simplify the development works. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Effect of decrease in both postprandial blood glucose (PBG) and fasting blood glucose (FBG) levels in normal beagle dogs with nateglinide enteric coated granules and immediate release tablets.

    PubMed

    Makino, Chisato; Ninomiya, Nobutaka; Sakai, Hidetoshi; Orita, Haruo; Okano, Akira; Yabuki, Akira

    2006-04-01

    Nateglinide is a new quick action/short duration (QRSD) type of oral blood glucose regulator, and nateglinide immediate release tablets are used for patients with mild diabetes under the trade name of Fastic((R)) tablets. In this study, we attempted to determine if it was possible to control both post-prandial blood glucose level (PBG) and fasting blood glucose level (FBG) for moderate or severe diabetes through controlled release of nateglinide. Enteric coated granules were selected for the administration form for controlled release of nateglinide, and three types of enteric coated granules were prepared having dissolution pH values of 5.5, 6.5 and 7.2. The three types of enteric coated granules were each administered separately or the enteric coated granules having an dissolution pH of 6.5 were administered simultaneous to administration of nateglinide immediate release tablets to normal beagle dogs just before feeding followed by measurement of plasma nateglinide concentration, plasma insulin concentration and blood glucose level. In the case of administering enteric coated granules alone (nateglinide: 9 mg/kg), the absorption of nateglinide was confirmed to tend to be delayed as the dissolution pH increased. In the case of an dissolution pH of 5.5, decreases in both PBG and FBG were observed. In the case of dissolution pH values of 6.5 and 7.2, only decrease in FBG was observed. In case of nateglinide immediate release tablets (nateglinide: 9 mg/kg), only decrease in PBG was observed. Decreases in both PBG and FBG were observed in the case of simultaneous administration of dissolution pH 6.5 enteric coated granules and nateglinide immediate release tablets just before feeding (nateglinide: 90 mg/head+60 mg/head). A correlation was observed between plasma nateglinide concentrations and blood glucose levels. On the other hand, there were no correlations observed between changes in plasma insulin concentrations and blood glucose levels. In case of nateglinide

  11. Non-destructive prediction of enteric coating layer thickness and drug dissolution rate by near-infrared spectroscopy and X-ray computed tomography.

    PubMed

    Ariyasu, Aoi; Hattori, Yusuke; Otsuka, Makoto

    2017-06-15

    The coating layer thickness of enteric-coated tablets is a key factor that determines the drug dissolution rate from the tablet. Near-infrared spectroscopy (NIRS) enables non-destructive and quick measurement of the coating layer thickness, and thus allows the investigation of the relation between enteric coating layer thickness and drug dissolution rate. Two marketed products of aspirin enteric-coated tablets were used in this study, and the correlation between the predicted coating layer thickness and the obtained drug dissolution rate was investigated. Our results showed correlation for one product; the drug dissolution rate decreased with the increase in enteric coating layer thickness, whereas, there was no correlation for the other product. Additional examination of the distribution of coating layer thickness by X-ray computed tomography (CT) showed homogenous distribution of coating layer thickness for the former product, whereas the latter product exhibited heterogeneous distribution within the tablet, as well as inconsistent trend in the thickness distribution between the tablets. It was suggested that this heterogeneity and inconsistent trend in layer thickness distribution contributed to the absence of correlation between the layer thickness of the face and side regions of the tablets, which resulted in the loss of correlation between the coating layer thickness and drug dissolution rate. Therefore, the predictability of drug dissolution rate from enteric-coated tablets depended on the homogeneity of the coating layer thickness. In addition, the importance of micro analysis, X-ray CT in this study, was suggested even if the macro analysis, NIRS in this study, are finally applied for the measurement. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Relationship between Adverse Gastric Reactions and the Timing of Enteric-Coated Aspirin Administration.

    PubMed

    Guo, Weijun; Lu, Wenlin; Xu, Yujun; Wang, Liansheng; Wei, Qin; Zhao, Qingyun

    2017-02-01

    This study aimed to elucidate the association between the adverse gastric effects of enteric-coated aspirin and the timing of its administration. The study population comprised 572 patients (age range 45-84 years) admitted to Huaiyin Hospital between August 2012 and October 2014. Patients were administered a 100 mg enteric-coated aspirin tablet once daily: before a meal (30 min before a meal), during a meal, after a meal (30 min after a meal), or before sleep, and all patients were followed up for 6-9 months to observe for adverse gastric reactions and other side effects. Gastroscopy was performed if indicated by the patient's condition after obtaining due consent. In addition, release tests for an enteric-coated aspirin tablet were conducted using the chromatography method. Enteric-coated aspirin tablets released completely, with a release rate of >99 % under 20-120 min at pH > 5.5. Furthermore, the number of patients with recurring adverse stomach reactions was significantly lower in the before-meal and before-sleep groups than that observed in the during-meal and after-meal groups (p < 0.05). No significant between-group differences were observed with respect to damage to other organs. Similarly, the number of patients with gastric lesions was significantly lower in the before-meal and before-sleep groups than that observed in the during-meal and after-meal groups (p < 0.05). The optimal time for once-daily administration of low-dose enteric-coated aspirin tablets was before a meal or before sleep owing to the increase in pH level during and after meals.

  13. Moisture plasticization for enteric Eudragit® L30D-55-coated pellets prior to compression into tablets.

    PubMed

    Rujivipat, Soravoot; Bodmeier, Roland

    2012-05-01

    Enteric polymers such as cellulose esters (cellulose acetate phthalate, hydroxypropylmethylcellulose acetate succinate) and methacrylic acid-acrylate copolymers (Eudragit® L100-55 and S100) are quite brittle in the dry state and thus not suitable as pellet coatings for compression into tablets. The objective of this study was to investigate the role of humidity treatment for moisture plasticization in order to successfully compress the enterically coated pellets. The mechanical properties of Eudragit® L100-55 improved dramatically, while the properties of the other enteric polymers showed only minor changes after storage at higher humidity. The significant increase in flexibility of the Eudragit® L film was caused by hydration/plasticization; its elongation value changed from approx. 3% in the dry state to approx. 140% at the higher storage humidity. Storage at 84% relative humidity resulted in comparable release profiles of compressed and uncompressed pellets. The glass transition temperature of Eudragit® L films decreased below the compression temperature (room temperature) at storage humidities between 75% and 84%. The glass transition relative humidity leading to a change from the glassy to the rubbery state was determined by dynamic vapor sorption (DVS) to be 76.8%. Moisture resulted in superior plasticization for Eudragit® L than the conventional plasticizer triethyl citrate. The improved compressibility of high humidity treated Eudragit® L-coated pellets was also shown with single pellet compression data as indicated by an increased crushing force and deformation. In conclusion, moisture plasticization was a highly effective tool to enable the successful compression of pellets coated with the brittle enteric polymer Eudragit® L. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Effects of Enteric-coated Lactoferrin Tablets Containing Lactobacillus brevis subsp. coagulans on Fecal Properties, Defecation Frequency and Intestinal Microbiota of Japanese Women with a Tendency for Constipation: a Randomized Placebo-controlled Crossover Study

    PubMed Central

    SUZUKI, Noriyuki; MURAKOSHI, Michiaki; ONO, Tomoji; MORISHITA, Satoru; KOIDE, Misao; BAE, Min Jung; TOTSUKA, Mamoru; SHIMIZU, Makoto; SUGIYAMA, Keikichi; NISHINO, Hoyoku; IIDA, Norio

    2013-01-01

    The effects of oral administration of enteric-coated tablets containing lactoferrin (LF; 100 mg/tablet) and heat-killed Lactobacillus brevis subsp. coagulans FREM BP-4693 (LB; 6×109 bacteria/tablet) on fecal properties were examined in 32 Japanese women (20–60 years of age) with a tendency for constipation (defecation frequency at equal to or less than 10 times/2 weeks) by a double-blind placebo-controlled crossover design. A significant increase in defecation days per week was obserbed in the subjects who ingested the tablets containing LF and LB compared with the placebo group. The number of bifidobacteria in feces also significantly increased compared with the placebo group. In an in vitro study, LF and tryptic hydrolysate of LF, but not peptic hydrolysate of LF, upregulated the growth of Bifidobacterium longum ATCC15707 when added to the culture. These results demonstrate the capability of the enteric-coated tablets containing LF and LB in improving intestinal function and suggest that they have a growth promoting function for bifidobacteria. PMID:24936358

  15. Effect of Calcium Ions on the Disintegration of Enteric-Coated Solid Dosage Forms.

    PubMed

    Al-Gousous, Jozef; Langguth, Peter

    2016-02-01

    To investigate the effect of calcium ions on the disintegration of enteric-coated dosage forms, disintegration testing was performed on enteric-coated aspirin tablets in the presence and absence of calcium in the test media. The results show that the presence of calcium ions retards the disintegration of enteric-coated dosage forms. This finding, which has not been reported in scientific literature, sheds light on the importance of conducting well-designed detailed investigations into the potential of calcium from dietary sources, calcium supplements, antacids, and/or phosphate binders affecting the absorption of drugs formulated into enteric-coated dosage forms. Moreover, it shows the necessity to investigate the potential of the occurrence of additional nutrient-excipient interactions. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  16. Automated Dissolution for Enteric-Coated Aspirin Tablets: A Case Study for Method Transfer to a RoboDis II.

    PubMed

    Ibrahim, Sarah A; Martini, Luigi

    2014-08-01

    Dissolution method transfer is a complicated yet common process in the pharmaceutical industry. With increased pharmaceutical product manufacturing and dissolution acceptance requirements, dissolution testing has become one of the most labor-intensive quality control testing methods. There is an increased trend for automation in dissolution testing, particularly for large pharmaceutical companies to reduce variability and increase personnel efficiency. There is no official guideline for dissolution testing method transfer from a manual, semi-automated, to automated dissolution tester. In this study, a manual multipoint dissolution testing procedure for an enteric-coated aspirin tablet was transferred effectively and reproducibly to a fully automated dissolution testing device, RoboDis II. Enteric-coated aspirin samples were used as a model formulation to assess the feasibility and accuracy of media pH change during continuous automated dissolution testing. Several RoboDis II parameters were evaluated to ensure the integrity and equivalency of dissolution method transfer from a manual dissolution tester. This current study provides a systematic outline for the transfer of the manual dissolution testing protocol to an automated dissolution tester. This study further supports that automated dissolution testers compliant with regulatory requirements and similar to manual dissolution testers facilitate method transfer. © 2014 Society for Laboratory Automation and Screening.

  17. Quantitative Appearance Inspection for Film Coated Tablets.

    PubMed

    Yoshino, Hiroyuki; Yamashita, Kazunari; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

    2016-01-01

    The decision criteria for the physical appearance of pharmaceutical products are subjective and qualitative means of evaluation that are based entirely on human interpretation. In this study, we have developed a comprehensive method for the quantitative analysis of the physical appearance of film coated tablets. Three different kinds of film coated tablets with considerable differences in their physical appearances were manufactured as models, and their surface roughness, contact angle, color measurements and physicochemical properties were investigated as potential characteristics for the quantitative analysis of their physical appearance. All of these characteristics were useful for the quantitative evaluation of the physical appearances of the tablets, and could potentially be used to establish decision criteria to assess the quality of tablets. In particular, the analysis of the surface roughness and film coating properties of the tablets by terahertz spectroscopy allowed for an effective evaluation of the tablets' properties. These results indicated the possibility of inspecting the appearance of tablets during the film coating process.

  18. Preparation of bilayer-core osmotic pump tablet by coating the indented core tablet.

    PubMed

    Liu, Longxiao; Xu, Xiangning

    2008-03-20

    In this paper, a bilayer-core osmotic pump tablet (OPT) which does not require laser drilling to form the drug delivery orifice is described. The bilayer-core consisted of two layers: (a) push layer and (b) drug layer, and was made with a modified upper tablet punch, which produced an indentation at the center of the drug layer surface. The indented tablets were coated by using a conventional pan-coating process. Although the bottom of the indentation could be coated, the side face of the indentation was scarcely sprayed by the coating solution and this part of the tablet remained at least partly uncoated leaving an aperture from which drug release could occur. Nifedipine was selected as the model drug. Sodium chloride was used as osmotic agent, polyvinylpyrrolidone as suspending agent and croscarmellose sodium as expanding agent. The indented core tablet was coated by ethyl cellulose as semipermeable membrane containing polyethylene glycol 400 for controlling the membrane permeability. The formulation of core tablet was optimized by orthogonal design and the release profiles of various formulations were evaluated by similarity factor (f(2)). It was found that the optimal OPT was able to deliver nifedipine at an approximate zero-order up to 24 h, independent on both release media and agitation rates. The preparation of bilayer-core OPT was simplified by coating the indented core tablet, by which sophisticated technology of the drug layer identification and laser drilling could be eliminated. It might be promising in the field of preparation of bilayer-core OPT.

  19. Assessing the influence of media composition and ionic strength on drug release from commercial immediate-release and enteric-coated aspirin tablets.

    PubMed

    Karkossa, Frank; Klein, Sandra

    2017-10-01

    The objective of this test series was to elucidate the importance of selecting the right media composition for a biopredictive in-vitro dissolution screening of enteric-coated dosage forms. Drug release from immediate-release (IR) and enteric-coated (EC) aspirin formulations was assessed in phosphate-based and bicarbonate-based media with different pH, electrolyte composition and ionic strength. Drug release from aspirin IR tablets was unaffected by media composition. In contrast, drug release from EC aspirin formulations was affected by buffer species and ionic strength. In all media, drug release increased with increasing ionic strength, but in bicarbonate-based buffers was delayed when compared with that in phosphate-based buffers. Interestingly, the cation species in the dissolution medium had also a clear impact on drug release. Drug release profiles obtained in Blank CarbSIF, a new medium simulating pH and average ionic composition of small intestinal fluid, were different from those obtained in all other buffer compositions studied. Results from this study in which the impact of various media parameters on drug release of EC aspirin formulations was systematically screened clearly show that when developing predictive dissolution tests, it is important to simulate the ionic composition of intraluminal fluids as closely as possible. © 2017 Royal Pharmaceutical Society.

  20. Demonstration of pharmaceutical tablet coating process by injection molding technology.

    PubMed

    Puri, Vibha; Brancazio, David; Harinath, Eranda; Martinez, Alexander R; Desai, Parind M; Jensen, Keith D; Chun, Jung-Hoon; Braatz, Richard D; Myerson, Allan S; Trout, Bernhardt L

    2018-01-15

    We demonstrate the coating of tablets using an injection molding (IM) process that has advantage of being solvent free and can provide precision coat features. The selected core tablets comprising 10% w/w griseofulvin were prepared by an integrated hot melt extrusion-injection molding (HME-IM) process. Coating trials were conducted on a vertical injection mold machine. Polyethylene glycol and polyethylene oxide based hot melt extruded coat compositions were used. Tablet coating process feasibility was successfully demonstrated using different coating mold designs (with both overlapping and non-overlapping coatings at the weld) and coat thicknesses of 150 and 300 μm. The resultant coated tablets had acceptable appearance, seal at the weld, and immediate drug release profile (with an acceptable lag time). Since IM is a continuous process, this study opens opportunities to develop HME-IM continuous processes for transforming powder to coated tablets. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Influence of polymeric subcoats on the drug release properties of tablets powder-coated with pre-plasticized Eudragit L 100-55.

    PubMed

    Sauer, Dorothea; Watts, Alan B; Coots, Lonique B; Zheng, Weijia C; McGinity, James W

    2009-02-09

    The aim of the study was to investigate the properties of sodium valproate tablets that were dry powder-coated with pre-plasticized Eudragit L 100-55. Polyethylene glycol 3350 (PEG 3350) was used as primer to facilitate initial coating powder adhesion. Solubility parameters were employed to determine the wetting properties of the PEG 3350 primer. Additional PEG 3350 within the powder coating formulation was required to enable powder adhesion to the tablet cores. The application of a subcoat of either Eudragit E PO or Eudragit RL PO facilitated adhesion of the enteric polymer to the tablet cores and reduced the amount PEG 3350 required in the coating formulation. Since reduction of the PEG 3350 content produced less water-vapor permeable films, the enteric coating level necessary to control the drug release was decreased. PEG 3350 and Methocel K4M were incorporated in both Eudragit E PO and Eudragit RL PO subcoating formulations as pore forming agents. The influence of the pore forming excipients on physicochemical properties of free powder-cast films was investigated. The miscibility of the PEG 3350 and Methocel K4M in the film coating was correlated with their ability to function as pore forming agent.

  2. Tablet coating by injection molding technology - Optimization of coating formulation attributes and coating process parameters.

    PubMed

    Desai, Parind M; Puri, Vibha; Brancazio, David; Halkude, Bhakti S; Hartman, Jeremy E; Wahane, Aniket V; Martinez, Alexander R; Jensen, Keith D; Harinath, Eranda; Braatz, Richard D; Chun, Jung-Hoon; Trout, Bernhardt L

    2018-01-01

    We developed and evaluated a solvent-free injection molding (IM) coating technology that could be suitable for continuous manufacturing via incorporation with IM tableting. Coating formulations (coating polymers and plasticizers) were prepared using hot-melt extrusion and screened via stress-strain analysis employing a universal testing machine. Selected coating formulations were studied for their melt flow characteristics. Tablets were coated using a vertical injection molding unit. Process parameters like softening temperature, injection pressure, and cooling temperature played a very important role in IM coating processing. IM coating employing polyethylene oxide (PEO) based formulations required sufficient room humidity (>30% RH) to avoid immediate cracks, whereas other formulations were insensitive to the room humidity. Tested formulations based on Eudrajit E PO and Kollicoat IR had unsuitable mechanical properties. Three coating formulations based on hydroxypropyl pea starch, PEO 1,000,000 and Opadry had favorable mechanical (<700MPa Young's modulus, >35% elongation, >95×10 4 J/m 3 toughness) and melt flow (>0.4g/min) characteristics, that rendered acceptable IM coats. These three formulations increased the dissolution time by 10, 15 and 35min, respectively (75% drug release), compared to the uncoated tablets (15min). Coated tablets stored in several environmental conditions remained stable to cracking for the evaluated 8-week time period. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Stability of cyanocobalamin in sugar-coated tablets.

    PubMed

    Ohmori, Shinji; Kataoka, Masumi; Koyama, Hiroyoshi

    2007-06-07

    The purpose of this study was to clarify the stability of cyanocobalamin (VB(12)-CN) in sugar-coated tablets containing fursultiamine hydrochloride (TTFD-HCl), riboflavin (VB(2)), and pyridoxine hydrochloride (VB(6)), and to identify the factors affecting the stability of VB(12)-CN in these sugar-coated tablets. The stability of VB(12)-CN was investigated using high-performance liquid chromatography while decomposition was evaluated kinetically. The decomposition of VB(12)-CN in sugar-coated tablets with high equilibrium relative humidity (more than 60%) under closed conditions showed complex kinetics and followed an Avrami-Erofe'ev equation, which expresses a random nucleation (two-dimensional growth of nuclei) model. We showed that equilibrium relative humidity, the incorporation of VB(2) and VB(6), and sugar coating, are the main factors influencing decomposition and that these factors cause the complex decomposition kinetics.

  4. [Preparation of coated tablets of glycyrrhetic acid-HP-beta-cyclodextrin tablets for colon-specific release].

    PubMed

    Cui, Qi-Hua; Cui, Jing-Hao; Zhang, Jin-Jin

    2008-10-01

    To prepare coated tablets of glycyrrhetinic acid and hydroxypropyl-beta-cyclodextrin (GTA-HP-beta-CYD) inclusion complex tablets for colon-specific release. In order to improve the solubility of GTA, the GTA-HP-beta-CYD inclusion complex was prepared by ultrasonic-lyophilization technique and its formation were characterized by X-ray powder diffraction profiles and infrared spectrometry. The effects of inclusion condition on the inclusion efficiency and stability coefficient of inclusion complex were investigated, respectively. After prepared GTA-HP-beta-CYD tablets by powder direct compression, the pH dependant polymer Eudragit III and/or mixed with Eudragit II were used for further coating materials in fluid-bed coater. The influences of coating weight on the GTA release in different pH conditions were evaluated to establish the method for prepering colon specific delivery tablets with pulsed release properties. The formation of inclusion complexes were proved by X-ray powder diffraction profile and phase solubility curve. The effect of pH value of solvent was played critical role on the preparation of GTA- HP-beta-CYD inclusion complex. And the inclusion efficiency of GTA was 9. 3% and the solubility was increased to 54. 6 times at optimized method. The Eudragit III coated GTA- HP-beta-CYD tablets with coating weight 10% and 16% were showed pH dependant colon specific release profiles with slow release rate. The release profile of tablets coated with the mixture of Eudragit II and Eudragit III (1:2) were indicated typical pH dependant colon specific and pulsed release properties while the coating weight was 17%. The preliminary method for preparation of colon specific release tablets containing glycyrrhetinic acid with improved solubility was established for further in vivo therapeutic experiment.

  5. Investigation on Raman spectral features of a coated tablet under variation of its orientation respective to laser illumination and measurement of nominal coating thickness of packed tablets.

    PubMed

    Kim, Jaejin; Hwang, Jinyoung; Woo, Young-Ah; Chung, Hoeil

    2016-11-30

    To investigate Raman spectral features of a coated biconvex tablet under variation of its orientation respective to laser illumination, spectra of the tablet were collected by illuminating laser on 12 different locations on the tablet with 3 different illumination angles of 45, 75 and 90°. The spectral variations were more substantial when the tablet faces with engraved letters and greater surface curvature were measured, since the sampled volume of coating relative to that of a core tablet changed significantly under these circumstances as the illumination angle varied. The preliminary examination confirmed that the acquisition of tablet-representative spectra was the requisite for reliable measurement of coating thickness. Then, to mimic real monitoring of coating process, Raman spectra were directly collected on a packing of 30 tablets with repetition of random tablet packing up to 15 times and univariate models utilizing the intensity of coating peak at 638cm -1 were developed using the cumulatively averaged spectra with an average weight of the 30 tablets as a reference. To acquire less tablet orientation-sensitive spectra, a wide area illumination (WAI) scheme providing a large sampling area (28.3mm 2 ) on a tablet with a long focal length (∼25cm) was employed. The averaging of the first to seventh spectra, equivalently utilizing more packing-representative spectra for quantitative analysis, made the measurement of nominal coating thickness of packed tablets accurate. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Alternative method for enteric coating of HPMC capsules resulting in ready-to-use enteric-coated capsules.

    PubMed

    Huyghebaert, Nathalie; Vermeire, An; Remon, Jean Paul

    2004-04-01

    The aim of this study was to develop an alternative method for enteric coating of HPMC capsules that avoids the sealing step before coating, resulting in ready-to-use enteric-coated capsules for the use in retail or hospital pharmacy or R&D sections of pharmaceutical industry and for the production of enteric-coated heat and moisture sensitive biomaterials. HPMC caps and bodies 00 (Vcaps, Capsugel) were coated separately in a fluid bed apparatus prior to filling (GPCG-1, Glatt) with Eudragit L30D-55 or Eudragit FS 30 D (Röhm), Aqoat AS-HF (Shin-Etsu) and Sureteric (Colorcon), using an optimised coating process. The coated bodies were filled and closed with the coated caps without encountering problems of coating damage. The release in 0.1N HCl after 2h from capsules coated with Eudragit L30D-55, Eudragit FS 30 D, Aqoat AS-HF and Sureteric was 0.6+/-.03, 0.6+/-0.3, 1.2+/-0.2 and 7.3+/-1.9%, respectively. The alternative method was reproducible and offered a way to overcome the time-consuming and expensive sealing step required using the conventional coating procedure. The obtained enteric-coated HPMC capsules can be stored (un)-filled for at least 6 months without loosing enteric properties.

  7. Tablet Velocity Measurement and Prediction in the Pharmaceutical Film Coating Process.

    PubMed

    Suzuki, Yasuhiro; Yokohama, Chihiro; Minami, Hidemi; Terada, Katsuhide

    2016-01-01

    The purpose of this study was to measure the tablet velocity in pan coating machines during the film coating process in order to understand the impact of the batch size (laboratory to commercial scale), coating machine type (DRIACOATER, HICOATER® and AQUA COATER®) and manufacturing conditions on tablet velocity. We used a high speed camera and particle image velocimetry to measure the tablet velocity in the coating pans. It was observed that increasing batch sizes resulted in increased tablet velocities under the same rotation number because of the differences in circumferential rotation speeds. We also observed the tendency that increase in the filling ratio of tablets resulted in an increased tablet velocity for all coating machines. Statistical analysis was used to make a tablet velocity predictive equation by employing the filling ratio and rotation speed as the parameters from these measured values. The correlation coefficients of predicted value and experimental value were more than 0.959 in each machine. Using the predictive equation to determine tablet velocities, the manufacturing conditions of previous products were reviewed, and it was found that the tablet velocities of commercial scales, in which tablet chipping and breakage problems had occurred, were higher than those of pilot scales or laboratory scales.

  8. 21 CFR 520.88a - Amoxicillin trihydrate film-coated tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Amoxicillin trihydrate film-coated tablets. 520.88a Section 520.88a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Amoxicillin trihydrate film-coated tablets. (a) Specifications. Each tablet contains amoxicillin trihydrate...

  9. Determining the coating thickness of tablets by chiseling and image analysis.

    PubMed

    Sasić, Slobodan

    2010-09-15

    Several tablets are chiseled and imaged in order to determine the variation in the coating thickness with the addition of the coating material (weight-gain). Chiseling is carried out with an ultrasonic chisel. The chiseled tablets are imaged in full and these images are exported into programming language Matlab in order to numerically analyze all the pixels along one side of the tablet. The coating thickness is statistically assessed at four cutting depths for three tablets obtained from four weight-gain experiments, a total of 48 images. The coating layer is clearly visible and determinable in the 'white-light' images even for the smallest weight gain of 1% but with sizeable errors due to the diffused boundaries between the coating and the core on one, and the coating and the background on the other side. Addition of the coating material clearly increases the coating thickness which is found to be somewhat higher at the top of the tablets than at the edges. Two approaches for assessment of the coating thickness are tested and are found to be in a very good agreement except for the thinnest coating layer. Copyright 2010 Elsevier B.V. All rights reserved.

  10. Optical coherence tomography for non-destructive analysis of coatings in pharmaceutical tablets

    NASA Astrophysics Data System (ADS)

    Markl, Daniel; Hannesschläger, Günther; Sacher, Stephan; Khinast, Johannes G.; Leitner, Michael

    2013-04-01

    Tablet coating is a common pharmaceutical technique to apply a thin continuous layer of solid on the top of a tablet or a granule containing active pharmaceutical ingredients (APIs). Coating thickness and homogeneity are critical parameters regarding the drug release rate, and consequently a direct or indirect monitoring strategy of these critical process parameters is essential. With the aid of Optical Coherence Tomography (OCT) it is not only possible to measure the absolute coating thickness, but also to detect inhomogeneities in the coating or substrate material. In this work the possible application of OCT as in-line method for monitoring pharmaceutical tablet film coating is studied. Firstly, the feasibility of OCT for analysis tablet coating is examined. Seven different commercially available film-coated tablets with different shapes, formulations and coating thicknesses were investigated off-line. OCT images were acquired by two different spectral-domain OCT systems operating at center wavelengths of 830 and 1325 nm. Since the images of both systems allow the analysis of the coatings, the OCT system employing the shorter wavelength and thus providing a higher axial resolution was selected for the further experiments. The influence of a moving tablet bed on OCT images was analyzed by considering a static tablet bed and moving the sensor head along the tablet bed. The ability to analyze the coating homogeneity is limited to a speed up to 0.3 m/s. However, determining the coating thickness and inter-coating uniformity is still possible up to a speed of 0.7 m/s.

  11. Pharmacokinetics of ketorolac tromethamine compression-coated tablets for colon delivery.

    PubMed

    Vemula, Sateesh Kumar; Veerareddy, Prabhakar Reddy; Devadasu, Venkat Ratnam

    2014-08-01

    Present research efforts are focused in developing compression-coated ketorolac tromethamine tablets to improve the drug levels in colon by retarding the drug release in the stomach and small intestine. To achieve this objective, core tablets containing ketorolac tromethamine were prepared by direct compression and compression coated with sodium alginate. The developed tablets were evaluated for physical properties, in vitro drug release, X-ray imaging, and pharmacokinetic studies in human volunteers. Based on the in vitro drug release study, the optimized formulation showed very little drug release (6.75 ± 0.49 %) in the initial lag period of 5 h, followed by progressive release up to 97.47 ± 0.93 % within 24 h. The X-ray imaging of tablets in human volunteers showed that the tablets reached the colon without disintegrating in the upper gastrointestinal tract. From the pharmacokinetic study, the C max of colon-targeted tablets was 3,486.70 ng/ml at T max 10 h, whereas in the case of immediate-release tablets, the C max of 4,506.31 ng/ml at T max 2 h signifies the ability of compression-coated tablets to target the colon. In conclusion, compression-coated tablets are suitable to deliver ketorolac tromethamine to the colon.

  12. Correlating bilayer tablet delamination tendencies to micro-environmental thermodynamic conditions during pan coating.

    PubMed

    Zacour, Brian M; Pandey, Preetanshu; Subramanian, Ganeshkumar; Gao, Julia Z; Nikfar, Faranak

    2014-06-01

    The objective of this study was to determine the impact that the micro-environment, as measured by PyroButton data loggers, experienced by tablets during the pan coating unit operation had on the layer adhesion of bilayer tablets in open storage conditions. A full factorial design of experiments (DOE) with three center points was conducted to study the impact of final tablet hardness, film coating spray rate and film coating exhaust temperature on the delamination tendencies of bilayer tablets. PyroButton data loggers were placed (fixed) at various locations in a pan coater and were also allowed to freely move with the tablet bed to measure the micro-environmental temperature and humidity conditions of the tablet bed. The variance in the measured micro-environment via PyroButton data loggers accounted for 75% of the variance in the delamination tendencies of bilayer tablets on storage (R(2 )= 0.75). A survival analysis suggested that tablet hardness and coating spray rate significantly impacted the delamination tendencies of the bilayer tablets under open storage conditions. The coating exhaust temperature did not show good correlation with the tablets' propensity to crack indicating that it was not representative of the coating micro-environment. Models created using data obtained from the PyroButton data loggers outperformed models created using primary DOE factors in the prediction of bilayer tablet strength, especially upon equipment or scale transfers. The coating micro-environment experienced by tablets during the pan coating unit operation significantly impacts the strength of the bilayer interface of tablets on storage.

  13. A novel electrostatic dry powder coating process for pharmaceutical dosage forms: immediate release coatings for tablets.

    PubMed

    Qiao, Mingxi; Zhang, Liqiang; Ma, Yingliang; Zhu, Jesse; Chow, Kwok

    2010-10-01

    An electrostatic dry powder coating process for pharmaceutical solid dosage forms was developed for the first time by electrostatic dry powder coating in a pan coater system. Two immediate release coating compositions with Opadry® AMB and Eudragit® EPO were successfully applied using this process. A liquid plasticizer was sprayed onto the surface of the tablet cores to increase the conductivity of tablet cores to enhance particle deposition, electrical resistivity reduced from greater than 1×10(13)Ωm to less than 1×10(9)Ωm, and to lower the glass transition temperature (T(g)) of the coating polymer for film forming in the pan coater. The application of liquid plasticizer was followed by spraying charged coating particles using an electrostatic charging gun to enhance the uniform deposition on tablet surface. The coating particles were coalesced into a thin film by curing at an acceptable processing temperature as formation was confirmed by SEM micrographs. The results also show that the optimized dry powder coating process produces tablets with smooth surface, good coating uniformity and release profile that are comparable to that of the tablet cores. The data also suggest that this novel electrostatic dry powder coating technique is an alternative to aqueous- or solvent-based coating process for pharmaceutical products. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

  14. Crystal coating via spray drying to improve powder tabletability.

    PubMed

    Vanhoorne, V; Peeters, E; Van Snick, B; Remon, J P; Vervaet, C

    2014-11-01

    A continuous crystal coating method was developed to improve both flowability and tabletability of powders. The method includes the introduction of solid, dry particles into an atomized spray during spray drying in order to coat and agglomerate individual particles. Paracetamol was used as a model drug as it exhibits poor flowability and high capping tendency upon compaction. The particle size enlargement and flowability were evaluated by the mean median particle size and flow index of the resulting powders. The crystal coating coprocessing method was successful for the production of powders containing 75% paracetamol with excellent tableting properties. However, the extent of agglomeration achieved during coprocessing was limited. Tablets compressed on a rotary tablet press in manual mode showed excellent compression properties without capping tendency. A formulation with 75% paracetamol, 5% PVP and 20% amorphous lactose yielded a tensile strength of 1.9 MPa at a compression pressure of 288 MPa. The friability of tablets compressed at 188 MPa was only 0.6%. The excellent tabletability of this formulation was attributed to the coating of paracetamol crystals with amorphous lactose and PVP through coprocessing and the presence of brittle and plastic components in the formulation. The coprocessing method was also successfully applied for the production of directly compressible lactose showing improved tensile strength and friability in comparison to a spray dried direct compression lactose grade.

  15. Aqueous Polymer Dispersion Coating Used for Osmotic Pump Tablets: Membrane Property Investigation and IVIVC Evaluation.

    PubMed

    Cheng, Lizhen; Gai, Xiumei; Wen, Haoyang; Liu, Dandan; Tang, Xin; Wang, Yanyan; Wang, Tuanjie; Pan, Weisan; Yang, Xinggang

    2018-01-01

    The objective of this study was to investigate the fundamental properties of propranolol hydrochloride osmotic pump tablets coated by aqueous polymer dispersion, simultaneously exploring the in vitro and in vivo correlation of the tablet. The physicochemical properties and parameters of aqueous polymer dispersion membranes (SEM, water uptake, and water vapor transmission coefficient) were investigated. In addition, the release behavior and the in vitro release and in vivo absorption profiles of the tablets coated by aqueous polymer dispersion were investigated by comparing with propranolol hydrochloride osmotic pump tablets coated by an organic solvent. Results showed that the similarity factor (f 2 ) between cellulose acetate-coated tablet and Eudragit-coated tablet was 78.1, and f 2 between cellulose acetate-coated tablet and Kollicoat-coated tablet was 77.6. The linear IVIVC of Eudragit-coated and Kollicoat-coated osmotic pump tablets was determined, which confirmed excellent correlation between the absorption in vivo and the drug release in vitro. Consequently, the membrane coated by aqueous polymer dispersion or organic solvent has similar in vitro release rates of controlled release. Also, compared with organic solvent coating, aqueous polymer dispersion has numerous advantages, such as reduced toxicity and no environmental damage. Therefore, the aqueous polymer dispersion technology has enormous potential as a replacement of organic solvent coating.

  16. Formulation and process strategies to minimize coat damage for compaction of coated pellets in a rotary tablet press: A mechanistic view.

    PubMed

    Xu, Min; Heng, Paul Wan Sia; Liew, Celine Valeria

    2016-02-29

    Compaction of multiple-unit pellet system (MUPS) tablets has been extensively studied in the past few decades but with marginal success. This study aims to investigate the formulation and process strategies for minimizing pellet coat damage caused by compaction and elucidate the mechanism of damage sustained during the preparation of MUPS tablets in a rotary tablet press. Blends containing ethylcellulose-coated pellets and cushioning agent (spray dried aggregates of micronized lactose and mannitol), were compacted into MUPS tablets in a rotary tablet press. The effects of compaction pressure and dwell time on the physicomechanical properties of resultant MUPS tablets and extent of pellet coat damage were systematically examined. The coated pellets from various locations at the axial and radial peripheral surfaces and core of the MUPS tablets were excavated and assessed for their coat damage individually. Interestingly, for a MUPS tablet formulation which consolidates by plastic deformation, the tablet mechanical strength could be enhanced without exacerbating pellet coat damage by extending the dwell time in the compaction cycle during rotary tableting. However, the increase in compaction pressure led to faster drug release rate. The location of the coated pellets in the MUPS tablet also contributed to the extent of their coat damage, possibly due to uneven force distribution within the compact. To ensure viability of pellet coat integrity, the formation of a continuous percolating network of cushioning agent is critical and the applied compaction pressure should be less than the pellet crushing strength. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. In-vitro characterization of 5-aminosalicylic acid release from MMX mesalamine tablets and determination of tablet coating thickness.

    PubMed

    Tenjarla, Srini; Abinusawa, Adeyinka

    2011-01-01

    Substantial variability in gastrointestinal pH is observed in patients with ulcerative colitis (UC). We characterized the effect of pH on 5-aminosalicylic acid (5-ASA) release from MMX mesalamine tablets (Shire Pharmaceuticals Inc., Wayne, PA, USA), examined thickness/uniformity of tablet film coatings, and explored the influence of simulating altered gastrointestinal motility. Nondestructive, three-dimensional, terahertz pulse imaging (TPI) was used to characterize the film coating of three lots of MMX mesalamine tablets (n=36). Thereafter, 5-ASA release from these tablets was evaluated using United States Pharmacopeia (USP) apparatus II at pH 6.8 and 7.2. Onset of tablet film-coat breach and mean dissolution time were determined for each lot. 5-ASA release was also assessed at three different paddle rotation speeds (50, 75, and 100 rpm) at pH 7.2. The mean ± SD film-coating thickness of the three lots of MMX mesalamine tablets were 109.2 ± 16.8, 113.1 ± 19.5, and 113.8 ± 19.8 μM, respectively. At pH 6.8 (100 rpm), the onset of film-coat breach was 10-30 minutes, whereas at pH 7.2 this was observed within 10 minutes. 5-ASA release was uniform at both pH conditions, with minimal lot-to-lot variability. Complete drug release was achieved within 6 hours under both pH conditions. 5-ASA release increased in proportion with paddle speed, but remained prolonged at all speeds. 5-ASA release from MMX mesalamine is unaffected by normal variations in simulated intracolonic pH. The dissolution profile of 5-ASA from MMX mesalamine tablets may be attributed to consistent outer film coatings and the hydrogel-forming matrix that controls the drug release after dissolution of the film coating.

  18. Analysis of large-scale tablet coating: Modeling, simulation and experiments.

    PubMed

    Boehling, P; Toschkoff, G; Knop, K; Kleinebudde, P; Just, S; Funke, A; Rehbaum, H; Khinast, J G

    2016-07-30

    This work concerns a tablet coating process in an industrial-scale drum coater. We set up a full-scale Design of Simulation Experiment (DoSE) using the Discrete Element Method (DEM) to investigate the influence of various process parameters (the spray rate, the number of nozzles, the rotation rate and the drum load) on the coefficient of inter-tablet coating variation (cv,inter). The coater was filled with up to 290kg of material, which is equivalent to 1,028,369 tablets. To mimic the tablet shape, the glued sphere approach was followed, and each modeled tablet consisted of eight spheres. We simulated the process via the eXtended Particle System (XPS), proving that it is possible to accurately simulate the tablet coating process on the industrial scale. The process time required to reach a uniform tablet coating was extrapolated based on the simulated data and was in good agreement with experimental results. The results are provided at various levels of details, from thorough investigation of the influence that the process parameters have on the cv,inter and the amount of tablets that visit the spray zone during the simulated 90s to the velocity in the spray zone and the spray and bed cycle time. It was found that increasing the number of nozzles and decreasing the spray rate had the highest influence on the cv,inter. Although increasing the drum load and the rotation rate increased the tablet velocity, it did not have a relevant influence on the cv,inter and the process time. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Characterization of the coating and tablet core roughness by means of 3D optical coherence tomography.

    PubMed

    Markl, Daniel; Wahl, Patrick; Pichler, Heinz; Sacher, Stephan; Khinast, Johannes G

    2018-01-30

    This study demonstrates the use of optical coherence tomography (OCT) to simultaneously characterize the roughness of the tablet core and coating of pharmaceutical tablets. OCT is a high resolution non-destructive and contactless imaging methodology to characterize structural properties of solid dosage forms. Besides measuring the coating thickness, it also facilitates the analysis of the tablet core and coating roughness. An automated data evaluation algorithm extracts information about coating thickness, as well as tablet core and coating roughness. Samples removed periodically from a pan coating process were investigated, on the basis of thickness and profile maps of the tablet core and coating computed from about 480,000 depth measurements (i.e., 3D data) per sample. This data enables the calculation of the root mean square deviation, the skewness and the kurtosis of the assessed profiles. Analyzing these roughness parameters revealed that, for the given coating formulation, small valleys in the tablet core are filled with coating, whereas coarse features of the tablet core are still visible on the final film-coated tablet. Moreover, the impact of the tablet core roughness on the coating thickness is analyzed by correlating the tablet core profile and the coating thickness map. The presented measurement method and processing could be in the future transferred to in-line OCT measurements, to investigate core and coating roughness during the production of film-coated tablets. Copyright © 2017. Published by Elsevier B.V.

  20. Modulation of venlafaxine hydrochloride release from press coated matrix tablet.

    PubMed

    Gohel, M C; Soni, C D; Nagori, S A; Sarvaiya, K G

    2008-01-01

    The aim of present study was to prepare novel modified release press coated tablets of venlafaxine hydrochloride. Hydroxypropylmethylcellulose K4M and hydroxypropylmethylcellulose K100M were used as release modifier in core and coat, respectively. A 3(2) full factorial design was adopted in the optimization study. The drug to polymer ratio in core and coat were chosen as independent variables. The drug release in the first hour and drug release rate between 1 and 12 h were chosen as dependent variables. The tablets were characterized for dimension analysis, crushing strength, friability and in vitro drug release. A check point batch, containing 1:2.6 and 1:5.4 drug to polymer in core and coat respectively, was prepared. The tablets of check point batch were subjected to in vitro drug release in dissolution media with pH 5, 7.2 and distilled water. The kinetics of drug release was best explained by Korsmeyer and Peppas model (anomalous non-Fickian diffusion). The systematic formulation approach enabled us to develop modified release venlafaxine hydrochloride tablets.

  1. Development and evaluation of a dimensionless mechanistic pan coating model for the prediction of coated tablet appearance.

    PubMed

    Niblett, Daniel; Porter, Stuart; Reynolds, Gavin; Morgan, Tomos; Greenamoyer, Jennifer; Hach, Ronald; Sido, Stephanie; Karan, Kapish; Gabbott, Ian

    2017-08-07

    A mathematical, mechanistic tablet film-coating model has been developed for pharmaceutical pan coating systems based on the mechanisms of atomisation, tablet bed movement and droplet drying with the main purpose of predicting tablet appearance quality. Two dimensionless quantities were used to characterise the product properties and operating parameters: the dimensionless Spray Flux (relating to area coverage of the spray droplets) and the Niblett Number (relating to the time available for drying of coating droplets). The Niblett Number is the ratio between the time a droplet needs to dry under given thermodynamic conditions and the time available for the droplet while on the surface of the tablet bed. The time available for drying on the tablet bed surface is critical for appearance quality. These two dimensionless quantities were used to select process parameters for a set of 22 coating experiments, performed over a wide range of multivariate process parameters. The dimensionless Regime Map created can be used to visualise the effect of interacting process parameters on overall tablet appearance quality and defects such as picking and logo bridging. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Modeling the motion and orientation of various pharmaceutical tablet shapes in a film coating pan using DEM.

    PubMed

    Ketterhagen, William R

    2011-05-16

    Film coating uniformity is an important quality attribute of pharmaceutical tablets. Large variability in coating thickness can limit process efficiency or cause significant variation in the amount or delivery rate of the active pharmaceutical ingredient to the patient. In this work, the discrete element method (DEM) is used to computationally model the motion and orientation of several novel pharmaceutical tablet shapes in a film coating pan in order to predict coating uniformity. The model predictions are first confirmed with experimental data obtained from an equivalent film coating pan using a machine vision system. The model is then applied to predict coating uniformity for various tablet shapes, pan speeds, and pan loadings. The relative effects of these parameters on both inter- and intra-tablet film coating uniformity are assessed. The DEM results show intra-tablet coating uniformity is strongly influenced by tablet shape, and the extent of this can be predicted by a measure of the tablet shape. The tablet shape is shown to have little effect on the mixing of tablets, and thus, the inter-tablet coating uniformity. The pan rotation speed and pan loading are shown to have a small effect on intra-tablet coating uniformity but a more significant impact on inter-tablet uniformity. These results demonstrate the usefulness of modeling in guiding drug product development decisions such as selection of tablet shape and process operating conditions. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Automated pharmaceutical tablet coating layer evaluation of optical coherence tomography images

    NASA Astrophysics Data System (ADS)

    Markl, Daniel; Hannesschläger, Günther; Sacher, Stephan; Leitner, Michael; Khinast, Johannes G.; Buchsbaum, Andreas

    2015-03-01

    Film coating of pharmaceutical tablets is often applied to influence the drug release behaviour. The coating characteristics such as thickness and uniformity are critical quality parameters, which need to be precisely controlled. Optical coherence tomography (OCT) shows not only high potential for off-line quality control of film-coated tablets but also for in-line monitoring of coating processes. However, an in-line quality control tool must be able to determine coating thickness measurements automatically and in real-time. This study proposes an automatic thickness evaluation algorithm for bi-convex tables, which provides about 1000 thickness measurements within 1 s. Beside the segmentation of the coating layer, optical distortions due to refraction of the beam by the air/coating interface are corrected. Moreover, during in-line monitoring the tablets might be in oblique orientation, which needs to be considered in the algorithm design. Experiments were conducted where the tablet was rotated to specified angles. Manual and automatic thickness measurements were compared for varying coating thicknesses, angles of rotations, and beam displacements (i.e. lateral displacement between successive depth scans). The automatic thickness determination algorithm provides highly accurate results up to an angle of rotation of 30°. The computation time was reduced to 0.53 s for 700 thickness measurements by introducing feasibility constraints in the algorithm.

  4. Accelerating the dissolution of enteric coatings in the upper small intestine: evolution of a novel pH 5.6 bicarbonate buffer system to assess drug release.

    PubMed

    Varum, Felipe J O; Merchant, Hamid A; Goyanes, Alvaro; Assi, Pardis; Zboranová, Veronika; Basit, Abdul W

    2014-07-01

    Despite rapid dissolution in compendial phosphate buffers, gastro resistant (enteric coated) products can take up to 2 h to disintegrate in the human small intestine, which clearly highlights the inadequacy of the in vitro test method to predict in vivo behaviour of these formulations. The aim of this study was to establish the utility of a novel pH 5.6 bicarbonate buffer, stabilized by an Auto pH™ System, as a better surrogate of the conditions of the proximal small intestine to investigate the dissolution behaviour of standard and accelerated release enteric double coating formulations. Prednisolone tablets were coated with 3 or 5 mg/cm(2) of partially neutralized EUDRAGIT(®) L 30 D-55, HP-55 or HPMC adjusted to pH 6 or 8. An outer layer of EUDRAGIT(®) L 30 D-55 was applied at 5mg/cm(2). For comparison purposes, a standard single layer of EUDRAGIT(®) L 30 D-55 was applied to the tablets. Dissolution was carried out using USP II apparatus in 0.1 M HCl for 2 h, followed by pH 5.6 bicarbonate buffer. EUDRAGIT(®) L 30 D-55 single-coated tablets showed a slow drug release with a lag time of 75 min in buffer, whereas release from the EUDRAGIT(®) L 30 D-55 double-coated tablets was accelerated. These in vitro lag times closely match the in vivo disintegration times for these coated tablets reported previously. Drug release was further accelerated from modified double coatings, particularly in the case of coatings with a thinner inner layer of HP-55 or HPMC (pH 8 and KH2PO4). This study confirms that the pH 5.6 bicarbonate buffer system offers significant advantages during the development of dosage forms designed to release the drug in the upper small intestine. Copyright © 2014. Published by Elsevier B.V.

  5. Colon targeted guar gum compression coated tablets of flurbiprofen: formulation, development, and pharmacokinetics.

    PubMed

    Vemula, Sateesh Kumar; Bontha, Vijaya Kumar

    2013-01-01

    The rationale of the present study is to formulate flurbiprofen colon targeted compression coated tablets using guar gum to improve the therapeutic efficacy by increasing drug levels in colon, and also to reduce the side effects in upper gastrointestinal tract. Direct compression method was used to prepare flurbiprofen core tablets, and they were compression coated with guar gum. Then the tablets were optimized with the support of in vitro dissolution studies, and further it was proved by pharmacokinetic studies. The optimized formulation (F4) showed almost complete drug release in the colon (99.86%) within 24 h without drug loss in the initial lag period of 5 h (only 6.84% drug release was observed during this period). The pharmacokinetic estimations proved the capability of guar gum compression coated tablets to achieve colon targeting. The C(max) of colon targeted tablets was 11956.15 ng/mL at T max of 10 h whereas it was 15677.52 ng/mL at 3 h in case of immediate release tablets. The area under the curve for the immediate release and compression coated tablets was 40385.78 and 78214.50 ng-h/mL and the mean resident time was 3.49 and 10.78 h, respectively. In conclusion, formulation of guar gum compression coated tablets was appropriate for colon targeting of flurbiprofen.

  6. Angular circulation speed of tablets in a vibratory tablet coating pan.

    PubMed

    Kumar, Rahul; Wassgren, Carl

    2013-03-01

    In this work, a single tablet model and a discrete element method (DEM) computer simulation are developed to obtain the angular circulation speed of tablets in a vibratory tablet coating pan for range of vibration frequencies and amplitudes. The models identify three important dimensionless parameters that influence the speed of the tablets: the dimensionless amplitude ratio (a/R), the Froude number (aω2/g), and the tablet-wall friction coefficient, where a is the peak vibration amplitude at the drum center, ω is the vibration angular frequency, R is the drum radius, and g is the acceleration due to gravity. The models predict that the angular circulation speed of tablets increases with an increase in each of these parameters. The rate of increase in the angular circulation speed is observed to decrease for larger values of a/R. The angular circulation speed reaches an asymptote beyond a tablet-wall friction coefficient value of about 0.4. Furthermore, it is found that the Froude number should be greater than one for the tablets to start circulating. The angular circulation speed increases as Froude number increases but then does not change significantly at larger values of the Froude number. Period doubling, where the motion of the bed is repeated every two cycles, occurs at a Froude number larger than five. The single tablet model, although much simpler than the DEM model, is able to predict the maximum circulation speed (the limiting case for a large value of tablet-wall friction coefficient) as well as the transition to period doubling.

  7. Colon Targeted Guar Gum Compression Coated Tablets of Flurbiprofen: Formulation, Development, and Pharmacokinetics

    PubMed Central

    Bontha, Vijaya Kumar

    2013-01-01

    The rationale of the present study is to formulate flurbiprofen colon targeted compression coated tablets using guar gum to improve the therapeutic efficacy by increasing drug levels in colon, and also to reduce the side effects in upper gastrointestinal tract. Direct compression method was used to prepare flurbiprofen core tablets, and they were compression coated with guar gum. Then the tablets were optimized with the support of in vitro dissolution studies, and further it was proved by pharmacokinetic studies. The optimized formulation (F4) showed almost complete drug release in the colon (99.86%) within 24 h without drug loss in the initial lag period of 5 h (only 6.84% drug release was observed during this period). The pharmacokinetic estimations proved the capability of guar gum compression coated tablets to achieve colon targeting. The C max of colon targeted tablets was 11956.15 ng/mL at T max of 10 h whereas it was 15677.52 ng/mL at 3 h in case of immediate release tablets. The area under the curve for the immediate release and compression coated tablets was 40385.78 and 78214.50 ng-h/mL and the mean resident time was 3.49 and 10.78 h, respectively. In conclusion, formulation of guar gum compression coated tablets was appropriate for colon targeting of flurbiprofen. PMID:24260738

  8. Applying terahertz technology for nondestructive detection of crack initiation in a film-coated layer on a swelling tablet

    PubMed Central

    Momose, Wataru; Yoshino, Hiroyuki; Katakawa, Yoshifumi; Yamashita, Kazunari; Imai, Keiji; Sako, Kazuhiro; Kato, Eiji; Irisawa, Akiyoshi; Yonemochi, Etsuo; Terada, Katsuhide

    2012-01-01

    Here, we describe a nondestructive approach using terahertz wave to detect crack initiation in a film-coated layer on a drug tablet. During scale-up and scale-down of the film coating process, differences in film density and gaps between the film-coated layer and the uncoated tablet were generated due to differences in film coating process parameters, such as the tablet-filling rate in the coating machine, spray pressure, and gas–liquid ratio etc. Tablets using the PEO/PEG formulation were employed as uncoated tablets. We found that heat and humidity caused tablets to swell, thereby breaking the film-coated layer. Using our novel approach with terahertz wave nondestructively detect film surface density (FSD) and interface density differences (IDDs) between the film-coated layer and an uncoated tablet. We also found that a reduced FSD and IDD between the film-coated layer and uncoated tablet increased the risk of crack initiation in the film-coated layer, thereby enabling us to nondestructively predict initiation of cracks in the film-coated layer. Using this method, crack initiation can be nondestructively assessed in swelling tablets after the film coating process without conducting accelerated stability tests, and film coating process parameters during scale-up and scale-down studies can be appropriately established. PMID:25755992

  9. Optimization of propranolol HCl release kinetics from press coated sustained release tablets.

    PubMed

    Ali, Adel Ahmed; Ali, Ahmed Mahmoud

    2013-01-01

    Press-coated sustained release tablets offer a valuable, cheap and easy manufacture alternative to the highly expensive, multi-step manufacture and filling of coated beads. In this study, propranolol HCl press-coated tablets were prepared using hydroxylpropylmethylcellulose (HPMC) as tablet coating material together with carbopol 971P and compressol as release modifiers. The prepared formulations were optimized for zero-order release using artificial neural network program (INForm, Intelligensys Ltd, North Yorkshire, UK). Typical zero-order release kinetics with extended release profile for more than 12 h was obtained. The most important variables considered by the program in optimizing formulations were type and proportion of polymer mixture in the coat layer and distribution ratio of drug between core and coat. The key elements found were; incorporation of 31-38 % of the drug in the coat, fixing the amount of polymer in coat to be not less than 50 % of coat layer. Optimum zero-order release kinetics (linear regression r2 = 0.997 and Peppas model n value > 0.80) were obtained when 2.5-10 % carbopol and 25-42.5% compressol were incorporated into the 50 % HPMC coat layer.

  10. Experimental analysis of tablet properties for discrete element modeling of an active coating process.

    PubMed

    Just, Sarah; Toschkoff, Gregor; Funke, Adrian; Djuric, Dejan; Scharrer, Georg; Khinast, Johannes; Knop, Klaus; Kleinebudde, Peter

    2013-03-01

    Coating of solid dosage forms is an important unit operation in the pharmaceutical industry. In recent years, numerical simulations of drug manufacturing processes have been gaining interest as process analytical technology tools. The discrete element method (DEM) in particular is suitable to model tablet-coating processes. For the development of accurate simulations, information on the material properties of the tablets is required. In this study, the mechanical parameters Young's modulus, coefficient of restitution (CoR), and coefficients of friction (CoF) of gastrointestinal therapeutic systems (GITS) and of active-coated GITS were measured experimentally. The dynamic angle of repose of these tablets in a drum coater was investigated to revise the CoF. The resulting values were used as input data in DEM simulations to compare simulation and experiment. A mean value of Young's modulus of 31.9 MPa was determined by the uniaxial compression test. The CoR was found to be 0.78. For both tablet-steel and tablet-tablet friction, active-coated GITS showed a higher CoF compared with GITS. According to the values of the dynamic angle of repose, the CoF was adjusted to obtain consistent tablet motion in the simulation and in the experiment. On the basis of this experimental characterization, mechanical parameters are integrated into DEM simulation programs to perform numerical analysis of coating processes.

  11. Hydrophilic excipients modulate the time lag of time-controlled disintegrating press-coated tablets.

    PubMed

    Lin, Shan-Yang; Li, Mei-Jane; Lin, Kung-Hsu

    2004-08-16

    An oral press-coated tablet was developed by means of direct compression to achieve the time-controlled disintegrating or rupturing function with a distinct predetermined lag time. This press-coated tablet containing sodium diclofenac in the inner core was formulated with an outer shell by different weight ratios of hydrophobic polymer of micronized ethylcellulose (EC) powder and hydrophilic excipients such as spray-dried lactose (SDL) or hydroxypropyl methylcellulose (HPMC). The effect of the formulation of an outer shell comprising both hydrophobic polymer and hydrophilic excipients on the time lag of drug release was investigated. The release profile of the press-coated tablet exhibited a time period without drug release (time lag) followed by a rapid and complete release phase, in which the outer shell ruptured or broke into 2 halves. The lag phase was markedly dependent on the weight ratios of EC/SDL or EC/HPMC in the outer shell. Different time lags of the press-coated tablets from 1.0 to 16.3 hours could be modulated by changing the type and amount of the excipients. A semilogarithmic plot of the time lag of the tablet against the weight ratios of EC/SDL or EC/HPMC in the outer shell demonstrated a good linear relationship, with r = 0.976 and r = 0.982, respectively. The predetermined time lag prior to the drug release from a press-coated tablet prepared by using a micronized EC as a retarding coating shell can be adequately scheduled with the addition of hydrophilic excipients according to the time or site requirements.

  12. Structural changes of polymer-coated microgranules and excipients on tableting investigated by microtomography using synchrotron X-ray radiation.

    PubMed

    Kajihara, Ryusuke; Noguchi, Shuji; Iwao, Yasunori; Suzuki, Yoshio; Terada, Yasuko; Uesugi, Kentaro; Itai, Shigeru

    2015-03-15

    Multiple-unit tablets consisting of polymer-coated microgranules and excipients have a number of advantageous pharmaceutical properties. Polymer-coated microgranules are known to often lose their functionality because of damage to the polymer coating caused by tableting, and the mechanism of polymer coating damage as well as the structural changes of excipients upon tableting had been investigated but without in-situ visualization and quantitative analysis. To elucidate the mechanism of coating damage, the internal structures of multiple-unit tablets were investigated by X-ray computed microtomography using synchrotron X-rays. Cross sectional images of the tablets with sub-micron spatial resolution clearly revealed that void spaces remained around the compressed excipient particles in the tablets containing an excipient composed of cellulose and lactose (Cellactose(®) 80), whereas much smaller void spaces remained in the tablets containing an excipient made of sorbitol (Parteck(®) SI 150). The relationships between the void spaces and the physical properties of the tablets such as hardness and disintegration were investigated. Damage to the polymer coating in tablets was found mainly where polymer-coated microgranules were in direct contact with each other in both types of tablets, which could be attributed to the difference in hardness of excipient particles and the core of the polymer-coated microgranules. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Surface properties of semi-synthetic enteric coating films: Opportunities to develop bio-based enteric coating films for colon- targeted delivery

    USDA-ARS?s Scientific Manuscript database

    This study investigated the surface properties of the semi-synthetic enteric coating materials for potential colon- targeted bioactive delivery. The enteric coating materials were produced by combining nanoscale resistant starch, pectin, and carboxymethylcellulose. The surface properties of the co...

  14. 21 CFR 520.88g - Amoxicillin trihydrate and clavulanate potassium film-coated tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Amoxicillin trihydrate and clavulanate potassium film-coated tablets. 520.88g Section 520.88g Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... ANIMAL DRUGS § 520.88g Amoxicillin trihydrate and clavulanate potassium film-coated tablets. (a...

  15. Preparation of monolithic osmotic pump system by coating the indented core tablet.

    PubMed

    Liu, Longxiao; Che, Binjie

    2006-10-01

    A method for the preparation of monolithic osmotic pump tablet was obtained by coating the indented core tablet compressed by the punch with a needle. Atenolol was used as the model drug, sodium chloride as osmotic agent and polyethylene oxide as suspending agent. Ethyl cellulose was employed as semipermeable membrane containing polyethylene glycol 400 as plasticizer for controlling membrane permeability. The formulation of atenolol osmotic pump tablet was optimized by orthogonal design and evaluated by similarity factor (f2). The optimal formulation was evaluated in various release media and agitation rates. Indentation size of core tablet hardly affected drug release in the range of (1.00-1.14) mm. The optimal osmotic tablet was found to be able to deliver atenolol at an approximately constant rate up to 24h, independent of both release media and agitation rate. The method that is simplified by coating the indented core tablet with the elimination of laser drilling may be promising in the field of the preparation of osmotic pump tablet.

  16. Study of controlled-release floating tablets of dipyridamole using the dry-coated method.

    PubMed

    Chen, Kai; Wen, Haoyang; Yang, Feifei; Yu, Yibin; Gai, Xiumei; Wang, Haiying; Li, Pingfei; Pan, Weisan; Yang, Xinggang

    2018-01-01

    Dipyridamole (DIP), having a short biological half-life, has a narrow absorption window and is primarily absorbed in the stomach. So, the purpose of this study was to prepare controlled-release floating (CRF) tablets of dipyridamole by the dry-coated method. The influence of agents with different viscosity, hydroxypropylmethylcellulose (HPMC) and polyvinylpyrollidon K30 (PVP K30) in the core tablet and low-viscosity HPMC and PVP K30 in the coating layer on drug release, were investigated. Then, a study with a three-factor, three-level orthogonal experimental design was used to optimize the formulation of the CRF tablets. After data processing, the optimized formulation was found to be: 80 mg HPMC K4M in the core tablet, 80 mg HPMC E15 in core tablet and 40 mg PVP K30 in the coating layer. Moreover, an in vitro buoyancy study showed that the optimized formulation had an excellent floating ability and could immediately float without a lag time and this lasted more than 12 h. Furthermore, an in vivo gamma scintigraphic study showed that the gastric residence time of the CRF tablet was about 8 h.

  17. Impact of Processing Conditions on Inter-tablet Coating Thickness Variations Measured by Terahertz In-Line Sensing

    PubMed Central

    Lin, Hungyen; May, Robert K; Evans, Michael J; Zhong, Shuncong; Gladden, Lynn F; Shen, Yaochun; Zeitler, J Axel

    2015-01-01

    A novel in-line technique utilising pulsed terahertz radiation for direct measurement of the film coating thickness of individual tablets during the coating process was previously developed and demonstrated on a production-scale coater. Here, we use this technique to monitor the evolution of tablet film coating thickness and its inter-tablet variability during the coating process under a number of different process conditions that have been purposefully induced in the production-scale coating process. The changes that were introduced to the coating process include removing the baffles from the coater, adding uncoated tablets to the running process, halting the drum, blockage of spray guns and changes to the spray rate. The terahertz sensor was able to pick up the resulting changes in average coating thickness in the coating drum and we report the impact of these process changes on the resulting coating quality. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:2513–2522, 2015 PMID:26037660

  18. Optimization of process parameters for a quasi-continuous tablet coating system using design of experiments.

    PubMed

    Cahyadi, Christine; Heng, Paul Wan Sia; Chan, Lai Wah

    2011-03-01

    The aim of this study was to identify and optimize the critical process parameters of the newly developed Supercell quasi-continuous coater for optimal tablet coat quality. Design of experiments, aided by multivariate analysis techniques, was used to quantify the effects of various coating process conditions and their interactions on the quality of film-coated tablets. The process parameters varied included batch size, inlet temperature, atomizing pressure, plenum pressure, spray rate and coating level. An initial screening stage was carried out using a 2(6-1(IV)) fractional factorial design. Following these preliminary experiments, optimization study was carried out using the Box-Behnken design. Main response variables measured included drug-loading efficiency, coat thickness variation, and the extent of tablet damage. Apparent optimum conditions were determined by using response surface plots. The process parameters exerted various effects on the different response variables. Hence, trade-offs between individual optima were necessary to obtain the best compromised set of conditions. The adequacy of the optimized process conditions in meeting the combined goals for all responses was indicated by the composite desirability value. By using response surface methodology and optimization, coating conditions which produced coated tablets of high drug-loading efficiency, low incidences of tablet damage and low coat thickness variation were defined. Optimal conditions were found to vary over a large spectrum when different responses were considered. Changes in processing parameters across the design space did not result in drastic changes to coat quality, thereby demonstrating robustness in the Supercell coating process. © 2010 American Association of Pharmaceutical Scientists

  19. A novel in-line NIR spectroscopy application for the monitoring of tablet film coating in an industrial scale process.

    PubMed

    Möltgen, C-V; Puchert, T; Menezes, J C; Lochmann, D; Reich, G

    2012-04-15

    Film coating of tablets is a multivariate pharmaceutical unit operation. In this study an innovative in-line Fourier-Transform Near-Infrared Spectroscopy (FT-NIRS) application is described which enables real-time monitoring of a full industrial scale pan coating process of heart-shaped tablets. The tablets were coated with a thin hydroxypropyl methylcellulose (HPMC) film of up to approx. 28 μm on the tablet face as determined by SEM, corresponding to a weight gain of 2.26%. For a better understanding of the aqueous coating process the NIR probe was positioned inside the rotating tablet bed. Five full scale experimental runs have been performed to evaluate the impact of process variables such as pan rotation, exhaust air temperature, spray rate and pan load and elaborate robust and selective quantitative calibration models for the real-time determination of both coating growth and tablet moisture content. Principal Component (PC) score plots allowed each coating step, namely preheating, spraying and drying to be distinguished and the dominating factors and their spectral effects to be identified (e.g. temperature, moisture, coating growth, change of tablet bed density, and core/coat interactions). The distinct separation of HPMC coating growth and tablet moisture in different PCs enabled a real-time in-line monitoring of both attributes. A PLS calibration model based on Karl Fischer reference values allowed the tablet moisture trajectory to be determined throughout the entire coating process. A 1-latent variable iPLS weight gain calibration model with calibration samples from process stages dominated by the coating growth (i.e. ≥ 30% of the theoretically applied amount of coating) was sufficiently selective and accurate to predict the progress of the thin HPMC coating layer. At-line NIR Chemical Imaging (NIR-CI) in combination with PLS Discriminant Analysis (PLSDA) verified the HPMC coating growth and physical changes at the core/coat interface during the initial

  20. A new formulation for orally disintegrating tablets using a suspension spray-coating method.

    PubMed

    Okuda, Y; Irisawa, Y; Okimoto, K; Osawa, T; Yamashita, S

    2009-12-01

    The aim of this study was to design a new orally disintegrating tablet (ODT) that has high tablet hardness and a fast oral disintegration rate using a new preparation method. To obtain rapid disintegration granules (RDGs), a saccharide, such as trehalose, mannitol, or lactose, was spray-coated with a suspension of corn starch using a fluidized-bed granulator (suspension method). As an additional disintegrant, crospovidone, light anhydrous silicic acid, or hydroxypropyl starch was also included in the suspension. The RDGs obtained possessed extremely large surface areas, narrow particle size distribution, and numerous micro-pores. When tabletting these RDGs, it was found that the RDGs increased tablet hardness by decreasing plastic deformation and increasing the contact frequency between granules. In all tablets, a linear relationship was observed between tablet hardness and oral disintegration time. From each linear correlation line, a slope (D/H value) and an intercept (D/H(0) value) were calculated. Tablets with small D/H and D/H(0) values could disintegrate immediately in the oral cavity regardless of the tablet hardness and were considered to be appropriate for ODTs. Therefore, these values were used as key parameters to select better ODTs. Of all the RDGs prepared in this study, mannitol spray-coated with a suspension of corn starch and crospovidone (2.5:1 w/w ratio) showed most appropriate properties for ODTs; fast in vivo oral disintegration time, and high tablet hardness. In conclusion, this simple method to prepare superior formulations for new ODTs was established by spray-coating mannitol with a suspension of appropriate disintegrants.

  1. Assessment of the pharmaceutical quality of marketed enteric coated pantoprazole sodium sesquihydrate products.

    PubMed

    Mostafa, Haitham F; Ibrahim, Mohamed A; Mahrous, Gamal M; Sakr, Adel

    2011-04-01

    Pantoprazole sodium sesquihydrate (PSS) is a proton pump inhibitor, used in acid-related disorders, like peptic ulcer and gastroesophageal reflux. Increasing the number of pantoprazole containing products in the market, raises questions of its efficacy and generic substitution. The pharmaceutical quality of 6 generic PSS enteric coated tablets in 2 local markets was assessed relative to the innovator product (pantozol®). Uniformity of dosage unit, disintegration and in vitro drug release were determined using United States pharmacopeia for delayed release tablets. The similarity factor (f2) was assessed using the FDA recommended approach (f2 similarity factor). The content uniformity of the innovator product was 98.39% of the labeled claim with RSD value of 1.08%, while the content of generic products ranged from 96.98% to 98.80% with RSD values of 1.24-2.19%. All the products showed no disintegration, cracks or swelling in 0.1 N HCl, except product 1, which showed complete disintegration after 20 min. However, the disintegration of all the products in phosphate buffer met USP requirements. Dissolution of tablets in 0.1 N HCl showed no drug release after 2 h except product 1 in which one tablet showed a drug release more than 10% at acid stage level A1. In addition, three tablets of this product showed dissolution of 45%, 48% and 69% at acid stage level A2. The similarity factor f2 of the products was between 71 and 74 indicating the similarity in dissolution profiles of all the products in accordance to FDA requirements, except product 1 in which f2 value was 18.67.

  2. Effect of the External Lubrication Method for a Rotary Tablet Press on the Adhesion of the Film Coating Layer.

    PubMed

    Kondo, Hisami; Toyota, Hiroyasu; Kamiya, Takayuki; Yamashita, Kazunari; Hakomori, Tadashi; Imoto, Junko; Kimura, Shin-Ichiro; Iwao, Yasunori; Itai, Shigeru

    2017-01-01

    External lubrication is a useful method which reduces the adhesion of powder to punches and dies by spraying lubricants during the tableting process. However, no information is available on whether the tablets prepared using an external lubrication system can be applicable for a film coating process. In this study, we evaluated the adhesion force of the film coating layer to the surface of tablets prepared using an external lubrication method, compared with those prepared using internal lubrication method. We also evaluated wettability, roughness and lubricant distribution state on the tablet surface before film coating, and investigated the relationship between peeling of the film coating layer and these tablet surface properties. Increasing lubrication through the external lubrication method decreased wettability of the tablet surface. However, no change was observed in the adhesion force of the film coating layer. On the other hand, increasing lubrication through the internal lubrication method, decreased both wettability of the tablet surface and the adhesion force of the film coating layer. The magnesium stearate distribution state on the tablet surface was assessed using an X-ray fluorescent analyzer and lubricant agglomerates were observed in the case of the internal lubrication method. However, the lubricant was uniformly dispersed in the external lubrication samples. These results indicate that the distribution state of the lubricant affects the adhesion force of the film coating layer, and external lubrication maintained sufficient lubricity and adhesion force of the film coating layer with a small amount of lubricant.

  3. Formulation and evaluation of press coated tablets for pulsatile drug delivery using hydrophilic and hydrophobic polymers.

    PubMed

    Rane, Ashish Babulal; Gattani, Surendra Ganeshlal; Kadam, Vinayak Dinkar; Tekade, Avinash Ramrao

    2009-11-01

    The aim of present investigation was to develop press coated tablet for pulsatile drug delivery of ketoprofen using hydrophilic and hydrophobic polymers. The drug delivery system was designed to deliver the drug at such a time when it could be most needful to patient of rheumatoid arthritis. The press coated tablets containing ketoprofen in the inner core was formulated with an outer shell by different weight ratio of hydrophobic polymer (micronized ethyl cellulose powder) and hydrophilic polymers (glycinemax husk or sodium alginate). The release profile of press coated tablet exhibited a lag time followed by burst release, in which outer shell ruptured into two halves. Authors also investigated factors influencing on lag time such as particle size and viscosity of ethyl cellulose, outer coating weight and paddle rpm. The surface morphology of the tablet was examined by a scanning electron microscopy. Differential scanning calorimeter and Fourier transformed infrared spectroscopy study showed compatibility between ketoprofen and coating material.

  4. Development of a novel tablet-in-capsule formulation of mesalamine for inflammatory bowel disease.

    PubMed

    Patel, Mayur M; Amin, Avani F

    2013-01-01

    The objective of the present work was to develop a tablet-in-capsule type of multiunit system, which releases the drug in a controlled manner at pre-programmed time intervals. The system consists of an enteric-coated hydroxypropyl methylcellulose capsule filled with four units of mesalamine minitablets, each of which was further coated with different ratios of Eudragit(®) E100 and Eudragit(®) RS100. In vitro evaluation of tablets coated with Eudragit(®) E100 and Eudragit(®) RS100 at different pH conditions revealed that at lower pH levels (2.0, 3.6 and 5.5 pH), the drug release is mainly governed by the dissolution of Eudragit(®) E100 from the Eudragit(®) E100 and Eudragit(®) RS100 coat. In vitro evaluation of capsules enteric coated with Eudragit(®) L100 and Eudragit(®) S100 revealed that a maximum lag time of 3 h and 4 h was obtained, respectively. In vivo roentgenographic evaluation in rabbits revealed that the developed system remained intact until it reaches the targeted region of the gastrointestinal tract, i.e. ileum and colon, where the tablets were released after the dissolution of the enteric coat Eudragit(®) L100 and Eudragit(®) S100, respectively. The developed system exhibited a promising targeting behavior and hence may be used for the treatment of inflammatory bowel disease.

  5. Preparation of delayed release tablet dosage forms by compression coating: effect of coating material on theophylline release.

    PubMed

    El-Malah, Yasser; Nazzal, Sami

    2010-06-01

    In this study, compression-coated tablets were prepared and examined by real-time swelling/erosion analysis and dissolution studies. Of the coating materials, PVP showed no swelling behavior and had no impact on theophylline release. Polyox(®) exhibited swelling behavior of an entangled polymer, which was reflected in its > 14-hour delayed-release profile. Hydroxypropyl methylcellulose (HPMC), which revealed the characteristics of a disentangled polymer, caused a 2-h delay in theophylline release. Based on preliminary texture analysis data, Polyox(®)/PVP blends were used as coating materials to manipulate the onset of drug release from the compression-coated tablets. Of the blends, at a 1:1 ratio, for example, resulted in a burst release after 10 h, which demonstrated the feasibility of preparing delayed release dosage forms by compression coating. Furthermore, it was feasible to predict the dissolution behavior of polymers from their swelling/erosion data, which were generated from texture analysis.

  6. Bilayer tablets of Paliperidone for Extended release osmotic drug delivery

    NASA Astrophysics Data System (ADS)

    Chowdary, K. Sunil; Napoleon, A. A.

    2017-11-01

    The purpose of this study is to develop and optimize the formulation of paliperidone bilayer tablet core and coating which should meet in vitro performance of trilayered Innovator sample Invega. Optimization of core formulations prepared by different ratio of polyox grades and optimization of coating of (i) sub-coating build-up with hydroxy ethyl cellulose (HEC) and (ii).enteric coating build-up with cellulose acetate (CA). Some important influence factors such as different core tablet compositions and different coating solution ingredients involved in the formulation procedure were investigated. The optimization of formulation and process was conducted by comparing different in vitro release behaviours of Paliperidone. In vitro dissolution studies of Innovator sample (Invega) with formulations of different release rate which ever close release pattern during the whole 24 h test is finalized.

  7. Preparation and in-vivo pharmacokinetic study of a novel extended release compression coated tablets of fenoterol hydrobromide.

    PubMed

    Elshafeey, Ahmed H; Sami, Elshaimaa I

    2008-01-01

    The aim of this study was to formulate extended release compression coated core tablets of fenoterol hydrobromide, a selective beta(2) adrenergic receptor agonist, in an attempt to prevent nocturnal asthma. Two hydrophilic polymers viz Kollidon SR, Polyox WSR 303 and a hydrophobic one (Precirol ATO5) were employed. Compression coated tablets were formulated by preparing a core tablet containing 7.5 mg drug and various amounts of polymer and Emcompress then compressed coated with the same polymeric materials. For comparison purpose different matrix tablets were also prepared employing the same polymers. In-vitro release studies were carried out at different pH (1.2 and 6.8). Pharmacokinetics of extended release tablets as well as commercially available immediate release tablets (Berotec) were studied after oral administration to beagle dogs using a new developed LC-MS/MS method with a lower limit of quantification of 1 ng/ml. Fenoterol release from compression coated tablets was significantly lower than matrix tablets. The mechanism of release was changed with the nature and content of polymer. The release pattern of drug from F16 containing 40 mg Kollidon SR divided in the core tablet (15 mg) and the rest in the compressed coat (25 mg) showed a typical zero order release kinetic that could extend drug release >10 h and reasonable time for 75% to be released (t(75)) (8.92 h). When compared to immediate release Berotec tablet the MRT was significantly extended from 7.03 +/- 0.76 to 10.93 +/- 1.25 h (P < 0.001) and HVD(t 50%Cmax) was also significantly extended from 2.71 +/- 0.68 to 6.81 +/- 0.67 h with expected prevention of nocturnal asthma.

  8. In vitro dissolution and in vivo gamma scintigraphic evaluation of press-coated salbutamol sulfate tablets.

    PubMed

    Li, Wei; Shi, Cai-Hong; Sheng, Yi-Ling; Cui, Ping; Zhao, Yu-Qing; Zhang, Xiang-Rong

    2013-12-01

    The aim of this study was to investigate the in vitro and in vivo performance of salbutamol sulfate press-coated tablets for delayed release. The in vitro release behavior of press-coated tablets with the outer layer of PEG 6000/ Eudragit S100 blends (2:1) in pH 1.2 (0.1 mol L-1 HCl) and then pH 6.8 buffer solution was examined. Morphological change of the press-coated tablet during in vitro release was recorded with a digital camera. Release of salbutamol sulfate from press-coated tablets was less than 5 % before 3 h and was completed after 8 h in pH 6.8 phosphate buffer solution. In vivo gamma scintigraphy study carried out on healthy men indicated that the designed system released the drug in lower parts of the GI tract after a lag time of 5 hours. The results showed the capability of the system of achieving delayed release of the drug in both in vitro and in vivo gamma scintigraphy studies.

  9. Dry coating of micronized API powders for improved dissolution of directly compacted tablets with high drug loading.

    PubMed

    Han, Xi; Ghoroi, Chinmay; Davé, Rajesh

    2013-02-14

    Motivated by our recent study showing improved flow and dissolution rate of the active pharmaceutical ingredient (API) powders (20 μm) produced via simultaneous micronization and surface modification through continuous fluid energy milling (FEM) process, the performance of blends and direct compacted tablets with high drug loading is examined. Performance of 50 μm API powders dry coated without micronization is also considered for comparison. Blends of micronized, non-micronized, dry coated or uncoated API powders at 30, 60 and 70% drug loading, are examined. The results show that the blends containing dry coated API powders, even micronized ones, have excellent flowability and high bulk density compared to the blends containing uncoated API, which are required for direct compaction. As the drug loading increases, the difference between dry coated and uncoated blends is more pronounced, as seen in the proposed bulk density-FFC phase map. Dry coating led to improved tablet compactibility profiles, corresponding with the improvements in blend compressibility. The most significant advantage is in tablet dissolution where for all drug loadings, the t(80) for the tablets with dry coated APIs was well under 5 min, indicating that this approach can produce nearly instant release direct compacted tablets at high drug loadings. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Implementation of quality by design approach in manufacturing process optimization of dry granulated, immediate release, coated tablets - a case study.

    PubMed

    Teżyk, Michał; Jakubowska, Emilia; Milanowski, Bartłomiej; Lulek, Janina

    2017-10-01

    The aim of this study was to optimize the process of tablets compression and identification of film-coating critical process parameters (CPPs) affecting critical quality attributes (CQAs) using quality by design (QbD) approach. Design of experiment (DOE) and regression methods were employed to investigate hardness, disintegration time, and thickness of uncoated tablets depending on slugging and tableting compression force (CPPs). Plackett-Burman experimental design was applied to identify critical coating process parameters among selected ones that is: drying and preheating time, atomization air pressure, spray rate, air volume, inlet air temperature, and drum pressure that may influence the hardness and disintegration time of coated tablets. As a result of the research, design space was established to facilitate an in-depth understanding of existing relationship between CPPs and CQAs of intermediate product (uncoated tablets). Screening revealed that spray rate and inlet air temperature are two most important factors that affect the hardness of coated tablets. Simultaneously, none of the tested coating factors have influence on disintegration time. The observation was confirmed by conducting film coating of pilot size batches.

  11. Influence of the aqueous film coating process on the properties and stability of tablets containing a moisture-labile drug.

    PubMed

    Ruotsalainen, Mirja; Heinämäki, Jyrki; Taipale, Krista; Yliruusi, Jouko

    2003-01-01

    The effects of an aqueous film coating process on the morphology and storage stability of hydroxypropyl methylcellulose-coated tablets containing a moisture-labile model drug (acetylsalicylic acid, ASA) were evaluated using an instrumented side-vented tablet pan coater. Coating parameters studied were inlet air absolute humidity 5 g/m3 and 12 g/m3, spraying air pressure 100 kPa and 500 kPa, pan air temperature 35 degrees C and 55 degrees C, and coating solution flow rate 2.2 g/min and 7.8 g/min. The surface roughness of the coatings was measured with a laser profilometer and the chemical hydrolysis of the model drug ASA with an UV-spectrophotometer. The film-coated tablets were stored at 25 degrees C/60% RH and 40 degrees C/75% RH for three months. The high absolute humidity of the inlet air increased the residual water content and surface roughness of the coated tablets. Using a lower coating solution flow rate, higher spraying air pressure and pan temperature the coatings were smooth and homogeneous. In both ambient and accelerated storage conditions, the roughness of the coatings and the hydrolysis of ASA increased, but this was independent of the film coating process. Uniform and smooth hydroxypropyl methylcellulose coatings can be achieved by improved control of process parameters related to the application of the coating solution and water evaporation of the tablet surface.

  12. A novel coating concept for ileo-colonic drug targeting: proof of concept in humans using scintigraphy.

    PubMed

    Varum, F J O; Hatton, G B; Freire, A C; Basit, A W

    2013-08-01

    The in vivo proof of concept of a novel double-coating system, based on enteric polymers, which accelerated drug release in the ileo-colonic region, was investigated in humans. Prednisolone tablets were coated with a double-coating formulation by applying an inner layer composed of EUDRAGIT S neutralised to pH 8.0 and a buffer salt (10% KH₂PO₄), which was overcoated with layer of standard EUDRAGIT S organic solution. For comparison, a single coating system was produced by applying the same amount of EUDRAGIT S organic solution on the tablet cores. Dissolution tests on the tablets were carried out using USP II apparatus in 0.1N HCl for 2 h and subsequently in pH 7.4 Krebs bicarbonate buffer. For comparison, tablets were also tested under the USP method established for modified release mesalamine formulations. Ten fasted volunteers received the double-coated and single-coated tablets in a two-way crossover study. The formulations were radiolabelled and followed by gamma scintigraphy; the disintegration times and positions were recorded. There was no drug release from the single-coated or double-coated tablets in 0.1N HCl for 2h. The single-coated tablets showed slow release in subsequent Krebs bicarbonate buffer with a lag time of 120 min, while in contrast drug release from the double-coated tablets was initiated at 60 min. In contrast, using the USP dissolution method, normally employed for modified release mesalamine products, no discrimination was attained. The in vivo disintegration of the single-coated EUDRAGIT S tablets in the large intestine was erratic. Furthermore, in 2 volunteers, the single-coated tablet was voided intact. Double-coated tablets disintegrated in a more consistent way, mainly in the ileo-caecal junction or terminal ileum. The accelerated in vivo disintegration of the double-coating EUDRAGIT S system can overcome the limitations of conventional enteric coatings targeting the colon and avoid the pass-through of intact tablets. Moreover

  13. Development and Efficacy Assessment of an Enteric Coated Porous Tablet Loaded With F4 Fimbriae for Oral Vaccination of Piglets against F4+ Escherichia coli Infections.

    PubMed

    Srivastava, Atul; Gowda, D V; Madhunapantula, SubbaRao V; Siddaramaiah

    2016-01-01

    Enterotoxigenic Escherichia coli (ETEC) infection is one of the major causes contributing to the development of diarrhoea and mortality in new born, suckling and newly weaned piglets. To date, no preventive/treatment strategy showed promising results, which could be due to the lack of potent vaccines, and/or due to the development of resistance of ETEC to antibiotics. Therefore, in the present investigation, a novel porous sodium alginate (SA) tablet formulation loaded with F4 fimbriae antigen was developed and tested for efficacy against ETEC infections in piglet models. Precompression parameters of the powder mixes and post compression parameters of tablets have been evaluated and results were found to be satisfactory. Loading of F4 fimbrial antigens into the tablets was achieved by inducing pores in the tablets via the sublimation of camphor followed by incubation with purified F4 fimbriae. The loaded tablets have been coated with Eudragit L100 to protect the F4 fimbriae from (a) highly acidic gastric environment; (b) proteolytic cleavage by pepsin; and (c) to promote subsequent release in the intestine. Evaluation of developed F4 fimbrial tablets in a Pig model demonstrated induction of mucosal immunity, and a significant reduction of F4+ E. coli in faeces. Therefore, F4 fimbriae loaded porous tablets could be a novel oral vaccination candidate to induce mucosal and systemic immunity against ETEC infections.

  14. A Novel Approach to Flurbiprofen Pulsatile Colonic Release: Formulation and Pharmacokinetics of Double-Compression-Coated Mini-Tablets.

    PubMed

    Vemula, Sateesh Kumar

    2015-12-01

    A significant plan is executed in the present study to study the effect of double-compression coating on flurbiprofen core mini-tablets to achieve the pulsatile colonic delivery to deliver the drug at a specific time as per the patho-physiological need of the disease that results in improved therapeutic efficacy. In this study, pulsatile double-compression-coated tablets were prepared based on time-controlled hydroxypropyl methylcellulose K100M inner compression coat and pH-sensitive Eudragit S100 outer compression coat. Then, the tablets were evaluated for both physical evaluation and drug-release studies, and to prove these results, in vivo pharmacokinetic studies in human volunteers were conducted. From the in vitro drug-release studies, F6 tablets were considered as the best formulation, which retarded the drug release in the stomach and small intestine (3.42 ± 0.12% in 5 h) and progressively released to the colon (99.78 ± 0.74% in 24 h). The release process followed zero-order release kinetics, and from the stability studies, similarity factor between dissolution data before and after storage was found to be 88.86. From the pharmacokinetic evaluation, core mini-tablets producing peak plasma concentration (C max) was 14,677.51 ± 12.16 ng/ml at 3 h T max and pulsatile colonic tablets showed C max = 12,374.67 ± 16.72 ng/ml at 12 h T max. The area under the curve for the mini and pulsatile tablets was 41,238.52 and 72,369.24 ng-h/ml, and the mean resident time was 3.43 and 10.61 h, respectively. In conclusion, development of double-compression-coated tablets is a promising way to achieve the pulsatile colonic release of flurbiprofen.

  15. Multiple-layer compression-coated tablets: formulation and humidity studies of novel chewable amoxicillin/clavulanate tablet formulations.

    PubMed

    Wardrop, J; Jaber, A B; Ayres, J W

    1998-08-01

    The purpose of this study was to produce novel multiple-layer, compression-coated, chewable tablet formulations containing amoxicillin trihydrate, and clavulanic acid as potassium clavulanate, and to test in vitro dissolution characteristics and the effect of humidity stability compared to Augmentin chewable tablets as a reference. Double- and triple-layer tablets were manufactured on a laboratory scale by multiple-layer dry compression, and dissolution profiles of both active ingredients were determined. Tablets were subjected to stability evaluation in laboratory-scale humidity tanks maintained at constant humidity. Assay of content was determined by HPLC or UV spectroscopy. Physical characteristics of the powder mixture, such as angle of repose, and of tablets for hardness and friability, were also determined. Chewable tablets showed similar dissolution profiles in vitro for both active ingredients, compared to the marketed reference, Augmentin. The stability of clavulanic acid, but not amoxicillin, was increased in the novel triple or bilayer formulation. The tablets showed suitable friability, hardness, and angle of repose for starting materials to suggest that industrial scale-up is feasible. This approach to formulation of drugs containing multiple or moisture-sensitive ingredients has been shown to increase the stability of the central core drug without changing the dissolution pattern of the active ingredients. This formulation is expected to be bioequivalent in vivo based on these in vitro results.

  16. Pharmacokinetics of hydrocodone extended-release tablets formulated with different levels of coating to achieve abuse deterrence compared with a hydrocodone immediate-release/acetaminophen tablet in healthy subjects.

    PubMed

    Darwish, Mona; Bond, Mary; Tracewell, William; Robertson, Philmore; Yang, Ronghua

    2015-01-01

    A hydrocodone extended-release (ER) formulation employing the CIMA(®) Abuse-Deterrence Technology platform was developed to provide resistance against rapid release of hydrocodone when tablets are comminuted or taken with alcohol. This study evaluated the pharmacokinetics of three hydrocodone ER tablet prototypes with varying levels of polymer coating to identify the prototype expected to have the greatest abuse deterrence potential based on pharmacokinetic characteristics that maintain systemic exposure to hydrocodone comparable to that of a commercially available hydrocodone immediate-release (IR) product. In this four-period crossover study, healthy subjects aged 18-45 years were randomized to receive a single intact, oral 45-mg tablet of one of three hydrocodone ER prototypes (low-, intermediate-, or high-level coating) or an intact, oral tablet of hydrocodone IR/acetaminophen (APAP) 10/325 mg every 6 h until four tablets were administered, with each of the four treatments administered once over the four study periods. Dosing periods were separated by a minimum 5-day washout. Naltrexone 50 mg was administered to block opioid receptors. Blood samples for pharmacokinetic assessments were collected predose and through 72 h postdose. Parameters assessed included maximum observed plasma hydrocodone concentration (C(max)), time to C(max) (t(max)), and area under the concentration-time curve from time 0 to infinity (AUC(0-∞)). Mean C(max) values were 49.2, 32.6, and 28.4 ng/mL for the low-, intermediate-, and high-level coating hydrocodone ER tablet prototypes, respectively, and 37.3 ng/mL for the hydrocodone IR/APAP tablet; respective median t(max) values were 5.9, 8.0, 8.0, and 1.0 h. Total systemic exposure to hydrocodone (AUC(0-∞)) was comparable between hydrocodone ER tablet prototypes (640, 600, and 578 ng·h/mL, respectively) and hydrocodone IR/APAP (581 ng·h/mL). No serious adverse events or deaths were reported. The most common adverse events included

  17. Formulation and characterization of 5-Fluorouracil enteric coated nanoparticles for sustained and localized release in treating colorectal cancer

    PubMed Central

    Tummala, Shashank; Satish Kumar, M.N.; Prakash, Ashwati

    2014-01-01

    5-Fluorouracil is used in the treatment of colorectal cancer along with oxaliplatin as first line treatment, but it is having lack of site specificity and poor therapeutic effect. Also toxic effects to healthy cells and unavailability of major proportion of drug at the colon region remain as limitations. Toxic effects prevention and drug localization at colon area was achieved by preparing enteric-coated chitosan polymeric nanoparticles as it can be delivered directly to large bowel. Enteric coating helps in preventing the drug degradation at gastric pH. So the main objective was to prepare chitosan polymeric nanoparticles by solvent evaporation emulsification method by using different ratios of polymer (1:1, 1:2, 1:3, 1:4). Optimized polymer ratio was characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), entrapment efficiency and particle size and further subjected to enteric coating. In vitro drug release studies were done using dialysis bag technique using simulated fluids at various pH (1.2, 4.5, 7.5, 7.0) to mimic the GIT tract. 5-FU nanoparticles with drug: polymer ratio of 1:2 and 1:3 has shown better particle size (149 ± 1.28 nm and 138 ± 1.01 nm respectively), entrapment efficiency (48.12 ± 0.08% and 69.18 ± 1.89 respectively). 5-FU E1 has shown better drug release after 4 h and has shown 82% drug release till 24 h in a sustained manner comparable to the non-enteric coated tablets, which released more than 50% of the drug before entering the colon region. So we can conclude that nanoparticles prepared by this method using the same polymer with the optimized ratio can represent as potential drug delivery approach for effective delivery of the active pharmaceutical ingredient to the colorectal tumors. PMID:26106279

  18. Improved properties of fine active pharmaceutical ingredient powder blends and tablets at high drug loading via dry particle coating.

    PubMed

    Kunnath, Kuriakose; Huang, Zhonghui; Chen, Liang; Zheng, Kai; Davé, Rajesh

    2018-05-30

    It has been shown that dry coating cohesive active pharmaceutical ingredients (APIs) with nano-silica can improve packing and flow of their blends, facilitating high speed direct compression tableting. This paper examines the broader scope and generality of previous work by examining three fine APIs; micronized Acetaminophen (mAPAP), coarse Acetaminophen (cAPAP) and micronized Ibuprofen (mIBU), and considers dry coating with both hydrophobic or hydrophilic nano-silica to examine the effect not only on packing density and flow of their blends, but also dissolution and tensile strength of their tablets. The impact of the excipient size on blend and tablet properties are also investigated, indicating blend flow is most improved when matching API particle size with excipient particle size. In all cases where the API is dry coated, the blend packing and flow improve, so as to suggest such high drug loaded blends could enable direct compression. Using dry coated API along with finer excipients in blends lead to improved hardness of the corresponding tablets. Interestingly, dissolution profiles show dry coated API tablets generally have faster dissolution rates, regardless of silica hydrophilicity, suggesting API powder deagglomeration via nano-silica coating plays a crucial role. The most significant conclusion is that, although there are differences in properties of blends that depend on the API, hydrophobic or hydrophilic nano-silica coating, as well as large or fine excipients, in all cases, dry coating of APIs significantly improves the possibility of using the specific blend at high drug loading in direct compression tableting. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Non-destructive quantification of pharmaceutical tablet coatings using terahertz pulsed imaging and optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Zhong, Shuncong; Shen, Yao-Chun; Ho, Louise; May, Robert K.; Zeitler, J. Axel; Evans, Mike; Taday, Philip F.; Pepper, Michael; Rades, Thomas; Gordon, Keith C.; Müller, Ronny; Kleinebudde, Peter

    2011-03-01

    Optical coherence tomography (OCT) and terahertz pulsed imaging (TPI) are two powerful techniques allowing high quality cross-sectional images from within scattering media to be obtained non-destructively. In this paper, we report experimental results of using OCT and TPI for quantitatively characterizing pharmaceutical tablet coatings in the thickness range of 10-140 μm. We found that the spectral OCT system developed in-house has an axial resolution of 0.9 μm, and is capable of quantifying very thin coatings in the range of 10-60 μm. The upper limit of 60 μm within the tablet coating and core is owed to the strong scattering of OCT light, which has relatively short wavelengths in the range of 0.5-1.0 μm. On the other hand, TPI utilizes terahertz radiation that has substantially long wavelengths in the range of hundreds of microns, and thus is less prone to the scattering problem. Consequently TPI has been demonstrated to be able to quantify thicker coatings in the range of 40-140 μm and beyond. We concluded that OCT and TPI are two complementary analytical techniques for non-destructive and quantitative characterization of pharmaceutical tablet coatings.

  20. Solid state properties and drug release behavior of co-amorphous indomethacin-arginine tablets coated with Kollicoat® Protect.

    PubMed

    Petry, Ina; Löbmann, Korbinian; Grohganz, Holger; Rades, Thomas; Leopold, Claudia S

    2017-10-01

    A promising approach to improve the solubility of poorly water-soluble drugs and to overcome the stability issues related to the plain amorphous form of the drugs, is the formulation of drugs as co-amorphous systems. Although polymer coatings have been proven very useful with regard to tablet stability and modifying drug release, there is little known on coating co-amorphous formulations. Hence, the aim of the present study was to investigate whether polymer coating of co-amorphous formulations is possible without inducing recrystallization. Tablets containing either a physical mixture of crystalline indomethacin and arginine or co-amorphous indomethacin-arginine were coated with a water soluble polyvinyl alcohol-polyethylene glycol graft copolymer (Kollicoat® Protect) and stored at 23°C/0% RH and 23°C/75% RH. The solid state properties of the coated tablets were analyzed by XRPD and FTIR and the drug release behavior was tested for up to 4h in phosphate buffer pH 4.5. The results showed that the co-amorphous formulation did not recrystallize during the coating process or during storage at both storage conditions for up to three months, which confirmed the high physical stability of this co-amorphous system. Furthermore, the applied coating could partially inhibit recrystallization of indomethacin during drug release testing, as coated tablets reached a higher level of supersaturation compared to the respective uncoated formulations and showed a lower decrease of the dissolved indomethacin concentration upon precipitation. Thus, the applied coating enhanced the AUC of the dissolution curve of the co-amorphous tablets by about 30%. In conclusion, coatings might improve the bioavailability of co-amorphous formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. [Preparation and evaluation of press-coated aminophylline tablet using crystalline cellulose and polyethylene glycol in the outer shell for timed-release dosage forms].

    PubMed

    Watanabe, Yoshiteru; Mukai, Baku; Kawamura, Ken-ichi; Ishikawa, Tatsuya; Namiki, Michihiro; Utoguchi, Naoki; Fujii, Makiko

    2002-02-01

    In an attempt to achieve chronopharmacotherapy for asthma, press-coated tablets (250 mg), which contained aminophylline in the core tablet in the form of low-substituted hydroxypropylcellulose (L-HPC) and coated with crystalline cellulose (PH-102) and polyethylene glycol (PEG) at various molecular weights and mixing ratios in the amounts of PH-102 and PEG as the outer shell (press-coating material), were prepared (chronopharmaceutics). Their applicability as timed-release (delayed-release) tablets with a lag time of disintegration and a subsequent rapid drug release phase was investigated. Various types of press-coated tablets were prepared using a tableting machine, and their aminophylline dissolution profiles were evaluated by the JP paddle method. Tablets with the timed-release characteristics could be prepared, and the lag time of disintegration was prolonged as the molecular weight and the amount of PEG, for example PEG 500,000, in the outer shell were increased. The lag time of disintegration could be controlled by the above-mentioned method, however, the pH of the medium had no effect on disintegration of the tablet and dissolution behavior of theophylline. The press-coated tablet (core tablet:aminophylline 50 mg, L-HPC and PEG 6000; outer shell:PH-102:PEG = 8:2 200 mg) with the timed-release characteristics was administered orally to rabbits for an in vivo test. Theophylline was first detected in plasma more than 2 h after administration; thus, this tablet showed a timed-release characteristics in the gastrointestinal tract. The time (tmax) required to reach the maximum plasma theophylline concentration (Cmax) observed after administration of the press-coated tablet was significantly (p < 0.05) delayed compared with that observed after administration of aminophylline solution in the control experiment. However, there was no difference in Cmax and area under the plasma theophylline concentration-time curve (AUC0-->24) between the press-coated tablet and

  2. Guargum and Eudragit ® coated curcumin liquid solid tablets for colon specific drug delivery.

    PubMed

    S Kumar, Vrinda; Rijo, John; M, Sabitha

    2018-04-15

    Colorectal cancer, also known as bowel cancer, is the uncontrolled cell growth in the colon or rectum (parts of the large intestine), or in the appendix. The colon specific drug delivery would alleviate the systemic side effects and would assure the safe therapy for colonic disorders with minimum dose and duration of therapy. The liquisolid technique refers to solubilisation of drug in a non-volatile solvent combined with inclusion of appropriate carrier and coating agent required for tableting. Colon specific degradation of natural polymer, guar gum and pH dependant degradative (pH-7) property of eudragit L100 restricts the delivery of curcumin in gastric and intestinal pH. Formulated curcumin liquisolid powder was evaluated for the micrometric properties, solubility and by differential thermal analysis, X ray powder diffraction and scanning electron microscopy. Curcumin loaded liquisolid tablet showed more anticancer activity against HCT-15 compared with free curcumin. Bioavailability study of the coated and uncoated liquisolid tablets were performed using Newzealand white rabbits. The present study concludes that liquisolid technique is a promising alternative for improving oral bioavailability and dissolution rate of water insoluble drug and coating liquisolid tablet with colon sensitive polymers showed site specific release of drug in the colon. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Vapor Phase Alkyne Coating of Pharmaceutical Excipients: Discrimination Enhancement of Raman Chemical Imaging for Tablets.

    PubMed

    Yamashita, Mayumi; Sasaki, Hiroaki; Moriyama, Kei

    2015-12-01

    Raman chemical imaging has become a powerful analytical tool to investigate the crystallographic characteristics of pharmaceutical ingredients in tablet. However, it is often difficult to discriminate some pharmaceutical excipients from each other by Raman spectrum because of broad and overlapping signals, limiting their detailed assessments. To overcome this difficulty, we developed a vapor phase coating method of excipients by an alkyne, which exhibits a distinctive Raman signal in the range of 2100-2300 cm(-1) . We found that the combination of two volatile reagents, propargyl bromide and triethylamine, formed a thin and nonvolatile coating on the excipient and observed the Raman signal of the alkyne at the surface. We prepared alkyne-coated cellulose by this method and formed a tablet. The Raman chemical imaging of the tablet cross-section using the alkyne peak area intensity of 2120 cm(-1) as the index showed a much clearer particle image of cellulose than using the peak area intensity of 1370 cm(-1) , which originated from the cellulose itself. Our method provides an innovative technique to analyze the solid-state characteristics of pharmaceutical excipients in tablets. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  4. Studies on applicability of press-coated tablets using hydroxypropylcellulose (HPC) in the outer shell for timed-release preparations.

    PubMed

    Fukui, E; Uemura, K; Kobayashi, M

    2000-08-10

    Press-coated tablets, containing diltiazem hydrochloride (DIL) in the core tablet and coated with hydroxypropylcellulose (HPC) as the outer shell, were examined for applicability as timed-release tablets with a predetermined lag time and subsequent rapid drug release phase. Various types of press-coated tablets were prepared using a rotary tabletting machine and their DIL dissolution behavior was evaluated by the JP paddle method. The results indicated that tablets with the timed-release function could be prepared, and that the lag times were prolonged as the viscosity of HPC and the amount of the outer shell were increased. The lag times could be controlled widely by the above method, however, the compression load had little effect. Two different kinds of timed-release press-coated tablets that showed lag times of 3 and 6 h in the in vitro test (denoted PCT(L3) and PCT(L6), respectively) were administered to beagle dogs. DIL was first detected in the plasma more than 3 h after administration, and both tablets showed timed-release. The lag times showed a good agreement between the in vivo and in vitro tests in PCT(L3). However, the in vivo lag times were about 4 h in PCT(L6) and were much shorter than the in vitro lag time. The dissolution test was performed at different paddle rotation speeds, and good agreement was obtained between the in vivo and in vitro lag times at 150 rpm. This suggested that the effects of gastrointestinal peristalsis and contraction should also be taken into consideration for the further development of drug delivery systems.

  5. Development of a chitosan based double layer-coated tablet as a platform for colon-specific drug delivery

    PubMed Central

    Kim, Min Soo; Yeom, Dong Woo; Kim, Sung Rae; Yoon, Ho Yub; Kim, Chang Hyun; Son, Ho Yong; Kim, Jin Han; Lee, Sangkil; Choi, Young Wook

    2017-01-01

    A double layer-coated colon-specific drug delivery system (DL-CDDS) was developed, which consisted of chitosan (CTN) based polymeric subcoating of the core tablet containing citric acid for microclimate acidification, followed by an enteric coating. The polymeric composition ratio of Eudragit E100 and ethyl cellulose and amount of subcoating were optimized using a two-level factorial design method. Drug-release characteristics in terms of dissolution efficiency and controlled-release duration were evaluated in various dissolution media, such as simulated colonic fluid in the presence or absence of CTNase. Microflora activation and a stepwise mechanism for drug release were postulated. Consequently, the optimized DL-CDDS showed drug release in a controlled manner by inhibiting drug release in the stomach and intestine, but releasing the drug gradually in the colon (approximately 40% at 10 hours and 92% at 24 hours in CTNase-supplemented simulated colonic fluid), indicating its feasibility as a novel platform for CDD. PMID:28053506

  6. Biopharmaceutical evaluation of time-controlled press-coated tablets containing polymers to adjust drug release.

    PubMed

    Halsas, M; Ervasti, P; Veski, P; Jürjenson, H; Marvola, M

    1998-01-01

    This paper deals with press-coated modified release tablets in which the drug dose is situated in the core or is divided between the core and the coat. The coat contains polymer (sodium alginate or hydroxypropylmethyl cellulose, HPMC) to control drug release. The main objective was to investigate how the pharmacokinetic profile of the model drug could be modified by altering the proportion of the drug between the core and the coat. The effect of the amount of the polymer in the coat was also studied. Bioavailability tests were carried out on healthy volunteers. In the absorption curves of the tablets containing 50%, 67% and 80% of the drug in the core and 180 mg HPMC in the coat a bimodal profile was observed. No bimodal release pattern in the in vitro dissolution studies was found. If the whole dose was incorporated in the core the absorption curve has only one clear t(max) value at about 10 h. Doubling the amount of HPMC in the coat dramatically decreased drug absorption. It was concluded that, if a slightly reduced t(max)-value was required, the viscosity grade of HPMC used should be lowered.

  7. Enteric coating of granules containing the probiotic Lactobacillus acidophilus.

    PubMed

    Pyar, Hassan; Peh, Kok-Khiang

    2014-06-01

    In the present study, a capsule formulation composed of enteric coated granules of Lactobacillus acidophilus ATCC 4962 was developed using Eudragit L30D-55 as enteric polymer. Optimization of the capsule formulation was achieved with a maximum viable cell count after 2 h of incubation in acid medium and disintegration time of 1 h in buffer pH 6.8. The amount of Eudragit L30D-55 in the capsules correlated with gastric juice resistance. The best protective qualities against artificial gastric juice were observed when capsules were prepared from granules composed of L. acidophilus, corn starch, lactose monohydrate, polyvinylpyrrolidone and coated with 12.5 % (m/V) of Eudragit L30D-55. Capsule formulation of L. acidophilus in edible broth medium suspension serves as a cheap alternative to the expensive freeze-drying procedure for preparing L. acidophilus. In addition, the enteric coating using Eudragit L30D-55 could protect probiotics from the acidic gastric environment and enhance the bioactivity of probiotics along with replacement of pathogenic microbes in human intestine.

  8. Design and In Vitro Evaluation of Compression-coated Pulsatile Release Tablets of Losartan Potassium

    PubMed Central

    Bajpai, M.; Singh, D. C. P.; Bhattacharya, A.; Singh, A.

    2012-01-01

    In majority of individuals blood pressure rises in the early morning hours, which lead to serious cardiovascular complications. Formulation of pulsatile system makes it possible to deliver drug at definite period of time when symptoms of the disease condition are most critical. The purpose of the present work was to develop pulsatile release tablet of losartan potassium for chronotherapy in hypertension. The prepared system consisted of a core tablet coated with versatile and safe hydrophilic cellulosic ethers such as, hydroxypropyl methylcellulose, hydroxypropyl cellulose and sodium carboxy methylcellulose to produce burst release after predetermined lag time. Various formulation factors were studied through series of test and in vitro dissolution study. It was found that core tablets containing superdisintegrant failed to produce burst drug release pattern while effervescent agent was able to do so. Results also reveal that coating composition and coating level affects lag time. Formulation containing effervescent agent in core and coated with 200 mg hydroxypropyl cellulose provide lag time of 4.5 h with 73% drug release in 6 h that followed a sigmoidal release pattern. These values were close to the desired objective of producing lag time of 5-6 h followed by fast drug release. This approach can thus provide a useful means for timed release of losartan and is helpful for patients with morning surge. PMID:23325989

  9. How do tablet properties influence swallowing behaviours?

    PubMed

    Yamamoto, Shinya; Taniguchi, Hiroshige; Hayashi, Hirokazu; Hori, Kazuhiro; Tsujimura, Takanori; Nakamura, Yuki; Sato, Hideaki; Inoue, Makoto

    2014-01-01

    Behavioural performance of tablet swallowing was evaluated with different tablet conditions in terms of size, number and surface coating. Four different types of tablets were prepared: small or large, and with or without a surface coating. Fourteen normal male adults were instructed to swallow the prepared tablets with 15 ml of water. The number of tablets in one trial was changed from one to three. To evaluate swallowing and tablet transport, electromyographic activity was recorded in the left suprahyoid muscles, and videofluorographic images were examined. All tablet conditions (size, number and surface coating) affected the swallowing performance in terms of total number of swallows, electromyographic burst patterns and location of remaining tablets. Increases in the size and number of tablets increased the number of swallows and electromyographic burst area and duration. In addition, all of these parameters increased while swallowing tablets without a coating compared with tablets with a coating. Location of the remaining tablets was mainly within the mouth. This study only clarified the normal pattern of tablet swallowing under several conditions in healthy subjects, but the results may facilitate comprehensive evaluation and treatment planning in terms of administering medication to dysphagic patients. © 2013 Royal Pharmaceutical Society.

  10. A Novel Strategy for Bitter Taste Masking of Gankeshuangqing Dispersible Tablets Based on Particle Coating Technology.

    PubMed

    Han, Xue; Zhang, Ding-Kun; Zhang, Fang; Lin, Jun-Zhi; Jiang, Hong; Lan, Yang; Xiong, Xi; Han, Li; Yang, Ming; Fu, Chao-Mei

    2017-01-01

    Currently, acute upper respiratory tract infections (AURTIs) are increasingly becoming a significant health burden. Gankeshuangqing dispersible tablets (GKSQDT) which have a good effect on treating AURTIs. GKSQDT is composed of baicalin and andrographolide. However, its severe bitterness limits application of patients. Due to the addition of plentiful accessories, common masking methods are unsuitable for GKSQDT. It is thus necessary to develop a new masking method. The Previous study showed that baicalin was less bitter than andrographolide. Thus, particle coating technology was adapted to prepare composite particles that baicalin coated on the surface of andrographolide to decrease bitterness. Initially, particle size of baicalin and coating time of composite was investigated to prepare composite. Then, scanning electron microscopy, wettability, and infrared (IR) spectrogram were used to characterize the microstructure of composite. Furthermore, electronic tongue test, animal preference experiment, and human sensory test were applied to evaluate the masking effect. To produce composite, baicalin should be ground in vibromill for 6 min. Then, andrographolide fine powder was added to grind together for 6 min. Contact angle of composite was smaller than mixture, and more similar to baicalin. Other physical characterization including microstructure, wettability, and IR also suggested that andrographolide was successfully coated by baicalin superfine. Furthermore, taste-masking test indicated taste-masked tablets was less bitter than original tablets. The study indicated that particle coating technology can be used for taste masking of GKSQDT without adding other substance. Moreover, it provides a new strategy of taste masking for national medicine. A new strategy to mask bitterness without adding any other substance based on coating technology was providedThe masking effect was confirmed by electronic tongue test, animal preference experiment and human sensory test

  11. Improved blend and tablet properties of fine pharmaceutical powders via dry particle coating.

    PubMed

    Huang, Zhonghui; Scicolone, James V; Han, Xi; Davé, Rajesh N

    2015-01-30

    The improvements in the flow and packing of fine pharmaceutical powder blends due to dry coating of micronized acetaminophen (mAPAP, ∼11μm), a model poorly flowing drug, are quantified. Poor flow and packing density of fine excipients (∼20μm) allowed testing the hypothesis that dry coating of cohesive API may counteract poor flow and packing of fine pharmaceutical powder blends. Further, fine excipients could improve compaction and reduce segregation tendency. It was found that flow function coefficient (FFC) and bulk density enhancements for 10%, 30%, and 60% (w/w), API loading blends with dry coated API are significantly higher than those without coated silica. At the highest API loading, for which coarser excipients were also used as reference, the flow and packing of dry coated mAPAP blends were significantly increased regardless of the excipient particle size, exceeding those of a well compacting excipient, Avicel 102. In addition, tensile strength of tablets with fine excipients was significantly higher, indicating improved compactibility. These results show for the first time that dry coating of fine, cohesive API powder leads to significantly improved flow and packing of high API loading blends consisting of fine excipients, while achieving improved tablet compactibility, suggesting suitability for direct compaction. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Application of terahertz pulse imaging as PAT tool for non-destructive evaluation of film-coated tablets under different manufacturing conditions.

    PubMed

    Dohi, Masafumi; Momose, Wataru; Yoshino, Hiroyuki; Hara, Yuko; Yamashita, Kazunari; Hakomori, Tadashi; Sato, Shusaku; Terada, Katsuhide

    2016-02-05

    Film-coated tablets (FCTs) are a popular solid dosage form in pharmaceutical industry. Manufacturing conditions during the film-coating process affect the properties of the film layer, which might result in critical quality problems. Here, we analyzed the properties of the film layer using a non-destructive approach with terahertz pulsed imaging (TPI). Hydrophilic tablets that become distended upon water absorption were used as core tablets and coated with film under different manufacturing conditions. TPI-derived parameters such as film thickness (FT), film surface reflectance (FSR), and interface density difference (IDD) between the film layer and core tablet were affected by manufacturing conditions and influenced critical quality attributes of FCTs. Relative standard deviation of FSR within tablets correlated well with surface roughness. Tensile strength could be predicted in a non-destructive manner using the multivariate regression equation to estimate the core tablet density by film layer density and IDD. The absolute value of IDD (Lateral) correlated with the risk of cracking on the lateral film layer when stored in a high-humidity environment. Further, in-process control was proposed for this value during the film-coating process, which will enable a feedback control system to be applied to process parameters and reduced risk of cracking without a stability test. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Quantitative analysis of visible surface defect risk in tablets during film coating using terahertz pulsed imaging.

    PubMed

    Niwa, Masahiro; Hiraishi, Yasuhiro

    2014-01-30

    Tablets are the most common form of solid oral dosage produced by pharmaceutical industries. There are several challenges to successful and consistent tablet manufacturing. One well-known quality issue is visible surface defects, which generally occur due to insufficient physical strength, causing breakage or abrasion during processing, packaging, or shipping. Techniques that allow quantitative evaluation of surface strength and the risk of surface defect would greatly aid in quality control. Here terahertz pulsed imaging (TPI) was employed to evaluate the surface properties of core tablets with visible surface defects of varying severity after film coating. Other analytical methods, such as tensile strength measurements, friability testing, and scanning electron microscopy (SEM), were used to validate TPI results. Tensile strength and friability provided no information on visible surface defect risk, whereas the TPI-derived unique parameter terahertz electric field peak strength (TEFPS) provided spatial distribution of surface density/roughness information on core tablets, which helped in estimating tablet abrasion risk prior to film coating and predicting the location of the defects. TPI also revealed the relationship between surface strength and blending condition and is a nondestructive, quantitative approach to aid formulation development and quality control that can reduce visible surface defect risk in tablets. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. In-vitro studies of enteric coated diclofenac sodium-carboxymethylcellulose microspheres.

    PubMed

    Arica, B; Arica, M Y; Kaş, H S; Hincal, A A; Hasirci, V

    1996-01-01

    MIcrospheres containing diclofenac sodium (DS) were prepared using carboxymethylcellulose (CMC) as the main support material (1.0, 2.0, 3.0% (w/v)) and aluminum chloride as the crosslinker. Drug to polymer ratios of 1:1, 1:2 and 1:4 were used to obtain a range of microspheres. The microspheres were then coated with an enteric coating material, Eudragit S-100, efficiency, % yield value, particle sizes an in-vitro dissolution behaviour were investigated. The surface of the enteric coated microspheres seemed to be all covered with Eudragit S-100 from scanning electron microscopy observation. It was also observed that increasing the CMC concentration led to an increase in the encapsulation efficiency, % yield value and particle size and decreased the release rate. Eudragit S-100 coating did not significantly alter the size but the release rate was significantly lower even when the lower concentration solution was used.

  15. Improving tablet coating robustness by selecting critical process parameters from retrospective data.

    PubMed

    Galí, A; García-Montoya, E; Ascaso, M; Pérez-Lozano, P; Ticó, J R; Miñarro, M; Suñé-Negre, J M

    2016-09-01

    Although tablet coating processes are widely used in the pharmaceutical industry, they often lack adequate robustness. Up-scaling can be challenging as minor changes in parameters can lead to varying quality results. To select critical process parameters (CPP) using retrospective data of a commercial product and to establish a design of experiments (DoE) that would improve the robustness of the coating process. A retrospective analysis of data from 36 commercial batches. Batches were selected based on the quality results generated during batch release, some of which revealed quality deviations concerning the appearance of the coated tablets. The product is already marketed and belongs to the portfolio of a multinational pharmaceutical company. The Statgraphics 5.1 software was used for data processing to determine critical process parameters in order to propose new working ranges. This study confirms that it is possible to determine the critical process parameters and create design spaces based on retrospective data of commercial batches. This type of analysis is thus converted into a tool to optimize the robustness of existing processes. Our results show that a design space can be established with minimum investment in experiments, since current commercial batch data are processed statistically.

  16. Tablet potency of Tianeptine in coated tablets by near infrared spectroscopy: model optimisation, calibration transfer and confidence intervals.

    PubMed

    Boiret, Mathieu; Meunier, Loïc; Ginot, Yves-Michel

    2011-02-20

    A near infrared (NIR) method was developed for determination of tablet potency of active pharmaceutical ingredient (API) in a complex coated tablet matrix. The calibration set contained samples from laboratory and production scale batches. The reference values were obtained by high performance liquid chromatography (HPLC) and partial least squares (PLS) regression was used to establish a model. The model was challenged by calculating tablet potency of two external test sets. Root mean square errors of prediction were respectively equal to 2.0% and 2.7%. To use this model with a second spectrometer from the production field, a calibration transfer method called piecewise direct standardisation (PDS) was used. After the transfer, the root mean square error of prediction of the first test set was 2.4% compared to 4.0% without transferring the spectra. A statistical technique using bootstrap of PLS residuals was used to estimate confidence intervals of tablet potency calculations. This method requires an optimised PLS model, selection of the bootstrap number and determination of the risk. In the case of a chemical analysis, the tablet potency value will be included within the confidence interval calculated by the bootstrap method. An easy to use graphical interface was developed to easily determine if the predictions, surrounded by minimum and maximum values, are within the specifications defined by the regulatory organisation. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Evaluation of the tablets' surface flow velocities in pan coaters.

    PubMed

    Dreu, Rok; Toschkoff, Gregor; Funke, Adrian; Altmeyer, Andreas; Knop, Klaus; Khinast, Johannes; Kleinebudde, Peter

    2016-09-01

    The tablet pan coating process involves various types of transverse tablet bed motions, ranging from rolling to cascading. To preserve satisfactory results in terms of coating quality after scale-up, understanding the dynamics of pan coating process should be achieved. The aim of this study was to establish a methodology of estimating translational surface velocities of the tablets in a pan coater and to assess their dependence on the drum's filling degree, the pan speed, the presence of baffles and the selected tablet properties in a dry bed system and during coating while varying the drum's filling degree and the pan speed. Experiments were conducted on the laboratory scale and on the pilot scale in side-vented pan coaters. Surface movement of biconvex two-layer tablets was assessed before, during and after the process of active coating. In order to determine the tablets' surface flow velocities, a high-speed video of the tablet surface flow was recorded via a borescope inserted into the coating drum and analysed via a cross-correlation algorithm. The obtained tablet velocity data were arranged in a linear fashion as a function of the coating drum's radius and frequency. Velocity data obtained during coating were close to those of dry tablets after coating. The filling degree had little influence on the tablet velocity profile in a coating drum with baffles but clearly affected it in a coating drum without baffles. In most but not all cases, tablets with a lower static angle of repose had tablet velocity profiles with lower slopes than tablets with higher inter-tablet friction. This particular tablet velocity response can be explained by case specific values of tablet bed's dynamic angle of repose. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Stabilization Mechanism of Roxithromycin Tablets under Gastric pH Conditions.

    PubMed

    Inukai, Koki; Noguchi, Shuji; Kimura, Shin-Ichiro; Itai, Shigeru; Iwao, Yasunori

    2018-05-31

    Macrolide antibiotics are widely used at clinical sites. Clarithromycin (CAM), a 14-membered macrolide antibiotic, was reported to gelate under acidic conditions. Gelation allows oral administration of acid-sensitive CAM without enteric coating by hindering the penetration of gastric fluid into CAM tablets. However, it is unknown whether this phenomenon occurs in other macrolide antibiotics. In this study, we examined the gelation ability of three widely used macrolide antibiotics, roxithromycin (RXM), erythromycin A (EM), and azithromycin (AZM). The results indicated that not only CAM but also RXM gelated under acidic conditions. EM and AZM did not gelate under the same conditions. Gelation of RXM delayed the disintegration of the tablet and release of RXM from the tablet. Disintegration and release were also delayed in commercial RXM tablets containing disintegrants. This study showed that two of the four macrolides gelated, which affects tablet disintegration and dissolution and suggests that this phenomenon might also occur in other macrolides. Copyright © 2018. Published by Elsevier Inc.

  19. Application of a tablet film coating model to define a process-imposed transition boundary for robust film coating.

    PubMed

    van den Ban, Sander; Pitt, Kendal G; Whiteman, Marshall

    2018-02-01

    A scientific understanding of interaction of product, film coat, film coating process, and equipment is important to enable design and operation of industrial scale pharmaceutical film coating processes that are robust and provide the level of control required to consistently deliver quality film coated product. Thermodynamic film coating conditions provided in the tablet film coating process impact film coat formation and subsequent product quality. A thermodynamic film coating model was used to evaluate film coating process performance over a wide range of film coating equipment from pilot to industrial scale (2.5-400 kg). An approximate process-imposed transition boundary, from operating in a dry to a wet environment, was derived, for relative humidity and exhaust temperature, and used to understand the impact of the film coating process on product formulation and process control requirements. This approximate transition boundary may aid in an enhanced understanding of risk to product quality, application of modern Quality by Design (QbD) based product development, technology transfer and scale-up, and support the science-based justification of critical process parameters (CPPs).

  20. Effects of tablet formulation and subsequent film coating on the supersaturated dissolution behavior of amorphous solid dispersions.

    PubMed

    Sakai, Toshiro; Hirai, Daiki; Kimura, Shin-Ichiro; Iwao, Yasunori; Itai, Shigeru

    2018-04-05

    The effects of tablet preparation and subsequent film coating with amorphous solid dispersion (ASD) particles that were composed of a drug with poor water solubility and hydrophilic polymers were investigated. ASD particles were prepared with a drug and vinylpyrrolidone-vinyl acetate copolymer (PVPVA) or polyvinylpyrrolidone (PVP) at a weight ratio of 1:1 or 1:2 using a melt extrusion technique. Tablets were prepared by conventional direct compression followed by pan coating. A mathematical model based on the Noyes-Whitney equation assuming that stable crystals precipitated at the changeable surface area of the solid-liquid interface used to estimate drug dissolution kinetics in a non-sink dissolution condition. All the ASD particles showed a maximum dissolution concentration approximately ten times higher than that of the crystalline drug. The ASD particles with PVPVA showed higher precipitation rate with lower polymer ratio, while PVP did not precipitate within 960 min regardless of the polymer ratio, suggesting the ASD particles of 1:1 drug:PVPVA (ASD-1) were the most unstable among the ASD particles considered. The dissolution of a core tablet with ASD-1 showed less supersaturation and a much higher precipitation rate than those of ASD-1 particles. However, a film-coated tablet or core tablet with a trace amount of hydroxypropylmethylcellulose (HPMC) showed a similar dissolution profile to that of the ASD-1 particles, indicating HPMC had a remarkable precipitation inhibition effect. Overall, these results suggest that tablet preparation with ASD may adversely affect the maintenance of supersaturation; however, this effect can be mitigated by adding an appropriate precipitation inhibitor to the formulation. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Design of Experiments to Study the Impact of Process Parameters on Droplet Size and Development of Non-Invasive Imaging Techniques in Tablet Coating

    PubMed Central

    Dennison, Thomas J.; Smith, Julian; Hofmann, Michael P.; Bland, Charlotte E.; Badhan, Raj K.; Al-Khattawi, Ali; Mohammed, Afzal R.

    2016-01-01

    Atomisation of an aqueous solution for tablet film coating is a complex process with multiple factors determining droplet formation and properties. The importance of droplet size for an efficient process and a high quality final product has been noted in the literature, with smaller droplets reported to produce smoother, more homogenous coatings whilst simultaneously avoiding the risk of damage through over-wetting of the tablet core. In this work the effect of droplet size on tablet film coat characteristics was investigated using X-ray microcomputed tomography (XμCT) and confocal laser scanning microscopy (CLSM). A quality by design approach utilising design of experiments (DOE) was used to optimise the conditions necessary for production of droplets at a small (20 μm) and large (70 μm) droplet size. Droplet size distribution was measured using real-time laser diffraction and the volume median diameter taken as a response. DOE yielded information on the relationship three critical process parameters: pump rate, atomisation pressure and coating-polymer concentration, had upon droplet size. The model generated was robust, scoring highly for model fit (R2 = 0.977), predictability (Q2 = 0.837), validity and reproducibility. Modelling confirmed that all parameters had either a linear or quadratic effect on droplet size and revealed an interaction between pump rate and atomisation pressure. Fluidised bed coating of tablet cores was performed with either small or large droplets followed by CLSM and XμCT imaging. Addition of commonly used contrast materials to the coating solution improved visualisation of the coating by XμCT, showing the coat as a discrete section of the overall tablet. Imaging provided qualitative and quantitative evidence revealing that smaller droplets formed thinner, more uniform and less porous film coats. PMID:27548263

  2. Comparative static curing versus dynamic curing on tablet coating structures.

    PubMed

    Gendre, Claire; Genty, Muriel; Fayard, Barbara; Tfayli, Ali; Boiret, Mathieu; Lecoq, Olivier; Baron, Michel; Chaminade, Pierre; Péan, Jean Manuel

    2013-09-10

    Curing is generally required to stabilize film coating from aqueous polymer dispersion. This post-coating drying step is traditionally carried out in static conditions, requiring the transfer of solid dosage forms to an oven. But, curing operation performed directly inside the coating equipment stands for an attractive industrial application. Recently, the use of various advanced physico-chemical characterization techniques i.e., X-ray micro-computed tomography, vibrational spectroscopies (near infrared and Raman) and X-ray microdiffraction, allowed new insights into the film-coating structures of dynamically cured tablets. Dynamic curing end-point was efficiently determined after 4h. The aim of the present work was to elucidate the influence of curing conditions on film-coating structures. Results demonstrated that 24h of static curing and 4h of dynamic curing, both performed at 60°C and ambient relative humidity, led to similar coating layers in terms of drug release properties, porosity, water content, structural rearrangement of polymer chains and crystalline distribution. Furthermore, X-ray microdiffraction measurements pointed out different crystalline coating compositions depending on sample storage time. An aging mechanism might have occur during storage, resulting in the crystallization and the upward migration of cetyl alcohol, coupled to the downward migration of crystalline sodium lauryl sulfate within the coating layer. Interestingly, this new study clearly provided further knowledge into film-coating structures after a curing step and confirmed that curing operation could be performed in dynamic conditions. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Delivery of prazosin hydrochloride from osmotic pump system prepared by coating the core tablet with an indentation.

    PubMed

    Liu, Longxiao; Wang, Jinchao; Zhu, Suyan

    2007-04-01

    The preparation of an osmotic pump tablet was simplified by elimination of laser drilling using prazosin hydrochloride as the model drug. The osmotic pump system was obtained by coating the indented core tablet compressed by the punch with a needle. A multiple regression equation was achieved with the experimental data of core tablet formulations, and then the formulation was optimized. The influences of the indentation size of the core tablet, environmental media, and agitation rate on drug release profile were investigated. The optimal osmotic pump tablet was found to deliver prazosin hydrochloride at an approximately constant rate up to 24 hr, and independent on both release media and agitation rate. Indentation size of core tablet hardly affected drug release in the range of 0.80-1.15 mm. The method that is simplified by elimination of laser drilling may be promising for preparation of an osmotic pump tablet.

  4. Assessment of Tablet Surface Hardness by Laser Ablation and Its Correlation With the Erosion Tendency of Core Tablets.

    PubMed

    Narang, Ajit S; Breckenridge, Lydia; Guo, Hang; Wang, Jennifer; Wolf, Abraham Avi; Desai, Divyakant; Varia, Sailesh; Badawy, Sherif

    2017-01-01

    Surface erosion of uncoated tablets results in processing problems such as dusting and defects during coating and is governed by the strength of particle bonding on tablet surface. In this study, the correlation between dusting tendency of tablets in a coating pan with friability and laser ablation surface hardness was assessed using tablets containing different concentrations of magnesium stearate and tartaric acid. Surface erosion propensity of different batches was evaluated by assessing their dusting tendency in the coating pan. In addition, all tablets were analyzed for crushing strength, friability, modified friability test using baffles in the friability apparatus, and weight loss after laser ablation. Tablets with similar crushing strength showed differences in their surface erosion and dusting tendency when rotated in a coating pan. These differences did not correlate well with tablet crushing strength or friability but did show reasonably good correlation with mass loss after laser ablation. These results suggest that tablet surface mass loss by laser ablation can be used as a minipiloting (small-scale) tool to assess tablet surface properties during early stages of drug product development to assess the risk of potential large-scale manufacturing issues. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  5. Investigational Aurora A kinase inhibitor alisertib (MLN8237) as an enteric-coated tablet formulation in non-hematologic malignancies: Phase 1 dose-escalation study

    PubMed Central

    Falchook, Gerald; Kurzrock, Razelle; Gouw, Launce; Hong, David; McGregor, Kimberly A.; Zhou, Xiaofei; Shi, Hongliang; Fingert, Howard; Sharma, Sunil

    2014-01-01

    Background This phase 1b study evaluated an enteric-coated tablet (ECT) formulation of the investigational Aurora A kinase inhibitor, alisertib (MLN8237). Methods Patients with advanced, non-hematologic malignancies received oral alisertib ECT for 7 days BID followed by 14 days treatment-free (21-day cycles; 3+3 dose escalation schema). Objectives were to assess safety, pharmacokinetics, and antitumor activity, and to define a recommended phase 2 dose (RP2D) of alisertib. Results 24 patients were treated. Median age was 57 years. Patients received a median of 2 cycles (range 1–12). The RP2D was determined as 50 mg BID for 7 days (21-day cycles). A cycle 1 dose-limiting toxicity of grade 4 febrile neutropenia was observed in 1 of 13 patients at RP2D. The most common drug-related adverse event (AE) was neutropenia (50%). At doses ≥40 mg BID, 7 patients had drug-related AEs that were serious but largely reversible/manageable by dose reduction and supportive care, including 3 with febrile neutropenia. Pharmacokinetic data were available in 24 patients. Following administration of alisertib ECT, the plasma peak concentration of alisertib was achieved at ~3 h; systemic exposure increased with increasing dose over 10–60 mg BID. Mean t½ was ~21 h following multiple dosing. Renal clearance was negligible. Nine patients achieved stable disease (3.98*, 5.59, 1.28*, 2.56, 5.45*, 3.48, 3.15, 8.31, and 6.93* months; *censored). Conclusions Alisertib ECT was generally well tolerated in adults with advanced, non-hematologic malignancies. The RP2D is 50 mg BID for 7 days and is being evaluated in ongoing phase 2 studies. PMID:24879333

  6. Clinical Efficacy and Residue Depletion of 10% Enrofloxacin Enteric-Coated Granules in Pigs.

    PubMed

    Lei, Zhixin; Liu, Qianying; Yang, Bing; Xiong, Jincheng; Li, Kun; Ahmed, Saeed; Hong, Liping; Chen, Pin; He, Qigai; Cao, Jiyue

    2017-01-01

    A new, more palatable formulation of 10% enrofloxacin enteric-coated granules was investigated to evaluate the pharmacokinetic effect in plasma, the residue elimination in tissues and the clinical efficacy against Actinobacillus pleuropneumonia (APP) and Mycoplasam suis (MS) in pigs. In this study, the enrofloxacin concentrations in plasma and tissues were detected using high-performance liquid chromatography with phosphate buffer (pH = 3) and acetonitrile. The pharmacokinetics and elimination of enrofloxacin enteric-coated granules were performed after oral administration at a single dose of 10 mg/kg body weight (bw) and 5 mg/kg twice per day for 5 consecutive days, respectively. The in vivo antibacterial efficacy and clinical effectiveness of enrofloxacin enteric-coated granules against APP and MS were assayed at 2.5, 5, 10 mg/kg, compared with tiamulin (8 mg/kg) based on establishment of APP and MS infection models. 56 APP strains were selected and tested for in vitro antibacterial activity of enrofloxacin enteric-coated granules. The main parameters of elimination half-life (t 1/2β ), T max , and area under the curve (AUC) were 14.99 ± 4.19, 3.99 ± 0.10, and 38.93 ± 1.52 μg h/ml, respectively, revealing that the enrofloxacin concentration remained high and with a sustainable distribution in plasma. Moreover, the analysis on the evaluation of enrofloxacin and ciprofloxacin in muscle, fat, liver and kidney showed that the recovery were more than 84% recovery in accordance with the veterinary drug residue guidelines of United States pharmacopeia, and the withdrawal periods were 4.28, 3.81, 4.84, and 3.51 days, respectively, suggesting that the withdrawal period was 5 d after oral administration of 5 mg/kg twice per day. The optimal dosage of enrofloxacin enteric-coated granules against APP and MS was 5 mg/kg, with over 90% efficacy, which was significantly different ( p < 0.05) to the 2.5 mg/kg group, but not to the 10 mg/kg group or the positive control

  7. Terahertz Technology: A Boon to Tablet Analysis

    PubMed Central

    Wagh, M. P.; Sonawane, Y. H.; Joshi, O. U.

    2009-01-01

    The terahertz gap has a frequency ranges from ∼0.3 THz to ∼10 THz in the electromagnetic spectrum which is in between microwave and infrared. The terahertz radiations are invisible to naked eye. In comparison with x-ray they are intrinsically safe, non-destructive and non-invasive. Terahertz spectroscopy enables 3D imaging of structures and materials, and the measurement of the unique spectral fingerprints of chemical and physical forms. Terahertz radiations are produced by a dendrimer based high power terahertz source and spectroscopy technologies. It resolves many of the questions left unanswered by complementary techniques, such as optical imaging, Raman and infrared spectra. In the pharmaceutical industries it enables nondestructive, internal, chemical analysis of tablets, capsules, and other dosage forms. Tablet coatings are a major factor in drug bioavailability. Therefore tablet coatings integrity and uniformity are of crucial importance to quality. Terahertz imaging gives an unparalleled certainty about the integrity of tablet coatings and the matrix performance of tablet cores. This article demonstrates the potential of terahertz pulse imaging for the analysis of tablet coating thickness by illustrating the technique on tablets. PMID:20490288

  8. Enteric-coated epichlorohydrin crosslinked dextran microspheres for site-specific delivery to colon.

    PubMed

    Rai, Gopal; Yadav, Awesh K; Jain, Narendra K; Agrawal, Govind P

    2015-01-01

    Enteric-coated epichlorohydrin crosslinked dextran microspheres containing 5-Fluorouracil (5-FU) for colon drug delivery was prepared by emulsification-crosslinking method. The formulation variables studied includes different molecular weights of dextran, volume of crosslinking agent, stirring speed, time and temperature. Dextran microspheres showed mean entrapment efficiencies ranging between 77 and 87% and mean particle size ranging between 10 and 25 µm. About 90% of drug was released from uncoated dextran microspheres within 8 h, suggesting the fast release and indicated the drug loaded in uncoated microspheres, released before they reached colon. Enteric coating (Eudragit-S-100 and Eudragit-L-100) of dextran microspheres was performed by oil-in-oil solvent evaporation method. The release study of 5-FU from coated dextran microspheres was complete retardation in simulated gastric fluid (pH 1.2) and once the coating layer of enteric polymer was dissolved at higher pH (7.4 and 6.8), a controlled release of the drug from the microspheres was observed. Further, the release of drug was found to be higher in the presence of dextranase and rat caecal contents, indicating the susceptibility of dextran microspheres to colonic enzymes. Organ distribution and pharmacokinetic study in albino rats was performed to establish the targeting potential of optimized formulation in the colon.

  9. Enteric-coated aspirin versus other antiplatelet drugs in acute non-cardioembolic ischemic stroke: post-marketing study in Japan.

    PubMed

    Takahashi, Shunichi; Mizuno, Osamu; Sakaguchi, Toshiaki; Yamada, Takashi; Inuyama, Lyo

    2014-01-01

    Japanese guidelines recommend aspirin 160-300 mg/day, starting within 48 h, for patients with acute cerebral infarction. However, there are few reports evaluated in Japanese patients. Our objective was to examine the safety and efficacy of enteric-coated aspirin, compared with other oral antiplatelet drugs, in Japanese patients with acute ischemic stroke. We performed a prospective, non-randomized, observational and multicenter study between June 2005 and December 2007. Patients with symptomatic acute ischemic stroke, including transient ischemic attack (TIA), who started enteric-coated aspirin or other antiplatelet drugs within 7 days of hospitalization were registered. Outcome measures evaluated within 3 months were incidence of cerebral and non-cerebral hemorrhagic events, recurrence of ischemic stroke or TIA, non-cerebral ischemic events and death from any cause. Overall, 2,548 and 830 patients treated with enteric-coated aspirin (100-300 mg/day) or other antiplatelet drugs, respectively, were registered; approximately 60% were male, mean age was 70 years, 85% had pre-existing cardiovascular disease or other complications. Enteric-coated aspirin of 100 mg was mainly prescribed, and only approximately half of the patients were started on it within 48 h after onset of ischemic stroke. Safety and efficacy population excluded patients without follow-up data were 2,521 in enteric-coated aspirin and 807 in other antiplatelets. Hemorrhagic events occurred in 46 (1.8%) in the enteric-coated aspirin group and in 13 (1.6%) in the other antiplatelet drugs group, there was not significant. Recurrent ischemic stroke or TIA occurred in 39 (1.5%) of the enteric-coated aspirin and in 18 (2.2%) of other antiplatelet drugs, and there were any-cause death in 16 (0.6%) and 8 (1.0%). Incidences were slightly lower in the enteric-coated aspirin group compared with the other antiplatelet drugs group, but not statistically significant. It seems that these results showed the

  10. Spaced administration of PA32540 and clopidogrel results in greater platelet inhibition than synchronous administration of enteric-coated aspirin and enteric-coated omeprazole and clopidogrel.

    PubMed

    Gurbel, Paul A; Bliden, Kevin P; Fort, John G; Jeong, Young-Hoon; Shuldiner, Alan; Chai, Sumbul; Gesheff, Tania; Antonino, Mark; Gesheff, Martin; Zhang, Ying; Tantry, Udaya S

    2013-02-01

    A common regimen for patients requiring dual-antiplatelet therapy who are at risk for gastrointestinal complications is the synchronous administration of enteric-coated (EC) aspirin, a proton pump inhibitor, and clopidogrel, although proton pump inhibitors have the potential for pharmacodynamic interaction with clopidogrel. Spaced administration of a clopidogrel and a single-tablet formulation of aspirin and immediate-release omeprazole (PA32540) was considered as an alternative that might reduce this potential pharmacodynamic interaction. A randomized, open-label, crossover study was conducted in healthy subjects (n = 30). Two 7-day treatments were separated by 14-day washout periods: (a) PA32540 + clopidogrel (300 mg loading/75 mg maintenance) 10 hours later and (b) synchronous dosing of clopidogrel + EC aspirin (81 mg) + EC omeprazole (40 mg). The primary end point was the inhibition of platelet aggregation (20 μM adenosine diphosphate, maximal extent) after 7 days. CYP2C19 and ABCB1 genotypes were determined. Inhibition of platelet aggregation was greater with spaced PA32540 + clopidogrel therapy vs synchronous clopidogrel + EC aspirin + EC omeprazole therapy (P = .004). There was no difference in day 7 arachidonic acid-induced aggregation. The effect of spacing on pharmacodynamics was independent of genotype. PA32540 and clopidogrel spaced 10 hours apart had greater antiplatelet effects than did synchronously administered EC aspirin (81 mg), clopidogrel (75 mg), and EC omeprazole in healthy volunteers. These finding are directly relevant to the treatment for patients with high gastrointestinal risk who require dual-antiplatelet therapy and gastroprotection. Copyright © 2013 Mosby, Inc. All rights reserved.

  11. Stabilization and target delivery of Nattokinase using compression coating.

    PubMed

    Law, D; Zhang, Z

    2007-05-01

    The aim of the work is to develop a new formulation in order to stabilize a nutraceutical enzyme Nattokinase (NKCP) in powders and to control its release rate when it passes through the gastrointestinal tract of human. NKCP powders were first compacted into a tablet, which was then coated with a mixture of an enteric material Eudragit L100-55 (EL100-55) and Hydroxypropylcellulose (HPC) by direct compression. The activity of the enzyme was determined using amidolytic assay and its release rates in artificial gastric juice and an intestinal fluid were quantified using bicinchoninic acid assay. Results have shown that the activity of NKCP was pressure independent and the coated tablets protected NKCP from being denatured in the gastric juice, and realized its controlled release to the intestine based on in vitro experiments.

  12. Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS): A rapid test for enteric coating thickness and integrity of controlled release pellet formulations.

    PubMed

    Alfarsi, Anas; Dillon, Amy; McSweeney, Seán; Krüse, Jacob; Griffin, Brendan; Devine, Ken; Sherry, Patricia; Henken, Stephan; Fitzpatrick, Stephen; Fitzpatrick, Dara

    2018-06-10

    There are no rapid dissolution based tests for determining coating thickness, integrity and drug concentration in controlled release pellets either during production or post-production. The manufacture of pellets requires several coating steps depending on the formulation. The sub-coating and enteric coating steps typically take up to six hours each followed by additional drying steps. Post production regulatory dissolution testing also takes up to six hours to determine if the batch can be released for commercial sale. The thickness of the enteric coating is a key factor that determines the release rate of the drug in the gastro-intestinal tract. Also, the amount of drug per unit mass decreases with increasing thickness of the enteric coating. In this study, the coating process is tracked from start to finish on an hourly basis by taking samples of pellets during production and testing those using BARDS (Broadband Acoustic Resonance Dissolution Spectroscopy). BARDS offers a rapid approach to characterising enteric coatings with measurements based on reproducible changes in the compressibility of a solvent due to the evolution of air during dissolution. This is monitored acoustically via associated changes in the frequency of induced acoustic resonances. A steady state acoustic lag time is associated with the disintegration of the enteric coatings in basic solution. This lag time is pH dependent and is indicative of the rate at which the coating layer dissolves. BARDS represents a possible future surrogate test for conventional USP dissolution testing as its data correlates directly with the thickness of the enteric coating, its integrity and also with the drug loading as validated by HPLC. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Influence of enteric-coated lactose on the release profile of 4-aminopyridine from HPMC matrix tablets.

    PubMed

    Martínez-González, Ilona; Villafuerte-Robles, Leopoldo

    2004-01-01

    A weakly basic experimental drug, 4-aminopyridine, was taken as a model to study the influence of enteric-coated lactose (EL) on the release profile from hydroxypropyl methylcellulose matrices. Powder mixtures were wet-granulated with water. The dried granulation was compressed with a hydraulic press at 85 MPa. Dissolution studies were made using HCl 0.1 N and then phosphate buffer pH 7.4. Dissolution curves were described by M(t)/M(inf) = k*t(N). A trend toward increasing exponent (n) and decreasing release constant (k) values is observed with increasing EL concentrations up to 9%; this is attributed to an increasing obstruction of the diffusion path by isolated EL particles that are insoluble in HCl and are surrounded by a water-filled space. After a critical EL concentration, the water-filled spaces surrounding EL particles percolate, producing the opposite effect, increasing the release constant and decreasing the exponent (n) values as the EL proportion increases from 10% to 50%. EL particles (2% to 9%) decrease the drug and water transport in matrices dissolving in HCl. Thereafter, at pH 7.4, the pores formed by dissolution of EL particles produce the opposite. Both processes contribute to flattening the release profile. Release profiles with decreasing release constant values show a logarithmic trend toward increasing values of the exponent (n), changing from diffusion toward relaxation-erosion-controlled processes.

  14. Gastrointestinal transit and disintegration of enteric coated magnetic tablets assessed by ac biosusceptometry.

    PubMed

    Corá, Luciana A; Romeiro, Fernando G; Américo, Madileine F; Oliveira, Ricardo Brandt; Baffa, Oswaldo; Stelzer, Murilo; Miranda, José Ricardo de Arruda

    2006-01-01

    The oral administration is a common route in the drug therapy and the solid pharmaceutical forms are widely used. Although much about the performance of these formulations can be learned from in vitro studies using conventional methods, evaluation in vivo is essential in product development. The knowledge of the gastrointestinal transit and how the physiological variables can interfere with the disintegration and drug absorption is a prerequisite for development of dosage forms. The aim of this work was to employing the ac biosusceptometry (ACB) to monitoring magnetic tablets in the human gastrointestinal tract and to obtain the magnetic images of the disintegration process in the colonic region. The ac biosusceptometry showed accuracy in the quantification of the gastric residence time, the intestinal transit time and the disintegration time (DT) of the magnetic formulations in the human gastrointestinal tract. Moreover, ac biosusceptometry is a non-invasive technique, radiation-free and harmless to the volunteers, as well as an important research tool in the pharmaceutical, pharmacological and physiological investigations.

  15. Investigating effects of hydroxypropyl methylcellulose (HPMC) molecular weight grades on lag time of press-coated ethylcellulose tablets.

    PubMed

    Patadia, Riddhish; Vora, Chintan; Mittal, Karan; Mashru, Rajashree

    2016-11-01

    The research undertaken exemplifies the effects of hydroxypropyl methylcellulose (HPMC) molecular weight (MW) grades of on lag time of press-coated ethylcellulose (EC) tablets. The formulation comprised an immediate release core (containing prednisone as a model drug) surrounded by compression coating with variegated EC-HPMC blends. Five selected HPMC grades (E5, E15, E50, K100LV and K4M) were explored at three different concentrations (10% w/w, 20% w/w and 30% w/w in outer coat) to understand their effects on lag time and drug release. In vitro drug release testing demonstrated that, with increase in concentration of E5 and E15, up to 30% w/w, the mean lag time decreased progressively; whereas with remaining grades, the mean lag time initially decreased up to 20% w/w level and thereafter increased for 30% w/w level. Importantly, with increase in HPMC concentration in the outer coat, the variability in lag time (%RSD; n = 6) was decreased for each of E5, E15 and E50, whereas increased for K100LV and K4M. In general, the variability in lag time was increased with increase in HPMC MW at studied concentration levels. Markedly, tablets with 30% w/w K4M in outer coat exhibited slight premature release (before the rupture of outer coat) along with high variability in lag time. Overall, the study concluded that low MW HPMCs (E5, E15 and E50) were found rather efficient than higher MW HPMCs for developing robust EC-based press-coated pulsatile release formulations where precise lag time followed by sharp burst release is desired.

  16. Dosage form design and in vitro/in vivo evaluation of cevimeline extended-release tablet formulations.

    PubMed

    Tajiri, Shinichiro; Kanamaru, Taro; Kamada, Makoto; Makoto, Kamada; Konno, Tsutomu; Nakagami, Hiroaki

    2010-01-04

    The objective of the present work is to develop an extended-release dosage form of cevimeline. Two types of extended-release tablets (simple matrix tablets and press-coated tablets) were prepared and their potential as extended-release dosage forms were assessed. Simple matrix tablets have a large amount of hydroxypropylcellulose as a rate-controlling polymer and the matrix is homogeneous throughout the tablet. The press-coated tablets consisted of a matrix core tablet, which was completely surrounded by an outer shell containing a large amount of hydroxypropylcellulose. The simple matrix tablets could not sustain the release of cevimeline effectively. In contrast, the press-coated tablets showed a slower dissolution rate compared with simple matrix tablets and the release curve was nearly linear. The dissolution of cevimeline from the press-coated tablets was not markedly affected by the pH of the dissolution medium or by a paddle rotating speed over the range of 50-200 rpm. Furthermore, cevimeline was constantly released from the press-coated tablets in the gastrointestinal tract and the steady-state plasma drug levels were maintained in beagle dogs. These results suggested that the designed PC tablets have a potential for extended-release dosage forms.

  17. Floating tablets for controlled release of ofloxacin via compression coating of hydroxypropyl cellulose combined with effervescent agent.

    PubMed

    Qi, Xiaole; Chen, Haiyan; Rui, Yao; Yang, Fengjiao; Ma, Ning; Wu, Zhenghong

    2015-07-15

    To prolong the residence time of dosage forms within gastrointestinal trace until all drug released at desired rate was one of the real challenges for oral controlled-release drug delivery system. Herein, we developed a fine floating tablet via compression coating of hydrophilic polymer (hydroxypropyl cellulose) combined with effervescent agent (sodium bicarbonate) to achieve simultaneous control of release rate and location of ofloxacin. Sodium alginate was also added in the coating layer to regulate the drug release rate. The effects of the weight ratio of drug and the viscosity of HPC on the release profile were investigated. The optimized formulations were found to immediately float within 30s and remain lastingly buoyant over a period of 12 h in simulated gastric fluid (SGF, pH 1.2) without pepsin, indicating a satisfactory floating and zero-order drug release profile. In addition, the oral bioavailability experiment in New Zealand rabbits showed that, the relative bioavailability of the ofloxacin after administrated of floating tablets was 172.19%, compared to marketed common release tablets TaiLiBiTuo(®). These results demonstrated that those controlled-released floating tables would be a promising gastro-retentive delivery system for drugs acting in stomach. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Protection of moisture-sensitive drugs with aqueous polymer coatings: importance of coating and curing conditions.

    PubMed

    Bley, O; Siepmann, J; Bodmeier, R

    2009-08-13

    The aim of this study was to better understand the importance of coating and curing conditions of moisture-protective polymer coatings. Tablets containing freeze-dried garlic powder were coated with aqueous solutions/dispersions of hydroxypropyl methylcellulose (HPMC), poly(vinyl alcohol), ethyl cellulose and poly(methacrylate-methylmethacrylates). The water content of the tablets during coating and during storage at different temperatures and relative humidities (RH) was determined gravimetrically. In addition, changes in the allicin (active ingredient in garlic powder) content were monitored. During the coating process, the water uptake was below 2.7% and no drug degradation was detectable. Thermally induced drug degradation occurred only at temperatures above the coating temperatures. Different polymer coatings effectively decreased the rate, but not the extent of water uptake during open storage at room temperature and 75% RH. Tablets coated with poly(vinyl alcohol) and poly(methacrylate-methylmethacrylates) showed the lowest moisture uptake rates (0.49 and 0.57%/d, respectively). Curing at elevated temperature after coating did not improve the moisture-protective ability of the polymeric films, but reduced the water content of the tablets. Drug stability was significantly improved with tablets coated with poly(vinyl alcohol) and poly(methacrylate-methylmethacrylates).

  19. Enteric-coated sustained-release nanoparticles by coaxial electrospray: preparation, characterization, and in vitro evaluation

    NASA Astrophysics Data System (ADS)

    Hao, Shilei; Wang, Bochu; Wang, Yazhou; Xu, Yingqian

    2014-02-01

    Enteric-coated formulations can delay the release of drugs until they have passed through the stomach. However, high concentration of drugs caused by rapidly released in the small intestine leads to the intestinal damage, and frequent administration would increase the probability of missing medication and reduce the patient compliance. To solve the above-mentioned problems, aspirin-loaded enteric-coated sustained-release nanoparticles with core-shell structure were prepared via one-step method using coaxial electrospray in this study. Eudragit L100-55 as pH-sensitive polymer and Eudragit RS as sustained-release polymer were used for the outer coating and inner core of the nanoparticles, respectively. The maximum loading capacity of nanoparticles was 23.66 % by changing the flow rate ratio of outer/inner solutions, and the entrapment efficiency was nearly 100 %. Nanoparticles with core-shell structure were observed via fluorescence microscope and transmission electron microscope. And pH-sensitive and sustained drug release profiles were observed in the media with different pH values (1.2 and 6.8). In addition, mild cytotoxicity in vitro was detected, and the nanoparticles could be taken up by Caco-2 cells within 1.0 h in cellular uptake study. These results indicate that prepared enteric-coated sustained-release nanoparticles would be a more safety and effective carrier for oral drug delivery.

  20. Optimization of the inter-tablet coating uniformity for an active coating process at lab and pilot scale.

    PubMed

    Just, Sarah; Toschkoff, Gregor; Funke, Adrian; Djuric, Dejan; Scharrer, Georg; Khinast, Johannes; Knop, Klaus; Kleinebudde, Peter

    2013-11-30

    The objective of this study was to enhance the inter-tablet coating uniformity in an active coating process at lab and pilot scale by statistical design of experiments. The API candesartan cilexetil was applied onto gastrointestinal therapeutic systems containing the API nifedipine to obtain fixed dose combinations of these two drugs with different release profiles. At lab scale, the parameters pan load, pan speed, spray rate and number of spray nozzles were examined. At pilot scale, the parameters pan load, pan speed, spray rate, spray time, and spray pressure were investigated. A low spray rate and a high pan speed improved the coating uniformity at both scales. The number of spray nozzles was identified as the most influential variable at lab scale. With four spray nozzles, the highest CV value was equal to 6.4%, compared to 13.4% obtained with two spray nozzles. The lowest CV of 4.5% obtained with two spray nozzles was further reduced to 2.3% when using four spray nozzles. At pilot scale, CV values between 2.7% and 11.1% were achieved. Since the test of uniformity of dosage units accepts CV values of up to 6.25%, this active coating process is well suited to comply with the pharmacopoeial requirements. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Multispectral UV imaging for surface analysis of MUPS tablets with special focus on the pellet distribution.

    PubMed

    Novikova, Anna; Carstensen, Jens M; Rades, Thomas; Leopold, Prof Dr Claudia S

    2016-12-30

    In the present study the applicability of multispectral UV imaging in combination with multivariate image analysis for surface evaluation of MUPS tablets was investigated with respect to the differentiation of the API pellets from the excipients matrix, estimation of the drug content as well as pellet distribution, and influence of the coating material and tablet thickness on the predictive model. Different formulations consisting of coated drug pellets with two coating polymers (Aquacoat ® ECD and Eudragit ® NE 30 D) at three coating levels each were compressed to MUPS tablets with various amounts of coated pellets and different tablet thicknesses. The coated drug pellets were clearly distinguishable from the excipients matrix using a partial least squares approach regardless of the coating layer thickness and coating material used. Furthermore, the number of the detected drug pellets on the tablet surface allowed an estimation of the true drug content in the respective MUPS tablet. In addition, the pellet distribution in the MUPS formulations could be estimated by UV image analysis of the tablet surface. In conclusion, this study revealed that UV imaging in combination with multivariate image analysis is a promising approach for the automatic quality control of MUPS tablets during the manufacturing process. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Enteric-coated mycophenolate sodium.

    PubMed

    Gabardi, Steven; Tran, Jennifer L; Clarkson, Michael R

    2003-11-01

    To review the pharmacology, pharmacokinetics, efficacy, and safety of mycophenolate sodium. Primary literature was obtained via a MEDLINE search (1966-June 2003). Abstracts were obtained from the manufacturer and included in the analysis. All studies and abstracts evaluating mycophenolate sodium in solid organ transplantation were considered for inclusion. English-language studies and abstracts were selected for inclusion, but were limited to those consisting of human subjects. Mycophenolate sodium, a mycophenolic acid prodrug, is an inhibitor of T-lymphocyte proliferation. Mycophenolic acid reduces the incidence of acute rejection in renal transplantation. Mycophenolate sodium is enteric coated and has been suggested as a potential method to reduce the gastrointestinal adverse events seen with mycophenolate mofetil. Both mycophenolate mofetil and mycophenolate sodium have been shown to be therapeutically equivalent at decreasing the incidence of allograft rejection and loss. The frequency of adverse events is similar between both compounds, with the most common events being diarrhea and leukopenia. Mycophenolate sodium is effective in preventing acute rejection in renal transplant recipients. At doses of 720 mg twice daily, the efficacy and safety profiles are similar to those of mycophenolate mofetil 1000 mg twice daily. Mycophenolate sodium has been approved in Switzerland; approval in the US is pending.

  3. Analysis of Counterfeit Coated Tablets and Multi-Layer Packaging Materials Using Infrared Microspectroscopic Imaging.

    PubMed

    Winner, Taryn L; Lanzarotta, Adam; Sommer, André J

    2016-06-01

    An effective method for detecting and characterizing counterfeit finished dosage forms and packaging materials is described in this study. Using attenuated total internal reflection Fourier transform infrared spectroscopic imaging, suspect tablet coating and core formulations as well as multi-layered foil safety seals, bottle labels, and cigarette tear tapes were analyzed and compared directly with those of a stored authentic product. The approach was effective for obtaining molecular information from structures as small as 6 μm.

  4. Improving Powder Tableting Performance through Materials Engineering

    NASA Astrophysics Data System (ADS)

    Osei-Yeboah, Frederick

    Adequate mechanical strength is a critical requirement to the successful development of a tablet product. Before tablet compression, powders are often engineered by various processes including wet granulation and surface coating, which may improve or adversely affect the powder tableting performance. Such effects, commonly, result from a change in either particle mechanical properties or particulate (size, shape) properties. In this work, tableting performance is interpreted based on the qualitative bonding-area and bonding-strength (BABS) model. The tabletability of the microcrystalline cellulose (MCC) granules deteriorates rapidly with increasing amount of granulating water and eventually leads to over-granulation at high water level. Granule surface smoothing, size enlargement, granule densification and shape rounding are the dominant factors leading to the tabletability reduction of plastic MCC. Incorporation of increasing amounts of brittle excipients, such as lactose or dibasic calcium phosphate reduces the rate of tabletability reduction by promoting more granule fragmentation, introducing more surface area available for bonding. When a sufficient amount of brittle excipients is used, the over-granulation phenomenon can be eliminated. Surface coating of incompressible MCC pellets with highly bonding polymer leads to sufficient surface deformation and adhesion to enable direct compression of the pellets into tablets of adequate mechanical strength. This improvement is enhanced by the presence of moisture, which plasticizes the polymer to allow the development of a larger bonding area between coated pellets. The relationship between mechanical properties and tableting behavior is systematically investigated in polymeric composites using celecoxib-polyvinylpyrrolidone vinyl acetate solid dispersions. Mechanical properties such as indentation hardness of the solid dispersions were measured using nanoindentation. Incorporation of celecoxib up to 60% by weight

  5. Molecular insights into shellac film coats from different aqueous shellac salt solutions and effect on disintegration of enteric-coated soft gelatin capsules.

    PubMed

    Al-Gousous, J; Penning, M; Langguth, P

    2015-04-30

    The purpose of this investigation was to study the effect of using different salts of shellac on the disintegration properties of shellac-based enteric coatings. In the last two decades, shellac has been increasingly used as an aqueous solution for enteric coating purposes, with the ammonium salt being the form typically used. Little investigation has been performed on using other salts, and therefore, this was the focus of our work. Enteric coatings, based on different shellac salts (ammonium, sodium, potassium and composite ammonium-sodium), were applied onto soft gelatin capsules. Disintegration testing of the coated soft gelatin capsules showed that alkali metal salts promote faster disintegration than ammonium salts. In order to determine the causes behind these differences, the solubility, thermal and spectroscopic properties of films cast from the different salts were investigated. The results show that films cast from ammonium-based salts of shellac are, unlike those cast from alkali metal-based salts, water-insoluble. Spectroscopic evidence suggests that this might be due to partial salt dissociation resulting in loss of ammonium as ammonia and reduced degree of shellac ionization during drying. In addition, oxidation of shellac aldehyde groups of the ammonium-based shellac salts could also play a role. And possible higher extent of shellac hydrolysis during the preparation of alkali metal salts might also be a factor. Therefore, the nature of the shellac salt used in the preparation of shellac-based aqueous coating solutions is a significant formulation factor affecting product performance. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Effects of different doses, enteric-coated preparation of aspirin, and sex on urinary 11-dehydrothromboxane B2 in healthy volunteers.

    PubMed

    Dharmasaroja, Pornpatr A; Sae-Lim, Suvaraporn

    2010-10-01

    There is scarce information about the effects of different doses and enteric-coated preparation of aspirin on platelet function, especially in Asian people, evaluated by the measurement of urinary 11-dehydrothromboxane B2 (dTXB2). The objective of the present study was to assess the effects of different doses, enteric-coated preparation of aspirin, sex and also the effects of timing of urine collection on urinary dTXB2 level in healthy volunteers. Thirty healthy volunteers were included. Each volunteer took three preparations of aspirin (aspirin 81 mg, enteric-coated aspirin 300 mg and aspirin 300 mg) for 7 days. Urine dTXB2 level was measured at baseline, day 3, and day 7 after taking each preparation of aspirin. There was no significant difference in the effects of different doses of aspirin (81 vs. 300 mg, 50.7 vs. 61.8 ng/mmol creatinine, P = 0.248), preparations (enteric-coated vs. nonenteric-coated aspirin, 61.8 vs. 67.9 ng/mmol creatinine, P = 0.527) and time of urine collection (day 3 vs. day 7, 51.7 vs. 49.9 ng/mmol creatinine, P = 0.448). Female volunteers showed a trend to have higher urinary dTXB2 than male volunteers at baseline and after taking aspirin. This study showed no significant difference in urinary dTXB2 level after taking different doses and enteric-coated preparation of aspirin in healthy volunteers.

  7. Investigating critical effects of variegated lubricants, glidants and hydrophilic additives on lag time of press coated ethylcellulose tablets.

    PubMed

    Patadia, Riddhish; Vora, Chintan; Mittal, Karan; Mashru, Rajashree

    2016-01-01

    The research envisaged focuses on vital impacts of variegated lubricants, glidants and hydrophilic additives on lag time of press coated ethylcellulose (EC) tablets using prednisone as a model drug. Several lubricants and glidants such as magnesium stearate, colloidal SiO2, sodium stearyl fumarate, talc, stearic acid, polyethylene glycol (6000) and glyceryl behenate were investigated to understand their effects on lag time by changing their concentrations in outer coat. Further, the effects of hydrophilic additives on lag time were examined for hydroxypropylmethylcellulose (E5), hydroxypropylcellulose (EF and SSL), povidone (K30), copovidone, polyethylene glycol (4000), lactose and mannitol. In vitro drug release testing revealed that each selected lubricant/glidant, if present even at concentration of 0.25% w/w, significantly reduced the lag time of press coated tablets. Specifically, colloidal SiO2 and/or magnesium stearate were detrimental while other lubricants/glidants were relatively less injurious. Among hydrophilic additives, freely water soluble fillers had utmost influence in lag time, whereas, comparatively less impact was observed with polymeric binders. Concisely, glidant and lubricant should be chosen to have minimal impact on lag time and further judicious selection of hydrophilic additives should be exercised for modulating lag time of pulsatile release formulations.

  8. Delayed release film coating applications on oral solid dosage forms of proton pump inhibitors: case studies.

    PubMed

    Missaghi, Shahrzad; Young, Cara; Fegely, Kurt; Rajabi-Siahboomi, Ali R

    2010-02-01

    Formulation of proton pump inhibitors (PPIs) into oral solid dosage forms is challenging because the drug molecules are acid-labile. The aim of this study is to evaluate different formulation strategies (monolithic and multiparticulates) for three PPI drugs, that is, rabeprazole sodium, lansoprazole, and esomeprazole magnesium, using delayed release film coating applications. The core tablets of rabeprazole sodium were prepared using organic wet granulation method. Multiparticulates of lansoprazole and esomeprazole magnesium were prepared through drug layering of sugar spheres, using powder layering and suspension layering methods, respectively. Tablets and drug-layered multiparticulates were seal-coated, followed by delayed release film coating application, using Acryl-EZE(R), aqueous acrylic enteric system. Multiparticulates were then filled into capsules. The final dosage forms were evaluated for physical properties, as well as in vitro dissolution testing in both compendial acid phase, 0.1N HCl (pH 1.2), and intermediate pH, acetate buffer (pH 4.5), followed by phosphate buffer, pH 6.8. The stability of the delayed release dosage forms was evaluated upon storage in accelerated conditions [40 degrees C/75% relative humidity] for 3 months. All dosage forms demonstrated excellent enteric protection in the acid phase, followed by rapid release in their respective buffer media. Moreover, the delayed release dosage forms remained stable under accelerated stability conditions for 3 months. Results showed that Acryl-EZE enteric coating systems provide excellent performance in both media (0.1N HCl and acetate buffer pH 4.5) for monolithic and multiparticulate dosage forms.

  9. Pharmacokinetics of colon-specific pH and time-dependent flurbiprofen tablets.

    PubMed

    Vemula, Sateesh Kumar; Veerareddy, Prabhakar Reddy; Devadasu, Venkat Ratnam

    2015-09-01

    Present research deals with the development of compression-coated flurbiprofen colon-targeted tablets to retard the drug release in the upper gastro intestinal system, but progressively release the drug in the colon. Flurbiprofen core tablets were prepared by direct compression method and were compression coated using sodium alginate and Eudragit S100. The formulation is optimized based on the in vitro drug release study and further evaluated by X-ray imaging and pharmacokinetic studies in healthy humans for colonic delivery. The optimized formulation showed negligible drug release (4.33 ± 0.06 %) in the initial lag period followed by progressive release (100.78 ± 0.64 %) for 24 h. The X-ray imaging in human volunteers showed that the tablets reached the colon without disintegrating in the upper gastrointestinal tract. The C max of colon-targeted tablets was 12,374.67 ng/ml at T max 10 h, where as in case of immediate release tablets the C max was 15,677.52 ng/ml at T max 3 h, that signifies the ability of compression-coated tablets to target the colon. Development of compression-coated tablets using combination of time-dependent and pH-sensitive approaches was suitable to target the flurbiprofen to colon.

  10. Novel mesalamine-loaded beads in tablets for delayed release of drug to the colon.

    PubMed

    Nguyen, Chien; Christensen, J Mark; Ayres, James W

    2012-01-01

    Novel 'beads-in-a-tablet' formulations (total weight ∼740-780 mg) have been prepared that meet USP 31 requirements for Delayed Release of mesalamine. Several methods are presented that overcome breakage of beads during tablet compaction were explored. Bead formulations comprise a combination of extrusion and spheronization to produce a relatively high drug load (80%), followed by coating (25%) with a colonic-targeted drug release polymer (polymethacrylates, Eudragit(®) S100), overcoated (3%) with hydroxypropyl methylcellulose (Opadry(®)) to improve bead binding and compactability, and using 20% coat of lactose/sodium starch glycolate (Explotab(®)) as binder/disintegrant/cushioning agent, thus allowing a sufficiently thick coating to be uniform and without being broken during tablet compaction. Then, the aforementioned beads were compressed into tablets at 1500 pounds of pressure containing 400 mg of mesalamine, and finally coating the compressed tablets with Surelease(®) (ethylcellulose):Opadry(®) = 1:0.5 ranging from 1.5-2.5% weight gain; the resulting tablets met USP 31 dissolution requirements for delayed release tablets.

  11. Formulation of multiparticulate systems as lyophilised orally disintegrating tablets.

    PubMed

    Alhusban, Farhan; Perrie, Yvonne; Mohammed, Afzal R

    2011-11-01

    The current study aimed to exploit the electrostatic associative interaction between carrageenan and gelatin to optimise a formulation of lyophilised orally disintegrating tablets (ODTs) suitable for multiparticulate delivery. A central composite face centred (CCF) design was applied to study the influence of formulation variables (gelatin, carrageenan and alanine concentrations) on the crucial responses of the formulation (disintegration time, hardness, viscosity and pH). The disintegration time and viscosity were controlled by the associative interaction between gelatin and carrageenan upon hydration which forms a strong complex that increases the viscosity of the stock solution and forms tablet with higher resistant to disintegration in aqueous medium. Therefore, the levels of carrageenan, gelatin and their interaction in the formulation were the significant factors. In terms of hardness, increasing gelatin and alanine concentration was the most effective way to improve tablet hardness. Accordingly, optimum concentrations of these excipients were needed to find the best balance that fulfilled all formulation requirements. The revised model showed high degree of predictability and optimisation reliability and therefore was successful in developing an ODT formulation with optimised properties that were able deliver enteric coated multiparticulates of omeprazole without compromising their functionality. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Studies on stercuia gum formulations in the form of osmotic core tablet for colon-specific drug delivery of azathioprine.

    PubMed

    Nath, Bipul; Nath, Lila Kanta

    2013-01-01

    The purpose of this research is to evaluate Sterculia urens gum as a carrier for a colon-targeted drug delivery system. Microflora degradation studies of Sterculia gum was conducted in phosphate-buffered saline pH 7.4 containing rat caecal medium under an anaerobic environment. Solubility, swelling index, viscosity, and pH of the polymer solution were determined. Different formulation aspects considered were gum concentration (10-40%) and concentration of citric acid (10-30%) on the swelling index and in-vitro dissolution release. The results of the isothermal stress testing showed that there is no degradation of samples of model drug, azathioprine, the drug polymer mixture, and the core tablet excipients. Differential scanning calorimetry and Fourier transform infrared spectroscopy study proved the compatibility of the drug with Sterculia gum and other tablet excipients. Microflora degradation study revealed that Sterculia gum can be used as tablet excipient for drug release in the colonic region by utilizing the action of enterobacteria. The swelling force of the Sterculia gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the mixed film coating under colonic microflora-activated environment. Sterculia gum gives premature drug release in the upper gastrointestinal tract without enteric coating and may not reach the colonic region. Sterculia gum as a colon-targeting carrier is possible via double-layer coating with chitosan/Eudragit RLPO (ammonio-methacrylate copolymer) mixed blend as well as enteric polymers, which would provide acid as well as intestinal resistance but undergo enzymatic degradation once reaching the colon. The aim of the research is to evaluate wheather Sterculia urens, which is a polysaccharide, is suitable as a carrier for colonic delivery of drugs acting locally in the colon. Sterculia gum has been reported to have wide pharmaceutical applications such as tablet binder, disintegrant, gelling agent, and

  13. Development and in vitro evaluation of mesalamine delayed release pellets and tableted reservoir-type pellets.

    PubMed

    Bendas, Ehab R; Christensen, J Mark; Ayres, James W

    2010-04-01

    The basic objective of this study was to develop a novel technique that aids in compaction of coated pellets into tablets and obtain a release pattern from compressed pellets resembling the same pattern before compression. Multi-unit dosage forms of mesalamine targeted to the colon were formulated by extrusion-spheronization, and then coated with Eudragit S (30%). These pellets were filled into gelatin capsules or further formulated and compressed into tablets. Tablets for colonic delivery of mesalamine were prepared by mixing the coated beads with cushioning agents like stearic acid and Explotab, or by applying an additional coat of gelatin (4% weight gain) onto the Eudragit S coated pellets, and then compressing into tablets (tableted reservoir-type pellets). Then additional coating of the tablets prepared by the coating technique was applied utilizing Eudragit L 100-55 (5% weight gain). This technique provides additive protection for the coated beads to withstand the compression force during tableting. Excellent in vitro dissolution results were obtained, which were comparable to the results of the release of mesalamine from uncompressed beads filled in capsules. Mesalamine release from the capsules was 0.3% after 2 hours in gastric pH, 0.37% was released after an additional 1 hour in pH 6, and 89% was released after 1.5 hours in colonic pH 7.2. Various formulation and process parameters have to be optimized in order to obtain tableted reservoir-type pellets having the same release properties as the uncompressed pellets. The coating technique delays the release of mesalamine until the beads reach the terminal ileum and colon. Once released in the colon, mesalamine is minimally absorbed and can act locally to treat ulcerative colitis.

  14. Construction of a novel pH-sensitive drug release system from mesoporous silica tablets coated with Eudragit

    NASA Astrophysics Data System (ADS)

    Xu, Yingpu; Qu, Fengyu; Wang, Yu; Lin, Huiming; Wu, Xiang; Jin, Yingxue

    2011-03-01

    A novel pH-sensitive drug release system has been established by coating Eudragit (Eud) on drug-loaded mesoporous silica (MS) tablets. The release rate of ibuprofen (IBU) from the MS was retarded by coating with Eudragit S-100, and the higher retardation was due to the increase of coating concentration and the coating layers. The target position of the release depended on the pH of the release medium, which was confirmed by the drug release from IBU/MS/Eud increasing rapidly with the change of medium pH from 1.2 to 7.4. This drug delivery system could prohibit irritant drug from leaking in the stomach and make it only release in the intestine. The loaded and unloaded drug samples were characterized by powder X-ray diffraction (XRD), Fourier transform infrared spectrometer (FTIR), N 2 adsorption/desorption, scanning electron microscopy (SEM), and transmission electron microscopy (TEM).

  15. Enteric-coating of pulsatile-release HPC capsules prepared by injection molding.

    PubMed

    Macchi, E; Zema, L; Maroni, A; Gazzaniga, A; Felton, L A

    2015-04-05

    Capsular devices based on hydroxypropyl cellulose (Klucel® LF) intended for pulsatile release were prepared by injection molding (IM). In the present work, the possibility of exploiting such capsules for the development of colonic delivery systems based on a time-dependent approach was evaluated. For this purpose, it was necessary to demonstrate the ability of molded cores to undergo a coating process and that coated systems yield the desired performance (gastric resistance). Although no information was available on the coating of IM substrates, some issues relevant to that of commercially-available capsules are known. Thus, preliminary studies were conducted on molded disks for screening purposes prior to the spray-coating of HPC capsular cores with Eudragit® L 30 D 55. The ability of the polymeric suspension to wet the substrate, spread, start penetrating and initiate hydration/swelling, as well as to provide a gastroresistant barrier was demonstrated. The coating of prototype HPC capsules was carried out successfully, leading to coated systems with good technological properties and able to withstand the acidic medium with no need for sealing at the cap/body joint. Such systems maintained the original pulsatile release performance after dissolution of the enteric film in pH 6.8 fluid. Therefore, they appeared potentially suitable for the development of a colon delivery platform based on a time-dependent approach. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Determination of acetylsalicylic acid in commercial tablets by SERS using silver nanoparticle-coated filter paper

    NASA Astrophysics Data System (ADS)

    Sallum, Loriz Francisco; Soares, Frederico Luis Felipe; Ardila, Jorge Armando; Carneiro, Renato Lajarim

    2014-12-01

    In this work, filter paper was used as a low cost substrate for silver nanoparticles in order to perform the detection and quantification of acetylsalicylic acid by SERS in a commercial tablet. The reaction conditions were 150 mM of ammonium hydroxide, 50 mM of silver nitrate, 500 mM of glucose, 12 min of the reaction time, 45 °C temperature, pretreatment with ammonium hydroxide and quantitative filter paper (1-2 μm). The average size of silver nanoparticles deposited on the paper substrate was 180 nm. Adsorption time of acetylsalicylic acid on the surface of the silver-coated filter paper was studied and an adsorption time of 80 min was used to build the analytical curve. It was possible to obtain a calibration curve with good precision with a coefficient of determination of 0.933. The method proposed in this work was capable to quantify acetylsalicylic acid in commercial tablets, at low concentration levels, with relative error of 2.06% compared to the HPLC. The preparation of filter paper coated with silver nanoparticles using Tollen's reagent presents several advantages such as low cost of synthesis, support and reagents; minimum amount of residuals, which are easily treated, despite the SERS spectroscopy presenting fast analysis, with low sample preparation and low amount of reactants as in HPLC analysis.

  17. Antiplatelet effects of aspirin with phytosterols: comparison with non-enteric coated aspirin alone.

    PubMed

    Antonino, Mark J; Coppolecchia, Rosa; Mahla, Elisabeth; Bliden, Kevin P; Tantry, Udaya S; Gurbel, Paul A

    2010-11-01

    The novel combination of aspirin and phytosterols may be a potential strategy to treat patients with cardiovascular disease. We sought to determine if the antiplatelet effects of a combination caplet of 81 mg aspirin with 400 mg phytosterols differed from the antiplatelet effects of non-enteric coated aspirin. The first five days of aspirin therapy alone (T1) produced marked reductions in collagen-induced, ADP-induced, and archidonic acid- induced platelet aggregation, and in serum and urine TxB(2) compared to baseline. Five days after randomization to aspirin alone versus aspirin+phytosterols (T2), there were no differences in any measurement of platelet function within each group compared to T1 or between groups. The present study suggests that the antiplatelet effect of non-enteric coated 81 mg twice-daily aspirin therapy alone is not affected by the addition of phytosterols in a combination product. Copyright © 2009 Elsevier Ltd. All rights reserved.

  18. Improving the quality of polymer-coated urea with recycled plastic, proper additives, and large tablets.

    PubMed

    Yang, Yue-Chao; Zhang, Min; Li, Yuncong; Fan, Xiao-Hui; Geng, Yu-Qing

    2012-11-14

    Polymer-coated urea (PCU) has great potential for increasing crop production and enhancing nitrogen (N) fertilizer use efficiency, benefiting the ecosystem. However, current PCUs are used only in a limited market, and the main obstacle to the wider use of PCUs is high cost compared to that of conventional N fertilizers. In this study, the low cost PCU and large tablet polymer-coated urea (LTPCU) were prepared by using recycling polystyrene foam and various sealants as the coating materials. The structural and chemical characteristics of the coating shells of the coated fertilizers were examined. The N release characteristics of coated fertilizers were determined in 25 °C water under laboratory conditions. The relationship between the N release longevity and the amount of coating material and the percentage of different sealants were evaluated. The results indicated that recycling polystyrene foam was the ideal coating material of the controlled release fertilizer. The polyurethane that was synthesized by the reaction of castor oil and isocyanate was better than the wax as the additive to delay the N release rate of coated urea. The coating material used for LTPCU was 70-80% less than those used for commercial PCUs under the same N release longevity. The cost of the recycling polystyrene foam used for coating one ton of pure N of the LTPCU was about one-seventh to one-eighth of the cost of the traditional polymer used for the commercial PCU. The experimental data showed that the LTPCU with good controlled-release capacities, being economical and eco-friendly, could be promising for wide use in agriculture and horticulture.

  19. Development, evaluation and pharmacokinetics of time-dependent ketorolac tromethamine tablets.

    PubMed

    Vemula, Sateesh Kumar; Veerareddy, Prabhakar Reddy

    2013-01-01

    The present study was intended to develop a time-dependent colon-targeted compression-coated tablets of ketorolac tromethamine (KTM) using hydroxypropyl methylcellulose (HPMC) that release the drug slowly but completely in the colonic region by retarding the drug releases in stomach and small intestine. KTM core tablets were prepared by direct compression method and were compression coated with HPMC. The formulation is optimized based on the in vitro drug release studies and further evaluated by X-ray imaging technique in healthy humans to ensure the colonic delivery. To prove these results, in vivo pharmacokinetic studies in human volunteers were designed to study the in vitro-in vivo correlation. From the in vitro dissolution study, optimized formulation F3 showed negligible drug release (6.75 ± 0.49%) in the initial lag period followed by slow release (97.47 ± 0.93%) for 24 h which clearly indicates that the drug is delivered to the colon. The X-ray imaging studies showed that the tablets reached the colon without disintegrating in upper gastrointestinal system. From the pharmacokinetic evaluation, the immediate-release tablets producing peak plasma concentration (C(max)) was 4482.74 ng/ml at 2 h T(max) and colon-targeted tablets showed C(max) = 3562.67 ng/ml at 10 h T(max). The area under the curve for the immediate-release and compression-coated tablets was 10595.14 and 18796.70 ng h/ml and the mean resident time was 3.82 and 10.75 h, respectively. Thus, the compression-coated tablets based on time-dependent approach were preferred for colon-targeted delivery of ketorolac.

  20. Key Technical Aspects Influencing the Accuracy of Tablet Subdivision.

    PubMed

    Teixeira, Maíra T; Sá-Barreto, Lívia C L; Gratieri, Taís; Gelfuso, Guilherme M; Silva, Izabel C R; Cunha-Filho, Marcílio S S

    2017-05-01

    Tablet subdivision is a common practice used mainly for dose adjustment. The aim of this study was to investigate how the technical aspects of production as well as the method of tablets subdivision (employing a tablet splitter or a kitchen knife) influence the accuracy of this practice. Five drugs commonly used as subdivided tablets were selected. For each drug, the innovator drug product, a scored-generic and a non-scored generic were investigated totalizing fifteen drug products. Mechanical and physical tests, including image analysis, were performed. Additionally, comparisons were made between tablet subdivision method, score, shape, diluent composition and coating. Image analysis based on surface area was a useful tool as an alternative assay to evaluate the accuracy of tablet subdivision. The tablet splitter demonstrates an advantage relative to a knife as it showed better results in weight loss and friability tests. Oblong, coated and scored tablets had better results after subdivision than round, uncoated and non-scored tablets. The presence of elastic diluents such as starch and dibasic phosphate dehydrate conferred a more appropriate behaviour for the subdivision process than plastic materials such as microcrystalline cellulose and lactose. Finally, differences were observed between generics and their innovator products in all selected drugs with regard the quality control assays in divided tablet, which highlights the necessity of health regulations to consider subdivision performance at least in marketing authorization of generic products.

  1. Impact of salt form and molecular weight of chitosan on swelling and drug release from chitosan matrix tablets.

    PubMed

    Huanbutta, Kampanart; Cheewatanakornkool, Kamonrak; Terada, Katsuhide; Nunthanid, Jurairat; Sriamornsak, Pornsak

    2013-08-14

    Magnetic resonance imaging (MRI) and gravimetric techniques were used to assess swelling and erosion behaviors of hydrophilic matrix tablets made of chitosan. The impact of salt form, molecular weight (MW) and dissolution medium on swelling behavior and drug (theophylline) release was studied. The matrix tablets made of chitosan glycolate (CGY) showed the greatest swelling in both acid and neutral media, compared to chitosan aspartate, chitosan glutamate and chitosan lactate. MRI illustrated that swelling region of CGY in both media was not different in the first 100 min but glassy region (dry core) in 0.1N HCl was less than in pH 6.8 buffer. The tablets prepared from chitosan with high MW swelled greater than those of low MW. Moreover, CGY can delay drug release in the acid condition due to thick swollen gel and low erosion rate. Therefore, CGY may be suitably applied as sustained drug release polymer or enteric coating material. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Neuroleptic bioequivalency: tablet versus concentrate.

    PubMed

    Fann, W E; Moreira, A F

    1985-01-01

    Two forms of the antipsychotic neuroleptic molindone were administered to newly admitted psychotic patients. A coated tablet was administered for ten days, followed by administration of liquid concentrate in equivalent doses for four days. Plasma was analyzed by gas chromatography with electron capture for the parent compound following each dosing phase. Our data suggest that oral doses of the tablet and concentrate forms of this neuroleptic are equivalent in clinical bioavailability.

  3. Enteric polymers as acidifiers for the pH-independent sustained delivery of a weakly basic drug salt from coated pellets.

    PubMed

    Körber, Martin; Ciper, Mesut; Hoffart, Valerie; Pearnchob, Nantharat; Walther, Mathias; Macrae, Ross J; Bodmeier, Roland

    2011-08-01

    Weakly basic drugs and their salts exhibit a decrease in aqueous solubility at higher pH, which can result in pH-dependent or even incomplete release of these drugs from extended release formulations. The objective of this study was to evaluate strategies to set-off the very strong pH-dependent solubility (solubility: 80 mg/ml at pH 2 and 0.02 mg/ml at pH 7.5, factor 4000) of a mesylate salt of weakly basic model drug (pK(a) 6.5), in order to obtain pH-independent extended drug release. Three approaches for pH-independent release were investigated: (1) organic acid addition in the core, (2) enteric polymer addition to the extended release coating and (3) an enteric polymer subcoating below the extended release coating. The layering of aspartic acid onto drug cores as well as the coating of drug cores with an ethylcellulose/Eudragit L (enteric polymer) blend were not effective to avoid the formation of the free base at pH 7.5 and thus failed to significantly improve the completeness of the release compared to standard ethylcellulose/hydroxypropyl cellulose (EC/HPC)-coated drug pellets. Interestingly, the incorporation of an enteric polymer layer underneath the EC/HPC coating decreased the free base formation at pH 7.5 and thus resulted in a more complete release of up to 90% of the drug loading over 18 h. The release enhancing effect was attributed to an extended acidification through the enteric polymer layer. Flexible release patterns with approximately pH-independent characteristics were successfully achieved. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. A blinded randomised controlled trial to determine the effect of enteric coating on enzyme treatment for canine exocrine pancreatic efficiency.

    PubMed

    Mas, Aran; Noble, Peter-John M; Cripps, Peter J; Batchelor, Daniel J; Graham, Peter; German, Alexander J

    2012-07-28

    Enzyme treatment is the mainstay for management of exocrine pancreatic insufficiency (EPI) in dogs. 'Enteric-coated' preparations have been developed to protect the enzyme from degradation in the stomach, but their efficacy has not been critically evaluated. The hypothesis of the current study was that enteric coating would have no effect on the efficacy of pancreatic enzyme treatment for dogs with EPI.Thirty-eight client-owned dogs with naturally occurring EPI were included in this multicentre, blinded, randomised controlled trial. Dogs received either an enteric-coated enzyme preparation (test treatment) or an identical preparation without the enteric coating (control treatment) over a period of 56 days. There were no significant differences in either signalment or cobalamin status (where cobalamin deficient or not) between the dogs on the test and control treatments. Body weight and body condition score increased in both groups during the trial (P<0.001) but the magnitude of increase was greater for the test treatment compared with the control treatment (P<0.001). By day 56, mean body weight increase was 17% (95% confidence interval 11-23%) in the test treatment group and 9% (95% confidence interval 4-15%) in the control treatment group. The dose of enzyme required increased over time (P<0.001) but there was no significant difference between treatments at any time point (P=0.225). Clinical disease severity score decreased over time for both groups (P=0.011) and no difference was noted between groups (P=0.869). No significant adverse effects were reported, for either treatment, for the duration of the trial. Enteric coating a pancreatic enzyme treatment improves response in canine EPI.

  5. Authentication of gold nanoparticle encoded pharmaceutical tablets using polarimetric signatures.

    PubMed

    Carnicer, Artur; Arteaga, Oriol; Suñé-Negre, Josep M; Javidi, Bahram

    2016-10-01

    The counterfeiting of pharmaceutical products represents concerns for both industry and the safety of the general public. Falsification produces losses to companies and poses health risks for patients. In order to detect fake pharmaceutical tablets, we propose producing film-coated tablets with gold nanoparticle encoding. These coated tablets contain unique polarimetric signatures. We present experiments to show that ellipsometric optical techniques, in combination with machine learning algorithms, can be used to distinguish genuine and fake samples. To the best of our knowledge, this is the first report using gold nanoparticles encoded with optical polarimetric classifiers to prevent the counterfeiting of pharmaceutical products.

  6. Mechanistic investigation of drug release from asymmetric membrane tablets: effect of media gradients (osmotic pressure and concentration), and potential coating failures on in vitro release.

    PubMed

    Am Ende, Mary Tanya; Miller, Lee A

    2007-02-01

    An asymmetric membrane (AM) tablet was developed for a soluble model compound to study the in vitro drug release mechanisms in challenge conditions, including osmotic gradients, concentration gradients, and under potential coating failure modes. Porous, semipermable membrane integrity may be compromised by a high fat meal or by the presence of a defect in the coating that could cause a safety concern about dose-dumping. The osmotic and diffusional release mechanisms of the AM tablet were independently shut down such that their individual contribution to the overall drug release was measured. Shut off of osmotic and diffusional release was accomplished by performing dissolution studies into receptor solutions with osmotic pressure above the internal core osmotic pressure and into receptor solutions saturated with drug, respectively. The effect of coating failure modes on in vitro drug release from the AM tablet was assessed through a simulated high-fat meal and by intentionally compromising the coating integrity. The predominant drug release mechanism for the AM tablet was osmotic and accounted for approximately 90-95% of the total release. Osmotic release was shutoff when the receptor media osmotic pressure exceeded 76 atm. Diffusional release of the soluble drug amounted to 5-10% of the total release mechanism. The observed negative in vitro food effect was attributed to the increased osmotic pressure from the high fat meal when compared to the predicted release rates in sucrose media with the same osmotic pressure. This suppression in drug release rate due to a high fat meal is not anticipated to affect in vivo performance of the dosage form, as the rise in pressure is short-lived. Drug release from the AM system studied was determined to be robust to varying and extreme challenge conditions. The conditions investigated included varying pH, agitation rate, media osmotic pressure, media saturated with drug to eliminate the concentration gradient, simulated high

  7. Enteric-coated, highly standardized cranberry extract reduces risk of UTIs and urinary symptoms during radiotherapy for prostate carcinoma

    PubMed Central

    Bonetta, Alberto; Di Pierro, Francesco

    2012-01-01

    Background Cranberry (Vaccinium macrocarpon) proanthocyanidins can interfere with adhesion of bacteria to uroepithelial cells, potentially preventing lower urinary tract infections (LUTIs). Because LUTIs are a common side effect of external beam radiotherapy (EBRT) for prostate cancer, we evaluated the clinical efficacy of enteric-coated tablets containing highly standardized V. msacrocarpon (ecVM) in this condition. Methods A total of 370 consecutive patients were entered into this study. All patients received intensity-modulated radiotherapy for prostate cancer; 184 patients were also treated with ecVM while 186 served as controls. Cranberry extract therapy started on the simulation day, at which time a bladder catheterization was performed. During EBRT (over 6–7 weeks), all patients underwent weekly examination for urinary tract symptoms, including regular urine cultures during the treatment period. Results Compliance was excellent, with no adverse effects or allergic reactions being observed, apart from gastric pain in two patients. In the cranberry cohort (n = 184), 16 LUTIs (8.7%) were observed, while in the control group (n = 186) 45 LUTIs (24.2%) were recorded. This difference was statistically significant. Furthermore, lower rates of nocturia, urgency, micturition frequency, and dysuria were observed in the group that received cranberry extract. Conclusion Cranberry extracts have been reported to reduce the incidence of LUTIs significantly in women and children. Our data extend these results to patients with prostate cancer undergoing irradiation to the pelvis, who had a significant reduction in LUTIs compared with controls. These results were accompanied by a statistically significant reduction in urinary tract symptoms (dysuria, nocturia, urinary frequency, urgency), suggesting a generally protective effect of cranberry extract on the bladder mucosa. PMID:22977312

  8. Development and optimization of enteric coated mucoadhesive microspheres of duloxetine hydrochloride using 32 full factorial design

    PubMed Central

    Setia, Anupama; Kansal, Sahil; Goyal, Naveen

    2013-01-01

    Background: Microspheres constitute an important part of oral drug delivery system by virtue of their small size and efficient carrier capacity. However, the success of these microspheres is limited due to their short residence time at the site of absorption. Objective: The objective of the present study was to formulate and systematically evaluate in vitro performance of enteric coated mucoadhesive microspheres of duloxetine hydrochloride (DLX), an acid labile drug. Materials and Methods: DLX microspheres were prepared by simple emulsification phase separation technique using chitosan as carrier and glutaraldehyde as a cross-linking agent. Microspheres prepared were coated with eudragit L-100 using an oil-in-oil solvent evaporation method. Eudragit L-100was used as enteric coating polymer with the aim to release the drug in small intestine The microspheres prepared were characterized by particle size, entrapment efficiency, swelling index (SI), mucoadhesion time, in vitro drug release and surface morphology. A 32 full factorial design was employed to study the effect of independent variables polymer-to-drug ratio (X1) and stirring speed (X2) on dependent variables, particle size, entrapment efficiency, SI, in vitro mucoadhesion and drug release up to 24 h (t24). Results: Microspheres formed were discrete, spherical and free flowing. The microspheres exhibited good mucoadhesive property and also showed high percentage entrapment efficiency. The microspheres were able to sustain the drug release up to 24 h. Conclusion: Thus, the prepared enteric coated mucoadhesive microspheres may prove to be a potential controlled release formulation of DLX for oral administration. PMID:24167786

  9. Development and optimization of enteric coated mucoadhesive microspheres of duloxetine hydrochloride using 3(2) full factorial design.

    PubMed

    Setia, Anupama; Kansal, Sahil; Goyal, Naveen

    2013-07-01

    Microspheres constitute an important part of oral drug delivery system by virtue of their small size and efficient carrier capacity. However, the success of these microspheres is limited due to their short residence time at the site of absorption. The objective of the present study was to formulate and systematically evaluate in vitro performance of enteric coated mucoadhesive microspheres of duloxetine hydrochloride (DLX), an acid labile drug. DLX microspheres were prepared by simple emulsification phase separation technique using chitosan as carrier and glutaraldehyde as a cross-linking agent. Microspheres prepared were coated with eudragit L-100 using an oil-in-oil solvent evaporation method. Eudragit L-100was used as enteric coating polymer with the aim to release the drug in small intestine The microspheres prepared were characterized by particle size, entrapment efficiency, swelling index (SI), mucoadhesion time, in vitro drug release and surface morphology. A 3(2) full factorial design was employed to study the effect of independent variables polymer-to-drug ratio (X1) and stirring speed (X2) on dependent variables, particle size, entrapment efficiency, SI, in vitro mucoadhesion and drug release up to 24 h (t24). Microspheres formed were discrete, spherical and free flowing. The microspheres exhibited good mucoadhesive property and also showed high percentage entrapment efficiency. The microspheres were able to sustain the drug release up to 24 h. Thus, the prepared enteric coated mucoadhesive microspheres may prove to be a potential controlled release formulation of DLX for oral administration.

  10. Development of enteric-coated fixed dose combinations of amorphous solid dispersions of ezetimibe and lovastatin: Investigation of formulation and process parameters.

    PubMed

    Riekes, Manoela K; Dereymaker, Aswin; Berben, Philippe; Augustijns, Patrick; Stulzer, Hellen K; Van den Mooter, Guy

    2017-03-30

    Enteric-coated fixed-dose combinations of ezetimibe and lovastatin were prepared by fluid bed coating aiming to avoid the acidic conversion of lovastatin to its hydroxyacid derivative. In a two-step process, sucrose beads were layered with a glass solution of ezetimibe, lovastatin and Soluplus ® , top-coated with an enteric layer. The impact of different bead size, enteric polymers (Eudragit L100 ® and Eudragit L100-55 ® ) and coating time was investigated. Samples were evaluated by X-ray diffraction, scanning electron microscopy, laser diffraction and in vitro studies in 0.1M HCl and phosphate buffer pH 6.8. Results showed that smaller beads tend to agglomerate and release was jeopardized in acidic conditions, most likely due to irregular coating layer. Eudragit L100-55 ® required longer processing, but thinner coating layers provided lower drug release. Both polymers showed low drug release in acidic environment and fast release at pH 6.8. The off-line measurement of the coating thickness determined the ideal coating time as 15 and 30min for Eudragit L100-55 ® and Eudragit L100 ® -based samples, respectively. Both compounds were molecularly dispersed in Soluplus ® , and Eudragit L100 ® formulations showed concave pores on the surface, presenting higher drug release in acidic conditions. Stability studies after 6 months showed unaltered physical properties and drug release. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Development and characterization of enteric-coated immediate-release pellets of aceclofenac by extrusion/spheronization technique using kappa-carrageenan as a pelletizing agent.

    PubMed

    Kilor, Vaishali A; Sapkal, Nidhi P; Awari, Jasmine G; Shewale, Bharti D

    2010-03-01

    In the present study, an attempt was made to prepare immediate-release enteric-coated pellets of aceclofenac, a poorly soluble nonsteroidal anti-inflammatory drug that has a gastrointestinal intolerance as its serious side effect. Formulation of enteric-coated pellets with improved solubility of aceclofenac could address both of these problems. To achieve these goals, pellets were prepared by extrusion-spheronization method using pelletizing agents that can contribute to the faster disintegration and thereby improve the solubility of the drug. Different disintegrants like beta-cyclodextrin, kollidon CL, Ac-Di-Sol, and sodium starch glycolate were tried in order to further improve disintegration time. The pellets were characterized for drug content, particle size distribution, flow properties, infrared spectroscopy, surface morphology, disintegration rate, and dissolution profile. The formulations, which showed best disintegration and dissolution profiles, were coated with Eudragit L100-55, an enteric-coated polymer which does not dissolve at gastric pH but dissolves at intestinal pH, releasing the drug immediately in the dissolution medium. The optimized enteric-coated formulation containing 20% kappa-carrageenan, lactose, and sodium starch glycolate as a disintegrant did inhibit the release of the drug for 2 h in 0.1 N HCl, whereas 87% of the drug was released within 45 min. The improvement was substantial when it was compared with solubility of pure drug under the same conditions. Thus, dissolution profiles suggested that combination of kappa-carrageenan and sodium starch glycolate resulted into fast-disintegrating, immediate-release pellets, overcoming the bioavailability problem of the poorly soluble drug, aceclofenac, and enteric coating of these pellets avoids the exposure of aceclofenac to ulcer-prone areas of the gastrointestinal tract.

  12. Formulation and evaluation of novel coated floating tablets of bergenin and cetirizine dihydrochloride for gastric delivery.

    PubMed

    He, Shuang; Li, Feng; Zhou, Dan; Du, Junrong; Huang, Yuan

    2012-10-01

    A novel coated gastric floating drug-delivery system (GFDDS) of bergenin (BN) and cetirizine dihydrochloride (CET) was developed. First, the pharmacodynamic studies were performed and the results revealed that the new compounds of bergenin/cetirizine dihydrochloride had comparative efficacy as commercial products (bergenin/chlorphenamine maleate) but with fewer side effects on central nervous system (CNS). Subsequently, bergenin was formulated as an extended-release core tablet while cetirizine dihydrochloride was incorporated into the gastric coating film for immediate release. The formulation of GFDDS was optimized by CET content uniformity test, in vitro buoyancy and drug release. Herein, the effects of sodium bicarbonate (effervescent), hydroxypropyl methylcellulose (HPMC, matrix polymer) and coating weight gain were investigated respectively. The optimized GFDDS exhibited good floating properties (buoyancy lag time < 2 min; floating duration > 10 h) and satisfactory drug-release profiles (immediate release of CET in 10 min and sustained release of BN for 12 h). In vivo gamma scintigraphy proved that the optimized GFDDS could retain in the stomach with a prolonged gastric retention time (GRT) of 5 h, and the coating layer showed no side effect for gastric retention. The novel coated gastric floating drug-delivery system offers a new approach to enhance BN's absorption at its absorption site and the efficacy of both CET and BN.

  13. Mini-tablets versus pellets as promising multiparticulate modified release delivery systems for highly soluble drugs.

    PubMed

    Gaber, Dina M; Nafee, Noha; Abdallah, Osama Y

    2015-07-05

    Whether mini-tablets (tablets, diameters ≤6mm) belong to single- or multiple-unit dosage forms is still questionable. Accordingly, Pharmacopoeial evaluation procedures for mini-tablets are lacking. In this study, the aforementioned points were discussed. Moreover, their potential for oral controlled delivery was assessed. The antidepressant venlafaxine hydrochloride (Vx), a highly soluble drug undergoing first pass effect, low bioavailability and short half-life was selected as a challenging payload. In an attempt to weigh up mini-tablets versus pellets as multiparticulate carriers, Vx-loaded mini-tablets were compared to formulated pellets of the same composition and the innovator Effexor(®)XR pellets. Formulations were prepared using various polymer hydrogels in the core and ethyl cellulose film coating with increasing thickness. Mini-tablets (diameter 2mm) showed extended Vx release (<60%, 8h). Indeed, release profiles comparable to Effexor(®)XR pellets were obtained. Remarkably higher coating thickness was required for pellets to provide equivalent retardation. Ethyl cellulose in the core ensured faster release due to polymer migration to the surface and pore formation in the coat. mini-tablets showed higher stability to pellets upon storage. Industrially speaking, mini-tablets proved to be superior to pellets in terms of manufacturing, product quality and economical aspects. Results point out the urgent need for standardized evaluation procedures for mini-tablets. Copyright © 2015. Published by Elsevier B.V.

  14. Alendronate Sodium as Enteric Coated Solid Lipid Nanoparticles; Preparation, Optimization, and In Vivo Evaluation to Enhance Its Oral Bioavailability

    PubMed Central

    Hosny, Khaled Mohamed

    2016-01-01

    Treatment of osteoporosis with alendronate sodium has several challenges. The first challenge is the low bioavailability. The second main challenge is side effects, which include oesophageal ulceration. The aim of this research was to reformulate alendronate sodium as enteric coated solid lipid nanoparticles in order to enhance its bioavailability, and preventing the free alendronate sodium from coming into direct contact with the gastrointestinal mucosa, and thereby reducing the possibility of side effects. Enteric coated solid lipid nanoparticles were prepared according to the Box-Behnken design employing Design expert® software, and characterized for size, morphology, and entrapment efficiency. The optimized formula was coated with an Eudragit S100 and evaluated for drug release in acidic and basic media, stability studies and pharmacokinetic evaluations on rabbits. The results indicated that, using Derringer's desirability functional tool for optimization, the highest entrapment efficiency value of 74.3% and the smallest size value of 98 nm were predicted under optimum conditions with a desirability value of 0.917. The optimized nanoparticles released alendronate sodium only at an alkaline pH. The pharmacokinetic evaluation revealed that alendronate sodium bioavailability was enhanced by more than 7.4-fold in rabbits. In conclusion, enteric coated solid lipid nanoparticles is a promising formula for the delivery of alendronate sodium, eliminating its oesophageal side effects and enhancing its bioavailability. PMID:27148747

  15. Alendronate Sodium as Enteric Coated Solid Lipid Nanoparticles; Preparation, Optimization, and In Vivo Evaluation to Enhance Its Oral Bioavailability.

    PubMed

    Hosny, Khaled Mohamed

    2016-01-01

    Treatment of osteoporosis with alendronate sodium has several challenges. The first challenge is the low bioavailability. The second main challenge is side effects, which include oesophageal ulceration. The aim of this research was to reformulate alendronate sodium as enteric coated solid lipid nanoparticles in order to enhance its bioavailability, and preventing the free alendronate sodium from coming into direct contact with the gastrointestinal mucosa, and thereby reducing the possibility of side effects. Enteric coated solid lipid nanoparticles were prepared according to the Box-Behnken design employing Design expert® software, and characterized for size, morphology, and entrapment efficiency. The optimized formula was coated with an Eudragit S100 and evaluated for drug release in acidic and basic media, stability studies and pharmacokinetic evaluations on rabbits. The results indicated that, using Derringer's desirability functional tool for optimization, the highest entrapment efficiency value of 74.3% and the smallest size value of 98 nm were predicted under optimum conditions with a desirability value of 0.917. The optimized nanoparticles released alendronate sodium only at an alkaline pH. The pharmacokinetic evaluation revealed that alendronate sodium bioavailability was enhanced by more than 7.4-fold in rabbits. In conclusion, enteric coated solid lipid nanoparticles is a promising formula for the delivery of alendronate sodium, eliminating its oesophageal side effects and enhancing its bioavailability.

  16. EFFECT OF MAGNESIUM STEARATE CONCENTRATION ON DISSOLUTION PROPERTIES OF RANITIDINE HYDROCHLORIDE COATED TABLETS

    PubMed Central

    Uzunović, Alija; Vranić, Edina

    2007-01-01

    Most pharmaceutical formulations also include a certain amount of lubricant to improve their flowability and prevent their adhesion to the surfaces of processing equipment. Magnesium stearate is an additive that is most frequently used as a lubricant. Magnesium stearate is capable of forming films on other tablet excipients during prolonged mixing, leading to a prolonged drug liberation time, a decrease in hardness, and an increase in disintegration time. It is hydrophobic, and there are many reports in the literature concerning its adverse effect on dissolution rates. The objective of this study was to evaluate the effects of two different concentrations of magnesium stearate on dissolution properties of ranitidine hydrochloride coated tablet formulations labeled to contain 150 mg. The uniformity content was also checked. During the drug formulation development, several samples were designed for choice of the formulation. For this study, two formulations containing 0,77 and 1,1% of magnesium stearate added in the manufacture of cores were chosen. Fraction of ranitidine hydrochloride released in dissolution medium was calculated from calibration curves. The data were analyzed using pharmaco-peial test for similarity of dissolution profiles (f2 equation), previously proposed by Moore and Flanner. Application of f2 equation showed differences in time-course of ranitidine hydrochloride dissolution properties. The obtained values indicate differences in drug release from analyzed ranitidine hydrochloride formulations and could cause differences in therapeutic response. PMID:17848158

  17. In vitro and in vivo investigation of taste-masking effectiveness of Eudragit E PO as drug particle coating agent in orally disintegrating tablets.

    PubMed

    Drašković, Milica; Medarević, Djordje; Aleksić, Ivana; Parojčić, Jelena

    2017-05-01

    Considering that bitter taste of drugs incorporated in orally disintegrating tablets (ODTs) can be the main reason for avoiding drug therapy, it is of the utmost importance to achieve successful taste-masking. The evaluation of taste-masking effectiveness is still a major challenge. The objective of this study was to mask bitter taste of the selected model drugs by drug particle coating with Eudragit ® E PO, as well as to evaluate taste-masking effectiveness of prepared ODTs using compendial dissolution testing, dissolution in the small-volume shake-flask assembly and trained human taste panel. Model drugs were coated in fluidized bed. Disintequik™ ODT was used as a novel co-processed excipient for ODT preparation. Selected formulations were investigated in vitro and in vivo using techniques for taste-masking assessment. Significantly slower drug dissolution was observed from tablets with coated drug particles during the first 3 min of investigation. Results of in vivo taste-masking assessment demonstrated significant improvement in drug bitterness suppression in formulations with coated drug. Strong correlation between the results of drug dissolution in the small-volume shake-flask assembly and in vivo evaluation data was established (R ≥ 0.970). Drug particle coating with Eudragit ® E PO can be a suitable approach for bitter taste-masking. Strong correlation between in vivo and in vitro results implicate that small-volume dissolution method may be used as surrogate for human panel taste-masking assessment, in the case of physical taste-masking approach application.

  18. In Vitro Evaluation of Eslicarbazepine Delivery via Enteral Feeding Tubes.

    PubMed

    Reindel, Kristin; Zhao, Fang; Hughes, Susan; Dave, Vivek S

    2017-12-01

    Purpose: The feasibility of preparing an eslicarbazepine acetate suspension using Aptiom tablets for administration via enteral feeding tubes was evaluated. Methods: Eslicarbazepine acetate suspension (40 mg/mL) was prepared using Aptiom tablets after optimizing the tablet crushing methods and the vehicle composition. A stability-indicating high-performance liquid chromatography (HPLC) method was developed to monitor the eslicarbazepine stability in the prepared suspension. Three enteric feeding tubes of various composition and dimensions were evaluated for the delivery of the suspensions. The suspension was evaluated for the physical and chemical stability for 48 hours. Results: The reproducibility and consistency of particle size reduction was found to be best with standard mortar/pestle. The viscosity analysis and physical stability studies showed that ORA-Plus:water (50:50 v/v) was optimal for suspending ability and flowability of suspension through the tubes. The developed HPLC method was found to be stability indicating and suitable for the assay of eslicarbazepine acetate in the prepared suspension. The eslicarbazepine concentrations in separately prepared suspensions were within acceptable range (±3%), indicating accuracy and reproducibility of the procedure. The eslicarbazepine concentrations in suspensions before and after delivery through the enteric feeding tubes were within acceptable range (±4%), indicating absence of any physical/chemical interactions of eslicarbazepine with the tubes and a successful delivery of eslicarbazepine dosage via enteric feeding tubes. The stability study results showed that eslicarbazepine concentration in the suspension remained unchanged when stored at room temperature for 48 hours. Conclusion: The study presents a convenient procedure for the preparation of a stable suspension of eslicarbazepine acetate (40 mg/mL) using Aptiom tablets, for administration via enteral feeding tubes.

  19. Zero-order release and bioavailability enhancement of poorly water soluble Vinpocetine from self-nanoemulsifying osmotic pump tablet.

    PubMed

    El-Zahaby, Sally A; AbouGhaly, Mohamed H H; Abdelbary, Ghada A; El-Gazayerly, Omaima N

    2017-06-08

    Solid self-nanoemulsifying (S-SNEDDS) asymmetrically coated osmotic tablets of the poorly water-soluble drug Vinpocetine (VNP) were designed. The aim was to control the release of VNP by the osmotic technology taking advantage of the solubility and bioavailability-enhancing capacity of S-SNEDDS. Liquid SNEDDS loaded with 2.5 mg VNP composed of Maisine™ 35-1, Transcutol ® HP, and Cremophor ® EL was adsorbed on the solid carrier Aeroperl ® . S-SNEDDS was mixed with the osmotic tablet excipients (sodium chloride, Avicel ® , HPMC-K4M, PVP-K30, and Lubripharm ® ), then directly compressed to form the core tablet. The tablets were dip coated and mechanically drilled. A 3 2 *2 1 full factorial design was adopted. The independent variables were: type of coating material (X 1 ), concentration of coating solution (X 2 ), and number of drills (X 3 ). The dependent variables included % release at 2 h (Y 1 ), at 4 h (Y 2 ), and at 8 h (Y 3 ). The in vivo performance of the optimum formula was assessed in rabbits. Zero-order VNP release was obtained by the single drilled 1.5% Opadry ® CA coated osmotic tablets and twofold increase in VNP bioavailability was achieved. The combination of SNEDDS and osmotic pump tablet system was successful in enhancing the solubility and absorption of VNP as well as controlling its release.

  20. Measurements of the Diameter and Velocity Distributions of Atomized Tablet-Coating Solutions for Pharmaceutical Applications

    NASA Astrophysics Data System (ADS)

    Osterday, Kathryn; Aliseda, Alberto; Lasheras, Juan

    2009-11-01

    The atomization of colloidal suspensions is of particular interest to the manufacturing of tablets and pills used as drug delivery systems by the pharmaceutical industry. At various stages in the manufacturing process, the tablets are coated with a spray of droplets produced by co-axial atomizers. The mechanisms of droplet size and spray formation in these types of atomizers are dominated by Kelvin-Helmholtz and Raleigh-Taylor instabilities for both low[1] and high[2] Ohnesorge numbers. We present detailed phase Doppler measurements of the Sauter Mean Diameter of the droplets produced by co-axial spray atomizers using water-based colloidal suspensions with solid concentrations ranging from fifteen to twenty percent and acetone-based colloidal suspensions with solid concentrations ranging from five to ten percent. Our results compare favorably with predictions by Aliseda's model. This suggests that the final size distribution is mainly determined by the instabilities caused by the sudden acceleration of the liquid interface. [1]Varga, C. M., et al. (2003) J. Fluid Mech. 497:405-434 [2]Aliseda, A. et al. (2008). J. Int. J. Multiphase Flow, 34(2), 161-175.

  1. In-Line Monitoring of a Pharmaceutical Pan Coating Process by Optical Coherence Tomography.

    PubMed

    Markl, Daniel; Hannesschläger, Günther; Sacher, Stephan; Leitner, Michael; Buchsbaum, Andreas; Pescod, Russel; Baele, Thomas; Khinast, Johannes G

    2015-08-01

    This work demonstrates a new in-line measurement technique for monitoring the coating growth of randomly moving tablets in a pan coating process. In-line quality control is performed by an optical coherence tomography (OCT) sensor allowing nondestructive and contact-free acquisition of cross-section images of film coatings in real time. The coating thickness can be determined directly from these OCT images and no chemometric calibration models are required for quantification. Coating thickness measurements are extracted from the images by a fully automated algorithm. Results of the in-line measurements are validated using off-line OCT images, thickness calculations from tablet dimension measurements, and weight gain measurements. Validation measurements are performed on sample tablets periodically removed from the process during production. Reproducibility of the results is demonstrated by three batches produced under the same process conditions. OCT enables a multiple direct measurement of the coating thickness on individual tablets rather than providing the average coating thickness of a large number of tablets. This gives substantially more information about the coating quality, that is, intra- and intertablet coating variability, than standard quality control methods. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  2. New insights on poly(vinyl acetate)-based coated floating tablets: characterisation of hydration and CO2 generation by benchtop MRI and its relation to drug release and floating strength.

    PubMed

    Strübing, Sandra; Abboud, Tâmara; Contri, Renata Vidor; Metz, Hendrik; Mäder, Karsten

    2008-06-01

    The purpose of this study was to investigate the mechanism of floating and drug release behaviour of poly(vinyl acetate)-based floating tablets with membrane controlled drug delivery. Propranolol HCl containing tablets with Kollidon SR as an excipient for direct compression and different Kollicoat SR 30 D/Kollicoat IR coats varying from 10 to 20mg polymer/cm2 were investigated regarding drug release in 0.1N HCl. Furthermore, the onset of floating, the floating duration and the floating strength of the device were determined. In addition, benchtop MRI studies of selected samples were performed. Coated tablets with 10mg polymer/cm2 SR/IR, 8.5:1.5 coat exhibited the shortest lag times prior to drug release and floating onset, the fastest increase in and highest maximum values of floating strength. The drug release was delayed efficiently within a time interval of 24 h by showing linear drug release characteristics. Poly(vinyl acetate) proved to be an appropriate excipient to ensure safe and reliable drug release. Floating strength measurements offered the possibility to quantify the floating ability of the developed systems and thus to compare different formulations more efficiently. Benchtop MRI studies allowed a deeper insight into drug release and floating mechanisms noninvasively and continuously.

  3. Design of tablets for the delayed and complete release of poorly water-soluble weak base drugs using SBE7M-β-CD as a solubilizing agent.

    PubMed

    Rao, Venkatramana M; Zannou, Erika A; Stella, Valentino J

    2011-04-01

    The challenge of designing a delayed-release oral dosage form is significantly increased when the drug substance is poorly water soluble. This manuscript describes the design and characterization of a novel controlled-release film-coated tablet for the pH-triggered delayed and complete release of poorly water-soluble weak base drugs. Delivery of weak bases is specifically highlighted with the use of dipyridamole and prazosin as model compounds. Tailored delayed release is achieved with a combination of an insoluble but semipermeable polymer and an enteric polymer, such as cellulose acetate and hydroxypropyl cellulose phthalate, respectively, as coatings. The extent of the time lag prior to complete release depends on the film-coating composition and thickness. Complete release is achieved by the addition of a cyclodextrin, namely SBE7M-β-CD with or without a pH modifier added to the tablet core to ensure complete solubilization and release of the drug substance. The film-coating properties allow the complex formation/solubilization to occur in situ. Additionally, the drug release rate can be modulated on the basis of the cyclodextrin to drug molar ratio. This approach offers a platform technology for delayed release of potent but poorly soluble drugs and the release can be modulated by adjusting the film-coating composition and thickness and/or the cyclodextrin and pH modifier, if necessary. Copyright © 2010 Wiley-Liss, Inc.

  4. Adherence to iron chelation therapy in patients who switched from deferasirox dispersible tablets to deferasirox film-coated tablets.

    PubMed

    Cheng, Wendy Y; Said, Qayyim; Hao, Yanni; Xiao, Yongling; Vekeman, Francis; Bobbili, Priyanka; Duh, Mei Sheng; Nandal, Savita; Blinder, Morey

    2018-06-04

    To compare real-world adherence to and persistence with deferasirox film-coated tablets (DFX-FCT) and deferasirox dispersible tablets (DFX-DT) among patients who switched from DFX-DT to DFX-FCT, overall and by disease type (sickle cell disease [SCD], thalassemia, and myelodysplastic syndrome [MDS]). Patients were ≥2 years old and had ≥2 DFX-FCT claims over the study period and ≥2 DFX-DT claims before the index date (first DFX-FCT claim). The DFX-DT period was defined from the first DFX-DT claim to the index date; the DFX-FCT period was defined from the index date to the end of the study period. Adherence was measured as medication possession ratio (MPR) and proportion of days covered (PDC). Persistence was defined as continuous medication use without a gap ≥30 or 60 days between refills. Comparisons were conducted using paired-sample Wilcoxon sign-rank and McNemar's tests. In total, 606 patients were selected (SCD: 348; thalassemia: 107; MDS: 106; other: 45). Adherence and persistence in the DFX-FCT vs DFX-DT period was significantly higher across all measures: mean MPR was 0.80 vs 0.76 (p < .001); 60.9% vs 54.3% of patients had MPR ≥ 0.8 (p = .009); mean 3-month PDC was 0.83 vs 0.71 (p < .001); 64.2% vs 45.4% of patients had 3-month PDC ≥ 0.8 (p < .001); 87.2% vs 63.4% of patients had 3-month persistence with no gap ≥30 days and 96.1% vs 79.9% with no gap ≥60 days (p < .001). Adherence and persistence improved after switching across all diseases, particularly MDS. Adherence and persistence improved significantly after switching from DFX-DT to DFX-FCT for all diseases, but especially MDS.

  5. Real-time data processing for in-line monitoring of a pharmaceutical coating process by optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Markl, Daniel; Ziegler, Jakob; Hannesschläger, Günther; Sacher, Stephan; Buchsbaum, Andreas; Leitner, Michael; Khinast, Johannes G.

    2014-05-01

    Coating of tablets is a widely applied unit operation in the pharmaceutical industry. Thickness and uniformity of the coating layer are crucial for efficacy as well as for compliance. Not only due to different initiatives it is thus essential to monitor and control the coating process in-line. Optical coherence tomography (OCT) was already shown in previous works to be a suitable candidate for in-line monitoring of coating processes. However, to utilize the full potential of the OCT technology an automatic evaluation of the OCT measurements is essential. The automatic evaluation is currently implemented in MATLAB and includes several steps: (1) extraction of features of each A-scan, (2) classification of Ascan measurements based on their features, (3) detection of interfaces (air/coating and coating/tablet core), (4) correction of distortions due to the curvature of the bi-convex tablets and the oblique orientation of the tablets, and (5) determining the coating thickness. The algorithm is tested on OCT data acquired by moving the sensor head of the OCT system across a static tablet bed. The coating thickness variations of single tablets (i.e., intra-tablet coating variability) can additionally be analyzed as OCT allows the measurement of the coating thickness on multiple displaced positions on one single tablet. Specifically, the information about those parameters emphasizes the high capability of the OCT technology to improve process understanding and to assure a high product quality.

  6. X-ray powder diffractometry of intact film coated tablets--an approach to monitor the physical form of the active pharmaceutical ingredient during processing and storage.

    PubMed

    Yamada, Hiroyuki; Suryanarayanan, Raj

    2007-08-01

    The antiviral compound, 2-amino-6-(4-methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl)ester (MCC-478), can exist in several anhydrous polymorphic forms and also as a hemihydrate. The XRD patterns of the tablets, containing each form of the active pharmaceutical ingredient (API), revealed at least one peak unique to each form. A semiquantitative microdiffractometric method was developed to nondestructively characterize the physical form of the API in intact film-coated tablets. This was accomplished even though the weight fraction of the API was <0.2 and that of mannitol, a highly crystalline excipient, was approximately 0.6. The method was used to determine the effect of aqueous film-coating process on the physical form of the API. The final dosage form was also monitored following storage at 40 degrees C/75% RH for 6 months. There was no phase transformation of the API either due to the film-coating process or following accelerated storage. This technique has potential utility not only for process control during manufacture, but also for the quality control of the final product. (c) 2007 Wiley-Liss, Inc. and the American Pharmacists Association.

  7. Comparative effects of aspirin and enteric-coated aspirin on loss of chromium 51-labeled erythrocytes from the gastrointestinal tract

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Robbins, D.C.; Schwartz, R.S.; Kutny, K.

    Sodium chromate Cr 51 was used to label red blood cells of 19 healthy male volunteers, whose stools were collected for four days before and four days during oral administration of either uncoated (N . 9) or enteric-coated (N . 10) aspirin. Each subject received 2.925 gm/day of aspirin, in three equal doses separated by eight-hour intervals, for a total of seven days. During drug use, stools were collected on days 4 through 7. Fecal blood content, estimated by measuring radioactivity in the stools, was significantly higher (P less than 0.001) during use of either type of aspirin than atmore » baseline, but losses measured during use of the coated aspirin (mean, 1.54 ml/day) were significantly lower (P less than 0.001) than those measured during use of the uncoated aspirin (mean, 4.33 ml/day). The two types of aspirin produced equivalent serum concentrations of salicylates. We conclude that enteric-coated aspirin reduces gastrointestinal blood loss.« less

  8. Enteric coated spheres produced by extrusion/spheronization provide effective gastric protection and efficient release of live therapeutic bacteria.

    PubMed

    de Barros, João M S; Lechner, Tabea; Charalampopoulos, Dimitrios; Khutoryanskiy, Vitaliy V; Edwards, Alexander D

    2015-09-30

    We present a novel but simple enteric coated sphere formulation containing probiotic bacteria (Lactobacillus casei). Oral delivery of live bacterial cells (LBC) requires live cells to survive firstly manufacturing processes and secondly GI microbicidal defenses including gastric acid. We incorporated live L. casei directly in the granulation liquid, followed by granulation, extrusion, spheronization, drying and spray coating to produce dried live probiotic spheres. A blend of MCC, calcium-crosslinked alginate, and lactose was developed that gave improved live cell survival during manufacturing, and gave excellent protection from gastric acid plus rapid release in intestinal conditions. No significant loss of viability was observed in all steps except drying, which resulted in approximately 1 log loss of viable cells. Eudragit coating was used to protect dried live cells from acid, and microcrystalline cellulose (MCC) was combined with sodium alginate to achieve efficient sphere disintegration leading to rapid and complete bacterial cell release in intestinal conditions. Viability and release of L. casei was evaluated in vitro in simulated GI conditions. Uncoated spheres gave partial acid protection, but enteric coated spheres effectively protected dried probiotic LBC from acid for 2h, and subsequently released all viable cells within 1h of transfer into simulated intestinal fluid. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Optical coherence tomography as a novel tool for in-line monitoring of a pharmaceutical film-coating process.

    PubMed

    Markl, Daniel; Hannesschläger, Günther; Sacher, Stephan; Leitner, Michael; Khinast, Johannes G

    2014-05-13

    Optical coherence tomography (OCT) is a contact-free non-destructive high-resolution imaging technique based on low-coherence interferometry. This study investigates the application of spectral-domain OCT as an in-line quality control tool for monitoring pharmaceutical film-coated tablets. OCT images of several commercially-available film-coated tablets of different shapes, formulations and coating thicknesses were captured off-line using two OCT systems with centre wavelengths of 830nm and 1325nm. Based on the off-line image evaluation, another OCT system operating at a shorter wavelength was selected to study the feasibility of OCT as an in-line monitoring method. Since in spectral-domain OCT motion artefacts can occur as a result of the tablet or sensor head movement, a basic understanding of the relationship between the tablet speed and the motion effects is essential for correct quantifying and qualifying of the tablet coating. Experimental data was acquired by moving the sensor head of the OCT system across a static tablet bed. Although examining the homogeneity of the coating turned more difficult with increasing transverse speed of the tablets, the determination of the coating thickness was still highly accurate at a speed up to 0.7m/s. The presented OCT setup enables the investigation of the intra- and inter-tablet coating uniformity in-line during the coating process. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. A Three-Pulse Release Tablet for Amoxicillin: Preparation, Pharmacokinetic Study and Physiologically Based Pharmacokinetic Modeling.

    PubMed

    Li, Jin; Chai, Hongyu; Li, Yang; Chai, Xuyu; Zhao, Yan; Zhao, Yunfan; Tao, Tao; Xiang, Xiaoqiang

    2016-01-01

    Amoxicillin is a commonly used antibiotic which has a short half-life in human. The frequent administration of amoxicillin is often required to keep the plasma drug level in an effective range. The short dosing interval of amoxicillin could also cause some side effects and drug resistance, and impair its therapeutic efficacy and patients' compliance. Therefore, a three-pulse release tablet of amoxicillin is desired to generate sustained release in vivo, and thus to avoid the above mentioned disadvantages. The pulsatile release tablet consists of three pulsatile components: one immediate-release granule and two delayed release pellets, all containing amoxicillin. The preparation of a pulsatile release tablet of amoxicillin mainly includes wet granulation craft, extrusion/spheronization craft, pellet coating craft, mixing craft, tablet compression craft and film coating craft. Box-Behnken design, Scanning Electron Microscope and in vitro drug release test were used to help the optimization of formulations. A crossover pharmacokinetic study was performed to compare the pharmacokinetic profile of our in-house pulsatile tablet with that of commercial immediate release tablet. The pharmacokinetic profile of this pulse formulation was simulated by physiologically based pharmacokinetic (PBPK) model with the help of Simcyp®. Single factor experiments identify four important factors of the formulation, namely, coating weight of Eudragit L30 D-55 (X1), coating weight of AQOAT AS-HF (X2), the extrusion screen aperture (X3) and compression forces (X4). The interrelations of the four factors were uncovered by a Box-Behnken design to help to determine the optimal formulation. The immediate-release granule, two delayed release pellets, together with other excipients, namely, Avicel PH 102, colloidal silicon dioxide, polyplasdone and magnesium stearate were mixed, and compressed into tablets, which was subsequently coated with Opadry® film to produce pulsatile tablet of

  11. A Three-Pulse Release Tablet for Amoxicillin: Preparation, Pharmacokinetic Study and Physiologically Based Pharmacokinetic Modeling

    PubMed Central

    Li, Jin; Chai, Hongyu; Li, Yang; Chai, Xuyu; Zhao, Yan; Zhao, Yunfan; Tao, Tao; Xiang, Xiaoqiang

    2016-01-01

    Background Amoxicillin is a commonly used antibiotic which has a short half-life in human. The frequent administration of amoxicillin is often required to keep the plasma drug level in an effective range. The short dosing interval of amoxicillin could also cause some side effects and drug resistance, and impair its therapeutic efficacy and patients’ compliance. Therefore, a three-pulse release tablet of amoxicillin is desired to generate sustained release in vivo, and thus to avoid the above mentioned disadvantages. Methods The pulsatile release tablet consists of three pulsatile components: one immediate-release granule and two delayed release pellets, all containing amoxicillin. The preparation of a pulsatile release tablet of amoxicillin mainly includes wet granulation craft, extrusion/spheronization craft, pellet coating craft, mixing craft, tablet compression craft and film coating craft. Box–Behnken design, Scanning Electron Microscope and in vitro drug release test were used to help the optimization of formulations. A crossover pharmacokinetic study was performed to compare the pharmacokinetic profile of our in-house pulsatile tablet with that of commercial immediate release tablet. The pharmacokinetic profile of this pulse formulation was simulated by physiologically based pharmacokinetic (PBPK) model with the help of Simcyp®. Results and Discussion Single factor experiments identify four important factors of the formulation, namely, coating weight of Eudragit L30 D-55 (X1), coating weight of AQOAT AS-HF (X2), the extrusion screen aperture (X3) and compression forces (X4). The interrelations of the four factors were uncovered by a Box–Behnken design to help to determine the optimal formulation. The immediate-release granule, two delayed release pellets, together with other excipients, namely, Avicel PH 102, colloidal silicon dioxide, polyplasdone and magnesium stearate were mixed, and compressed into tablets, which was subsequently coated with Opadry

  12. Aqueous film coating to reduce recrystallization of guaifenesin from hot-melt extruded acrylic matrices.

    PubMed

    Bruce, Caroline D; Fegely, Kurt A; Rajabi-Siahboomi, Ali R; McGinity, James W

    2010-02-01

    This study investigated the effect of aqueous film coating on the recrystallization of guaifenesin from acrylic, hot-melt extruded matrix tablets. After hot-melt extrusion, matrix tablets were film-coated with either hypromellose or ethylcellulose. The effects of the coating polymer, curing and storage conditions, polymer weight gain, and core guaifenesin concentration on guaifenesin recrystallization were investigated. The presence of either film coating on the guaifenesin-containing tablets was found to prolong the onset time of drug crystallization. The coating polymer was the most important factor determining the delay in the onset of crystallization, with the more hydrophilic polymer, hypromellose, having a higher solubilization potential for the guaifenesin and delaying crystallization for longer period (3 or 6 months in tablets stored at 40 degrees C or 25 degrees C, respectively) than the more hydrophobic ethylcellulose, which displayed a lower solubilization potential for guaifenesin (crystal growth on tablets cured for 2 hours at 60 degrees C occurred within 3 weeks, whereas uncoated tablets displayed surface crystal growth after 30 minutes). Crystal morphology was also affected by the film coating. Elevated temperatures during both curing and storage, incomplete film coalescence, and high core drug concentrations all contributed to an earlier onset of crystal growth.

  13. Atomic layer deposition-A novel method for the ultrathin coating of minitablets.

    PubMed

    Hautala, Jaana; Kääriäinen, Tommi; Hoppu, Pekka; Kemell, Marianna; Heinämäki, Jyrki; Cameron, David; George, Steven; Juppo, Anne Mari

    2017-10-05

    We introduce atomic layer deposition (ALD) as a novel method for the ultrathin coating (nanolayering) of minitablets. The effects of ALD coating on the tablet characteristics and taste masking were investigated and compared with the established coating method. Minitablets containing bitter tasting denatonium benzoate were coated by ALD using three different TiO 2 nanolayer thicknesses (number of deposition cycles). The established coating of minitablets was performed in a laboratory-scale fluidized-bed apparatus using four concentration levels of aqueous Eudragit ® E coating polymer. The coated minitablets were studied with respect to the surface morphology, taste masking capacity, in vitro disintegration and dissolution, mechanical properties, and uniformity of content. The ALD thin coating resulted in minimal increase in the dimensions and weight of minitablets in comparison to original tablet cores. Surprisingly, ALD coating with TiO 2 nanolayers decreased the mechanical strength, and accelerated the in vitro disintegration of minitablets. Unlike previous studies, the studied levels of TiO 2 nanolayers on tablets were also inadequate for effective taste masking. In summary, ALD permits a simple and rapid method for the ultrathin coating (nanolayering) of minitablets, and provides nanoscale-range TiO 2 coatings on porous minitablets. More research, however, is needed to clarify its potential in tablet taste masking applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. The New Screen Time: Computers, Tablets, and Smartphones Enter the Equation

    ERIC Educational Resources Information Center

    Wiles, Bradford B.; Schachtner, Laura; Pentz, Julie L.

    2016-01-01

    Emerging technologies attract children and push parents' and caregivers' abilities to attend to their families. This article presents recommendations related to the new version of screen time, which includes time with computers, tablets, and smartphones. Recommendations are provided for screen time for very young children and those in middle and…

  15. Challenges in detecting magnesium stearate distribution in tablets.

    PubMed

    Lakio, Satu; Vajna, Balázs; Farkas, István; Salokangas, Henri; Marosi, György; Yliruusi, Jouko

    2013-03-01

    Magnesium stearate (MS) is the most commonly used lubricant in pharmaceutical industry. During blending, MS particles form a thin layer on the surfaces of the excipient and drug particles prohibiting the bonding from forming between the particles. This hydrophobic layer decreases the tensile strength of tablets and prevents water from penetrating into the tablet restraining the disintegration and dissolution of the tablets. Although overlubrication of the powder mass during MS blending is a well-known problem, the lubricant distribution in tablets has traditionally been challenging to measure. There is currently no adequate analytical method to investigate this phenomenon. In this study, the distribution of MS in microcrystalline cellulose (MCC) tablets was investigated using three different blending scales. The crushing strength of the tablets was used as a secondary response, as its decrease is known to result from the overlubrication. In addition, coating of the MCC particles by MS in intact tablets was detected using Raman microscopic mapping. MS blending was more efficient in larger scales. Raman imaging was successfully applied to characterize MS distribution in MCC tablets despite low concentration of MS. The Raman method can provide highly valuable visual information about the proceeding of the MS blending process. However, the measuring set-up has to be carefully planned to establish reliable and reproducible results.

  16. Field Trial of Attenuated Salmonella Typhi Live Oral Vaccine TY21A in Liquid and Enteric-Coated Formulations and Epidemiological Survey for Incidence of Diarrhea due to Shigella Species

    DTIC Science & Technology

    1989-03-01

    and absolute efficacy of three doses of Ty2la vaccine given in enteric-coated capsule or liquid formulation. Intensive clinical and bacteriologic...TABLES Table 1. Evaluation of the efficacy of three doses of the enteric-coated capsule formulation of Ty2la live oral vaccine given within one week in...November, 1986 thzough February, 1989 of a field trial in Area Sur Oriente and Area Norte assessing the efficacy of Ty21a vaccine in liquid or enteric

  17. Enteric-coated, pH-dependent peppermint oil capsules for the treatment of irritable bowel syndrome in children.

    PubMed

    Kline, R M; Kline, J J; Di Palma J; Barbero, G J

    2001-01-01

    In a randomized, double-blind controlled trial, 42 children with irritable bowel syndrome (IBS) were given pH-dependent, enteric-coated peppermint oil capsules or placebo. After 2 weeks, 75% of those receiving peppermint oil had reduced severity of pain associated with IBS. Peppermint oil may be used as a therapeutic agent during the symptomatic phase of IBS.

  18. Glucose-Coated Gold Nanoparticles Transfer across Human Brain Endothelium and Enter Astrocytes In Vitro

    PubMed Central

    Gromnicova, Radka; Davies, Heather A.; Sreekanthreddy, Peddagangannagari; Romero, Ignacio A.; Lund, Torben; Roitt, Ivan M.; Phillips, James B.; Male, David K.

    2013-01-01

    The blood-brain barrier prevents the entry of many therapeutic agents into the brain. Various nanocarriers have been developed to help agents to cross this barrier, but they all have limitations, with regard to tissue-selectivity and their ability to cross the endothelium. This study investigated the potential for 4 nm coated gold nanoparticles to act as selective carriers across human brain endothelium and subsequently to enter astrocytes. The transfer rate of glucose-coated gold nanoparticles across primary human brain endothelium was at least three times faster than across non-brain endothelia. Movement of these nanoparticles occurred across the apical and basal plasma membranes via the cytosol with relatively little vesicular or paracellular migration; antibiotics that interfere with vesicular transport did not block migration. The transfer rate was also dependent on the surface coating of the nanoparticle and incubation temperature. Using a novel 3-dimensional co-culture system, which includes primary human astrocytes and a brain endothelial cell line hCMEC/D3, we demonstrated that the glucose-coated nanoparticles traverse the endothelium, move through the extracellular matrix and localize in astrocytes. The movement of the nanoparticles through the matrix was >10 µm/hour and they appeared in the nuclei of the astrocytes in considerable numbers. These nanoparticles have the correct properties for efficient and selective carriers of therapeutic agents across the blood-brain barrier. PMID:24339894

  19. Investigation of Oral Preparation That Is Expected to Improve Medication Administration: Preparation and Evaluation of Oral Gelling Tablet Using Sodium Alginate.

    PubMed

    Ito, Ikumi; Ito, Akihiko; Unezaki, Sakae

    2017-01-01

    We investigated the preparation of a gelling tablet that swells and forms a gel upon absorbing water, and hence would be easy for patients to swallow. We prepared naked tablets and compressed coated tablets by the direct tableting or wet granule-compression methods, using the commonly prescribed drug acetaminophen (AA) and sodium alginate (AG) as a thickening agent. The tablets quickly absorbed water, had favorable gelling properties, low adhesiveness, appropriate drug dissolution profile, and at the same time, were easy to swallow. In the case of naked tablets, water absorption increased upon granulation, but gelling of AG interfere when AA and AG were present together. There was no change in the adhesiveness, and more than 30 min were required to achieve a 25% dissolution ratio. Compressed coated tablets that were made with AA in the inner layer and granulated AG in the outer layer showed improved dissolution behavior, it was about 90% dissolution ratio in 30 min, owing to the water absorption property of AG, and decreased adhesiveness. In this case, there was a difference in the outer layer thickness. As the outer layer amount increased, dissolution slowed, but it did not depend on the compression pressure. Our gelling tablet can be prepared by using AA (main drug) in the inner layer and an appropriate thickness of granulated AG in the outer layer of compressed coated tablets.

  20. Enabling the Tablet Product Development of 5-Fluorocytosine by Conjugate Acid Base Cocrystals.

    PubMed

    Perumalla, Sathyanarayana R; Paul, Shubhajit; Sun, Changquan C

    2016-06-01

    5-Fluorocytosine (FC) is a high-dose antifungal drug that challenges the development of a tablet product due to poor solid-state stability and tabletability. Using 2 pharmaceutically acceptable conjugate acid base (CAB) cocrystals of FC with HCl and acesulfame, we have developed commercially viable high loading FC tablets. The tablets were prepared by direct compression using nano-coated microcrystalline cellulose Avicel PH105 as a tablet binder, which provided both excellent tabletability and good flowability. Commercial manufacturability of formulations based on both CAB cocrystals was verified on a compaction simulator. The results from an expedited friability study were used to set the compaction force, which yielded tablets with sufficient mechanical strength and rapid tablet disintegration. This work demonstrates the potential value of CAB cocrystals in drug product development. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  1. Pharmaceutical Film Coating Catalog for Spectral Domain Optical Coherence Tomography.

    PubMed

    Lin, Hungyen; Dong, Yue; Markl, Daniel; Zhang, Zijian; Shen, Yaochun; Zeitler, J Axel

    2017-10-01

    Optical coherence tomography (OCT) has recently been demonstrated to measure the film coating thickness of pharmaceutical tablets and pellets directly. The results enable the analysis of inter- and intra-tablet coating variability at an off-line and in-line setting. To date, only a few coating formulations have been tried and there is very little information on the applicability of OCT to other coatings. As it is well documented that optical methods including OCT are prone to scattering leading to limited penetration, some pharmaceutical coatings may not be measurable altogether. This study presents OCT measurements of 22 different common coatings for the assessment of OCT applicability. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Safety, efficacy and pharmacokinetic evaluations of a new coated chloroquine tablet in a single-arm open-label non-comparative trial in Brazil: a step towards a user-friendly malaria vivax treatment.

    PubMed

    Pereira, Dhelio; Daher, André; Zanini, Graziela; Maia, Ivan; Fonseca, Lais; Pitta, Luciana; Ruffato, Rosilene; Marchesini, Paola; Fontes, Cor Jesus

    2016-09-17

    Malaria remains a major public health problem, with half the world population at risk of contracting malaria. The effects of Plasmodium vivax on prosperity and longevity have been highlighted in several recent clinical case reports. The first line of vivax treatment drugs has seen no radical innovation for more than 60 years. This study introduces a subtle incremental innovation to vivax treatment: a chloroquine and primaquine co-blister. The co-blister includes a new chloroquine formulation incorporating coated tablets to mask the drug's bitter taste and user-friendly packaging containing tablets of each drug, which may improve patient adherence and facilitate the appropriate use of the drugs. This new formulation will replace the non-coated chloroquine distributed in Brazil. Patients were orally treated with 150 mg coated chloroquine tablets for 3 days: an initial 450 mg dose, followed by two 300 mg doses. The patients were treated concomitantly with two 15 mg primaquine tablets for 7-9 days, according to their weight. The primary objective of this study was to prove parasitological and clinical cure rates above 90 % by day 28. This single-arm open-label non-comparative trial was conducted according to the WHO recommended methodology for the surveillance of anti-malarial drug efficacy in the Brazilian Amazon. On day 28, the parasitological and clinical response was adequate in 98.8 % of patients (CI 95 % 93.4-100 %). The success rate on day 3 was 100 %, and the cumulative success rate by day 28 was 98.8 % (CI 95 % 91.7-99.8 %). There were no serious adverse events, with most adverse events classified as mild. The pharmacokinetic parameters of chloroquine analysed in whole blood dry spot samples showed mean (coefficient of variation) Cmax and AUC0-t values of 374.44 (0.35) and 3700.43 (0.36) ng/mL, respectively. This study reports an appropriate safety and efficacy profile of a new formulation of coated chloroquine tablets for vivax malaria

  3. A Study of the Tablet Computer's Application in K-12 Schools in China

    ERIC Educational Resources Information Center

    Long, Taotao; Liang, Wenxin; Yu, Shengquan

    2013-01-01

    As an emerging mobile terminal, the tablet computer has begun to enter into the educational system. With the aim of having a better understanding of the application and people's perspectives on the new technology in K-12 schools in China, a survey was conducted to investigate the tablet computer's application, user's perspectives and requirements…

  4. Preparation and Evaluation of Enteric-Coated Chitosan Derivative-Based Microparticles Loaded with Salmon Calcitonin as an Oral Delivery System.

    PubMed

    Onishi, Hiraku; Tokuyasu, Ayako

    2016-09-13

    The production of protein drugs has recently increased due to advances in biotechnology, but their clinical use is generally limited to parenteral administration due to low absorption in non-parenteral administration. Therefore, non-parenteral delivery systems allowing sufficient absorption draw much attention. Microparticles (MP) were prepared using chitosan-4-thio-butylamidine conjugate (Ch-TBA), trimethyl-chitosan (TMC), and chitosan (Ch). Using salmon calcitonin (sCT) as a model protein drug, Ch-TBA-, Ch-TBA/TMC (4/1)-, and Ch-based MP were produced, and their Eudragit L100 (Eud)-coated MP, named Ch-TBA-MP/Eud, Ch-TBA/TMC-MP/Eud, and Ch-MP/Eud, respectively, were prepared as oral delivery systems. These enteric-coated microparticles were examined in vitro and in vivo. All microparticles before and after enteric coating had a submicron size (600-800 nm) and micrometer size (1300-1500 nm), respectively. In vitro release patterns were similar among all microparticles; release occurred gradually, and the release rate was slower at pH 1.2 than at pH 6.8. In oral ingestion, Ch-TBA-MP/Eud suppressed plasma Ca levels most effectively among the microparticles tested. The relative effectiveness of Ch-TBA-MP/Eud to the intramuscular injection was 8.6%, while the sCT solution showed no effectiveness. The results suggest that Eud-coated Ch-TBA-based microparticles should have potential as an oral delivery system of protein drugs.

  5. Preparation and Evaluation of Enteric-Coated Chitosan Derivative-Based Microparticles Loaded with Salmon Calcitonin as an Oral Delivery System

    PubMed Central

    Onishi, Hiraku; Tokuyasu, Ayako

    2016-01-01

    Background: The production of protein drugs has recently increased due to advances in biotechnology, but their clinical use is generally limited to parenteral administration due to low absorption in non-parenteral administration. Therefore, non-parenteral delivery systems allowing sufficient absorption draw much attention. Methods: Microparticles (MP) were prepared using chitosan-4-thio-butylamidine conjugate (Ch-TBA), trimethyl-chitosan (TMC), and chitosan (Ch). Using salmon calcitonin (sCT) as a model protein drug, Ch-TBA-, Ch-TBA/TMC (4/1)-, and Ch-based MP were produced, and their Eudragit L100 (Eud)-coated MP, named Ch-TBA-MP/Eud, Ch-TBA/TMC-MP/Eud, and Ch-MP/Eud, respectively, were prepared as oral delivery systems. These enteric-coated microparticles were examined in vitro and in vivo. Results: All microparticles before and after enteric coating had a submicron size (600–800 nm) and micrometer size (1300–1500 nm), respectively. In vitro release patterns were similar among all microparticles; release occurred gradually, and the release rate was slower at pH 1.2 than at pH 6.8. In oral ingestion, Ch-TBA-MP/Eud suppressed plasma Ca levels most effectively among the microparticles tested. The relative effectiveness of Ch-TBA-MP/Eud to the intramuscular injection was 8.6%, while the sCT solution showed no effectiveness. Conclusion: The results suggest that Eud-coated Ch-TBA-based microparticles should have potential as an oral delivery system of protein drugs. PMID:27649146

  6. Conceptuation, formulation and evaluation of sustained release floating tablets of captopril compression coated with gastric dispersible hydrochlorothiazide using 23 factorial design

    PubMed Central

    Sirisha, Pathuri Lakshmi; Babu, Govada Kishore; Babu, Puttagunta Srinivasa

    2014-01-01

    Ambulatory blood pressure monitoring is regarded as the gold standard for hypertensive therapy in non-dipping hypertension patients. A novel compression coated formulation of captopril and hydrochlorothiazide (HCTZ) was developed in order to improve the efficacy of antihypertensive therapy considering the half-life of both drugs. The synergistic action using combination therapy can be effectively achieved by sustained release captopril (t1/2= 2.5 h) and fast releasing HCTZ (average t1/2= 9.5 h). The sustained release floating tablets of captopril were prepared by using 23 factorial design by employing three polymers i.e., ethyl cellulose (EC), carbopol and xanthan gum at two levels. The formulations (CF1-CF8) were optimized using analysis of variance for two response variables, buoyancy and T50%. Among the three polymers employed, the coefficients and P values for the response variable buoyancy and T50% using EC were found to be 3.824, 0.028 and 0.0196, 0.046 respectively. From the coefficients and P values for the two response variables, formulation CF2 was optimized, which contains EC polymer alone at a high level. The CF2 formulation was further compression coated with optimized gastric dispersible HCTZ layer (HF9). The compression coated tablet was further evaluated using drug release kinetics. The Q value of HCTZ layer is achieved within 20 min following first order release whereas the Q value of captopril was obtained at 6.5 h following Higuchi model, from which it is proved that rapid release HCTZ and slow release of captopril is achieved. The mechanism of drug release was analyzed using Peppas equation, which showed an n >0.90 confirming case II transportation mechanism for drug release. PMID:25006552

  7. In vitro stability, potency, and dissolution of duloxetine enteric-coated pellets after exposure to applesauce, apple juice, and chocolate pudding.

    PubMed

    Wells, Kevin A; Losin, William G

    2008-07-01

    Difficulty swallowing is a common problem in the clinical setting, particularly in elderly patients, and can significantly affect an individual's ability to maintain a proper level of nutrition. The purpose of this in vitro study was to determine if mixing duloxetine enteric-coated pellets in food substances is an acceptable alternative method for administering this oral formulation to patients with swallowing difficulties. To determine whether administration in food substances with varying pH values (applesauce and apple juice, pH = approximately 3.5; chocolate pudding, pH = approximately 5.5-6.0) affects the enteric coating of the formulation, duloxetine pellets (ie, the contents of a 20-mg duloxetine capsule) were exposed to applesauce, apple juice, and chocolate pudding at room temperature and tested in triplicate for potency and impurities; for dissolution, 6 replicates were tested. To assess product stability and integrity of the enteric coating, potency, impurities, and dissolution tests of the pellets were conducted and compared with pellets not exposed to food. The duloxetine pellets were extracted from the food material using a solution of 0.1 normal (N) hydrochloric acid (HCl) prepared from concentrated HCl (commercially available) and deionized water. For the potency and impurities tests, a 40:60 solution of acetonitrile and pH 8.0 phosphate buffer was used as the sample solvent to extract the active pharmaceutical ingredient from the formulation to prepare the samples for testing. The amount of active pharmaceutical ingredient released (in vitro dissolution) from the pellets after exposure to the food substances was determined using 2 media solutions, 0.1 N HCl followed by pH 6.8 phosphate buffer. Applesauce and chocolate pudding were selected as vehicles for oral administration, while apple juice was intended to be used as a wash for a nasogastric tube. Mean (SD) potency results for the 20-mg capsule strength were 20.256 (0.066), 20.222 (0.163), and

  8. Poly(dimethylsiloxane) coatings for controlled drug release--polymer modifications.

    PubMed

    Schulze Nahrup, J; Gao, Z M; Mark, J E; Sakr, A

    2004-02-11

    Modifications of endhydroxylated poly(dimethylsiloxane) (PDMS) formulations were studied for their ability to be applied onto tablet cores in a spray-coating process and to control drug release in zero-order fashion. Modifications of the crosslinker from the most commonly used tetraethylorthosilicate (TEOS) to the trifunctional 3-(2,3-epoxypropoxy)propyltrimethoxysilane (SIG) and a 1:1 mixture of the two were undertaken. Addition of methylpolysiloxane-copolymers were studied. Lactose, microcrystalline cellulose (MCC) and polyethylene glycol 8000 (PEG) were the channeling agents applied. The effects on dispersion properties were characterized by particle size distribution and viscosity. Mechanical properties of resulting free films were studied to determine applicability in a pan-coating process. Release of hydrochlorothiazide (marker drug) was studied from tablets coated in a lab-size conventional coating pan. All dispersions were found suitable for a spray-coating process. Preparation of free films showed that copolymer addition was not possible due to great decline in mechanical properties. Tablets coated with formulations containing PEG were most suitable to control drug release, at only 5% coating weight. Constant release rates could be achieved for formulations with up to 25% PEG; higher amounts resulted in a non-linear release pattern. Upon adding 50% PEG, a drug release of 63% over 24 h could be achieved.

  9. A non-destructive method for quality control of the pellet distribution within a MUPS tablet by terahertz pulsed imaging.

    PubMed

    Novikova, Anna; Markl, Daniel; Zeitler, J Axel; Rades, Thomas; Leopold, Claudia S

    2018-01-01

    Terahertz pulsed imaging (TPI) was applied to analyse the inner structure of multiple unit pellet system (MUPS) tablets. MUPS tablets containing different amounts of theophylline pellets coated with Eudragit® NE 30 D and with microcrystalline cellulose (MCC) as cushioning agent were analysed. The tablets were imaged by TPI and the results were compared to X-ray microtomography. The terahertz pulse beam propagates through the tablets and is back-reflected at the interface between the MCC matrix and the coated pellets within the tablet causing a peak in the terahertz waveform. Cross-section images of the tablets were extracted at different depths and parallel to the tablet faces from 3D terahertz data to visualise the surface-near structure of the MUPS tablets. The images of the surface-near structure of the MUPS tablets were compared to X-ray microtomography images at the same depths. The surface-near structure could be clearly resolved by TPI at depths between 24 and 152μm below the tablet surface. An increasing amount of pellets within the MUPS tablets appears to slightly decrease the detectability of the pellets within the tablets by TPI. TPI was shown to be a non-destructive method for the detection of pellets within the tablets and could resolve structures thicker than 30μm. In conclusion, a proof-of-concept was provided for TPI as a method of quality control for MUPS tablets. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Tablet PCs in Engineering Mathematics Courses at the J.B. Speed School of Engineering

    ERIC Educational Resources Information Center

    Hieb, Jeffrey L.; Ralston, Patricia A. S.

    2010-01-01

    In fall 2007, J.B. Speed School of Engineering at the University of Louisville joined the ranks of universities requiring the purchase of Tablet PCs for all new entering students. This article presents a description of how the Department of Engineering Fundamentals incorporated Tablet PCs into their instruction, a review of the literature…

  11. In-vitro/in-vivo correlation of pulsatile drug release from press-coated tablet formulations: a pharmacoscintigraphic study in the beagle dog.

    PubMed

    Ghimire, Manish; McInnes, Fiona J; Watson, David G; Mullen, Alexander B; Stevens, Howard N E

    2007-09-01

    The aim of the current study was to investigate the in-vitro and in-vivo performance of a press-coated tablet (PCT) intended for time delayed drug release, consisting of a rapidly disintegrating theophylline core tablet, press-coated with barrier granules containing glyceryl behenate (GB) and low-substituted hydroxypropylcellulose (L-HPC). The PCTs showed pulsatile release with a lag time dependent upon the GB and L-HPC composition of the barrier layer. In-vivo gamma-scintigraphic studies were carried out for PCTs containing GB:L-HPC at 65:35 w/w and 75:25 w/w in the barrier layer in four beagle dogs, in either the fed or fasted state. The in-vivo lag time in both the fed and fasted states did not differ significantly (p>0.05) from the in-vitro lag time. Additionally, no significant difference (p<0.05) between in-vivo fed and fasted disintegration times was observed, demonstrating that in-vivo performance of the PCT was not influenced by the presence or absence of food in the gastrointestinal tract. A distinct lag time was obtained prior to the appearance of drug in plasma and correlated (R2=0.98) with disintegration time observed from scintigraphic images. However, following disintegration, no difference in pharmacokinetic parameters (AUC(0-6 dis), K(el), Cmax) was observed. The current study highlighted the potential use of these formulations for chronopharmaceutical drug delivery.

  12. Toward Biopredictive Dissolution for Enteric Coated Dosage Forms.

    PubMed

    Al-Gousous, J; Amidon, G L; Langguth, P

    2016-06-06

    The aim of this work was to develop a phosphate buffer based dissolution method for enteric-coated formulations with improved biopredictivity for fasted conditions. Two commercially available enteric-coated aspirin products were used as model formulations (Aspirin Protect 300 mg, and Walgreens Aspirin 325 mg). The disintegration performance of these products in a physiological 8 mM pH 6.5 bicarbonate buffer (representing the conditions in the proximal small intestine) was used as a standard to optimize the employed phosphate buffer molarity. To account for the fact that a pH and buffer molarity gradient exists along the small intestine, the introduction of such a gradient was proposed for products with prolonged lag times (when it leads to a release lower than 75% in the first hour post acid stage) in the proposed buffer. This would allow the method also to predict the performance of later-disintegrating products. Dissolution performance using the accordingly developed method was compared to that observed when using two well-established dissolution methods: the United States Pharmacopeia (USP) method and blank fasted state simulated intestinal fluid (FaSSIF). The resulting dissolution profiles were convoluted using GastroPlus software to obtain predicted pharmacokinetic profiles. A pharmacokinetic study on healthy human volunteers was performed to evaluate the predictions made by the different dissolution setups. The novel method provided the best prediction, by a relatively wide margin, for the difference between the lag times of the two tested formulations, indicating its being able to predict the post gastric emptying onset of drug release with reasonable accuracy. Both the new and the blank FaSSIF methods showed potential for establishing in vitro-in vivo correlation (IVIVC) concerning the prediction of Cmax and AUC0-24 (prediction errors not more than 20%). However, these predictions are strongly affected by the highly variable first pass metabolism

  13. Studies on the mechanism of printing film-coated tablets containing titanium dioxide in the film by using UV laser irradiation.

    PubMed

    Kato, Yoshiteru; Nakashima, Yasuhiko; Shino, Naoki; Sasaki, Koichi; Hosokawa, Akihiro; Ishihara, Hiroshi

    2010-04-01

    The purpose of this article is to study a detailed mechanism of printing when film-coated tablets were irradiated by UV laser at a wavelength of 355 nm. Hydroxypropylmethylcellulose (HPMC) film containing titanium dioxide (TiO(2)) and the film not containing TiO(2) and TiO(2) powder were lirradiated by the UV laser and estimated by the morphological observation by zoom stereo microscope, thermogravimetric analysis (TGA), total color difference (dE), X-ray powder diffraction (XRD), and dispersive Raman microscopy. In the case of the film containing TiO(2), the film showed a visible change in its color from white to gray by the UV laser irradiation. By zoom stereo microscope, it was found that the entire UV laser-irradiated area was not grayed uniformly, but many black particles, whose diameter was about 2 microm, were observed on the film. When TiO(2) powder was irradiated by the UV laser, a visible change in its color from white to gray was observed similar to the case of the film containing TiO(2). There were many black particles locally in the UV laser-treated TiO(2) powder by the morphological observation, and these black particles, agglomerates of the grayed oxygen-defected TiO(2), were associated with the visible change of the TiO(2). It was found that the film-coated tablets were printed utilizing the formation of the black particles by the agglomeration of the grayed oxygen-defected TiO(2) by the UV laser irradiation.

  14. Influence of disintegrants in different substrate physical form on dimensional recovery of multi-component tablet.

    PubMed

    Sarkar, Srimanta; Ooi, Shing Ming; Liew, Celine Valeria; Tan, Bing Xun; Heng, Paul Wan Sia

    2014-11-20

    This study investigated the influence of different disintegrants, present in different substrate physical forms, on dimensional recovery of multi-component tablets prepared at different compression pressures. Formulations containing model drug, metformin, (10%, w/w), different disintegrants (10%, w/w), and lactose (80%, w/w) were compressed directly or after granulation using polyvinyl pyrrolidone (1%, w/w) as binder, into tablets (350 mg, 10mm diameter) at 150, 200, and 250 N/mm(2) compression pressures. Tablets were characterized for immediate dimensional recovery (IR) after ejection from the die, latent dimensional recovery (LR) over 24 h, tensile strength, and disintegration. The IR was predominantly contributed by crystalline components whereas LR was brought about by polymeric materials. With increased compression pressure, higher degree of plastic deformation of the polymeric disintegrants resulted in tablet with lower LR and higher tensile strength. Presence of polyvinyl pyrrolidone in the granules contributed considerably to plastic deformation, and the tablets produced had lower LR, higher tensile strength, and longer disintegration time. This study indicated that use of granules as the feed substrate physical form and a prudent selection of components may enable the coating of resultant tablets immediately after compression without the risk of coat damage due to LR. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Development and optimization of press coated tablets of release engineered valsartan for pulsatile delivery.

    PubMed

    Shah, Sunny; Patel, Romik; Soniwala, Moinuddin; Chavda, Jayant

    2015-01-01

    The present work is aimed to develop and optimize pulsatile delivery during dissolution of an improved formulation of valsartan to coordinate the drug release with circadian rhythm. Preliminary studies suggested that β cyclodextrin could improve the solubility of valsartan and showed AL type solubility curve. A 1:1 stoichiometric ratio of valsartan to β cyclodextrin was revealed from phase solubility studies and Job's plot. The prepared complex showed significantly better dissolution efficiency (p < 0.05) compared to pure drug, which could be due to the formation of inclusion complex as revealed from FTIR and DSC studies. Continuous dissolution-absorption studies revealed that absorption of drug from valsartan β cyclodextrin complex was significantly higher (p < 0.05) compared to pure drug, in second part press-coated tablets of valsartan β cyclodextrin complex were subsequently prepared and application of the Plackett-Burman screening design revealed that HPMC K4M and EC showed significant effect on lag time. A 3(2) full factorial design was used to measure the response of HPMC K4M and EC on lag time and time taken for 90% drug release (T90). The optimized batch prepared according to the levels obtained from the desirability function had a lag time of 6 h and consisted of HPMC K4M:ethylcellulose in a 1:1.5 ratio with 180 mg of coating and revealed a close agreement between observed and predicted value (R(2 )= 0.9694).

  16. Enteric coated magnetic HPMC capsules evaluated in human gastrointestinal tract by AC biosusceptometry.

    PubMed

    Corá, Luciana A; Romeiro, Fernando G; Paixão, Fabiano C; Américo, Madileine F; Oliveira, Ricardo B; Baffa, Oswaldo; Miranda, José Ricardo A

    2006-08-01

    To employ the AC Biosusceptometry (ACB) technique to evaluate in vitro and in vivo characteristics of enteric coated magnetic hydroxypropyl methylcellulose (HPMC) capsules and to image the disintegration process. HPMC capsules filled with ferrite (MnFe2O4) and coated with Eudragit were evaluated using USP XXII method and administered to fasted volunteers. Single and multisensor ACB systems were used to characterize the gastrointestinal (GI) motility and to determine gastric residence time (GRT), small intestinal transit time (SITT) and orocaecal transit time (OCTT). Mean disintegration time (t50) was quantified from 50% increase of pixels in the imaging area. In vitro and in vivo performance of the magnetic HPMC capsules as well as the disintegration process were monitored using ACB systems. The mean disintegration time (t50) calculated for in vitro was 25+/-5 min and for in vivo was 13+/-5 min. In vivo also were determined mean values for GRT (55+/-19 min), SITT (185+/-82 min) and OCTT (240+/-88 min). AC Biosusceptometry is a non-invasive technique originally proposed to monitoring pharmaceutical dosage forms orally administered and to image the disintegration process.

  17. Spectrum of tablet computer use by medical students and residents at an academic medical center.

    PubMed

    Robinson, Robert

    2015-01-01

    Introduction. The value of tablet computer use in medical education is an area of considerable interest, with preliminary investigations showing that the majority of medical trainees feel that tablet computers added value to the curriculum. This study investigated potential differences in tablet computer use between medical students and resident physicians. Materials & Methods. Data collection for this survey was accomplished with an anonymous online questionnaire shared with the medical students and residents at Southern Illinois University School of Medicine (SIU-SOM) in July and August of 2012. Results. There were 76 medical student responses (26% response rate) and 66 resident/fellow responses to this survey (21% response rate). Residents/fellows were more likely to use tablet computers several times daily than medical students (32% vs. 20%, p = 0.035). The most common reported uses were for accessing medical reference applications (46%), e-Books (45%), and board study (32%). Residents were more likely than students to use a tablet computer to access an electronic medical record (41% vs. 21%, p = 0.010), review radiology images (27% vs. 12%, p = 0.019), and enter patient care orders (26% vs. 3%, p < 0.001). Discussion. This study shows a high prevalence and frequency of tablet computer use among physicians in training at this academic medical center. Most residents and students use tablet computers to access medical references, e-Books, and to study for board exams. Residents were more likely to use tablet computers to complete clinical tasks. Conclusions. Tablet computer use among medical students and resident physicians was common in this survey. All learners used tablet computers for point of care references and board study. Resident physicians were more likely to use tablet computers to access the EMR, enter patient care orders, and review radiology studies. This difference is likely due to the differing educational and professional demands placed on

  18. Spectrum of tablet computer use by medical students and residents at an academic medical center

    PubMed Central

    2015-01-01

    Introduction. The value of tablet computer use in medical education is an area of considerable interest, with preliminary investigations showing that the majority of medical trainees feel that tablet computers added value to the curriculum. This study investigated potential differences in tablet computer use between medical students and resident physicians. Materials & Methods. Data collection for this survey was accomplished with an anonymous online questionnaire shared with the medical students and residents at Southern Illinois University School of Medicine (SIU-SOM) in July and August of 2012. Results. There were 76 medical student responses (26% response rate) and 66 resident/fellow responses to this survey (21% response rate). Residents/fellows were more likely to use tablet computers several times daily than medical students (32% vs. 20%, p = 0.035). The most common reported uses were for accessing medical reference applications (46%), e-Books (45%), and board study (32%). Residents were more likely than students to use a tablet computer to access an electronic medical record (41% vs. 21%, p = 0.010), review radiology images (27% vs. 12%, p = 0.019), and enter patient care orders (26% vs. 3%, p < 0.001). Discussion. This study shows a high prevalence and frequency of tablet computer use among physicians in training at this academic medical center. Most residents and students use tablet computers to access medical references, e-Books, and to study for board exams. Residents were more likely to use tablet computers to complete clinical tasks. Conclusions. Tablet computer use among medical students and resident physicians was common in this survey. All learners used tablet computers for point of care references and board study. Resident physicians were more likely to use tablet computers to access the EMR, enter patient care orders, and review radiology studies. This difference is likely due to the differing educational and professional demands placed on

  19. High-Throughput Synthetic Chemistry Enabled by Organic Solvent Disintegrating Tablet.

    PubMed

    Li, Tingting; Xu, Lei; Xing, Yanjun; Xu, Bo

    2017-01-17

    Synthetic chemistry remains a time- and labor-intensive process of inherent hazardous nature. Our organic solvent disintegrating tablet (O-Tab) technology has shown potential to make industrial/synthetic chemistry more efficient. As is the case with pharmaceutical tablets, our reagent-containing O-Tabs are mechanically strong, but disintegrate rapidly when in contact with reaction media (organic solvents). For O-Tabs containing sensitive chemicals, they can be further coated to insulate them from air and moisture. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Fabrication of controlled-release budesonide tablets via desktop (FDM) 3D printing.

    PubMed

    Goyanes, Alvaro; Chang, Hanah; Sedough, Daniel; Hatton, Grace B; Wang, Jie; Buanz, Asma; Gaisford, Simon; Basit, Abdul W

    2015-12-30

    The aim of this work was to explore the feasibility of using fused deposition modelling (FDM) 3D printing (3DP) technology with hot melt extrusion (HME) and fluid bed coating to fabricate modified-release budesonide dosage forms. Budesonide was sucessfully loaded into polyvinyl alcohol filaments using HME. The filaments were engineered into capsule-shaped tablets (caplets) containing 9mg budesonide using a FDM 3D printer; the caplets were then overcoated with a layer of enteric polymer. The final printed formulation was tested in a dynamic dissolution bicarbonate buffer system, and two commercial budesonide products, Cortiment® (Uceris®) and Entocort®, were also investigated for comparison. Budesonide release from the Entocort® formulation was rapid in conditions of the upper small intestine while release from the Cortiment® product was more delayed and very slow. In contrast, the new 3D printed caplet formulation started to release in the mid-small intestine but release then continued in a sustained manner throughout the distal intestine and colon. This work has demonstrated the potential of combining FDM 3DP with established pharmaceutical processes, including HME and film coating, to fabricate modified release oral dosage forms. Copyright © 2015. Published by Elsevier B.V.

  1. Hydration, erosion, and release behavior of guar-based hydrophilic matrix tablets containing total alkaloids of Sophora alopecuroides.

    PubMed

    Zhao, Wenchang; Song, Lijun; Deng, Hongzhu; Yao, Hui

    2009-05-01

    It is a challenge to deliver water-soluble drug based on hydrophilic matrix to colon because of swelling and erosion of polysaccharides in contact with media. In our study, guar-based hydrophilic matrix tablets containing water-soluble total alkaloids of Sophora alopecuroides prepared by wet granulation technique were evaluated. A novel method was established to investigate the changes of swelling and volume for guar-based tablets in undynamic state, which generally showed a rapid swelling and volume change in the first 9 h, then the hydrated speed slowed down. On the other hand, the influence of different pH of the media on water uptake and erosion of various guar-based formulations in dynamic state indicated that the hydrated constants in simulated gastric fluid (SGF) was higher than that in SIF, which followed varied mechanism of water penetration by fitting Davidson and Peppas model. The extent of erosion was between 22.4 and 32.6% in SIF within 360 min. In vitro sophoridine release studies in successive different mimicking media showed that the guar matrix tablets released 13.5-25.6% of sophoridine in the first 6 h; therefore it was necessary to develop the bilayer matrix tablet by direct-compressing coating 100 mg guar granula on core tablet. The initial release of coated tablet was retarded and the bilayer matrix tablet was suitable for colon target.

  2. Ultrasound-assisted powder-coating technique to improve content uniformity of low-dose solid dosage forms.

    PubMed

    Genina, Natalja; Räikkönen, Heikki; Antikainen, Osmo; Heinämäki, Jyrki; Yliruusi, Jouko

    2010-09-01

    An ultrasound-assisted powder-coating technique was used to produce a homogeneous powder formulation of a low-dose active pharmaceutical ingredient (API). The powdered particles of microcrystalline cellulose (MCC; Avicel® PH-200) were coated with a 4% m/V aqueous solution of riboflavin sodium phosphate, producing a uniform drug layer on the particle surfaces. It was possible to regulate the amount of API in the treated powder. The thickness of the API layer on the surface of the MCC particles increased near linearly as the number of coating cycles increased, allowing a precise control of the drug content. The tablets (n = 950) prepared from the coated powder showed significantly improved weight and content uniformity in comparison with the reference tablets compressed from a physical binary powder mixture. This was due to the coated formulation remaining uniform during the entire tabletting process, whereas the physical mixture of the powders was subject to segregation. In conclusion, the ultrasound-assisted technique presented here is an effective tool for homogeneous drug coating of powders of irregular particle shape and broad particle size distribution, improving content uniformity of low-dose API in tablets, and consequently, ensuring the safe delivery of a potent active substance to patients.

  3. Analysis of coating structures and interfaces in solid oral dosage forms by three dimensional terahertz pulsed imaging.

    PubMed

    Zeitler, J Axel; Shen, Yaochun; Baker, Colin; Taday, Philip F; Pepper, Michael; Rades, Thomas

    2007-02-01

    Three dimensional terahertz pulsed imaging (TPI) was evaluated as a novel tool for the nondestructive characterization of different solid oral dosage forms. The time-domain reflection signal of coherent pulsed light in the far infrared was used to investigate film-coated tablets, sugar-coated tablets, multilayered controlled release tablets, and soft gelatin capsules. It is possible to determine the spatial and statistical distribution of coating thickness in single and multiple coated products using 3D TPI. The measurements are nondestructive even for layers buried underneath other coating structures. The internal structure of coating materials can be analyzed. As the terahertz signal penetrates up to 3 mm into the dosage form interfaces between layers in multilayered tablets can be investigated. In soft gelatin capsules it is possible to measure the thickness of the gelatin layer and to characterize the seal between the gelatin layers for quality control. TPI is a unique approach for the nondestructive characterization and quality control of solid dosage forms. The measurements are fast and fully automated with the potential for much wider application of the technique in the process analytical technology scheme. Copyright (c) 2006 Wiley-Liss, Inc.

  4. The practice and clinical implications of tablet splitting in international health

    PubMed Central

    Elliott, Ivo; Mayxay, Mayfong; Yeuichaixong, Sengchanh; Lee, Sue J; Newton, Paul N

    2014-01-01

    Objective Tablet splitting is frequently performed to facilitate correct dosing, but the practice and implications in low-income settings have rarely been discussed. Methods We selected eight drugs, with narrow therapeutic indices or critical dosages, frequently divided in the Lao PDR (Laos). These were split, by common techniques used in Laos, by four nurses and four laypersons. The mean percentage deviation from the theoretical expected weight and weight loss of divided tablets/capsules were recorded. Results Five of eight study drugs failed, on splitting, to meet European Pharmacopoeia recommendations for tablet weight deviation from the expected weight of tablet/capsule halves with 10% deviating by more than 25%. There was a significant difference in splitting accuracy between nurses and laypersons (P = 0.027). Coated and unscored tablets were less accurately split than uncoated (P = 0.03 and 0.0019 for each half) and scored (0.0001 for both halves) tablets. Conclusion These findings have potential clinical implications on treatment outcome and the development of antimicrobial resistance. Investment by drug companies in a wider range of dosage units, particularly for narrow therapeutic index and critical dosage medicines, is strongly recommended. PMID:24702766

  5. Bioequivalence study of a new sildenafil 100 mg orodispersible film compared to the conventional film-coated 100 mg tablet administered to healthy male volunteers

    PubMed Central

    Radicioni, Milko; Castiglioni, Chiara; Giori, Andrea; Cupone, Irma; Frangione, Valeria; Rovati, Stefano

    2017-01-01

    A new orodispersible film formulation of the phosphodiesterase type 5 inhibitor, sildenafil, has been developed to examine the advantages of an orally disintegrating film formulation and provide an alternative to the current marketed products for the treatment of erectile dysfunction. The pharmacokinetics of the sildenafil 100 mg orodispersible film (IBSA) was compared to that of the conventional marketed 100 mg film-coated tablet (Viagra®) after single-dose administration to 53 healthy male volunteers (aged 18–51 years) in a randomized, open, two-way crossover bioequivalence study. Each subject received a single oral dose of 100 mg of sildenafil as test or reference formulation administered under fasting conditions at each of the two study periods according to a randomized crossover design. There was a washout interval of ≥7 days between the two administrations of the investigational medicinal products. Blood samples for pharmacokinetic analysis were collected up to 24 h post-dosing. The primary objective was to compare the rate (peak plasma concentration; Cmax) and extent (area under the curve [AUC] from administration to last observed concentration time; AUC0–t) of sildenafil absorption after single-dose administration of test and reference. Secondary endpoints were observed to describe the plasma pharmacokinetic profiles of sildenafil and its metabolite N-desmethyl-sildenafil relative bioavailability and safety profile after single-dose administration. The mean sildenafil and N-desmethyl-sildenafil plasma concentration–time profiles up to 24 h after single-dose administration of sildenafil 100 mg orodispersible film and film-coated tablet were nearly superimposable. The bioequivalence test was fully satisfied for sildenafil and N-desmethyl-sildenafil in terms of rate and extent of bioavailability. Adverse events occurred at similar rates for the two formulations and were of mild-to-moderate severity. The results suggest that the new orodispersible film

  6. Bioequivalence study of a new sildenafil 100 mg orodispersible film compared to the conventional film-coated 100 mg tablet administered to healthy male volunteers.

    PubMed

    Radicioni, Milko; Castiglioni, Chiara; Giori, Andrea; Cupone, Irma; Frangione, Valeria; Rovati, Stefano

    2017-01-01

    A new orodispersible film formulation of the phosphodiesterase type 5 inhibitor, sildenafil, has been developed to examine the advantages of an orally disintegrating film formulation and provide an alternative to the current marketed products for the treatment of erectile dysfunction. The pharmacokinetics of the sildenafil 100 mg orodispersible film (IBSA) was compared to that of the conventional marketed 100 mg film-coated tablet (Viagra ® ) after single-dose administration to 53 healthy male volunteers (aged 18-51 years) in a randomized, open, two-way crossover bioequivalence study. Each subject received a single oral dose of 100 mg of sildenafil as test or reference formulation administered under fasting conditions at each of the two study periods according to a randomized crossover design. There was a washout interval of ≥7 days between the two administrations of the investigational medicinal products. Blood samples for pharmacokinetic analysis were collected up to 24 h post-dosing. The primary objective was to compare the rate (peak plasma concentration; C max ) and extent (area under the curve [AUC] from administration to last observed concentration time; AUC 0-t ) of sildenafil absorption after single-dose administration of test and reference. Secondary endpoints were observed to describe the plasma pharmacokinetic profiles of sildenafil and its metabolite N-desmethyl-sildenafil relative bioavailability and safety profile after single-dose administration. The mean sildenafil and N-desmethyl-sildenafil plasma concentration-time profiles up to 24 h after single-dose administration of sildenafil 100 mg orodispersible film and film-coated tablet were nearly superimposable. The bioequivalence test was fully satisfied for sildenafil and N-desmethyl-sildenafil in terms of rate and extent of bioavailability. Adverse events occurred at similar rates for the two formulations and were of mild-to-moderate severity. The results suggest that the new orodispersible film

  7. [Preparation of ondansetron hydrochloride osmotic pump tablets and their in vitro drug release].

    PubMed

    Zheng, Hang-sheng; Bi, Dian-zhou

    2005-12-01

    To prepare ondansetron hydrochloride osmotic pump tablets (OND-OPT) and investigate their in vitro drug release behavior. OND-OPT were prepared with a single punch press and pan coating technique. Osmotic active agents and plasticizer of coating film were chosen by drug release tests. The effects of the number, position and direction of drug release orifice on release behavior were investigated. The relation between drug release duration and thickness of coating film, PEG content of coating film and size of drug release orifice was established by uniform design experiment. The surface morphological change of coating film before and after drug release test was observed by scanning electron microscopy. The osmotic pumping release mechanism of OND-OPT was confirmed by drug release test with high osmotic pressure medium. Lactose-mannitol (1:2) was chosen as osmotic active agents and PEG400 as plasticizer of coating film. The direction of drug release orifice had great effect on the drug release of OND-OPT without HPMC, and had no effect on the drug release of OND-OPT with HPMC. The OND-OPT with one drug release orifice at the centre of the coating film on one surface of tablet released their drug with little fluctuation. The drug release duration of OND-OPT correlated with thickness of coating film and PEG content of coating film, and didn't correlate significantly with the size of drug release orifice. OND-OPT released their drug with osmotic pumping mechanism predominantly. OND-OPT are able to realize ideal controlled drug release.

  8. Development and optimization of buspirone oral osmotic pump tablet

    PubMed Central

    Derakhshandeh, K.; berenji, M. Ghasemnejad

    2014-01-01

    The aim of the current study was to design a porous osmotic pump–based drug delivery system for controlling the release of buspirone from the delivery system. The osmotic pump was successfully developed using symmetric membrane coating. The core of the tablets was prepared by direct compression technique and coated using dip-coating technique. Drug release from the osmotic system was studied using USP paddle type apparatus. The effect of various processing variables such as the amount of osmotic agent, the amount of swellable polymer, concentration of the core former, concentration of the plasticizer, membrane thickness, quantum of orifice on drug release from osmotic pump were evaluated. Different kinetic models (zero order, first order and Higuchi model) were applied to drug release data in order to establish the kinetics of drug release. It was found that the drug release was mostly affected by the amount of NaCl as osmotic agent, the swellable polymer; hydroxy propyl methyl cellulose (HPMC), the amount of PEG-400 and cellulose acetate in the coating solution and thickness of the semipermeable membrane. The optimized formulation released buspirone independent of pH and orifice quantum at the osmogen amount of 42%, hydrophilic polymer of 13% and pore size of 0.8 mm on the tablet surface. The drug release of osmotic formulation during 24 h showed zero order kinetics and could be suggested that this formulation as a once-daily regimen improves pharmacokinetic parameters of the drug and enhances patient compliance. PMID:25657794

  9. Development and optimization of buspirone oral osmotic pump tablet.

    PubMed

    Derakhshandeh, K; Berenji, M Ghasemnejad

    2014-01-01

    The aim of the current study was to design a porous osmotic pump-based drug delivery system for controlling the release of buspirone from the delivery system. The osmotic pump was successfully developed using symmetric membrane coating. The core of the tablets was prepared by direct compression technique and coated using dip-coating technique. Drug release from the osmotic system was studied using USP paddle type apparatus. The effect of various processing variables such as the amount of osmotic agent, the amount of swellable polymer, concentration of the core former, concentration of the plasticizer, membrane thickness, quantum of orifice on drug release from osmotic pump were evaluated. Different kinetic models (zero order, first order and Higuchi model) were applied to drug release data in order to establish the kinetics of drug release. It was found that the drug release was mostly affected by the amount of NaCl as osmotic agent, the swellable polymer; hydroxy propyl methyl cellulose (HPMC), the amount of PEG-400 and cellulose acetate in the coating solution and thickness of the semipermeable membrane. The optimized formulation released buspirone independent of pH and orifice quantum at the osmogen amount of 42%, hydrophilic polymer of 13% and pore size of 0.8 mm on the tablet surface. The drug release of osmotic formulation during 24 h showed zero order kinetics and could be suggested that this formulation as a once-daily regimen improves pharmacokinetic parameters of the drug and enhances patient compliance.

  10. Vardenafil orodispersible tablet.

    PubMed

    Sanford, Mark

    2012-01-01

    Vardenafil orodispersible tablet (ODT) is a supralingual formulation of vardenafil that is available for the on-demand treatment of erectile dysfunction. The pharmacokinetics of vardenafil ODT are not equivalent to those of the vardenafil film-coated tablet in that the ODT formulation provides consistently greater vardenafil systemic exposure. Therefore, the two formulations are not interchangeable. The efficacy of on-demand vardenafil ODT 10 mg was established in the POTENT I and II studies, which were 6-week, randomized, double-blind, multinational trials in men with erectile dysfunction of at least 6 months duration. In both trials, vardenafil ODT improved erectile function significantly more than placebo, as indicated by International Index of Erectile Function-Erectile Function subscale scores at week 12 and overall erection success rates during treatment according to responses to questions 2 and 3 of the Sexual Encounter Profile (coprimary endpoints). In a pooled analysis of both trials, vardenafil ODT improved erectile function regardless of age, severity of erectile dysfunction at baseline or the presence or absence of underlying medical conditions. Vardenafil ODT was generally well tolerated in clinical trials, including in men aged ≥65 years, and adverse events were mostly mild or moderate in severity.

  11. Feasibility of Raman spectroscopy as PAT tool in active coating.

    PubMed

    Müller, Joshua; Knop, Klaus; Thies, Jochen; Uerpmann, Carsten; Kleinebudde, Peter

    2010-02-01

    Active coating is a specific application of film coating where the active ingredient is comprised in the coating layer. This implementation is a challenging operation regarding the achievement of desired amount of coating and coating uniformity. To guarantee the quality of such dosage forms it is desirable to develop a tool that is able to monitor the coating operation and detect the end of the process. Coating experiments were performed at which the model drug diprophylline is coated in a pan coater on placebo tablets and tablets containing the active ingredient itself. During the active coating Raman spectra were recorded in-line. The spectral measurements were correlated with the average weight gain and the amount of coated active ingredient at each time point. The developed chemometric model was tested by monitoring further coated batches. Furthermore, the effects of pan rotation speed and working distance on the acquired Raman signal and, hence, resulting effect of the chemometric model were examined. Besides coating on placebo cores it was possible to determine the amount of active ingredient in the film when coated onto cores containing the same active ingredient. In addition, the method is even applicable when varying the process parameters and measurement conditions within a restricted range. Raman spectroscopy is an appropriate process analytical technology too.

  12. Feasibility of optimizing trimetazidine dihydrochloride release from controlled porosity osmotic pump tablets of directly compressed cores

    PubMed Central

    Habib, Basant A.; Rehim, Randa T. Abd El; Nour, Samia A.

    2013-01-01

    The aim of this study was to develop and optimize Trimetazidine dihydrochloride (TM) controlled porosity osmotic pump (CPOP) tablets of directly compressed cores. A 23 full factorial design was used to study the influence of three factors namely: PEG400 (10% and 25% based on coating polymer weight), coating level (10% and 20% of tablet core weight) and hole diameter (0 “no hole” and 1 mm). Other variables such as tablet cores, coating mixture of ethylcellulose (4%) and dibutylphthalate (2%) in 95% ethanol and pan coating conditions were kept constant. The responses studied (Yi) were cumulative percentage released after 2 h (Q%2h), 6 h (Q%6h), 12 h (Q%12h) and regression coefficient of release data fitted to zero order equation (RSQzero), for Y1, Y2, Y3, and Y4, respectively. Polynomial equations were used to study the influence of different factors on each response individually. Response surface methodology and multiple response optimization were used to search for an optimized formula. Response variables for the optimized formula were restricted to 10% ⩽ Y1 ⩽ 20%, 40% ⩽ Y2 ⩽ 60%, 80% ⩽ Y3 ⩽ 100%, and Y4 > 0.9. The statistical analysis of the results revealed that PEG400 had positive effects on Q%2h, Q%6h and Q%12h, hole diameter had positive effects on all responses and coating level had positive effect on Q%6h, Q%12h and negative effect on RSQzero. Full three factor interaction (3FI) equations were used for representation of all responses except Q%2h which was represented by reduced (3FI) equation. Upon exploring the experimental space, no formula in the tested range could satisfy the required constraints. Thus, direct compression of TM cores was not suitable for formation of CPOP tablets. Preliminary trials of CPOP tablets with wet granulated cores were promising with an intact membrane for 12 h and high RSQzero. Further improvement of these formulations to optimize TM release will be done in further studies. PMID:25685502

  13. Applications of terahertz-pulsed technology in the pharmaceutical industry

    NASA Astrophysics Data System (ADS)

    Taday, Philip F.

    2010-02-01

    Coatings are applied to pharmaceutical tablets (or pills) to for either cosmetic or release control reasons. Cosmetic coatings control the colour or to mask the taste of an active ingredient; the thickness of these coating is not critical to the performance of the product. On the other hand the thickness and uniformity of a controlled release coating has been found affect the release of the active ingredient. In this work we have obtained from a pharmacy single brand of pantoprazole tablet and mapped them using terahertz pulsed imaging (TPI) prior to additional dissolution testing. Three terahertz parameters were derived for univariate analysis for each layer: coating thickness, terahertz electric field peak strength and terahertz interface index. These parameters were then correlated dissolution tested. The best fit was found to be with combined coating layer thickness of the inert layer and enteric coating. The commercial tablets showed a large variation in coating thickness.

  14. VORTAB - A data-tablet method of developing input data for the VORLAX program

    NASA Technical Reports Server (NTRS)

    Denn, F. M.

    1979-01-01

    A method of developing an input data file for use in the aerodynamic analysis of a complete airplane with the VORLAX computer program is described. The hardware consists of an interactive graphics terminal equipped with a graphics tablet. Software includes graphics routines from the Tektronix PLOT 10 package as well as the VORTAB program described. The user determines the size and location of each of the major panels for the aircraft before using the program. Data is entered both from the terminal keyboard and the graphics tablet. The size of the resulting data file is dependent on the complexity of the model and can vary from ten to several hundred card images. After the data are entered, two programs READB and PLOTB, are executed which plot the configuration allowing visual inspection of the model.

  15. Time-controlled release pseudoephedrine tablets: bioavailability and in vitro/in vivo correlations.

    PubMed

    Halsas, M; Penttinen, T; Veski, P; Jürjenson, H; Marvola, M

    2001-09-01

    In chronopharmacotherapy, circadian changes in disease symptoms are taken into account. Press-coated, time-controlled release tablets containing pseudoephedrine hydrochloride as a model drug have been formulated and the suitability of this highly soluble drug in relation to the new drug delivery system was evaluated. Hydroxypropylmethylcellulose was used in the coat of the tablet to adjust drug release. If such a formulation was administered in the evening it would have maximal effect in the early morning, and would be useful for the treatment of nocturnal symptoms. Two cross-over, single-dose bioavailability studies were carried out on eight healthy volunteers. A dissolution test method was developed to establish level A and level C in vitro/in vivo correlation for four formulations. With a low viscosity grade of polymer, peak concentrations were achieved after five hours. The drug was absorbed much more slowly from tablets containing a high viscosity grade polymer, with a plasma peak at ten hours. For further development of the drug delivery system described, a dissolution test method at pH 7.2 at a rotation speed of 150 min-1 is recommended on the basis of level A in vitro/in vivo correlation.

  16. Development of press-coated, floating-pulsatile drug delivery of lisinopril.

    PubMed

    Jagdale, Swati C; Suryawanshi, Vishnu M; Pandya, Sudhir V; Kuchekar, Bhanudas S; Chabukswar, Aniruddha R

    2014-01-01

    Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor, primarily used for the treatment of hypertension, congestive heart failure, and heart attack. It belongs to BCS class III having a half-life of 12 hrs and 25% bioavailability. The purpose of the present work was to develop a press-coated, floating-pulsatile drug delivery system. The core tablet was formulated using the super-disintegrants crosprovidone and croscarmellose sodium. A press-coated tablet (barrier layer) contained the polymer carrageenan, xanthan gum, HPMC K4M, and HPMC K15M. The buoyant layer was optimized with HPMC K100M, sodium bicarbonate, and citric acid. The tablets were evaluated for physical characteristics, floating lag time, swelling index, FTIR, DSC, and in vitro and in vivo behavior. The 5% superdisintgrant showed good results. The FTIR and DSC study predicted no chemical interactions between the drug and excipients. The formulation containing xanthan gum showed drug retaining abilities, but failed to float. The tablet containing HPMC K15M showed a high swelling index. The lag time for the tablet coated with 200 mg carrageenan was 3±0.1 hrs with 99.99±1.5% drug release; with 140 mg HPMC K4M, the lag time was 3±0.1 hrs with 99.71±1.2% drug release; and with 120 mg HPMC K15M, the lag time was 3±0.2 hrs with 99.98±1.7% drug release. The release mechanism of the tablet followed the Korsmeyer-Peppas equation and a first-order release pattern. Floating and lag time behavior have shown good in vitro and in vivo correlations.

  17. Development of Press-Coated, Floating-Pulsatile Drug Delivery of Lisinopril

    PubMed Central

    Jagdale, Swati C.; Suryawanshi, Vishnu M.; Pandya, Sudhir V.; Kuchekar, Bhanudas S.; Chabukswar, Aniruddha R.

    2014-01-01

    Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor, primarily used for the treatment of hypertension, congestive heart failure, and heart attack. It belongs to BCS class III having a half-life of 12 hrs and 25% bioavailability. The purpose of the present work was to develop a press-coated, floating-pulsatile drug delivery system. The core tablet was formulated using the super-disintegrants crosprovidone and croscarmellose sodium. A press-coated tablet (barrier layer) contained the polymer carrageenan, xanthan gum, HPMC K4M, and HPMC K15M. The buoyant layer was optimized with HPMC K100M, sodium bicarbonate, and citric acid. The tablets were evaluated for physical characteristics, floating lag time, swelling index, FTIR, DSC, and in vitro and in vivo behavior. The 5% superdisintgrant showed good results. The FTIR and DSC study predicted no chemical interactions between the drug and excipients. The formulation containing xanthan gum showed drug retaining abilities, but failed to float. The tablet containing HPMC K15M showed a high swelling index. The lag time for the tablet coated with 200 mg carrageenan was 3±0.1 hrs with 99.99±1.5% drug release; with 140 mg HPMC K4M, the lag time was 3±0.1 hrs with 99.71±1.2% drug release; and with 120 mg HPMC K15M, the lag time was 3±0.2 hrs with 99.98±1.7% drug release. The release mechanism of the tablet followed the Korsmeyer-Peppas equation and a first-order release pattern. Floating and lag time behavior have shown good in vitro and in vivo correlations. PMID:24959410

  18. Tableting Properties and Compression Models of Labisia pumila Tablets.

    PubMed

    Etti, C J; Yusof, Y A; Chin, N L; Mohd Tahir, S

    2017-03-04

    The tableting properties of Labisia pumila herbal powder, which is well known for its therapeutic benefits was investigated. The herbal powder was compressed into tablets using a stainless steel cylindrical uniaxial die of 13-mm- diameter with compaction pressures ranging from 7 to 25 MPa. Two feed weights, 0.5 and 1.0 g were used to form tablets. Some empirical models were used to describe the compressibility behavior of Labisia pumila tablets. The strength and density of tablets increased with increase in compaction pressure and resulted in reduction in porosity of the tablets. Smaller feeds, higher forces and increase in compaction pressure, contributed to more coherent tablets. These findings can be used to enhance the approach and understanding of tableting properties of Labisia pumila herbal powder tablets.

  19. Investigation of the potential for direct compaction of a fine ibuprofen powder dry-coated with magnesium stearate.

    PubMed

    Qu, Li; Zhou, Qi Tony; Gengenbach, Thomas; Denman, John A; Stewart, Peter J; Hapgood, Karen P; Gamlen, Michael; Morton, David A V

    2015-05-01

    Intensive dry powder coating (mechanofusion) with tablet lubricants has previously been shown to give substantial powder flow improvement. This study explores whether the mechanofusion of magnesium stearate (MgSt), on a fine drug powder can substantially improve flow, without preventing the powder from being directly compacted into tablets. A fine ibuprofen powder, which is both cohesive and possesses a low-melting point, was dry coated via mechanofusion with between 0.1% and 5% (w/w) MgSt. Traditional low-shear blending was also employed as a comparison. No significant difference in particle size or shape was measured following mechanofusion. For the low-shear blended powders, only marginal improvement in flowability was obtained. However, after mechanofusion, substantial improvements in the flow properties were demonstrated. Both XPS and ToF-SIMS demonstrated high degrees of a nano-scale coating coverage of MgSt on the particle surfaces from optimized mechanofusion. The study showed that robust tablets were produced from the selected mechanofused powders, at high-dose concentration and tablet tensile strength was further optimized via addition of a Polyvinylpyrrolidone (PVP) binder (10% w/w). The tablets with the mechanofused powder (with or without PVP) also exhibited significantly lower ejection stress than those made of the raw powder, demonstrating good lubrication. Surprisingly, the release rate of drug from the tablets made with the mechanofused powder was not retarded. This is the first study to demonstrate such a single-step dry coating of model drug with MgSt, with promising flow improvement, flow-aid and lubrication effects, tabletability and also non-inhibited dissolution rate.

  20. Effect of food on the oral bioavailability of didanosine from encapsulated enteric-coated beads.

    PubMed

    Damle, Bharat D; Yan, Jing-He; Behr, Douglas; O'Mara, Edward; Nichola, Peter; Kaul, Sanjeev; Knupp, Catherine

    2002-04-01

    The objective of this study was to assess the effect of food and timing of meals on the bioavailability of didanosine from encapsulated enteric-coated beads. Four different independent, open-label, single-dose, randomized, crossover studies were conducted in healthy subjects (n = 20-30). Didanosine (400 mg) was given concomitantly with a high-fat meal, light meal, yogurt, and applesauce. In addition, didanosine was given 1, 1.5, 2, and 3 hours before and 2 hours after a light meal. Statistical comparison with fasting conditions was made using the equivalence approach for Cmax (70%-143%) and AUC (80%-125%). The high-fat meal, light meal, yogurt, and applesauce decreased the Cmax by 46%, 22%, 30%, and 24%, respectively, and lowered the AUC by 19%, 27%, 20%, and 18%, respectively; statistical analyses indicated an indeterminate food effect, except for the Cmax for the high-fat meal. For 1 hour before meal, Cmax and AUC were lower by 15% and 24% and, for 2 hours after meal, were lower by 15% and 10%, respectively. There was an indeterminate food effect for 1 hour before the meal treatment; in addition, 2 hours after the meal, treatment approached statistical equivalence, missing narrowly on the lower bounds. For 1.5, 2, and 3 hours before meal treatments, Cmax values were unchanged, but AUC was lower by 10%, 4%, and 0%, respectively; lack of food effect was observed for all three treatments. Across studies, median time to Cmix ranged from 1.67 to 2.67 hours but was delayed by 2.5 to 3 hours with high-fat and light meals compared to fasting conditions. The half-life of didanosine was 1.5 to 2 hours. It was concluded that the bioavailability of didanosine from encapsulated enteric-coated beads was reduced by approximately 20% to 25% with food, which can be circumvented by taking didanosine on an empty stomach. The clinical significance of such moderate reductions in didanosine exposure with food, especially as part of a highly active antiretroviral therapy, is not clear.

  1. Effect assessment of "film coating and packaging" on the photo-stability of highly photo-labile antihypertensive products.

    PubMed

    Mukharya, Amit; Patel, Paresh U; Chaudhary, Shivang

    2013-04-01

    Lacidipine (LCDP) is chemically a "1, 4-dihydropyridine derivative" Ca+(2) channel blocker used as an antihypertensive. Type and extent of packaging have a strong influence on the photo-stability of the 1,4-dihydropyridine derivatives. In standard, light protection of drug substance/drug product can be obtained either by use of an opaque additive in the formulation that competitively absorbs or reflects light reaching the sample and/or by blocking the access of light to the drug through external protection by packaging. External protection by covering tablets with an opaque film coating involving a light-reflecting inorganic pigment such as titanium dioxide and/or by using an opaque impermeable packaging material was an appropriate suitable option for establishing photo-stability. Thus, the main objective of the present study was to optimize the % level of film coating in LCDP core tablets, and selection of a final packaging material and its respective extent, that is, primary, secondary and/or tertiary packaging, for LCDP tablets. The main objective (% level of film coating) was optimized by directly exposing core tablets, 1% w/w, 2% w/w and 3% w/w film-coated tablets, to a light source as per Option-2 of ICH Q1B and its comparative analysis at the end of light exposure testing. The other objective (extent of drug product packaging) was established successfully by assessing whether or not an acceptable change has occurred at the end of the light exposure testing of the LCDP film-coated tablets in a direct exposure study or a primary immediate pack and/or secondary marketing pack.

  2. Press-coated tablets for time-programmed release of drugs.

    PubMed

    Conte, U; Maggi, L; Torre, M L; Giunchedi, P; La Manna, A

    1993-10-01

    A new dry-coated device for the release of drug after a programmable period of time is proposed. It is intended to be used mainly in the therapy of those diseases which depend on circadian rhythms. Some core formulations, characterized by different release rates and mechanisms (containing diltiazem hydrochloride or sodium diclofenac as model drugs), were coated by compression with different polymeric barrier layers (press-coated systems). The shell formulations tested contained either gellable or erodible polymers. The dissolution profiles of uncoated cores and press-coated devices were compared. The gellable and/or erodible characteristics (properties) of the barrier formulations were also examined by means of a penetrometer. The coatings prevent drug release from the core until the polymeric shell is completely eroded or swollen. This delay in release start is not influenced by the core composition and depends only on the shell formulation. Except for the time-lag, the release kinetics of the drug contained in the core are not significantly influenced by the presence of the erodible barrier, but can be widely modulated using a swellable polymeric shell.

  3. Colonic delivery of indometacin loaded PGA-co-PDL microparticles coated with Eudragit L100-55 from fast disintegrating tablets.

    PubMed

    Tawfeek, Hesham M; Abdellatif, Ahmed A H; Dennison, Thomas J; Mohammed, Afzal R; Sadiq, Younis; Saleem, Imran Y

    2017-10-05

    The aim of this work was to investigate the efficient targeting and delivery of indometacin (IND), as a model anti-inflammatory drug to the colon for treatment of inflammatory bowel disease. We prepared fast disintegrating tablets (FDT) containing IND encapsulated within poly(glycerol-adipate-co-ɷ-pentadecalactone), PGA-co-PDL, microparticles and coated with Eudragit L100-55 at different ratios (1:1.5, 1:1, 1:0.5). Microparticles encapsulated with IND were prepared using an o/w single emulsion solvent evaporation technique and coated with Eudragit L-100-55 via spray drying. The produced coated microparticles (PGA-co-PDL-IND/Eudragit) were formulated into optimised FTD using a single station press. The loading, in vitro release, permeability and transport of IND from PGA-co-PDL-IND/Eudragit microparticles was studied in Caco-2 cell lines. IND was efficiently encapsulated (570.15±4.2μg/mg) within the PGA-co-PDL microparticles. In vitro release of PGA-co-PDL-IND/Eudragit microparticles (1:1.5) showed significantly (p<0.05, ANOVA/Tukey) lower release of IND 13.70±1.6 and 56.46±3.8% compared with 1:1 (89.61±2.5, 80.13±2.6%) and 1:0.5 (39.46±0.9 & 43.38±3.12) after 3 and 43h at pH 5.5 and 6.8, respectively. The permeability and transport studies indicated IND released from PGA-co-PDL-IND/Eudragit microparticles had a lower permeability coefficient of 13.95±0.68×10 -6 cm/s compared to free IND 23.06±3.56×10 -6 cm/s. These results indicate the possibility of targeting anti-inflammatory drugs to the colon using FDTs containing microparticles coated with Eudragit. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Novel extraction and application of okra gum as a film coating agent using theophylline as a model drug.

    PubMed

    Ogaji, Ikoni J; Hoag, Stephen W

    2014-04-01

    The purpose of this study was to investigate the effect of extraction and application of okra gum as an aqueous film coating agent. Powdered okra pods dispersed in demineralized water was heated at 80 ± 2(o)C for 30 minutes in the presence of sodium chloride. The filtrate was successively centrifuged at 4000 rpm for 30, 60, or 120 minutes and freeze dried. The samples were used as film former at different concentrations in aqueous film coating operations. Near infrared (nIR) absorption spectra, photomicrographs, and some physicochemical properties of the coated tablets were evaluated. The okra gum samples had different nIR spectra and possessed good processing and application quality due to relatively low viscosity. A six-fold concentration of this gum from the novel extraction yielded glossy theophylline tablets within a short time. A t (18) = 2.895, P < 0.005, t critical = 1.734 were obtained for the independent analysis of the hardness of core and coated theophylline tablets. A 3.0% concentration of the okra samples at a flow rate of 3 ml/min for 100 minutes showed that F = 3.798, DF = 29, P < 0.035, F critical = 3.354 in tablet hardness among samples and F = 15.632, DF = 29, P < 0.0001, F critical = 2.152 were obtained on film thickness among tablet samples during the coating and drying operation. Novel extraction process enhanced the film coating potential of okra gum by delivering more solids on the substrate at a shorter time with improved operation efficiency.

  5. Preparation of surfactant-free nanoparticles of methacrylic acid copolymers used for film coating.

    PubMed

    Nguyen, Cung An; Konan-Kouakou, Yvette Niamien; Allémann, Eric; Doelker, Eric; Quintanar-Guerrero, David; Fessi, Hatem; Gurny, Robert

    2006-07-28

    The aim of the present study was to prepare surfactant-free pseudolatexes of various methacrylic acid copolymers. These aqueous colloidal dispersions of polymeric materials for oral administration are intended for film coating of solid dosage forms or for direct manufacturing of nanoparticles. Nanoparticulate dispersions were produced by an emulsification-diffusion method involving the use of partially water-miscible solvents and the mutual saturation of the aqueous and organic phases prior to the emulsification in order to reduce the initial thermodynamic instability of the emulsion. Because of the self-emulsifying properties of the methacrylic acid copolymers, it was possible to prepare aqueous dispersions of colloidal size containing up to 30% wt/vol of Eudragit RL, RS, and E using 2-butanone or methyl acetate as partially water-miscible solvents, but without any surfactant. However, in the case of the cationic Eudragit E, protonation of the tertiary amine groups by acidification of the aqueous phase was necessary to improve the emulsion stability in the absence of surfactant and subsequently to prevent droplet coalescence during evaporation. In addition, a pseudolatex of Eudragit E was used to validate the coating properties of the formulation for solid dosage forms. Film-coated tablets of quinidine sulfate showed a transparent glossy continuous film that was firmly attached to the tablet. The dissolution profile of quinidine sulfate from the tablets coated with the Eudragit E pseudolatex was comparable to that of tablets coated with an acetonic solution of Eudragit E. Furthermore, both types of coating ensured similar taste masking. The emulsification-evaporation method used was shown to be appropriate for the preparation of surfactant-free colloidal dispersions of the 3 types of preformed methacrylic acid copolymers; the dispersions can subsequently be used for film coating of solid dosage forms.

  6. Effect assessment of “film coating and packaging” on the photo-stability of highly photo-labile antihypertensive products

    PubMed Central

    Mukharya, Amit; Patel, Paresh U; Chaudhary, Shivang

    2013-01-01

    Introduction: Lacidipine (LCDP) is chemically a “1, 4-dihydropyridine derivative” Ca+2 channel blocker used as an antihypertensive. Type and extent of packaging have a strong influence on the photo-stability of the 1,4-dihydropyridine derivatives. In standard, light protection of drug substance/drug product can be obtained either by use of an opaque additive in the formulation that competitively absorbs or reflects light reaching the sample and/or by blocking the access of light to the drug through external protection by packaging. Materials and Methods: External protection by covering tablets with an opaque film coating involving a light-reflecting inorganic pigment such as titanium dioxide and/or by using an opaque impermeable packaging material was an appropriate suitable option for establishing photo-stability. Thus, the main objective of the present study was to optimize the % level of film coating in LCDP core tablets, and selection of a final packaging material and its respective extent, that is, primary, secondary and/or tertiary packaging, for LCDP tablets. Results and Conclusion: The main objective (% level of film coating) was optimized by directly exposing core tablets, 1% w/w, 2% w/w and 3% w/w film-coated tablets, to a light source as per Option-2 of ICH Q1B and its comparative analysis at the end of light exposure testing. The other objective (extent of drug product packaging) was established successfully by assessing whether or not an acceptable change has occurred at the end of the light exposure testing of the LCDP film-coated tablets in a direct exposure study or a primary immediate pack and/or secondary marketing pack. PMID:24015379

  7. An investigation into moisture barrier film coating efficacy and its relevance to drug stability in solid dosage forms.

    PubMed

    Mwesigwa, Enosh; Basit, Abdul W

    2016-01-30

    Barrier coatings are frequently employed on solid oral dosage forms under the assumption that they prevent moisture sorption into tablet cores thereby averting premature degradation of moisture-sensitive active ingredients. However, the efficacy of moisture barrier coatings remains unproven and they may actually accelerate degradation. This study aimed to investigate the barrier performance of four coating systems following application onto a low hygroscopic tablet formulation containing aspirin as a model moisture sensitive drug. Tablets were prepared by direct compaction and coated with aqueous dispersions of Eudragit(®) L30 D-55, Eudragit(®) EPO, Opadry(®) AMB and Sepifilm(®) LP at the vendors' recommended weight gains. Moisture uptake was studied by dynamic vapor sorption at 0 and 75% RH (25°C). Accelerated stability studies were undertaken at 75% RH/25°C for 90 days and HPLC assay was used to determine aspirin content. Uncoated tablet cores equilibrated rapidly and took up very little water (0.09%). The mean water uptake for coated cores was higher than for the uncoated formulation and varied as follows: 0.19% (Eudragit(®) L30 D-55), 0.35% (Opadry(®) AMB), 0.49% (Sepifilm(®) LP) and 0.76% (Eudragit(®) EPO). The level of aspirin decreased in all the samples such that by the time the study was terminated, the mean aspirin recovered was as follows: uncoated cores 80.0%; Eudragit® L30 D-55 coated cores 78.8%; Opadry(®) AMB coated cores 76.2%, Sepifilm(®) LP coated cores 76.0% and Eudragit(®) EPO coated samples 66.5%. From these results, it is concluded that the efficacy of moisture barrier polymer coatings on low hygroscopic cores is limited, and application of these coatings can, instead, enhance drug degradation in solid dosage forms. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. [Tablets and tablet production - with special reference to Icelandic conditions].

    PubMed

    Skaftason, Jóhannes F; Jóhannesson, Thorkell

    2013-04-01

    Modern tablet compression was instituted in England in 1844 by William Brockedon (1787-1854). The first tablets made according to Brockedon´s procedures contained watersoluble salts and were most likely compressed without expedients. In USA a watershed occurred around 1887 when starch (amylum maydis) was introduced to disperse tablets in aqueous milieu in order to corroborate bioavailability of drugs in the almentary canal. About the same time great advances in tablet production were introduced by the British firm Burroughs Wellcome and Co. In Denmark on the other hand tablet production remained on low scale until after 1920. As Icelandic pharmacies and drug firms modelled themselves mostly upon Danish firms tablet production was first instituted in Iceland around 1930. The first tablet machines in Iceland were hand-driven. More efficent machines came after 1945. Around 1960 three sizeable tablet producers were in Iceland; now there is only one. Numbers of individual tablet species (generic and proprietary) on the market rose from less than 10 in 1913 to 500 in 1965, with wide variations in numbers in between. Tablets have not wiped out other medicinal forms for peroral use but most new peroral drugs have been marketed in the form of tablets during the last decades.

  9. OPTIMIZATION OF FUROSEMIDE LIQUISOLID TABLETS PREPARATION PROCESS LEADING TO THEIR MASS AND SIZE REDUCTION.

    PubMed

    Kurek, Mateusz; Woyna-Orlewicz, Krzysztof; Khalid, Mohammad Hassan; Jachowicz, Renata

    2016-09-01

    The great number of drug substances currently used in solid oral dosage forms is characterized by poor water solubility. Therefore, various methods of dissolution rate enhancement are an important topic of research interest in modem drug technology. The purpose of this study was to enhance the furosemide dissolution rate from liquisolid tablets while maintaining an acceptable size and mass. Two types of dibasic calcium phosphate (Fujicalin®/Emcompress®) and microcrystalline cellulose (Vivapur® 102/Vivapur® 12) were used as carriers and magnesium aluminometasilicate (Neusilin® US2) was used as a coating material. The flowable liquid retention potential for those excipients was tested by measuring the angle of slide. To evaluate the impact of used excipients on tablet properties fourteen tablet formulations were prepared. It was found that LS2 tablets containing spherically granulated dibasic calcium phosphate and magnesium aluminometasilicate exhibit the best dissolution profile and mechanical properties while tablets composed only with Neusilin® US2 was characterized by the smallest size and mass with preserved good mechanical properties and furosemide dissolution.

  10. Development of modified release 3D printed tablets (printlets) with pharmaceutical excipients using additive manufacturing.

    PubMed

    Goyanes, Alvaro; Fina, Fabrizio; Martorana, Annalisa; Sedough, Daniel; Gaisford, Simon; Basit, Abdul W

    2017-07-15

    The aim of this study was to manufacture 3D printed tablets (printlets) from enteric polymers by single filament fused deposition modeling (FDM) 3D printing (3DP). Hot melt extrusion was used to generate paracetamol-loaded filaments from three different grades of the pharmaceutical excipient hypromellose acetate succinate (HPMCAS), grades LG, MG and HG. One-step 3DP was used to process these filaments into enteric printlets incorporating up to 50% drug loading with two different infill percentages (20 and 100%). X-ray Micro Computed Tomography (Micro-CT) analysis revealed that printlets with 20% infill had cavities in the core compared to 100% infill, and that the density of the 50% drug loading printlets was higher than the equivalent formulations loaded with 5% drug. In biorelevant bicarbonate dissolution media, drug release from the printlets was dependent on the polymer composition, drug loading and the internal structure of the formulations. All HPMCAS-based printlets showed delayed drug release properties, and in the intestinal conditions, drug release was faster from the printlets prepared with polymers with a lower pH-threshold: HPMCAS LG > HPMCAS MG > HPMCAS HG. These results confirm that FDM 3D printing makes it possible not only to manufacture delayed release printlets without the need for an outer enteric coating, but it is also feasible to adapt the release profile in response to the personal characteristics of the patient, realizing the full potential of additive manufacturing in the development of personalised dose medicines. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Development of Colorectal-Targeted Dietary Supplement Tablets Containing Natural Purple Rice Bran Oil as a Colorectal Chemopreventive.

    PubMed

    Sirithunyalug, Busaban; Saenjum, Chalermpong; Charumanee, Suporn; Sivamaruthi, Bhagavathi Sundaram; Chaiyasut, Chaiyavat; Sirithunyalug, Jakkapan; Tipduangta, Pratchaya

    2018-04-04

    Colorectal cancer occurs due to various factors. The important risks are dietary lifestyle and inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis. It has been found that the inhibitory enzyme cyclooxygenase-2 (COX-2) in the colorectal region can potentially reduce the risk of colorectal cancer. The present study investigated rice bran oil from natural purple rice bran, which exhibits antioxidant and anti-inflammatory activity. This study aimed to evaluate the bioactive compound content of natural purple rice bran oil (NPRBO) derived from native Thai purple rice and the anti-inflammatory activity of NPRBO in colorectal cancer cells, and to develop a colorectal delivery platform in the form of film-coated tablets. NPRBO from the rice bran of five different Thai purple rice cultivars, namely Khao’ Gam Leum-Phua (KGLP), Khao’ Gam Boung (KGB), Khao’ Gam Thor (KGT), Khao’ Gam Pah E-Kaw (KGPEK), and Khao’ Niaw Dam (KND), were extracted using the supercritical carbon dioxide extraction technique. The amount of γ-oryzanol (ORY), tocotrienols, and tocopherols present in NPRBOs and the in vitro anti-inflammatory activity of NPRBO were investigated. The highest anti-inflammatory NPRBO was transformed into a dry and free-flowing powder by liquisolid techniques. Then, it was compressed into core tablets and coated with Eudragit ® L100 and Eudragit ® NE30D. The in vitro release study of the film-coated NPRBO tablets was performed in three-phase simulated gastrointestinal media. The cultivar KGLP was superior to the other samples in terms of the ORY, tocotrienol and tocopherol contents and anti-inflammatory activity. Aerosil ® was the most suitable absorbent for transforming NPRBO into a free-flowing powder and was used to prepare the NPRBO core tablets. The in vitro KGLP-NPRBO film-coated tablet release profile showed that no ORY was released at gastric pH while 85% of ORY was released at pH 7.4 after

  12. Development of Colorectal-Targeted Dietary Supplement Tablets Containing Natural Purple Rice Bran Oil as a Colorectal Chemopreventive

    PubMed Central

    Sirithunyalug, Busaban; Saenjum, Chalermpong; Charumanee, Suporn; Chaiyasut, Chaiyavat; Sirithunyalug, Jakkapan; Tipduangta, Pratchaya

    2018-01-01

    Colorectal cancer occurs due to various factors. The important risks are dietary lifestyle and inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis. It has been found that the inhibitory enzyme cyclooxygenase-2 (COX-2) in the colorectal region can potentially reduce the risk of colorectal cancer. The present study investigated rice bran oil from natural purple rice bran, which exhibits antioxidant and anti-inflammatory activity. This study aimed to evaluate the bioactive compound content of natural purple rice bran oil (NPRBO) derived from native Thai purple rice and the anti-inflammatory activity of NPRBO in colorectal cancer cells, and to develop a colorectal delivery platform in the form of film-coated tablets. NPRBO from the rice bran of five different Thai purple rice cultivars, namely Khao’ Gam Leum-Phua (KGLP), Khao’ Gam Boung (KGB), Khao’ Gam Thor (KGT), Khao’ Gam Pah E-Kaw (KGPEK), and Khao’ Niaw Dam (KND), were extracted using the supercritical carbon dioxide extraction technique. The amount of γ-oryzanol (ORY), tocotrienols, and tocopherols present in NPRBOs and the in vitro anti-inflammatory activity of NPRBO were investigated. The highest anti-inflammatory NPRBO was transformed into a dry and free-flowing powder by liquisolid techniques. Then, it was compressed into core tablets and coated with Eudragit®L100 and Eudragit® NE30D. The in vitro release study of the film-coated NPRBO tablets was performed in three-phase simulated gastrointestinal media. The cultivar KGLP was superior to the other samples in terms of the ORY, tocotrienol and tocopherol contents and anti-inflammatory activity. Aerosil® was the most suitable absorbent for transforming NPRBO into a free-flowing powder and was used to prepare the NPRBO core tablets. The in vitro KGLP-NPRBO film-coated tablet release profile showed that no ORY was released at gastric pH while 85% of ORY was released at pH 7.4 after 6 h; this would be expected to occur in

  13. Field Trials of Attenuated Salmonella Typhi Live Oral Vaccine TY21A in Liquid and Enteric-Coated Capsule Formulations in Santiago, Chile

    DTIC Science & Technology

    1990-06-01

    inactive piacebo, children in the control group received viable Lactobacillus acidophilus because some experimental data suggest that L. acidophilus may...was the enteric-coating used to make the capsules acid-resistant. Such capsules, each containing 1-3 x 109 viable vaccine (or Lactobacillus ) organisms...formulation of vaccine (or of the Lactobacillus control preparation) consisted of two aluminum foil packets, one containing lyophilized vaccine (or

  14. Interaction between levodopa and enteral nutrition.

    PubMed

    Cooper, Mandelin K; Brock, David G; McDaniel, Cara M

    2008-03-01

    To report and discuss a drug-nutrient interaction involving levodopa and protein in enteral nutrition. A 77-year-old male with Parkinson's disease was admitted to an intensive care unit for an intracerebral hemorrhage. To provide nutritional support, an oral gastric tube was placed and continuous enteral nutrition was initiated, with 1.4 g/kg of protein administered daily. The following medications were continued during hospitalization: immediate-release carbidopa/levodopa 25 mg/100 mg, with 1.5 tablets administered 4 times daily; pramipexole 1.5 mg 3 times daily; and entacapone 200 mg 4 times daily. Despite this drug therapy, the patient developed severe rigidity. A review of the literature revealed a potential interaction between levodopa and protein intake. To resolve this interaction, the amount of protein in the enteral nutrition was decreased to 0.9 g/kg/day and the nutritional administration was changed from continuous enteral feeding to bolus feeding, with levodopa given between boluses. After these adjustments, the patient showed marked improvement of parkinsonian symptoms. The drug-nutrient interaction between protein and levodopa in outpatient settings has been reported widely in the literature; however, this interaction has not been previously reported with continuous enteral nutrition. Decreased parkinsonian symptom control, despite adherence to an established medication regimen, together with dramatic improvement observed after manipulation of enteral nutrition delivery and content, strongly suggest interference with levodopa absorption. Use of the Naranjo probability scale supports a probable interaction between the protein content in tube feeds and levodopa, resulting in decreased levodopa efficacy. Clinicians should be cognizant of the potential drug-nutrient interaction between levodopa and enteral nutrition.

  15. Medication administration through enteral feeding tubes.

    PubMed

    Williams, Nancy Toedter

    2008-12-15

    An overview of enteral feeding tubes, drug administration techniques, considerations for dosage form selection, common drug interactions with enteral formulas, and methods to minimize tube occlusion is given. Enteral nutrition through a feeding tube is the preferred method of nutrition support in patients who have a functioning gastrointestinal tract but who are unable to be fed orally. This method of delivering nutrition is also commonly used for administering medications when patients cannot swallow safely. However, several issues must be considered with concurrent administration of oral medications and enteral formulas. Incorrect administration methods may result in clogged feeding tubes, decreased drug efficacy, increased adverse effects, or drug-formula incompatibilities. Various enteral feeding tubes are available and are typically classified by site of insertion and location of the distal tip of the feeding tube. Liquid medications, particularly elixirs and suspensions, are preferred for enteral administration; however, these formulations may be hypertonic or contain large amounts of sorbitol, and these properties increase the potential for adverse effects. Before solid dosage forms are administered through the feeding tube, it should be determined if the medications are suitable for manipulation, such as crushing a tablet or opening a capsule. Medications should not be added directly to the enteral formula, and feeding tubes should be properly flushed with water before and after each medication is administered. To minimize drug-nutrient interactions, special considerations should be taken when administering phenytoin, carbamazepine, warfarin, fluoroquinolones, and proton pump inhibitors via feeding tubes. Precautions should be implemented to prevent tube occlusions, and immediate intervention is required when blockages occur. Successful drug delivery through enteral feeding tubes requires consideration of the tube size and placement as well as careful

  16. Measurement of the Intertablet Coating Uniformity of a Pharmaceutical Pan Coating Process With Combined Terahertz and Optical Coherence Tomography In-Line Sensing.

    PubMed

    Lin, Hungyen; Dong, Yue; Markl, Daniel; Williams, Bryan M; Zheng, Yalin; Shen, Yaochun; Zeitler, J Axel

    2017-04-01

    We present in-line coating thickness measurements acquired simultaneously using 2 independent sensing modalities: terahertz pulsed imaging (TPI) and optical coherence tomography (OCT). Both techniques are sufficiently fast to resolve the coating thickness of individual pharmaceutical tablets in situ during the film coating operation, and both techniques are direct structural imaging techniques that do not require multivariate calibration. The TPI sensor is suitable to measure coatings greater than 50 μm and can penetrate through thick coatings even in the presence of pigments over a wide range of excipients. Due to the long wavelength, terahertz radiation is not affected by scattering from dust within the coater. In contrast, OCT can resolve coating layers as thin as 20 μm and is capable of measuring the intratablet coating uniformity and the intertablet coating thickness distribution within the coating pan. However, the OCT technique is less robust when it comes to the compatibility with excipients, dust, and potentially the maximum coating thickness that can be resolved. Using a custom-built laboratory scale coating unit, the coating thickness measurements were acquired independently by the TPI and OCT sensors throughout a film coating operation. Results of the in-line TPI and OCT measurements were compared against one another and validated with off-line TPI and weight gain measurements. Compared with other process analytical technology sensors, such as near-infrared and Raman spectroscopy, the TPI and OCT sensors can resolve the intertablet thickness distribution based on sampling a significant fraction of the tablet populations in the process. By combining 2 complementary sensing modalities, it was possible to seamlessly monitor the coating process over the range of film thickness from 20 μm to greater than 250 μm. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Development and evaluation of a novel modified-release pellet-based tablet system for the delivery of loratadine and pseudoephedrine hydrochloride as model drugs.

    PubMed

    Zeeshan, Farrukh; Bukhari, Nadeem Irfan

    2010-06-01

    Modified-release multiple-unit tablets of loratadine and pseudoephedrine hydrochloride with different release profiles were prepared from the immediate-release pellets comprising the above two drugs and prolonged-release pellets containing only pseudoephedrine hydrochloride. The immediate-release pellets containing pseudoephedrine hydrochloride alone or in combination with loratadine were prepared using extrusion-spheronization method. The pellets of pseudoephedrine hydrochloride were coated to prolong the drug release up to 12 h. Both immediate- and prolonged-release pellets were filled into hard gelatin capsule and also compressed into tablets using inert tabletting granules of microcrystalline cellulose Ceolus KG-801. The in vitro drug dissolution study conducted using high-performance liquid chromatography method showed that both multiple-unit capsules and multiple-unit tablets released loratadine completely within a time period of 2 h, whereas the immediate-release portion of pseudoephedrine hydrochloride was liberated completely within the first 10 min of dissolution study. On the other hand, the release of pseudoephedrine hydrochloride from the prolonged release coated pellets was prolonged up to 12 hr and followed zero-order release kinetic. The drug dissolution profiles of multiple-unit tablets and multiple-unit capsules were found to be closely similar, indicating that the integrity of pellets remained unaffected during the compression process. Moreover, the friability, hardness, and disintegration time of multiple-unit tablets were found to be within BP specifications. In conclusion, modified-release pellet-based tablet system for the delivery of loratadine and pseudoephedrine hydrochloride was successfully developed and evaluated.

  18. Efficacy of a Creon delayed-release pancreatic enzyme protocol for clearing occluded enteral feeding tubes.

    PubMed

    Stumpf, Janice L; Kurian, Rebecca M; Vuong, Jennifer; Dang, Kimberlyn; Kraft, Michael D

    2014-04-01

    Alkalinized Viokase pancreatic enzyme tablets restored patency to 71.9% of occluded Dobhoff tubes in a prospective study. After removal of Viokase tablets from the US market, the hospital protocol for unclogging enteral feeding tubes was adapted to use Creon pancreatic enzyme delayed-release capsules, despite the lack of published data. To evaluate the effectiveness of a Creon-based protocol to clear occluded enteral feeding tubes. This retrospective study included all adult and pediatric patients seen in the emergency department or in an inpatient setting who received Creon 12 000 units lipase delayed-release capsule dissolved in a solution of sodium bicarbonate 650 mg and sterile water for clearing occluded enteral feeding tubes between May 1 and November 30, 2010. The Creon protocol was deemed effective if tube clearance was documented in the medical record or if enteral feedings were resumed with no note regarding tube replacement. Alkalinized Creon delayed-release capsules were administered to 83 patients with a total of 118 clogged tubes. Three poorly documented cases and 5 tubes with mechanical clogs were excluded from data analysis. Patency was restored to 53 of 110 (48.2%) occluded tubes. More than 1 treatment course was attempted in 5 cases, with success in 3. An alkalinized Creon pancreatic enzyme protocol was effective in clearing approximately half of the occluded enteral feeding tubes in this retrospective study, an efficacy rate much less than that previously reported in the literature with a Viokase-based protocol.

  19. Composition, Stability, and Bioavailability of Garlic Products Being Used in a Clinical Trial

    PubMed Central

    Lawson, Larry D.; Gardner, Christopher D.

    2008-01-01

    In support of a new clinical trial designed to compare the effects of crushed fresh garlic and two types of garlic supplement tablets (enteric-coated dried fresh garlic and dried aged garlic extract) on serum lipids, the three garlic products have been characterized for (a) composition (14 sulfur and 2 non-sulfur compounds), (b) stability of suspected active compounds, and (c) availability of allyl thiosulfinates (mainly allicin) under both simulated gastrointestinal (tablet dissolution) conditions and in vivo. The allyl thiosulfinates of blended fresh garlic were stable for at least two years when stored at −80 °C. The dissolution release of thiosulfinates from the enteric-coated garlic tablets was found to be >95%. The bioavailability of allyl thiosulfinates from these tablets, measured as breath allyl methyl sulfide, was found to be complete and equivalent to that of crushed fresh garlic. S-allylcysteine was stable for 12 months at ambient temperature. The stability of the suspected active compounds under the conditions of the study and the bioavailability of allyl thiosulfinates from the dried garlic supplement have validated the use of these preparations for comparison in a clinical trial. PMID:16076102

  20. How half-coated janus particles enter cells.

    PubMed

    Gao, Yuan; Yu, Yan

    2013-12-26

    Janus particles possess functional asymmetry and directionality within a single entity and thus are predicted to enable many promising biomedical applications that are not offered by homogeneous particles. However, it remains elusive what role the Janus principle plays in Janus particle-cell interactions, particularly in cellular uptake. We studied how asymmetric distribution of ligands on half-coated Janus microparticles dictates the membrane dynamics during receptor-mediated particle uptake, and found key differences from those characteristic of homogeneous particles. Live-cell fluorescence imaging combined with single-particle level quantification of particle-cell membrane interactions shows that the asymmetric distribution of ligands leads to a three-step endocytic process: membrane cup formation on the ligand-coated hemisphere, stalling at the Janus interface, and rapid membrane protrusion on the ligand-absent hemisphere to complete the particle engulfment. The direct correlation between the spatial presentation of ligands on Janus particles and the temporal changes of membrane dynamics revealed in this work elucidates the potential of using the Janus principle to fine-tune particle-cell interactions.

  1. Tablet splitting and weight uniformity of half-tablets of 4 medications in pharmacy practice.

    PubMed

    Tahaineh, Linda M; Gharaibeh, Shadi F

    2012-08-01

    Tablet splitting is a common practice for multiple reasons including cost savings; however, it does not necessarily result in weight-uniform half-tablets. To determine weight uniformity of half-tablets resulting from splitting 4 products available in the Jordanian market and investigate the effect of tablet characteristics on weight uniformity of half-tablets. Ten random tablets each of warfarin 5 mg, digoxin 0.25 mg, phenobarbital 30 mg, and prednisolone 5 mg were weighed and split by 6 PharmD students using a knife. The resulting half-tablets were weighed and evaluated for weight uniformity. Other relevant physical characteristics of the 4 products were measured. The average tablet hardness of the sampled tablets ranged from 40.3 N to 68.9 N. Digoxin, phenobarbital, and prednisolone half-tablets failed the weight uniformity test; however, warfarin half-tablets passed. Digoxin, warfarin, and phenobarbital tablets had a score line and warfarin tablets had the deepest score line of 0.81 mm. Splitting warfarin tablets produces weight-uniform half-tablets that may possibly be attributed to the hardness and the presence of a deep score line. Digoxin, phenobarbital, and prednisolone tablet splitting produces highly weight variable half-tablets. This can be of clinical significance in the case of the narrow therapeutic index medication digoxin.

  2. Molecular basis of crystal morphology-dependent adhesion behavior of mefenamic acid during tableting.

    PubMed

    Waknis, Vrushali; Chu, Elza; Schlam, Roxana; Sidorenko, Alexander; Badawy, Sherif; Yin, Shawn; Narang, Ajit S

    2014-01-01

    The molecular basis of crystal surface adhesion leading to sticking was investigated by exploring the correlation of crystal adhesion to oxidized iron coated atomic force microscope (AFM) tips and bulk powder sticking behavior during tableting of two morphologically different crystals of a model drug, mefenamic acid (MA), to differences in their surface functional group orientation and energy. MA was recrystallized into two morphologies (plates and needles) of the same crystalline form. Crystal adhesion to oxidized iron coated AFM tips and bulk powder sticking to tablet punches was assessed using a direct compression formulation. Surface functional group orientation and energies on crystal faces were modeled using Accelrys Material Studio software. Needle-shaped morphology showed higher sticking tendency than plates despite similar particle size. This correlated with higher crystal surface adhesion of needle-shaped morphology to oxidized iron coated AFM probe tips, and greater surface energy and exposure of polar functional groups. Higher surface exposure of polar functional groups correlates with higher tendency to stick to metal surfaces and AFM tips, indicating involvement of specific polar interactions in the adhesion behavior. In addition, an AFM method is identified to prospectively assess the risk of sticking during the early stages of drug development.

  3. Amoxicillin/clavulanic acid (875/125): bioequivalence of a novel Solutab tablet and rationale for a twice-daily dosing regimen.

    PubMed

    Sourgens, H; Bertola, M A; Verschoor, J S C; Kuipers, M; Rayer, B

    2004-03-01

    A new amoxicillin/clavulanic acid tablet formulation (Solutab tablet, Forcid Solutab) containing amoxicillin/clavulanic acid (875/125) has been developed. The aim of the present study was to demonstrate bioequivalence between the new tablet formulation (test), taken as an intact tablet and after prior dispersal, versus the originator product viz. Augmentan film-coated tablet (875/125) used as reference. The study was performed in 48 healthy volunteers according to an open, single-dose, crossover design. Bioequivalence was demonstrated using Cmax and AUC(0-infinity) as primary parameters of evaluation for both amoxicillin and clavulanic acid with 90% confidence intervals of the ratios Solutab tablet/Augmentan within the range of 0.8-1.25. The duration of the plasma concentration exceeding the amoxicillin minimal inhibitory concentration (MICs) was calculated using individual plasma concentration-time curves and compartmental analysis. The data showed that the bioavailability characteristics of the test tablet, taken intact or in dispersed form, and the reference tablets were very similar. The analysis, moreover, also confirmed the appropriateness of using a b.i.d. dosage regimen for both formulations, taking into account the pharmacodynamic breakpoint values for some major pathogens.

  4. Effects of coating layer and release medium on release profile from coated capsules with Eudragit FS 30D: an in vitro and in vivo study.

    PubMed

    Moghimipour, Eskandar; Rezaei, Mohsen; Kouchak, Maryam; Fatahiasl, Jafar; Angali, Kambiz Ahmadi; Ramezani, Zahra; Amini, Mohsen; Dorkoosh, Farid Abedin; Handali, Somayeh

    2018-05-01

    The aim of the present research was to evaluate the impact of coating layers on release profile from enteric coated dosage forms. Capsules were coated with Eudragit FS 30D using dipping method. The drug profile was evaluated in both phosphate buffer and Hank's solutions. Utilization X-ray imaging, gastrointestinal transmission of enteric coated capsules was traced in rats. According to the results, no release of the drug was found at pH 1.2, and the extent of release drug in pH 6.8 medium was decreased by adding the coating layers. The results indicated single-layer coated capsules in phosphate buffer were significantly higher than that in Hank's solution. However, no significant difference was observed from capsules with three coating layers in two different dissolution media. X-ray imaging showed that enteric coated capsules were intact in the stomach and in the small intestine, while disintegrated in the colon.

  5. Quantifying Pharmaceutical Film Coating with Optical Coherence Tomography and Terahertz Pulsed Imaging: An Evaluation.

    PubMed

    Lin, Hungyen; Dong, Yue; Shen, Yaochun; Zeitler, J Axel

    2015-10-01

    Spectral domain optical coherence tomography (OCT) has recently attracted a lot of interest in the pharmaceutical industry as a fast and non-destructive modality for quantification of thin film coatings that cannot easily be resolved with other techniques. Because of the relative infancy of this technique, much of the research to date has focused on developing the in-line measurement technique for assessing film coating thickness. To better assess OCT for pharmaceutical coating quantification, this paper evaluates tablets with a range of film coating thickness measured using OCT and terahertz pulsed imaging (TPI) in an off-line setting. In order to facilitate automated coating quantification for film coating thickness in the range of 30-200 μm, an algorithm that uses wavelet denoising and a tailored peak finding method is proposed to analyse each of the acquired A-scan. Results obtained from running the algorithm reveal an increasing disparity between the TPI and OCT measured intra-tablet variability when film coating thickness exceeds 100 μm. The finding further confirms that OCT is a suitable modality for characterising pharmaceutical dosage forms with thin film coatings, whereas TPI is well suited for thick coatings. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association.

  6. [Study on preparation and release mechanism of effervescent osmotic pump tablet of compound Danshen].

    PubMed

    Xue, Li'an; Li, Yuanbo; Guo, Dandan; Yin, Jianhua; Liu, Yanchun; Hou, Shixiang

    2009-04-01

    To prepare effervescent osmotic pump tablet (EOPTs) according to the rhythm of coronary heart disease based on efficacy material and the mechanism of compound Danshen and to study the mechanism of drug released of that tablets. Since compound Danshen consist of compounds with polyphenolic groups or carboxyl groups, such as phenolic acids, flavonoids, and triterpenoids that they were acidic. EOPTs were prepared from tablet cores which containing NaHCO3 as effervescent, NaCL and manitol as osmotic agents, HPMC as retarding agents coating with CA membrane. And study the mechanism of drug released according to the change of tablet osmotic pressure. The results of in vitro experiments showed that no difference was observed among the profiles of Danshensu, protocatechuic aldehyde, ginsenoside Rg1, Rb1, notoginsenoside R1 release EOPTs. The drug was completely released from the device with a zero-order release rate over 12 h. EOPTs are Successfully obtained EOPT which the drug is released from the device over 12 h and the release mechanism of EOPTs is explained.

  7. Performance of tablet disintegrants: impact of storage conditions and relative tablet density.

    PubMed

    Quodbach, Julian; Kleinebudde, Peter

    2015-01-01

    Tablet disintegration can be influenced by several parameters, such as storage conditions, type and amount of disintegrant, and relative tablet density. Even though these parameters have been mentioned in the literature, the understanding of the disintegration process is limited. In this study, water uptake and force development of disintegrating tablets are analyzed, as they reveal underlying processes and interactions. Measurements were performed on dibasic calcium phosphate tablets containing seven different disintegrants stored at different relative humidities (5-97%), and on tablets containing disintegrants with different mechanisms of action (swelling and shape recovery), compressed to different relative densities. Disintegration times of tablets containing sodium starch glycolate are affected most by storage conditions, which is displayed in decreased water uptake and force development kinetics. Disintegration times of tablets with a swelling disintegrant are only marginally affected by relative tablet density, whereas the shape recovery disintegrant requires high relative densities for quick disintegration. The influence of relative tablet density on the kinetics of water uptake and force development greatly depends on the mechanism of action. Acquired data allows a detailed analysis of the influence of storage conditions and mechanisms of action on disintegration behavior.

  8. A Pharmacokinetic Bioequivalence Study Comparing Pirfenidone Tablet and Capsule Dosage Forms in Healthy Adult Volunteers.

    PubMed

    Pan, Lin; Belloni, Paula; Ding, Han Ting; Wang, Jianshuang; Rubino, Christopher M; Putnam, Wendy S

    2017-09-01

    Pirfenidone film-coated tablets were developed to offer an alternative to the marketed capsule formulation. This study assessed the bioequivalence of the tablet and capsule formulations under fed and fasted states. A Phase I, open-label, randomized, four-treatment-period, four-sequence, crossover pharmacokinetics study (NCT02525484) was conducted. Each subject received an 801-mg single dose of pirfenidone as three 267-mg capsules or one 801-mg tablet under fasted and fed conditions. Pirfenidone plasma C max , AUC 0-t and AUC 0-∞ were used to assess bioequivalence. Forty-four subjects were randomized to treatment. The 801-mg tablet in the fasted state met bioequivalence criteria [90% confidence intervals (CI) 80.00-125.00%] for the GLSM ratios of natural log-transformed C max , AUC 0-t and AUC 0-∞ . Under fed conditions, the 801-mg tablet met the bioequivalence criteria for AUC 0-t and AUC 0-∞ , but slightly exceeded the bioequivalence criteria for the C max (90% CI of 108.26-125.60%). The tablet C max was approximately 17% higher than that of the capsules. In the fed state, the tablet C max , and both AUC 0-t and AUC 0-∞ were reduced by 39% and 17%, respectively, relative to the fasted state. The tablet and capsules had acceptable tolerability profiles. The pirfenidone 801-mg tablet met bioequivalence criteria when compared with three 267-mg capsules in the fasted state. The tablet C max was slightly higher relative to capsules in the fed state, but this is not expected to have a clinically meaningful impact on the benefit-risk profile of pirfenidone. This work was supported by F. Hoffmann-La Roche Ltd.

  9. Direct compression of chitosan: process and formulation factors to improve powder flow and tablet performance.

    PubMed

    Buys, Gerhard M; du Plessis, Lissinda H; Marais, Andries F; Kotze, Awie F; Hamman, Josias H

    2013-06-01

    Chitosan is a polymer derived from chitin that is widely available at relatively low cost, but due to compression challenges it has limited application for the production of direct compression tablets. The aim of this study was to use certain process and formulation variables to improve manufacturing of tablets containing chitosan as bulking agent. Chitosan particle size and flow properties were determined, which included bulk density, tapped density, compressibility and moisture uptake. The effect of process variables (i.e. compression force, punch depth, percentage compaction in a novel double fill compression process) and formulation variables (i.e. type of glidant, citric acid, pectin, coating with Eudragit S®) on chitosan tablet performance (i.e. mass variation, tensile strength, dissolution) was investigated. Moisture content of the chitosan powder, particle size and the inclusion of glidants had a pronounced effect on its flow ability. Varying the percentage compaction during the first cycle of a double fill compression process produced chitosan tablets with more acceptable tensile strength and dissolution rate properties. The inclusion of citric acid and pectin into the formulation significantly decreased the dissolution rate of isoniazid from the tablets due to gel formation. Direct compression of chitosan powder into tablets can be significantly improved by the investigated process and formulation variables as well as applying a double fill compression process.

  10. Design and evaluation of hydrophobic coated buoyant core as floating drug delivery system for sustained release of cisapride

    PubMed Central

    Jacob, Shery; Nair, Anroop B; Patil, Pandurang N

    2010-01-01

    An inert hydrophobic buoyant coated–core was developed as floating drug delivery system (FDDS) for sustained release of cisapride using direct compression technology. Core contained low density, porous ethyl cellulose, which was coated with an impermeable, insoluble hydrophobic coating polymer such as rosin. It was further seal coated with low viscosity hydroxypropyl methyl cellulose (HPMC E15) to minimize moisture permeation and better adhesion with an outer drug layer. It was found that stable buoyant core was sufficient to float the tablet more than 8 h without the aid of sodium bicarbonate and citric acid. Sustained release of cisapride was achieved with HPMC K4M in the outer drug layer. The floating lag time required for these novel FDDS was found to be zero, however it is likely that the porosity or density of the core is critical for floatability of these tablets. The in vitro release pattern of these tablets in simulated gastric fluid showed the constant and controlled release for prolonged time. It can be concluded that the hydrophobic coated buoyant core could be used as FDDS for gastroretentive delivery system of cisapride or other suitable drugs. PMID:24825997

  11. Tablet Use within Medicine

    ERIC Educational Resources Information Center

    Hogue, Rebecca J.

    2013-01-01

    This paper discusses the scholarly literature related to tablet computer use in medicine. Forty-four research-based articles were examined for emerging categories and themes. The most studied uses for tablet computers include: patients using tablets to complete diagnostic survey instruments, medical professionals using tablet computers to view…

  12. INFLUENCE OF TABLET SPLITTING ON CONTENT UNIFORMITY OF LISINOPRIL/ HYDROCHLORTHIAZIDE TABLETS

    PubMed Central

    Vranić, Edina; Uzunović, Alija

    2007-01-01

    Dose-related adverse effects of medications are a major problem in modern medical practice. The “correct” dose, based on drug company guidelines in package inserts, may not be correct for many patients. Tablet splitting or dividing has been an accepted practice for many years as a means of obtaining the prescribed dose of medication. As model tablets for this investigation, two batches of lisinopril-hydrochlorothiazide scored tablets labeled to contain 20/12,5 mg were used. The aim of this study was to establish possible influence of tablet splitting on content uniformity of lisinopril/hydrochlorthiazide tablets. Determination of the content uniformity of lisinopril and hydrochlorthiazide in our batches, was carried out by HPLC method. The results of content uniformity studies for halves of tablets containing combination of lisinopril-hydrochlorthiazide (supposed to contain 50% of stated 20/12,5 mg in the whole tablet) were: 49,60 ±3,29% and 49,29±0,60 % (lisinopril); 50,33±3,50% and 50,69±1,95% (hydrochlorthiazide) for batch I and II, respectively. We can conclude that the results obtained in this study support an option of tablet splitting, which is very important for obtaining the required dosage when a dosage form of the required strength is unavailable, and for better individualization of the therapy PMID:18039191

  13. Quantifying Pharmaceutical Film Coating with Optical Coherence Tomography and Terahertz Pulsed Imaging: An Evaluation

    PubMed Central

    Lin, Hungyen; Dong, Yue; Shen, Yaochun; Zeitler, J Axel

    2015-01-01

    Spectral domain optical coherence tomography (OCT) has recently attracted a lot of interest in the pharmaceutical industry as a fast and non-destructive modality for quantification of thin film coatings that cannot easily be resolved with other techniques. Because of the relative infancy of this technique, much of the research to date has focused on developing the in-line measurement technique for assessing film coating thickness. To better assess OCT for pharmaceutical coating quantification, this paper evaluates tablets with a range of film coating thickness measured using OCT and terahertz pulsed imaging (TPI) in an off-line setting. In order to facilitate automated coating quantification for film coating thickness in the range of 30–200 μm, an algorithm that uses wavelet denoising and a tailored peak finding method is proposed to analyse each of the acquired A-scan. Results obtained from running the algorithm reveal an increasing disparity between the TPI and OCT measured intra-tablet variability when film coating thickness exceeds 100 μm. The finding further confirms that OCT is a suitable modality for characterising pharmaceutical dosage forms with thin film coatings, whereas TPI is well suited for thick coatings. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3377–3385, 2015 PMID:26284354

  14. Quantifying Pharmaceutical Film Coating with Optical Coherence Tomography and Terahertz Pulsed Imaging: An Evaluation.

    PubMed

    Lin, Hungyen; Dong, Yue; Shen, Yaochun; Axel Zeitler, J

    2015-10-01

    Spectral domain optical coherence tomography (OCT) has recently attracted a lot of interest in the pharmaceutical industry as a fast and non-destructive modality for quantification of thin film coatings that cannot easily be resolved with other techniques. Because of the relative infancy of this technique, much of the research to date has focused on developing the in-line measurement technique for assessing film coating thickness. To better assess OCT for pharmaceutical coating quantification, this paper evaluates tablets with a range of film coating thickness measured using OCT and terahertz pulsed imaging (TPI) in an off-line setting. In order to facilitate automated coating quantification for film coating thickness in the range of 30-200μm, an algorithm that uses wavelet denoising and a tailored peak finding method is proposed to analyse each of the acquired A-scan. Results obtained from running the algorithm reveal an increasing disparity between the TPI and OCT measured intra-tablet variability when film coating thickness exceeds 100μm. The finding further confirms that OCT is a suitable modality for characterising pharmaceutical dosage forms with thin film coatings, whereas TPI is well suited for thick coatings. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3377-3385, 2015. Copyright © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  15. Enteric Coating and Aspirin Nonresponsiveness in Patients With Type 2 Diabetes Mellitus.

    PubMed

    Bhatt, Deepak L; Grosser, Tilo; Dong, Jing-Fei; Logan, Douglas; Jeske, Walter; Angiolillo, Dominick J; Frelinger, Andrew L; Lei, Lanyu; Liang, Juan; Moore, Jason E; Cryer, Byron; Marathi, Upendra

    2017-02-14

    A limitation of aspirin is that some patients, particularly those with diabetes, may not have an optimal antiplatelet effect. The goal of this study was to determine if oral bioavailability mediates nonresponsiveness. The rate and extent of serum thromboxane generation and aspirin pharmacokinetics were measured in 40 patients with diabetes in a randomized, single-blind, triple-crossover study. Patients were exposed to three 325-mg aspirin formulations: plain aspirin, PL2200 (a modified-release lipid-based aspirin), and a delayed-release enteric-coated (EC) aspirin. Onset of antiplatelet activity was determined by the rate and extent of inhibition of serum thromboxane B 2 (TXB 2 ) generation. Aspirin nonresponsiveness was defined as a level of residual serum TXB 2 associated with elevated thrombotic risk (<99.0% inhibition or TXB 2 >3.1 ng/ml) within 72 h after 3 daily aspirin doses. The rate of aspirin nonresponsiveness was 15.8%, 8.1%, and 52.8% for plain aspirin, PL2200, and EC aspirin, respectively (p < 0.001 for both comparisons vs. EC aspirin; p = 0.30 for comparison between plain aspirin and PL2200). Similarly, 56% of EC aspirin-treated subjects had serum TXB 2 levels >3.1 ng/ml, compared with 18% and 11% of subjects after administration of plain aspirin and PL2200 (p < 0.0001). Compared with findings for plain aspirin and PL2200, this high rate of nonresponsiveness with EC aspirin was associated with lower exposure to acetylsalicylic acid (63% and 70% lower geometric mean maximum plasma concentration [C max ] and 77% and 82% lower AUC 0-t [area under the curve from time 0 to the last time measured]) and 66% and 72% lower maximum decrease of TXB 2 , with marked interindividual variability. A high proportion of patients treated with EC aspirin failed to achieve complete inhibition of TXB 2 generation due to incomplete absorption. Reduced bioavailability may contribute to "aspirin resistance" in patients with diabetes. (Pharmacodynamic Evaluation of PL2200

  16. Dose uniformity of scored and unscored tablets: Application of the FDA Tablet Scoring Guidance for Industry.

    PubMed

    Ciavarella, Anthony; Khan, Mansoor; Gupta, Abhay; Faustino, Patrick

    2016-06-20

    This FDA laboratory study examines the impact of tablet splitting, the effect of tablet splitters, and the presence of a tablet score on the dose uniformity of two model drugs. Whole tablets were purchased from five manufacturers for amlodipine and six for gabapentin. Two splitters were used for each drug product and the gabapentin tablets were also split by hand. Whole and split amlodipine tablets were tested for content uniformity following the general chapter of the United States Pharmacopeia (USP) Uniformity of Dosage Units <905>, which is a requirement of the new FDA Guidance for Industry on tablet scoring. The USP weight variation method was used for gabapentin split tablets based on the recommendation of the guidance. All whole tablets met the USP acceptance criteria for the Uniformity of Dosage Units. Variation in whole tablet content ranged from 0.5-2.1 standard deviation (SD) of the % label claim. Splitting the unscored amlodipine tablets resulted in a significant increase in dose variability of 6.5-25.4 SD when compared to whole tablets. Split tablets from all amlodipine drug products did not meet the USP acceptance criteria for content uniformity. Variation in the weight for gabapentin split tablets was greater than the whole tablets, ranging from 1.3-9.3 SD. All fully scored gabapentin products met the USP acceptance criteria for weight variation. Size, shape, and the presence or absence of a tablet score can affect the content uniformity and weight variation of amlodipine and gabapentin tablets. Tablet splitting produced higher variability. Differences in dose variability and fragmentation were observed between tablet splitters and hand splitting. These results are consistent with the FDA's concerns that tablet splitting "can affect how much drug is present in the split tablet and available for absorption" as stated in the guidance (1). Copyright © 2016, Parenteral Drug Association.

  17. Extemporaneous procedures for dissolving risedronate tablets for oral administration and for feeding tubes.

    PubMed

    Dansereau, Richard J; Crail, Debbie J

    2005-01-01

    Risedronate (Actonel, Procter & Gamble Pharmaceuticals) is commercially available only as film-coated tablets. Extemporaneous procedures for dissolving tablets for feeding tubes and for preparation of an oral liquid have not previously been evaluated. To evaluate procedures for dissolving risedronate sodium tablets for administration in liquid form and drug recovery following dissolution in cups and following passage through different types of feeding tubes. Tablets (5 and 35 mg) were individually dispersed in 2 oz of water. After 2 minutes, the solution was stirred for 30 seconds, dispensed, and rinsed with an additional 4 oz of water. The sample was filtered and analyzed by HPLC. Ten replicates were performed using the various cups. Gastrostomy and nasoenteric tubes were flushed with 1 oz of water. Individual tablets were dispersed in 2 oz of water; after 2 minutes, the solution was stirred for 30 seconds and poured through the tube and flushed with 1 oz of water. Samples were filtered and analyzed by HPLC. Ten replicates were performed for each type of feeding tube. For cups, the mean amount of drug recovered ranged from 95.7% to 100.5% of the label claim, with a relative standard deviation (RSD) range of 1.1-6.3%. For gastrostomy and nasoenteric tubes, the mean amount of drug recovered ranged from 98.3% to 101.9% of label claim, with an RSD range of 0.9-3.3%. A simple and accurate procedure was developed for dissolving risedronate tablets in water to prepare a liquid formulation for administration orally or through feeding tubes.

  18. Calcification prevention tablets

    NASA Technical Reports Server (NTRS)

    Lindsay, Geoffrey A.; Hasting, Michael A.; Gustavson, Michael A.

    1991-01-01

    Citric acid tablets, which slowly release citric acid when flushed with water, are under development by the Navy for calcification prevention. The citric acid dissolves calcium carbonate deposits and chelates the calcium. For use in urinals, a dispenser is not required because the tablets are non-toxic and safe to handle. The tablets are placed in the bottom of the urinal, and are consumed in several hundred flushes (the release rate can be tailored by adjusting the formulation). All of the ingredients are environmentally biodegradable. Mass production of the tablets on commercial tableting machines was demonstrated. The tablets are inexpensive (about 75 cents apiece). Incidences of clogged pipes and urinals were greatly decreased in long term shipboard tests. The corrosion rate of sewage collection pipe (90/10 Cu/Ni) in citric acid solution in the laboratory is several mils per year at conditions typically found in traps under the urinals. The only shipboard corrosion seen to date is of the yellow brass urinal tail pieces. While this is acceptable, the search for a nontoxic corrosion inhibitor is underway. The shelf life of the tablets is at least one year if stored at 50 percent relative humidity, and longer if stored in sealed plastic buckets.

  19. A new tablet brittleness index.

    PubMed

    Gong, Xingchu; Sun, Changquan Calvin

    2015-06-01

    Brittleness is one of the important material properties that influences the success or failure of powder compaction. We have discovered that the reciprocal of diametrical elastic strain at fracture is the most suitable tablet brittleness indices (TBIs) for quantifying brittleness of pharmaceutical tablets. The new strain based TBI is supported by both theoretical considerations and a systematic statistical analysis of friability data. It is sufficiently sensitive to changes in both tablet compositions and compaction parameters. For all tested materials, it correctly shows that tablet brittleness increases with increasing tablet porosity for the same powder. In addition, TBI increases with increasing content of a brittle excipient, lactose monohydrate, in the mixtures with a plastic excipient, microcrystalline cellulose. A probability map for achieving less than 1% tablet friability at various combinations of tablet tensile strength and TBI was constructed. Data from marketed tablets validate this probability map and a TBI value of 150 is recommended as the upper limit for pharmaceutical tablets. This TBI can be calculated from the data routinely obtained during tablet diametrical breaking test, which is commonly performed for assessing tablet mechanical strength. Therefore, it is ready for adoption for quantifying tablet brittleness to guide tablet formulation development since it does not require additional experimental work. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Dose Uniformity of Scored and Unscored Tablets: Application of the FDA Tablet Scoring Guidance for Industry.

    PubMed

    Ciavarella, Anthony B; Khan, Mansoor A; Gupta, Abhay; Faustino, Patrick J

    This U.S. Food and Drug Administration (FDA) laboratory study examines the impact of tablet splitting, the effect of tablet splitters, and the presence of a tablet score on the dose uniformity of two model drugs. Whole tablets were purchased from five manufacturers for amlodipine and six for gabapentin. Two splitters were used for each drug product, and the gabapentin tablets were also split by hand. Whole and split amlodipine tablets were tested for content uniformity following the general chapter of the United States Pharmacopeia (USP) Uniformity of Dosage Units <905>, which is a requirement of the new FDA Guidance for Industry on tablet scoring. The USP weight variation method was used for gabapentin split tablets based on the recommendation of the guidance. All whole tablets met the USP acceptance criteria for the Uniformity of Dosage Units. Variation in whole tablet content ranged from 0.5 to 2.1 standard deviation (SD) of the percent label claim. Splitting the unscored amlodipine tablets resulted in a significant increase in dose variability of 6.5-25.4 SD when compared to whole tablets. Split tablets from all amlodipine drug products did not meet the USP acceptance criteria for content uniformity. Variation in the weight for gabapentin split tablets was greater than the whole tablets, ranging from 1.3 to 9.3 SD. All fully scored gabapentin products met the USP acceptance criteria for weight variation. Size, shape, and the presence or absence of a tablet score can affect the content uniformity and weight variation of amlodipine and gabapentin tablets. Tablet splitting produced higher variability. Differences in dose variability and fragmentation were observed between tablet splitters and hand splitting. These results are consistent with the FDA's concerns that tablet splitting can have an effect on the amount of drug present in a split tablet and available for absorption. Tablet splitting has become a very common practice in the United States and throughout

  1. Evaluation of the viability of Lactobacillus spp. after the production of different solid dosage forms.

    PubMed

    Brachkova, Mariya I; Duarte, Aida; Pinto, João F

    2009-09-01

    The work aims to provide evidence on the viability of Lactobacillus spp. and a spore form of Bacillus subtilis from nonprocessed bacteria to coated dosage forms (i.e., mini-tablets, pellets, and their coated forms). Lactobacillus spp. were cultivated overnight in MRS broth (10(9) cfu/mL) and B. subtilis spores were produced on plate count agar (10(7) cfu/mL) for 2 weeks. Bacteria and spores were freeze-dried in skim milk enriched with glycerol. The cakes were further processed into tablets (2.5 mm diameter) by direct compression with or without microcrystalline cellulose and inulin. Pellets (1-1.4 mm diameter) were produced by extrusion-spheronization of bacterial and spore suspensions with microcrystalline cellulose, lactose, inulin, and skim milk. Both tablets and pellets were film coated. The properties of the dosage forms, particularly the bacterial viability, were evaluated immediately after production and throughout storage for 6 months at 4 degrees C. The study has shown that for an adequate stabilization of the bacteria a protective matrix (e.g., skim milk) and cryoprotectors (e.g., glycerol) must be present at early stages of bacterial de-hydration. Tabletting had a less deleterious effect (<2 log units) on bacteria when compared to pelletization (in some cases 3 log units). Enteric coating (15%, w/w) of either tablets or pellets did not affect the viability of the bacteria.

  2. Study of drug release and tablet characteristics of silicone adhesive matrix tablets.

    PubMed

    Tolia, Gaurav; Li, S Kevin

    2012-11-01

    Matrix tablets of a model drug acetaminophen (APAP) were prepared using a highly compressible low glass transition temperature (T(g)) polymer silicone pressure sensitive adhesive (PSA) at various binary mixtures of silicone PSA/APAP ratios. Matrix tablets of a rigid high T(g) matrix forming polymer ethyl cellulose (EC) were the reference for comparison. Drug release study was carried out using USP Apparatus 1 (basket), and the relationship between the release kinetic parameters of APAP and polymer/APAP ratio was determined to estimate the excipient percolation threshold. The critical points attributed to both silicone PSA and EC tablet percolation thresholds were found to be between 2.5% and 5% w/w. For silicone PSA tablets, satisfactory mechanical properties were obtained above the polymer percolation threshold; no cracking or chipping of the tablet was observed above this threshold. Rigid EC APAP tablets showed low tensile strength and high friability. These results suggest that silicone PSA could eliminate issues related to drug compressibility in the formulation of directly compressed oral controlled release tablets of poorly compressible drug powder such as APAP. No routinely used excipients such as binders, granulating agents, glidants, or lubricants were required for making an acceptable tablet matrix of APAP using silicone PSA. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. NMR imaging of high-amylose starch tablets. 2. Effect of tablet size.

    PubMed

    Malveau, Cédric; Baille, Wilms E; Zhu, Xiao Xia; Marchessault, Robert H

    2002-01-01

    Carbohydrate polymers are widely used for pharmaceutical applications such as the controlled release of drugs. The swelling and water mobility in high-amylose starch tablets are important parameters to be determined for these applications. They have been studied at different time intervals by nuclear magnetic resonance imaging (NMRI) after the immersion of the samples in water. These tablets have a hydrophilic matrix, which swells anisotropically and forms a hydrogel in water. NMRI shows clearly the anisotropy of the water penetration and the swelling along the radial and axial dimensions of the tablets. Empirical relationships are established to describe the kinetics of water penetration and swelling of the tablets. Results show that water uptake and tablet swelling strongly depend on the size of the tablets. Gravimetric measurements of water uptake were also performed in comparison with the NMRI results.

  4. Effect of Green Tea-Added Tablets on Volatile Sulfur-Containing Compounds in the Oral Cavity.

    PubMed

    Porciani, Pier Francesco; Grandini, Simone

    2016-12-01

    A controlled, clinical, double-blind, cross-over study was conducted to assess the efficacy of sugar-free tablets containing green tea extract on oral volatile sulfur-containing compounds (VSC) versus placebo tablets for 30 minutes. To join the study, subjects had to have at least 24 teeth, no report of oral and systemic diseases, and no removable dentures. All eligible participants had to avoid professional oral hygiene and drugs for two weeks, to not be menstruating, to avoid brushing their teeth and tongue, to not smoke, to not consume alcohol, coffee or tea, nor onion, garlic, or licorice for six hours before the test. Moreover, they had to score a level of VSC ≥ 75 ppb at the basal measurement. Subjects were entered into their respective groups after a minimum 48-hour wash-out period. The test tablet (0.7 g) contained 0.05% green tea extract (equivalent of 1 mg polyphenols for three tablets); the control tablet was identical but without the active agent. The OralChroma2™ device was utilized to evaluate VSC in the oral air. The levels were recorded at baseline, after sucking three tablets in succession, and after 30 minutes. Data were analyzed with SPSS software and significance was set at α = 0.05. 54 subjects completed the trial (23 men, 31 women). None reported problems linked to green tea. The mean reductions in VSC level from baseline at the end of tablet sucking were 34% (p < 0.001) in the control and 55% (p < 0.001) in the test group; after 30 minutes, reductions were 7% in the control (p = NS) and 26% (p < 0.005) in the test group. The comparisons between the two groups after baseline adjustment showed a statistically significant difference in reductions both at the end of the sucking period (p < 0.01) and after 30 minutes (p < 0.01). Tablets containing green tea extract can statistically significantly reduce the oral VSC levels immediately, and after 30 minutes. Moreover, the test tablets reduced oral VSC significantly more than the control

  5. Development of orally disintegrating tablets comprising controlled-release multiparticulate beads

    PubMed Central

    2012-01-01

    Melperone is an atypical antipsychotic agent that has shown a wide spectrum of neuroleptic properties, particularly effective in the treatment of senile dementia and Parkinson’s-associated psychosis, and is marketed in Europe as an immediate-release (IR) tablet and syrup. An orally disintegrating tablet (ODT) dosage form would be advantageous for patients who experience difficulty in swallowing large tablets or capsules or those who experience dysphagia. Controlled-release (CR) capsule and ODT formulations containing melperone HCl were developed with target in vitro release profiles suitable for a once-daily dosing regimen. Both dosage forms allow for the convenient production of dose-proportional multiple strengths. Two ODT formulations exhibiting fast and medium release profiles and one medium release profile capsule formulation (each 50 mg) were tested in vivo using IR syrup as the reference. The two medium release formulations were shown to be bioequivalent to each other and are suitable for once-daily dosing. Based on the analytical and organoleptic test results, as well as the blend uniformity and in-process compression data at various compression forces using coated beads produced at one-tenth (1/10) commercial scale, both formulations in the form of CR capsules and CR ODTs have shown suitability for progression into further clinical development. PMID:22356215

  6. A squeeze-type osmotic tablet for controlled delivery of nifedipine.

    PubMed

    Park, Jung Soo; Shin, Jun Hyun; Lee, Dong Hun; Kim, Moon Suk; Rhee, John M; Lee, Hai Bang; Khang, Gilson

    2008-01-01

    Osmotic delivery systems are based on osmotic driving force. Nifedipine tablets, available under the trade names Procardia XL (Pfizer) and Adalat (Bayer), are commercialized drug-delivery systems of an elemental osmotic pump that the push-pull osmotic tablet operates successfully in delivering water-insoluble drugs. For the improvement of the release pattern and the solubility of the drug, we developed a squeeze-type osmotic tablet (SQT) for nifedipine as a model drug. The SQT was composed of one or more ring type of squeeze-push layer (squeeze-disc) and a centered drug core. Squeeze-discs were stacked up with different physicochemical properties with gradient such as viscosity, swelling ratio and water absorption ratio using the osmotic agents from a disc of bottom to top. The present work investigated the effect of different preparation factors, such as hydrophilic polymers, the molecular weight of polymers, coating process, orifice size and types of excipient on release performance of nifedipine. With the purpose of delivering water-insoluble nifedipine at an approximate zero-order rate and step-function rate for 24 h, SQT has been successfully prepared, and significantly improved in the release rate and patterns in comparison with the Adalat push-pull system in vitro release features.

  7. Impact of anti-tacking agents on properties of gas-entrapped membrane and effervescent floating tablets.

    PubMed

    Kriangkrai, Worawut; Puttipipatkhachorn, Satit; Sriamornsak, Pornsak; Pongjanyakul, Thaned; Sungthongjeen, Srisagul

    2014-12-01

    Tackiness caused by the gas-entrapped membrane (Eudragit(®)RL 30D) was usually observed during storage of the effervescent floating tablets, leading to failure in floatation and sustained release. In this work, common anti-tacking agents (glyceryl monostearate (GMS) and talc) were used to solve this tackiness problem. The impact of anti-tacking agent on the properties of free films and corresponding floating tablets was investigated. GMS was more effective than talc in reducing tackiness of the film. Addition and increasing amount of anti-tacking agents lowered the film mechanical strength, but the coating films were still strong and flexible enough to resist the generated gas pressure inside the floating tablet. Wettability and water vapor permeability of the film decreased with increasing level of anti-tacking agents as a result of their hydrophobicity. No interaction between anti-tacking agents and polymer was observed as confirmed by Fourier transform infrared spectroscopy, powder X-ray diffractometry, and differential scanning calorimetry studies. Increasing amount of anti-tacking agents decreased time to float and tended to retard drug release of the floating tablets. Floating properties and drug release were also influenced by type of anti-tacking agents. The obtained floating tablets still possessed good floating properties and controlled drug release even though anti-tacking agent had some effects. The results demonstrated that the tackiness problem of the floating tablets could be solved by incorporating anti-tacking agent into the gas-entrapped membrane.

  8. The Barrier Properties of PET Coated DLC Film Deposited by Microwave Surface-Wave PECVD

    NASA Astrophysics Data System (ADS)

    Yin, Lianhua; Chen, Qiang

    2017-12-01

    In this paper we report the investigation of diamond-like carbon (DLC) deposited by microwave surface-wave plasma enhanced chemical vapor deposition (PECVD) on the polyethylene terephthalate (PET) web for the purpose of the barrier property improvement. In order to characterize the properties of DLC coatings, we used several substrates, silicon wafer, glass, and PET web and KBr tablet. The deposition rate was obtained by surface profiler based on the DLC deposited on glass substrates; Fourier transform infrared spectroscope (FTIR) was carried out on KBr tablets to investigate chemical composition and bonding structure; the morphology of the DLC coating was analyzed by atomic force microscope (AFM) on Si substrates. For the barrier properties of PET webs, we measured the oxygen transmission rate (OTR) and water vapor transmission rate (WVTR) after coated with DLC films. We addressed the film barrier property related to process parameters, such as microwave power and pulse parameter in this work. The results show that the DLC coatings can greatly improve the barrier properties of PET webs.

  9. Phase transformation in thiamine hydrochloride tablets: Influence on tablet microstructure, physical properties, and performance.

    PubMed

    Chakravarty, Paroma; Suryanarayanan, Raj; Govindarajan, Ramprakash

    2012-04-01

    The objective of this article was to monitor phase transformation in thiamine hydrochloride, from a nonstoichiometric hydrate (NSH) to a hemihydrate (HH), in stored tablets, prepared both by direct compression and wet granulation, and to relate the storage-induced phase transformation with changes in tablet microstructure, physical properties, and performance. Raman spectroscopy revealed complete NSH → HH transformation in tablets, within 30 h of storage at 40°C/75% relative humidity. When the tablets were prepared by wet granulation of NSH alone, there was a marked increase in both tablet volume and hardness on storage. However, when microcrystalline cellulose (MCC) was included in granulation, the resulting stored tablets also exhibited a pronounced increase in disintegration time. In contrast, tablets prepared by dry processing via compression of a NSH-MCC physical mixture did not exhibit any changes in properties, despite the in situ solid form conversion. Scanning electron microscopy revealed growth of needle-like HH crystals in all stored tablets and mercury porosimetry revealed considerable changes in the pore size distribution during storage. Longer storage led to crystal growth (Ostwald ripening), causing further gradual but less dramatic changes in properties. The phase transformation and the complex interparticulate associations in the tablet influenced the changes in tablet microstructure, compact physical properties, and product behavior. Copyright © 2011 Wiley Periodicals, Inc.

  10. Direct Comparison of a Tablet Computer and a Personal Digital Assistant for Point-of-Care Documentation in Eye Care

    PubMed Central

    Silvey, Garry M.; Macri, Jennifer M.; Lee, Paul P.; Lobach, David F.

    2005-01-01

    New mobile computing devices including personal digital assistants (PDAs) and tablet computers have emerged to facilitate data collection at the point of care. Unfortunately, little research has been reported regarding which device is optimal for a given care setting. In this study we created and compared functionally identical applications on a Palm operating system-based PDA and a Windows-based tablet computer for point-of-care documentation of clinical observations by eye care professionals when caring for patients with diabetes. Eye-care professionals compared the devices through focus group sessions and through validated usability surveys. We found that the application on the tablet computer was preferred over the PDA for documenting the complex data related to eye care. Our findings suggest that the selection of a mobile computing platform depends on the amount and complexity of the data to be entered; the tablet computer functions better for high volume, complex data entry, and the PDA, for low volume, simple data entry. PMID:16779128

  11. Enteric coating of soft gelatin capsules by spouted bed: effect of operating conditions on coating efficiency and on product quality.

    PubMed

    Pissinati, Rafael; Oliveira, Wanderley Pereira

    2003-05-01

    The present study was conducted in order to analyze the viability of the spouted bed process for application of a gastric-resistant coating to soft gelatin capsules. The variables investigated were: included angle of conical base, (gamma), the relation between the feed mass flow rate of the coating suspension and the feed mass flow rate of spouting gas (W(s)/W(g)); the ratio between the flow rate of the spouting gas and the flow rate at minimum spouting condition (Q/Q(ms)); the mass of capsules in the bed (M(0)), and the capsule's size. The product quality was measured by disintegration tests, traction x deformation tests, image analysis and by the evaluation of the coating mass distribution and shape factor variation during the coating operation. The experiments were performed in a spouted bed with a column diameter of 200 mm and included a conical base angle of 40 degrees. The best coating efficiency values were obtained for M(0)=300 g. Coating efficiency tended to increase with increasing W(s)/W(g) ratio. Disintegration tests showed that the gastric-resistant effect was obtained with a coating mass of 3.86 mg/cm(2). The shape factor increase during the coating operation. The capsule's coating mass distribution tended to maintain the original distribution.

  12. Pharmaceutical counselling about different types of tablet-splitting methods based on the results of weighing tests and mechanical development of splitting devices.

    PubMed

    Somogyi, O; Meskó, A; Csorba, L; Szabó, P; Zelkó, R

    2017-08-30

    The division of tablets and adequate methods of splitting them are a complex problem in all sectors of health care. Although tablet-splitting is often required, this procedure can be difficult for patients. Four tablets were investigated with different external features (shape, score-line, film-coat and size). The influencing effect of these features and the splitting methods was investigated according to the precision and "weight loss" of splitting techniques. All four types of tablets were halved by four methods: by hand, with a kitchen knife, with an original manufactured splitting device and with a modified tablet splitter based on a self-developed mechanical model. The mechanical parameters (harness and friability) of the products were measured during the study. The "weight loss" and precision of splitting methods were determined and compared by statistical analysis. On the basis of the results, the external features (geometry), the mechanical parameters of tablets and the mechanical structure of splitting devices can influence the "weight loss" and precision of tablet-splitting. Accordingly, a new decision-making scheme was developed for the selection of splitting methods. In addition, the skills of patients and the specialties of therapy should be considered so that pharmaceutical counselling can be more effective regarding tablet-splitting. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Esophageal transit and in vivo disintegration of branded risedronate sodium tablets and two generic formulations of alendronic acid tablets: a single-center, single-blind, six-period crossover study in healthy female subjects.

    PubMed

    Perkins, Alan C; Blackshaw, P Elaine; Hay, Peter D; Lawes, Simon C; Atherton, Clare T; Dansereau, Richard J; Wagner, Leigh K; Schnell, Dan J; Spiller, Robin C

    2008-05-01

    Delayed esophageal transit or disintegration of oral bisphosphonate tablets before they enter the stomach may be of concern with respect to iatrogenic complications among patients receiving longterm treatment. Different formulations of generic bisphosphonate tablets meeting regulatory requirements may have substantial differences in pharmaceutical attributes from the branded product that may result in different characteristics during esophageal transit. The primary objective of this study was to evaluate and compare esophageal transit times and in vivo disintegration of 3 bisphosphonate formulations, one branded and the others generic, that are commercially available in Canada and the United Kingdom. This was a single-center, randomized, singleblind, 6-period crossover study in healthy postmenopausal women aged >50 years. Each subject received a single oral dose of a branded risedronate sodium 35-mg tablet and 2 generic formulations of alendronic acid 70-mg tablets (Novopharm Limited, Toronto, Canada, and Teva UK Limited, Morley, United Kingdom) in both the erect and semisupine (45 degrees ) positions. Although the products are labeled to be taken in the erect position, the semisupine position was included to simulate dosing in bedridden patients. Subjects took tablets with 30 mL of water in the morning after an overnight fast. The tablets were radiolabeled with technetium-99m ion-exchange resins to enable visualization and measurement of esophageal transit time and disintegration using a gamma camera. Dynamic scintigraphic images were obtained for a total of 10 minutes: 2 images per second for the first 30 seconds and 1 image every 15 seconds for 9.5 minutes. This was a mechanistic study and tolerability was not assessed. The study was conducted in 20 healthy white female subjects with a mean age of 62 years (range, 51-77 years). The effect of body position was statistically significant (P = 0.043), with the estimated hazard ratio (HR) of 0.74 indicating longer

  14. Controlled release of acidic drugs in compendial and physiological hydrogen carbonate buffer from polymer blend-coated oral solid dosage forms.

    PubMed

    Wulff, R; Rappen, G-M; Koziolek, M; Garbacz, G; Leopold, C S

    2015-09-18

    The objective of this study was to investigate the suitability of "Eudragit® RL/Eudragit® L55" (RL/L55) blend coatings for a pH-independent release of acidic drugs. A coating for ketoprofen and naproxen mini tablets was developed showing constant drug release rate under pharmacopeial two-stage test conditions for at least 300 min. To simulate drug release from the mini tablets coated with RL/L55 blends in the gastrointestinal (GI) tract, drug release profiles in Hanks buffer pH 6.8 were recorded and compared with drug release profiles in compendial media. RL/L55 blend coatings showed increased drug permeability in Hanks buffer pH 6.8 compared to phosphate buffer pH 6.8 due to its higher ion concentration. However, drug release rates of acidic drugs were lower in Hanks buffer pH 6.8 because of the lower buffer capacity resulting in reduced drug solubility. Further dissolution tests were performed in Hanks buffer using pH sequences simulating the physiological pH conditions in the GI tract. Drug release from mini tablets coated with an RL/L55 blend (8:1) was insensitive to pH changes of the medium within the pH range of 5.8-7.5. It was concluded that coatings of RL/L55 blends show a high potential for application in coated oral drug delivery systems with a special focus on pH-independent release of acidic drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Enteric Micromotor Can Selectively Position and Spontaneously Propel in the Gastrointestinal Tract.

    PubMed

    Li, Jinxing; Thamphiwatana, Soracha; Liu, Wenjuan; Esteban-Fernández de Ávila, Berta; Angsantikul, Pavimol; Sandraz, Elodie; Wang, Jianxing; Xu, Tailin; Soto, Fernando; Ramez, Valentin; Wang, Xiaolei; Gao, Weiwei; Zhang, Liangfang; Wang, Joseph

    2016-09-22

    The gastrointestinal (GI) tract, which hosts hundreds of bacteria species, becomes the most exciting organ for the emerging microbiome research. Some of these GI microbes are hostile and cause a variety of diseases. These bacteria colonize in different segments of the GI tract dependent on the local physicochemical and biological factors. Therefore, selectively locating therapeutic or imaging agents to specific GI segments is of significant importance for studying gut microbiome and treating various GI-related diseases. Herein, we demonstrate an enteric micromotor system capable of precise positioning and controllable retention in desired segments of the GI tract. These motors, consisting of magnesium-based tubular micromotors coated with an enteric polymer layer, act as a robust nanobiotechnology tool for site-specific GI delivery. The micromotors can deliver payload to a particular location via dissolution of their enteric coating to activate their propulsion at the target site toward localized tissue penetration and retention.

  16. PAT-tools for process control in pharmaceutical film coating applications.

    PubMed

    Knop, Klaus; Kleinebudde, Peter

    2013-12-05

    Recent development of analytical techniques to monitor the coating process of pharmaceutical solid dosage forms such as pellets and tablets are described. The progress from off- or at-line measurements to on- or in-line applications is shown for the spectroscopic methods near infrared (NIR) and Raman spectroscopy as well as for terahertz pulsed imaging (TPI) and image analysis. The common goal of all these methods is to control or at least to monitor the coating process and/or to estimate the coating end point through timely measurements. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Defined drug release from 3D-printed composite tablets consisting of drug-loaded polyvinylalcohol and a water-soluble or water-insoluble polymer filler.

    PubMed

    Tagami, Tatsuaki; Nagata, Noriko; Hayashi, Naomi; Ogawa, Emi; Fukushige, Kaori; Sakai, Norihito; Ozeki, Tetsuya

    2018-05-30

    3D-printed tablets are a promising new approach for personalized medicine. In this study, we fabricated composite tablets consisting of two components, a drug and a filler, by using a fused deposition modeling-type 3D printer. Polyvinylalcohol (PVA) polymer containing calcein (a model drug) was used as the drug component and PVA or polylactic acid (PLA) polymer without drug was used as the water-soluble or water-insoluble filler, respectively. Various kinds of drug-PVA/PVA and drug-PVA/PLA composite tablets were designed, and the 3D-printed tablets exhibited good formability. The surface area of the exposed drug component is highly correlated with the initial drug release rate. Composite tablets with an exposed top and a bottom covered with a PLA layer were fabricated. These tablets showed zero-order drug release by maintaining the surface area of the exposed drug component during drug dissolution. In contrast, the drug release profile varied for tablets whose exposed surface area changed. Composite tablets with different drug release lag times were prepared by changing the thickness of the PVA filler coating the drug component. These results which used PVA and PLA filler will provide useful information for preparing the tablets with multi-components and tailor-made tablets with defined drug release profiles using 3D printers. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Six Sigma: Process of Understanding the Control and Capability of Ranitidine Hydrochloride Tablet

    PubMed Central

    Chabukswar, AR; Jagdale, SC; Kuchekar, BS; Joshi, VD; Deshmukh, GR; Kothawade, HS; Kuckekar, AB; Lokhande, PD

    2011-01-01

    The process of understanding the control and capability (PUCC) is an iterative closed loop process for continuous improvement. It covers the DMAIC toolkit in its three phases. PUCC is an iterative approach that rotates between the three pillars of the process of understanding, process control, and process capability, with each iteration resulting in a more capable and robust process. It is rightly said that being at the top is a marathon and not a sprint. The objective of the six sigma study of Ranitidine hydrochloride tablets is to achieve perfection in tablet manufacturing by reviewing the present robust manufacturing process, to find out ways to improve and modify the process, which will yield tablets that are defect-free and will give more customer satisfaction. The application of six sigma led to an improved process capability, due to the improved sigma level of the process from 1.5 to 4, a higher yield, due to reduced variation and reduction of thick tablets, reduction in packing line stoppages, reduction in re-work by 50%, a more standardized process, with smooth flow and change in coating suspension reconstitution level (8%w/w), a huge cost reduction of approximately Rs.90 to 95 lakhs per annum, an improved overall efficiency by 30% approximately, and improved overall quality of the product. PMID:21607050

  19. Six sigma: process of understanding the control and capability of ranitidine hydrochloride tablet.

    PubMed

    Chabukswar, Ar; Jagdale, Sc; Kuchekar, Bs; Joshi, Vd; Deshmukh, Gr; Kothawade, Hs; Kuckekar, Ab; Lokhande, Pd

    2011-01-01

    The process of understanding the control and capability (PUCC) is an iterative closed loop process for continuous improvement. It covers the DMAIC toolkit in its three phases. PUCC is an iterative approach that rotates between the three pillars of the process of understanding, process control, and process capability, with each iteration resulting in a more capable and robust process. It is rightly said that being at the top is a marathon and not a sprint. The objective of the six sigma study of Ranitidine hydrochloride tablets is to achieve perfection in tablet manufacturing by reviewing the present robust manufacturing process, to find out ways to improve and modify the process, which will yield tablets that are defect-free and will give more customer satisfaction. The application of six sigma led to an improved process capability, due to the improved sigma level of the process from 1.5 to 4, a higher yield, due to reduced variation and reduction of thick tablets, reduction in packing line stoppages, reduction in re-work by 50%, a more standardized process, with smooth flow and change in coating suspension reconstitution level (8%w/w), a huge cost reduction of approximately Rs.90 to 95 lakhs per annum, an improved overall efficiency by 30% approximately, and improved overall quality of the product.

  20. Risk of upper gastrointestinal bleeding and perforation associated with low-dose aspirin as plain and enteric-coated formulations

    PubMed Central

    de Abajo, Francisco J; García Rodríguez, Luis A

    2001-01-01

    Background The use of low-dose aspirin has been reported to be associated with an increased risk of upper gastrointestinal complications (UGIC). The coating of aspirin has been proposed as an approach to reduce such a risk. To test this hypothesis, we carried out a population based case-control study. Methods We identified incident cases of UGIC (bleeding or perforation) aged 40 to 79 years between April 1993 to October 1998 registered in the General Practice Research Database. Controls were selected randomly from the source population. Adjusted estimates of relative risk (RR) associated with current use of aspirin as compared to non use were computed using unconditional logistic regression. Results We identified 2,105 cases of UGIC and selected 11,500 controls. Among them, 287 (13.6%) cases and 837 (7.3%) controls were exposed to aspirin, resulting in an adjusted RR of 2.0 (1.7-2.3). No clear dose-effect was found within the range of 75-300 mg. The RR associated with enteric-coated formulations (2.3, 1.6-3.2) was similar to the one of plain aspirin (1.9, 1.6-2.3), and no difference was observed depending on the site. The first two months of treatment was the period of greater risk (RR= 4.5, 2.9-7.1). The concomitant use of aspirin with high-dose NSAIDs greatly increased the risk of UGIC (13.3, 8.5-20.9) while no interaction was apparent with low-medium doses (2.2, 1.0-4.6). Conclusions Low-dose aspirin increases by twofold the risk of UGIC in the general population and its coating does not modify the effect. Concomitant use of low-dose aspirin and NSAIDs at high doses put patients at a specially high risk of UGIC. PMID:11228592

  1. Food-dependent disintegration of immediate release fosamprenavir tablets: in vitro evaluation using magnetic resonance imaging and a dynamic gastrointestinal system.

    PubMed

    Brouwers, Joachim; Anneveld, Bart; Goudappel, Gert-Jan; Duchateau, Guus; Annaert, Pieter; Augustijns, Patrick; Zeijdner, Evelijn

    2011-02-01

    In the present study, we demonstrated the value of two advanced tools, the TNO gastric and small Intestinal Model (TIM-1) and magnetic resonance imaging (MRI), for the in vitro evaluation of food-dependent disintegration of immediate release fosamprenavir tablets. Upon introduction of a tablet with the nutritional drink Scandishake Mix® in the stomach compartment of TIM-1, simulating the fed state, disintegration and fosamprenavir dissolution were significantly postponed compared to the fasted state (lag time 80 ± 23 min). This resulted in a lag in the appearance of bioaccessible fosamprenavir (<5% during the first 2h), even though the nutritional state did not significantly alter the cumulative bioaccessibility after 5h. These results were in agreement with the previously observed postprandial delay in gastric fosamprenavir tablet disintegration and subsequent amprenavir absorption in healthy volunteers. Therefore, TIM-1 can be used in tablet development to identify food-induced disintegration issues causing unexpected clinical behavior. From a mechanistic perspective, we applied MRI to illustrate impaired water ingress in fosamprenavir tablets immersed in the nutritional drink compared to simulated gastric fluid. This effect may be attributed to both competition between nutritional components and the tablet for the available water (indicated by reduced rotational and translational diffusion) as well as the possible formation of a food-dependent precipitation layer on the HPMC-coated tablet. Copyright © 2010 Elsevier B.V. All rights reserved.

  2. Evaluation of the ease of taking mini-tablets compared with other tablet formulations in healthy volunteers.

    PubMed

    Hayakawa, Yoshiyuki; Uchida, Shinya; Namiki, Noriyuki

    2016-03-10

    "Mini-tablets" (MTs) are tablets of diameter≤3mm and have been widely studied and developed. However, reports comparing MTs with other tablet formulations are few. We wished to evaluate the ease of taking a MT quantitatively in comparison with an orally disintegrating mini-tablet (ODMT), conventional tablet (CT) and conventional orally disintegrating tablet (ODT). Four types of tablets were prepared. We prepared tablets of two diameters (3mm for MTs and ODMTs vs. 8mm for CTs and ODTs) and two formulations (MTs and CTs vs. ODMTs and ODTs). Our randomized crossover trial in 18 healthy volunteers (8 men and 10 women; mean age, 22.5years) indicated that the visual analog scale (VAS) score for the ease and amount of water required for intake of MTs was significantly lower than those of CTs. An ODMT required the least amount of water and smallest VAS score for the ease of taking a tablet. Our results showed that the advantage of MTs with regard to the ease of taking and decreased amount of water required was exerted for a unit of dosing comprising <5 tablets. These data suggested the usefulness of MTs and the importance of the number of MTs for comfortable consumption by patients. Copyright © 2015. Published by Elsevier B.V.

  3. Development and evaluation of orally disintegrating tablets comprising taste-masked mirtazapine granules.

    PubMed

    Yıldız, Simay; Aytekin, Eren; Yavuz, Burçin; Bozdağ Pehlivan, Sibel; Vural, İmran; Ünlü, Nurşen

    2018-06-01

    Orally disintegrating tablets (ODTs) provide an important treatment option for pediatric, geriatric and psychiatric patients. In our previous study, we have performed the initial studies for the formulation development and characterization of new ODT formulations containing a bitter taste drug, mirtazapine, coated with 6% (w/w) Eudragit ® E-100 (first group of formulations, FGF) without taste evaluation. In present study, coating ratio of the drug was increased to 8% (w/w) (second group of formulations, SGF) to examine the effect of increased coating ratio of drug on in vitro characterization of the formulations including in vitro taste masking study. Coacervation technique using Eudragit ® E-100 was employed to obtain taste-masked mirtazapine granules. FGF and SGF were compared to original product (Remeron SolTab, an antidepressant drug which produced by pellet technology) in terms of in vitro permeability, in vitro taste masking efficiency which was performed by dissolution studies in salivary medium and dissolution stability. Also, the other tablet characteristics (such as diameter, thickness) of SGF were examined. The disintegration time of the SGF were found as A1 < A2 < A3 < A5 < A4 (8% Eudragit ® E-100), but all of the formulations dissolved under 30 seconds and friability values were less than 1%. In vitro taste masking efficiency studies demonstrated that C2 formulation (in FGF) had the most similar dissolution profile to Remeron SolTab. According to these findings, B2 or C2 (with citric acid or sodium bicarbonate, respectively, with 6% Eudragit ® E-100) formulations could be promising alternatives to Remeron SolTab.

  4. Willingness and Ability of Older Adults in the Emergency Department to Provide Clinical Information Using a Tablet Computer.

    PubMed

    Brahmandam, Sruti; Holland, Wesley C; Mangipudi, Sowmya A; Braz, Valerie A; Medlin, Richard P; Hunold, Katherine M; Jones, Christopher W; Platts-Mills, Timothy F

    2016-11-01

    To estimate the proportion of older adults in the emergency department (ED) who are willing and able to use a tablet computer to answer questions. Prospective, ED-based cross-sectional study. Two U.S. academic EDs. Individuals aged 65 and older. As part of screening for another study, potential study participants were asked whether they would be willing to use a tablet computer to answer eight questions instead of answering questions orally. A custom user interface optimized for older adults was used. Trained research assistants observed study participants as they used the tablets. Ability to use the tablet was assessed based on need for assistance and number of questions answered correctly. Of 365 individuals approached, 248 (68%) were willing to answer screening questions, 121 of these (49%) were willing to use a tablet computer; of these, 91 (75%) were able to answer at least six questions correctly, and 35 (29%) did not require assistance. Only 14 (12%) were able to answer all eight questions correctly without assistance. Individuals aged 65 to 74 and those reporting use of a touchscreen device at least weekly were more likely to be willing and able to use the tablet computer. Of individuals with no or mild cognitive impairment, the percentage willing to use the tablet was 45%, and the percentage answering all questions correctly was 32%. Approximately half of this sample of older adults in the ED was willing to provide information using a tablet computer, but only a small minority of these were able to enter all information correctly without assistance. Tablet computers may provide an efficient means of collecting clinical information from some older adults in the ED, but at present, it will be ineffective for a significant portion of this population. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

  5. Compounding rifampin suspensions with improved injectability for nasogastric enteral feeding tube administration.

    PubMed

    de Villiers, Melgardt M; Vogel, Laura; Bogenschutz, Monica C; Fingerhut, Bonnie J; D'Silva, Joseph B; Moore, Anne

    2010-01-01

    Often medications that have to be administered to patients via a nasogastric enteral feeding tubes are only available as tablets and capsules with no suitable commercial liquid alternatives. In such situations, pharmacists and nurses have to compound the tablets and capsule contents into liquid suspension formulations for dosing. The risk of occlusion of the enteral tubes during administration is reduced by employing liquid suspensions that are composed of small and uniform particles, not subject to rapid rates of settling, resistant to caking, and easily and uniformly re-suspended upon agitation. Present techniques often employ a manual process, such as a mortar and pestle, to accomplish the particle size reduction and subsequent incorporation into a suitable liquid diluent. A new compounding device has been invented that employs an automated wet-milling process in a single-use disposable plastic container to compound the suspensions. The two processes were compared using Rifampin capsules and various liquid diluents. A prototype version of the new device was employed in the experiments. The physical characteristics of the compounded suspensions were evaluated by determining sedimentation rate, sedimentation volume, and particle size and shape using laser light scattering, optical microscopy, and scanning electron microscopy techniques. The use characteristic of the compounded suspensions was evaluated using a nasogastric tube inject ability test. The results indicated that suspensions prepared using the new device were more resistant to sedimentation and caking and were easier to re-disperse into a uniform mixture by gentle shaking. The results were a consequence of the particles generated by the new device which were found to be smaller and more uniform in shape and size. The suspensions prepared using the new device did not cause blockage of the enteral feeding tubes in comparison to those prepared using a mortar and pastle. In conclusion, the results indicate

  6. Review of bilayer tablet technology.

    PubMed

    Abebe, Admassu; Akseli, Ilgaz; Sprockel, Omar; Kottala, Niranjan; Cuitiño, Alberto M

    2014-01-30

    Therapeutic strategies based on oral delivery of bilayer (and multilayer) tablets are gaining more acceptance among brand and generic products due to a confluence of factors including advanced delivery strategies, patient compliance and combination therapy. Successful manufacturing of these ever more complex systems needs to overcome a series of challenges from formulation design to tablet press monitoring and control. This article provides an overview of the state-of-the-art of bilayer tablet technology, highlighting the main benefits of this type of oral dosage forms while providing a description of current challenges and advances toward improving manufacturing practices and product quality. Several aspects relevant to bilayer tablet manufacturing are addressed including material properties, lubrication, layer ordering, layer thickness, layer weight control, as well as first and final compression forces. A section is also devoted to bilayer tablet characterization that present additional complexities associated with interfaces between layers. The available features of the manufacturing equipment for bilayer tablet production are also described indicating the different strategies for sensing and controls offered by bilayer tablet press manufacturers. Finally, a roadmap for bilayer tablet manufacturing is advanced as a guideline to formulation design and selection of process parameters and equipment. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Effect of repeated compaction of tablets on tablet properties and work of compaction using an instrumented laboratory tablet press.

    PubMed

    Gamlen, Michael John Desmond; Martini, Luigi G; Al Obaidy, Kais G

    2015-01-01

    The repeated compaction of Avicel PH101, dicalcium phosphate dihydrate (DCP) powder, 50:50 DCP/Avicel PH101 and Starch 1500 was studied using an instrumented laboratory tablet press which measures upper punch force, punch displacement and ejection force and operates using a V-shaped compression profile. The measurement of work compaction was demonstrated, and the test materials were ranked in order of compaction behaviour Avicel PH101 > DCP/Avicel PH101 > Starch > DCP. The behaviour of the DCP/Avicel PH101 mixture was distinctly non-linear compared with the pure components. Repeated compaction and precompression had no effect on the tensile fracture strength of Avicel PH101 tablets, although small effects on friability and disintegration time were seen. Repeated compaction and precompression reduced the tensile strength and the increased disintegration time of the DCP tablets, but improved the strength and friability of Starch 1500 tablets. Based on the data reported, routine laboratory measurement of tablet work of compaction may have potential as a critical quality attribute of a powder blend for compression. The instrumented press was suitable for student use with minimal supervisor input.

  8. Development of modified-release tablets of zolpidem tartrate by biphasic quick/slow delivery system.

    PubMed

    Mahapatra, Anjan Kumar; Sameeraja, N H; Murthy, P N

    2015-06-01

    Zolpidem tartrate is a non-benzodiazepine analogue of imidazopyridine of sedative and hypnotic category. It has a short half-life with usual dosage regimen being 5 mg, two times a day, or 10 mg, once daily. The duration of action is considered too short in certain circumstances. Thus, it is desirable to lengthen the duration of action. The formulation design was implemented by preparing extended-release tablets of zolpidem tartrate using the biphasic delivery system technology, where sodium starch glycolate acts as a superdisintegrant in immediate-release part and hydroxypropyl methyl cellulose as a release retarding agent in extended-release core. Tablets were prepared by direct compression. Both the core and the coat contained the drug. The pre-compression blends were evaluated for angle of repose, bulk density, and compressibility index. The tablets were evaluated for thickness, hardness, weight variation test, friability, and in vitro release studies. No interaction was observed between zolpidem tartrate and excipients from the Fourier transform infrared spectroscopy and differential scanning calorimetry analysis. The results of all the formulations prepared were compared with reference product Stilnoct®. Optimized formulations showed release patterns that match the United States Pharmacopeia (USP) guidelines for zolpidem tartrate extended-release tablets. The mechanism of drug release was studied using different mathematical models, and the optimized formulation has shown Fickian diffusion. Accelerated stability studies were performed on the optimized formulation.

  9. In vitro disintegration and dissolution studies of once-weekly copies of alendronate sodium tablets (70 mg) and in vivo implications.

    PubMed

    Dansereau, Richard J; Crail, Debbie J; Perkins, Alan C

    2008-04-01

    The aim of this study was to evaluate the in vitro disintegration and dissolution of 26 alendronic acid tablets (70 mg) on the market in Canada, Germany, the Netherlands, and the United Kingdom compared to the branded product (Fosamax). The disintegration and dissolution times were determined using the methods described in the United States Pharmacopeia 30 (USP 30). The disintegration of four orally disintegrating tablets (non-bisphosphonates) and branded film-coated risedronate sodium tablets were included for comparison. The mean disintegration times of the alendronic acid tablets ranged from 14 s for Pharmachemie (Netherlands) to 342 s (5.7 min) for Betapharm (Germany). The mean disintegration time of the branded product tablets ranged from 43 to 78 s. Six of the 26 companies market alendronic acid tablets with very rapid disintegration times which are similar to those of orally disintegrating tablets (non-bisphosphonates). The alendronic acid tablets with very rapid mean disintegration times are as follows: Pharmachemie (Netherlands), 14 s; Novopharm (Canada), 13-24 s; GRY-Pharma (Germany), 21 s; Juta Pharma (Germany), 30 s; APS/Teva (United Kingdom), 26 and 37 s; and Teva (UK), 14-29 s. Since there is no established disintegration time for alendronic acid tablets there can be no assurance that the copy tablets are equivalent to the branded product in terms of esophageal drug exposure. However, the in vitro disintegration times have not been correlated with in vivo disintegration and performance. The dissolution of all the bisphosphonate tablets was rapid with greater than 80% dissolved in 15 min and all products conformed to the USP 30 specification. The dissolution of all alendronic acid tablets was rapid and complete and conformed to the established USP 30 specifications which should ensure adequate drug absorption from the copy products. However, copies of alendronic acid tablets are approved based on the results of single-dose bioavailability studies in

  10. Can Tablet Computers Enhance Faculty Teaching?

    PubMed Central

    Narayan, Aditee P.; Whicker, Shari A.; Benjamin, Robert W.; Hawley, Jeffrey; McGann, Kathleen A.

    2015-01-01

    Background Learner benefits of tablet computer use have been demonstrated, yet there is little evidence regarding faculty tablet use for teaching. Objective Our study sought to determine if supplying faculty with tablet computers and peer mentoring provided benefits to learners and faculty beyond that of non–tablet-based teaching modalities. Methods We provided faculty with tablet computers and three 2-hour peer-mentoring workshops on tablet-based teaching. Faculty used tablets to teach, in addition to their current, non–tablet-based methods. Presurveys, postsurveys, and monthly faculty surveys assessed feasibility, utilization, and comparisons to current modalities. Learner surveys assessed perceived effectiveness and comparisons to current modalities. All feedback received from open-ended questions was reviewed by the authors and organized into categories. Results Of 15 eligible faculty, 14 participated. Each participant attended at least 2 of the 3 workshops, with 10 to 12 participants at each workshop. All participants found the workshops useful, and reported that the new tablet-based teaching modality added value beyond that of current teaching methods. Respondents developed the following tablet-based outputs: presentations, photo galleries, evaluation tools, and online modules. Of the outputs, 60% were used in the ambulatory clinics, 33% in intensive care unit bedside teaching rounds, and 7% in inpatient medical unit bedside teaching rounds. Learners reported that common benefits of tablet computers were: improved access/convenience (41%), improved interactive learning (38%), and improved bedside teaching and patient care (13%). A common barrier faculty identified was inconsistent wireless access (14%), while no barriers were identified by the majority of learners. Conclusions Providing faculty with tablet computers and having peer-mentoring workshops to discuss their use was feasible and added value. PMID:26221443

  11. Can Tablet Computers Enhance Faculty Teaching?

    PubMed

    Narayan, Aditee P; Whicker, Shari A; Benjamin, Robert W; Hawley, Jeffrey; McGann, Kathleen A

    2015-06-01

    Learner benefits of tablet computer use have been demonstrated, yet there is little evidence regarding faculty tablet use for teaching. Our study sought to determine if supplying faculty with tablet computers and peer mentoring provided benefits to learners and faculty beyond that of non-tablet-based teaching modalities. We provided faculty with tablet computers and three 2-hour peer-mentoring workshops on tablet-based teaching. Faculty used tablets to teach, in addition to their current, non-tablet-based methods. Presurveys, postsurveys, and monthly faculty surveys assessed feasibility, utilization, and comparisons to current modalities. Learner surveys assessed perceived effectiveness and comparisons to current modalities. All feedback received from open-ended questions was reviewed by the authors and organized into categories. Of 15 eligible faculty, 14 participated. Each participant attended at least 2 of the 3 workshops, with 10 to 12 participants at each workshop. All participants found the workshops useful, and reported that the new tablet-based teaching modality added value beyond that of current teaching methods. Respondents developed the following tablet-based outputs: presentations, photo galleries, evaluation tools, and online modules. Of the outputs, 60% were used in the ambulatory clinics, 33% in intensive care unit bedside teaching rounds, and 7% in inpatient medical unit bedside teaching rounds. Learners reported that common benefits of tablet computers were: improved access/convenience (41%), improved interactive learning (38%), and improved bedside teaching and patient care (13%). A common barrier faculty identified was inconsistent wireless access (14%), while no barriers were identified by the majority of learners. Providing faculty with tablet computers and having peer-mentoring workshops to discuss their use was feasible and added value.

  12. Investigation of the effect of tablet surface area/volume on drug release from hydroxypropylmethylcellulose controlled-release matrix tablets.

    PubMed

    Reynolds, Thomas D; Mitchell, Shawn A; Balwinski, Karen M

    2002-04-01

    The purpose of this study was to investigate the influence of tablet surface area/volume (SA/Vol) on drug release from controlled-release matrix tablets containing hydroxypropylmethylcellulose (HPMC). Soluble drugs (promethazine HCl, diphenhydramine HCl, and propranolol HCl) were utilized in this study to give predominantly diffusion-controlled release. Drug release from HPMC matrix tablets with similar values of SA/Vol was comparable within the same tablet shape (i.e., flat-faced round tablets) and among different shapes (i.e., oval, round concave, flat-faced beveled-edge, and flat-faced round tablets). Tablets having the same surface area but different SA/Vol values did not result in similar drug release; tablets with larger SA/Vol values hadfaster release profiles. Utility of SA/Vol to affect drug release was demonstrated by changing drug doses, and altering tablet shape to adjust SA/Vol. When SA/Vol was held constant, similar release profiles were obtained with f2 metric values greater than 70. Thus, surface area/volume is one of the key variables in controlling drug release from HPMC matrix tablets. Proper use of this variable has practical application by formulators who may need to duplicate drug release profiles from tablets of different sizes and different shapes.

  13. Microstructure of Tablet-Pharmaceutical Significance, Assessment, and Engineering.

    PubMed

    Sun, Changquan Calvin

    2017-05-01

    To summarize the microstructure - property relationship of pharmaceutical tablets and approaches to improve tablet properties through tablet microstructure engineering. The main topics reviewed here include: 1) influence of material properties and manufacturing process parameters on the evolution of tablet microstructure; 2) impact of tablet structure on tablet properties; 3) assessment of tablet microstructure; 4) development and engineering of tablet microstructure. Microstructure plays a decisive role on important pharmaceutical properties of a tablet, such as disintegration, drug release, and mechanical strength. Useful information on mechanical properties of a powder can be obtained from analyzing tablet porosity-pressure data. When helium pycnometry fails to accurately measure true density of a water-containing powder, non-linear regression of tablet density-pressure data is a useful alternative method. A component that is more uniformly distributed in a tablet generally exerts more influence on the overall tablet properties. During formulation development, it is highly recommended to examine the relationship between any property of interest and tablet porosity when possible. Tablet microstructure can be engineered by judicious selection of formulation composition, including the use of the optimum solid form of the drug and appropriate type and amount of excipients, and controlling manufacturing process.

  14. Design and evaluation of a dry coated drug delivery system with floating-pulsatile release.

    PubMed

    Zou, Hao; Jiang, Xuetao; Kong, Lingshan; Gao, Shen

    2008-01-01

    The objective of this work was to develop and evaluate a floating-pulsatile drug delivery system intended for chronopharmacotherapy. Floating-pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. To overcome limitations of various approaches for imparting buoyancy, we generated the system which consisted of three different parts, a core tablet, containing the active ingredient, an erodible outer shell and a top cover buoyant layer. The dry coated tablet consists in a drug-containing core, coated by a hydrophilic erodible polymer which is responsible for a lag phase in the onset of pulsatile release. The buoyant layer, prepared with Methocel K4M, Carbopol 934P and sodium bicarbonate, provides buoyancy to increase the retention of the oral dosage form in the stomach. The effect of the hydrophilic erodible polymer characteristics on the lag time and drug release was investigated. Developed formulations were evaluated for their buoyancy, dissolution and pharmacokinetic, as well gamma-scintigraphically. The results showed that a certain lag time before the drug released generally due to the erosion of the dry coated layer. Floating time was controlled by the quantity and composition of the buoyant layer. Both pharmacokinetic and gamma-scintigraphic data point out the capability of the system of prolonged residence of the tablets in the stomach and releasing drugs after a programmed lag time. (c) 2007 Wiley-Liss, Inc.

  15. Pancreatic enzymes prepared in bicarbonate solution for administration through enteral feeding tubes.

    PubMed

    Boullata, Angela M; Boullata, Joseph I

    2015-07-15

    The dissolution and physicochemical effects of preparing delayed-release pancrelipase in a sodium bicarbonate solution before administration via an enteral feeding tube were studied. Several doses of four delayed-release pancrelipase products (Creon, Pancreaze, Ultresa, Zenpep) were studied. The intact contents of pancrelipase capsules was added to 20 mL of 8.4% sodium bicarbonate solution to dissolve the enteric coating and liberate the enzymes into solution. In addition to visual observation, the pH, relative particle count, and osmolality of each admixture were assessed immediately and 5, 10, 20, and 30 minutes after admixture preparation. The only dose of Creon that was completely dissolved at 30 minutes was the 24,000 lipase unit dose. None of the doses of Pancreaze and only the lowest dose (23,000 lipase units) of Ultresa were completely dissolved at 30 minutes. However, Zenpep doses of 20,000 and 40,000 lipase units were completely dissolved 30 minutes after preparation. Higher doses of each pancrelipase product did not completely dissolve. The baseline pH of the solvent decreased slightly at the first few time points after pancrelipase was added. The relative particle count increased over time and with increasing doses. The osmolality of the mixtures varied by pancrelipase product. The dissolution of enteric coated granules in sodium bicarbonate varied with the pancrelipase product and dose. Zenpep 40,000 lipase units was found to most efficiently dissolve in sodium bicarbonate, possibly due to the consistent size of the product's granules and visibly thinner and uniform enteric coating. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  16. Pharmaceutical and analytical evaluation of triphalaguggulkalpa tablets

    PubMed Central

    Savarikar, Shreeram S.; Barbhind, Maneesha M.; Halde, Umakant K.; Kulkarni, Alpana P.

    2011-01-01

    Aim of the Study: Development of standardized, synergistic, safe and effective traditional herbal formulations with robust scientific evidence can offer faster and more economical alternatives for the treatment of disease. The main objective was to develop a method of preparation of guggulkalpa tablets so that the tablets meet the criteria of efficacy, stability, and safety. Materials and Methods: Triphalaguggulkalpa tablet, described in sharangdharsanhita and containing guggul and triphala powder, was used as a model drug. Preliminary experiments on marketed triphalaguggulkalpa tablets exhibited delayed in vitro disintegration that indicated probable delayed in vivo disintegration. The study involved preparation of triphalaguggulkalpa tablets by Ayurvedic text methods and by wet granulation, dry granulation, and direct compression method. The tablets were evaluated for loss on drying, volatile oil content, % solubility, and steroidal content. The tablets were evaluated for performance tests like weight variation, disintegration, and hardness. Results: It was observed that triphalaguggulkalpa tablets, prepared by direct compression method, complied with the hardness and disintegration tests, whereas tablets prepared by Ayurvedic text methods failed. Conclusion: Direct compression is the best method of preparing triphalaguggulkalpa tablets. PMID:21731383

  17. A Novel Scale Up Model for Prediction of Pharmaceutical Film Coating Process Parameters.

    PubMed

    Suzuki, Yasuhiro; Suzuki, Tatsuya; Minami, Hidemi; Terada, Katsuhide

    2016-01-01

    In the pharmaceutical tablet film coating process, we clarified that a difference in exhaust air relative humidity can be used to detect differences in process parameters values, the relative humidity of exhaust air was different under different atmospheric air humidity conditions even though all setting values of the manufacturing process parameters were the same, and the water content of tablets was correlated with the exhaust air relative humidity. Based on this experimental data, the exhaust air relative humidity index (EHI), which is an empirical equation that includes as functional parameters the pan coater type, heated air flow rate, spray rate of coating suspension, saturated water vapor pressure at heated air temperature, and partial water vapor pressure at atmospheric air pressure, was developed. The predictive values of exhaust relative humidity using EHI were in good correlation with the experimental data (correlation coefficient of 0.966) in all datasets. EHI was verified using the date of seven different drug products of different manufacturing scales. The EHI model will support formulation researchers by enabling them to set film coating process parameters when the batch size or pan coater type changes, and without the time and expense of further extensive testing.

  18. COMPARISON OF HYDROCORTISONE 10 MG TABLETS: TABLET HARDNESS OPTIMISED FOR ADULT USE HAS NEGATIVE CONSEQUENCES FOR PAEDIATRIC USE.

    PubMed

    Saimbi, Sarina; Madden, Valerie; Stirling, Heather; Yahyouche, Asma; Batchelor, Hannah

    2016-09-01

    Children's medicines are not always readily available as an age appropriate product and manipulation of adult products is often required. Recently the commercial manufacturing process for 10 mg hydrocortisone tablets has changed and the compression force increased due to tablets fracturing on removal from the blister pack. However, this change led to parents of children requiring hydrocortisone reporting that the tablets were more difficult to manipulate.This study evaluated 10 mg hydrocortisone tablets for their suitability for manipulation in order to deliver an appropriate dose to children (2 mg dose). The physical properties of tablets with the old and new compression force were compared as well as the accuracy of obtaining the paediatric dose. The tablets compared were hydrocortisone Auden 10 mg tablets (Brand A, PL16876/002)-these are the newer, harder tablets- and hydrocortisone 10 mg tablets (Brand B, PL17507/0097). Tablet physical properties including friability (Copley FRV200) and tablet hardness (Copley TBF1000) were compared. The accuracy of split doses (halve and quarter tablets) were recorded on a Sartorius analytical balance. The accuracy of the 2 mg paediatric dosing was assessed by crushing the tablet, adding 10 mL of water and extracting 2 mL. The concentration was measured using UV analysis (Jenway Genova Plus) according to a calibration curve (wavelength=246 nm). Two devices were used to crush the tablets: a spoon onto a plate and a commercially available crushing device (Apothecary Ezy Crush Pill Crusher With Ergo Grip). As anticipated Brand A tablets were harder (51.85 ±5.1 N) compared to Brand B (30.99±4.1 N). Brand A tablets passed the friability testing with <1% weight loss whereas Brand B failed as 5 tablets broke during testing.The accuracy of split doses using the score lines to halve and quarter the tablets showed that Brand A were generally better with smaller ranges for both halves (Range for A=41-55%; B=29

  19. Integrated Application of Quality-by-Design Principles to Drug Product Development: A Case Study of Brivanib Alaninate Film-Coated Tablets.

    PubMed

    Badawy, Sherif I F; Narang, Ajit S; LaMarche, Keirnan R; Subramanian, Ganeshkumar A; Varia, Sailesh A; Lin, Judy; Stevens, Tim; Shah, Pankaj A

    2016-01-01

    Modern drug product development is expected to follow quality-by-design (QbD) paradigm. At the same time, although there are several issue-specific examples in the literature that demonstrate the application of QbD principles, a holistic demonstration of the application of QbD principles to drug product development and control strategy, is lacking. This article provides an integrated case study on the systematic application of QbD to product development and demonstrates the implementation of QbD concepts in the different aspects of product and process design for brivanib alaninate film-coated tablets. Using a risk-based approach, the strategy for development entailed identification of product critical quality attributes (CQAs), assessment of risks to the CQAs, and performing experiments to understand and mitigate identified risks. Quality risk assessments and design of experiments were performed to understand the quality of the input raw materials required for a robust formulation and the impact of manufacturing process parameters on CQAs. In addition to the material property and process parameter controls, the proposed control strategy includes use of process analytical technology and conventional analytical tests to control in-process material attributes and ensure quality of the final product. Copyright © 2016. Published by Elsevier Inc.

  20. Current status and approaches to developing press-coated chronodelivery drug systems.

    PubMed

    Lin, Shan-Yang; Kawashima, Yoshiaki

    2012-02-10

    The past several decades have seen the development of many controlled-release preparations featuring constant release rates to maintain drug concentrations in the human body, regardless of the patient's physiological condition. However, long-term constant drug concentrations in the blood and tissue can cause problems such as resistance, tolerability, and drug side effects. People vary considerably in their physiological and biochemical conditions during any 24 h period, due to the circadian rhythm, and thus, the constant delivery of a drug into the body seems both unnecessary and undesirable. If the drug release profile mimics a living system's pulsatile hormone secretion, then it may improve drug efficacy, and reduce the toxicity of a specific drug administration schedule. Medication and treatments provided according to the body's circadian rhythms will result in better outcomes. This may be provided by a chronopharmaceutical dosage regimen with pulsatile release that matches the circadian rhythm resulting from a disease state, so optimizing the therapeutic effect while minimizing side effects. The press coating technique is a simple and unique technology used to provide tablets with a programmable lag phase, followed by a fast, or rate-controlled, drug release after administration. The technique offers many advantages, and no special coating solvent or coating equipment is required for manufacturing this type of tablet. The present review article introduces chronopharmaceutical press-coated products from a patient physiological needs perspective. The contents of this article include biological rhythms and pulsatile hormone secretion in humans, the reasons for using pulsatile drug delivery for disease treatment, recent chronopharmaceutical preparations appearing on the market, updated compilation of all research articles and press-coated delivery techniques, factors affecting the performance and drug release characteristics of press-coated delivery systems, and

  1. Evaluation of in-line Raman data for end-point determination of a coating process: Comparison of Science-Based Calibration, PLS-regression and univariate data analysis.

    PubMed

    Barimani, Shirin; Kleinebudde, Peter

    2017-10-01

    A multivariate analysis method, Science-Based Calibration (SBC), was used for the first time for endpoint determination of a tablet coating process using Raman data. Two types of tablet cores, placebo and caffeine cores, received a coating suspension comprising a polyvinyl alcohol-polyethylene glycol graft-copolymer and titanium dioxide to a maximum coating thickness of 80µm. Raman spectroscopy was used as in-line PAT tool. The spectra were acquired every minute and correlated to the amount of applied aqueous coating suspension. SBC was compared to another well-known multivariate analysis method, Partial Least Squares-regression (PLS) and a simpler approach, Univariate Data Analysis (UVDA). All developed calibration models had coefficient of determination values (R 2 ) higher than 0.99. The coating endpoints could be predicted with root mean square errors (RMSEP) less than 3.1% of the applied coating suspensions. Compared to PLS and UVDA, SBC proved to be an alternative multivariate calibration method with high predictive power. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. A critical review on tablet disintegration.

    PubMed

    Quodbach, Julian; Kleinebudde, Peter

    2016-09-01

    Tablet disintegration is an important factor for drug release and can be modified with excipients called tablet disintegrants. Tablet disintegrants act via different mechanisms and the efficacy of these excipients is influenced by various factors. In this review, the existing literature on tablet disintegration is critically reviewed. Potential disintegration mechanisms, as well as impact factors on the disintegration process will be discussed based on experimental evidence. Search terms for Scopus and Web of Science included "tablet disintegration", "mechanism tablet disintegration", "superdisintegrants", "disintegrants", "swelling force", "disintegration force", "disintegration mechanisms", as well as brand names of commonly applied superdisintegrants. References of identified papers were screened as well. Experimental data supports swelling and shape recovery as main mechanisms of action of disintegrants. Other tablet excipients and different manufacturing techniques greatly influence the disintegration process. The use of different excipients, experimental setups and manufacturing techniques, as well as the demand for original research led to a distinct patchwork of knowledge. Broader, more systematic approaches are necessary not only to structure the past but also future findings.

  3. 21 CFR 520.1284 - Sodium liothyronine tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Sodium liothyronine tablets. 520.1284 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1284 Sodium liothyronine tablets. (a) Specifications. Sodium liothyronine tablets consist of tablets intended for oral...

  4. 21 CFR 520.1284 - Sodium liothyronine tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sodium liothyronine tablets. 520.1284 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1284 Sodium liothyronine tablets. (a) Specifications. Sodium liothyronine tablets consist of tablets intended for oral...

  5. 21 CFR 520.1284 - Sodium liothyronine tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Sodium liothyronine tablets. 520.1284 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1284 Sodium liothyronine tablets. (a) Specifications. Sodium liothyronine tablets consist of tablets intended for oral...

  6. 21 CFR 520.1284 - Sodium liothyronine tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Sodium liothyronine tablets. 520.1284 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1284 Sodium liothyronine tablets. (a) Specifications. Sodium liothyronine tablets consist of tablets intended for oral...

  7. 21 CFR 520.1445 - Milbemycin oxime tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Milbemycin oxime tablets. 520.1445 Section 520... tablets. (a) Specifications—(1) Dogs. Each tablet contains 2.3, 5.75, 11.5, or 23.0 milligrams of milbemycin oxime. (2) Cats. Each tablet contains 5.75, 11.5, or 23.0 milligrams of milbemycin oxime. (b...

  8. 21 CFR 520.1310 - Marbofloxacin tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Marbofloxacin tablets. 520.1310 Section 520.1310... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1310 Marbofloxacin tablets. (a) Specifications. Each tablet contains 25, 50, 100, or 200 milligrams (mg) marbofloxacin. (b...

  9. 21 CFR 520.2330 - Sulfisoxazole tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sulfisoxazole tablets. 520.2330 Section 520.2330... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2330 Sulfisoxazole tablets. (a) Specifications. Each tablet contains 260 milligrams (4 grains) of sulfisoxazole. (b) Sponsor. See...

  10. Enteritis

    MedlinePlus

    ... enteritis E coli enteritis Food poisoning Radiation enteritis Salmonella enteritis Shigella enteritis Staph aureus food poisoning Symptoms ... store food that needs to stay chilled. Images Salmonella typhi organism Yersinia enterocolitica organism Campylobacter jejuni organism ...

  11. 21 CFR 520.370 - Cefpodoxime tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Cefpodoxime tablets. 520.370 Section 520.370 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.370 Cefpodoxime tablets. (a) Specifications. Each tablet contains cefpodoxime proxetil equivalent to 100 or 200 milligrams (mg) cefpodoxime...

  12. 21 CFR 520.1380 - Methocarbamol tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Methocarbamol tablets. 520.1380 Section 520.1380... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1380 Methocarbamol tablets. (a) Chemical name. 3-(O-Methoxyphenoxy)-1,2-propanediol 1-carbamate. (b) Specifications. Each tablet...

  13. Evaluation of the performance characteristics of bilayer tablets: Part II. Impact of environmental conditions on the strength of bilayer tablets.

    PubMed

    Kottala, Niranjan; Abebe, Admassu; Sprockel, Omar; Bergum, James; Nikfar, Faranak; Cuitiño, Alberto M

    2012-12-01

    Ambient air humidity and temperature are known to influence the mechanical strength of tablets. The objective of this work is to understand the influence of processing parameters and environmental conditions (humidity and temperature) on the strength of bilayer tablets. As part of this study, bilayer tablets were compressed with different layer ratios, dwell times, layer sequences, material properties (plastic and brittle), first and second layer forces, and lubricant concentrations. Compressed tablets were stored in stability chambers controlled at predetermined conditions (40C/45%RH, 40C/75%RH) for 1, 3, and 5 days. The axial strength of the stored tablets was measured and a statistical model was developed to determine the effects of the aforementioned factors on the strength of bilayer tablets. As part of this endeavor, a full 3 × 2(4) factorial design was executed. Responses of the experiments were analyzed using PROC GLM of SAS (SAS Institute Inc, Cary, North Carolina, USA). A model was fit using all the responses to determine the significant interactions (p < 0.05). Results of this study indicated that storage conditions and storage time have significant impact on the strength of bilayer tablets. For Avicel-lactose and lactose-Avicel tablets, tablet strength decreased with the increasing humidity and storage time. But for lactose-lactose tablets, due to the formation of solid bridges upon storage, an increase in tablet strength was observed. Significant interactions were observed between processing parameters and storage conditions on the strength of bilayer tablets.

  14. A novel multivariate approach using science-based calibration for direct coating thickness determination in real-time NIR process monitoring.

    PubMed

    Möltgen, C-V; Herdling, T; Reich, G

    2013-11-01

    This study demonstrates an approach, using science-based calibration (SBC), for direct coating thickness determination on heart-shaped tablets in real-time. Near-Infrared (NIR) spectra were collected during four full industrial pan coating operations. The tablets were coated with a thin hydroxypropyl methylcellulose (HPMC) film up to a film thickness of 28 μm. The application of SBC permits the calibration of the NIR spectral data without using costly determined reference values. This is due to the fact that SBC combines classical methods to estimate the coating signal and statistical methods for the noise estimation. The approach enabled the use of NIR for the measurement of the film thickness increase from around 8 to 28 μm of four independent batches in real-time. The developed model provided a spectroscopic limit of detection for the coating thickness of 0.64 ± 0.03 μm root-mean square (RMS). In the commonly used statistical methods for calibration, such as Partial Least Squares (PLS), sufficiently varying reference values are needed for calibration. For thin non-functional coatings this is a challenge because the quality of the model depends on the accuracy of the selected calibration standards. The obvious and simple approach of SBC eliminates many of the problems associated with the conventional statistical methods and offers an alternative for multivariate calibration. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Using a Virtual Tablet Machine to Improve Student Understanding of the Complex Processes Involved in Tablet Manufacturing.

    PubMed

    Mattsson, Sofia; Sjöström, Hans-Erik; Englund, Claire

    2016-06-25

    Objective. To develop and implement a virtual tablet machine simulation to aid distance students' understanding of the processes involved in tablet production. Design. A tablet simulation was created enabling students to study the effects different parameters have on the properties of the tablet. Once results were generated, students interpreted and explained them on the basis of current theory. Assessment. The simulation was evaluated using written questionnaires and focus group interviews. Students appreciated the exercise and considered it to be motivational. Students commented that they found the simulation, together with the online seminar and the writing of the report, was beneficial for their learning process. Conclusion. According to students' perceptions, the use of the tablet simulation contributed to their understanding of the compaction process.

  16. Using a Virtual Tablet Machine to Improve Student Understanding of the Complex Processes Involved in Tablet Manufacturing

    PubMed Central

    Sjöström, Hans-Erik; Englund, Claire

    2016-01-01

    Objective. To develop and implement a virtual tablet machine simulation to aid distance students’ understanding of the processes involved in tablet production. Design. A tablet simulation was created enabling students to study the effects different parameters have on the properties of the tablet. Once results were generated, students interpreted and explained them on the basis of current theory. Assessment. The simulation was evaluated using written questionnaires and focus group interviews. Students appreciated the exercise and considered it to be motivational. Students commented that they found the simulation, together with the online seminar and the writing of the report, was beneficial for their learning process. Conclusion. According to students’ perceptions, the use of the tablet simulation contributed to their understanding of the compaction process. PMID:27402990

  17. Relationships between response surfaces for tablet characteristics of placebo and API-containing tablets manufactured by direct compression method.

    PubMed

    Hayashi, Yoshihiro; Tsuji, Takahiro; Shirotori, Kaede; Oishi, Takuya; Kosugi, Atsushi; Kumada, Shungo; Hirai, Daijiro; Takayama, Kozo; Onuki, Yoshinori

    2017-10-30

    In this study, we evaluated the correlation between the response surfaces for the tablet characteristics of placebo and active pharmaceutical ingredient (API)-containing tablets. The quantities of lactose, cornstarch, and microcrystalline cellulose were chosen as the formulation factors. Ten tablet formulations were prepared. The tensile strength (TS) and disintegration time (DT) of tablets were measured as tablet characteristics. The response surfaces for TS and DT were estimated using a nonlinear response surface method incorporating multivariate spline interpolation, and were then compared with those of placebo tablets. A correlation was clearly observed for TS and DT of all APIs, although the value of the response surfaces for TS and DT was highly dependent on the type of API used. Based on this knowledge, the response surfaces for TS and DT of API-containing tablets were predicted from only two and four formulations using regression expression and placebo tablet data, respectively. The results from the evaluation of prediction accuracy showed that this method accurately predicted TS and DT, suggesting that it could construct a reliable response surface for TS and DT with a small number of samples. This technique assists in the effective estimation of the relationships between design variables and pharmaceutical responses during pharmaceutical development. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Higher Strength Lanthanum Carbonate Provides Serum Phosphorus Control With a Low Tablet Burden and Is Preferred by Patients and Physicians: A Multicenter Study

    PubMed Central

    Mehrotra, Rajnish; Martin, Kevin J.; Fishbane, Steven; Sprague, Stuart M.; Zeig, Steven; Anger, Michael

    2008-01-01

    Background and objectives: Management of hyperphosphatemia, a predictor of mortality in chronic kidney disease, is challenging. Nonadherence to dietary phosphate binders, in part, contributes to uncontrolled serum phosphorus levels. This phase IIIb trial assessed the efficacy of increased dosages (3000 to 4500 mg/d) of reformulated lanthanum carbonate (500-, 750-, and 1000-mg tablets) in nonresponders to dosages of up to 3000 mg/d. Design, setting, participants, & measurements: This 8-wk study with a 4-mo open-label extension enrolled 513 patients who were undergoing maintenance hemodialysis. Patients who achieved serum phosphorus control at week 4 with ≤3000 mg/d lanthanum carbonate entered cohort A; nonresponders were randomly assigned to receive 3000, 3750, or 4500 mg/d (cohort B). The primary outcome measure was the control rate for predialysis serum phosphorus levels at the end of week 8, among patients in cohort B. Results: At the end of week 4, 54% of patients achieved serum phosphorus control at dosages ≤3000 mg/d administered as one tablet per meal. Among patients who entered cohort B, control rates of 25, 38, and 32% for patients who were randomly assigned to 3000, 3750, or 4500 mg/d lanthanum carbonate, respectively, were achieved, with no increase in adverse events. Patients and physicians reported significantly higher levels of satisfaction with reformulated lanthanum carbonate compared with previous phosphate binders, partly because of reduced tablet burden with higher dosage strengths. Physicians and patients also expressed a preference for lanthanum carbonate over previous medication. Conclusions: Reformulated lanthanum carbonate is an effective phosphate binder that may reduce daily tablet burden. PMID:18579668

  19. 21 CFR 520.455 - Clomipramine tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Clomipramine tablets. 520.455 Section 520.455 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.455 Clomipramine tablets. (a) Specifications. Each tablet contains 5, 20, 40, or 80 milligrams (mg) clomipramine hydrochloride. (b) Sponsor...

  20. Touch Screen Tablets and Emergent Literacy

    ERIC Educational Resources Information Center

    Neumann, Michelle M.; Neumann, David L.

    2014-01-01

    The use of touch screen tablets by young children is increasing in the home and in early childhood settings. The simple tactile interface and finger-based operating features of tablets may facilitate preschoolers' use of tablet application software and support their educational development in domains such as literacy. This article reviews…

  1. 21 CFR 520.2088 - Roxarsone tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Roxarsone tablets. 520.2088 Section 520.2088 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2088 Roxarsone tablets. (a)(1) Specifications. Each tablet contains 36 milligrams of roxarsone (3-nitro-4-hydroxyphenylarsonic acid). (2...

  2. 21 CFR 520.1870 - Praziquantel tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Praziquantel tablets. 520.1870 Section 520.1870... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1870 Praziquantel tablets. (a) Specifications. Each tablet contains: (1) 34 milligrams (mg) praziquantel. (2) 11.5 or 23 mg praziquantel. (b...

  3. Bioequivalence study of levothyroxine tablets compared to reference tablets and an oral solution.

    PubMed

    Koytchev, Rossen; Lauschner, Reinhard

    2004-01-01

    The study was designed to evaluate the bioequivalence of three levothyroxine sodium (CAS 51-48-9) formulations, i.e. a test and a reference tablet and an oral solution. A bioequivalence study was carried out in 25 healthy volunteers, who were administered a single dose of 600 microg levothyroxine in the form of the test formulation (levothyroxine sodium tablets 200 microg; Eferox), the originator product, and an oral solution. The trial was performed in one study center according to an open, randomized, three-way cross-over design with wash-out periods of 35 days between administration. Blood samples were taken up to 48 h post dose, the plasma was separated and the concentrations of levothyroxine and triiodothyronine were determined by radioimmunoassay with I125 labeling method. The levothyroxine mean Cmax were 112.0+/-17.3 ng/ml, 113.4+/-18.5 ng/ ml and 111.3+/-15.1 ng/ml, while the mean AUC0-24 were 2263.7+/-332.8 ng x h/ ml, 2307.3+/-351.3 ng x h/ml and 2286.1+/-331.0 ng x h/ml for the test and reference tablets as well as for the oral solution, respectively. No significant differences were found of principal pharmacokinetic parameters between the studied formulations. The 90%-confidence interval for the primary target parameters, intra-individual ratios of AUC0-24 and Cmax of levothyroxine were within the acceptance ranges for bioequivalence trials, i.e. AUC0-24 0.954-1.016 and 0.966-1.011 as well as Cmax 0.948-1.027 and 0.968-1.032 for test tablets versus reference tablets and the oral solution, respectively. Similar results were observed for triiodothyronine. In the light of the present study it can be concluded that the levothyroxine test tablet is bioequivalent to the reference formulation in respect of extent and rate of absorption. The results of the present trial confirm the findings of a previous study, performed under steady-state conditions with Eferox tablets 100 microg in patients without thyroid function.

  4. Enteric protection of naproxen in a fixed-dose combination product produced by hot-melt co-extrusion.

    PubMed

    Vynckier, A-K; De Beer, M; Monteyne, T; Voorspoels, J; De Beer, T; Remon, J P; Vervaet, C

    2015-08-01

    In this study hot-melt co-extrusion is used as processing technique to manufacture a fixed-dose combination product providing enteric protection to naproxen incorporated in the core and immediate release to esomeprazole magnesium embedded in the coat. The plasticizing effect of naproxen and triethyl citrate (TEC) was tested on the enteric polymers investigated (Eudragit(®) L100-55, HPMC-AS-LF and HPMCP-HP-50). Core matrix formulations containing HPMC-AS-LF, TEC and a naproxen load of 15, 30 and 50% were processed and characterized. The in vitro naproxen release in 0.1N HCl was prevented for 2h for all formulations. The physicochemical state of the drug in the extrudates was determined and a stability study was performed. Intermolecular interactions between naproxen and polymer were identified using attenuated total reflection Fourier-transform infrared (ATR FT-IR) spectroscopy. When esomeprazole magnesium was formulated in a polyethylene oxide 100K:polyethylene glycol 4K (1:1) matrix, separated from the naproxen-containing layer, the formulation could be easily processed and complete in vitro drug release was observed after 45 min. When co-extruding the core/coat dosage form it was observed that a third layer of polymer, separating the naproxen loaded enteric formulation in the core from the coat, is required to prevent degradation of the acid-labile esomeprazole magnesium at the core/coat interface. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. 21 CFR 520.816 - Epsiprantel tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Epsiprantel tablets. 520.816 Section 520.816 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.816 Epsiprantel tablets. (a) Specifications. Each tablet contains either 12.5, 25, 50, or 100 milligrams of epsiprantel. (b) Sponsor. See No...

  6. 21 CFR 520.312 - Carnidazole tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Carnidazole tablets. 520.312 Section 520.312 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.312 Carnidazole tablets. (a) Specifications. Each tablet contains 10 milligrams of carnidazole. (b) Sponsor. See 053923 in § 510.600(c) of...

  7. 21 CFR 520.1451 - Moxidectin tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Moxidectin tablets. 520.1451 Section 520.1451 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1451 Moxidectin tablets. (a) Specifications. Each tablet contains 30, 68, or 136 micrograms of moxidectin. (b) Sponsor. See No. 000856 in...

  8. A new esomeprazole packet (sachet) formulation for suspension: in vitro characteristics and comparative pharmacokinetics versus intact capsules/tablets in healthy volunteers.

    PubMed

    Bladh, Nina; Blychert, Eva; Johansson, Karin; Backlund, Anna; Lundin, Christina; Niazi, Mohammad; Pettersson, Gunilla; Fjellman, Mia

    2007-04-01

    A packet (sachet) formulation of esomeprazole for suspension has been developed for use in patients who have difficulty swallowing. This article reports the in vitro characteristics of the new esomeprazole formulation, including stability in suspension and suitability for administration orally or via enteral tubes. It also describes the pharmacokinetic profile of the esomeprazole 40-mg packet compared with that of existing solid dosage forms (capsules and tablets) in a clinical bioequivalence study. The stability in suspension of the packet formulation was assessed after reconstitution at various strengths (2.5, 10, and 40 mg) and a different pH (3.4-5.0) in strength-appropriate volumes of water held at temperatures ranging from 5 degrees C to 37 degrees C for up to 60 minutes. Suitability for oral administration was examined in terms of reconstitution time and the actual dose delivered after simulated oral administration, as well as in terms of the actual dose delivered by enteral tubes ranging in diameter from 6 to 20 Fr. Chemical stability and suspension characteristics were also analyzed using alternative reconstitution vehicles (applesauce, apple juice, and orange juice). The comparative pharmacokinetics of the packet, capsule, and tablet formulations of esomeprazole were evaluated in a randomized, open-label, 3-way crossover study in healthy volunteers, who received single 40-mg doses of each formulation. Bioequivalence was assumed if the 90% CIs for the ratios of the geometric mean AUC and CmaX were between 0.80 and 1.25. Reversephase liquid chromatography with ultraviolet detection was used to assess the esomeprazole content and/or degradation products of esomeprazole in the tests for in-suspension stability, dose delivery, and acid resistance. Normal-phase liquid chromatography was used to assess the esomeprazole content of the plasma samples in the bioequivalence study. At the pH and temperature ranges investigated, the packet formulation was stable for

  9. Ghost tablet in feces.

    PubMed

    Iwamuro, Masaya; Morishita, Yosuke; Urata, Haruo; Okada, Hiroyuki

    2017-12-01

    Recently, we encountered a female patient who identified the presence of a ghost tablet in her fecal matter. Interestingly, although the patient was prescribed potassium chloride capsules, elemental composition analysis by energy-dispersive X-ray spectroscopy was unable to detect the presence of either potassium or chloride in the fecal tablet remnant.

  10. 21 CFR 520.1288 - Lufenuron tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Lufenuron tablets. 520.1288 Section 520.1288 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1288 Lufenuron tablets. (a) Specifications—(1) Tablets containing 45, 90, 204.9, or 409.8 milligrams (mg) lufenuron for use as in paragraphs...

  11. 21 CFR 520.804 - Enalapril tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Enalapril tablets. 520.804 Section 520.804 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.804 Enalapril tablets. (a) Specifications. Each tablet contains either 1.0, 2.5, 5.0, 10.0, or 20.0 milligrams of enalapril maleate. (b...

  12. 21 CFR 520.1900 - Primidone tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Primidone tablets. 520.1900 Section 520.1900 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1900 Primidone tablets. (a) Specifications. Each tablet contains 50 or 250 milligrams of primidone. (b) Sponsor. See No. 000010 in § 510.600...

  13. 21 CFR 520.1510 - Nitenpyram tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Nitenpyram tablets. 520.1510 Section 520.1510 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1510 Nitenpyram tablets. (a) Specifications. Each tablet contains 11.4 or 57 milligrams (mg) nitenpyram. (b) Sponsor. See No. 058198 in § 510...

  14. 21 CFR 520.812 - Enrofloxacin tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Enrofloxacin tablets. 520.812 Section 520.812 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.812 Enrofloxacin tablets. (a) Specifications. Each tablet contains either 22.7, 68.0, or 136.0 milligrams of enrofloxacin. (b) Sponsor. See No...

  15. 'Tablet burden' in patients with metastatic breast cancer.

    PubMed

    Milic, Marina; Foster, Anna; Rihawi, Karim; Anthoney, Alan; Twelves, Chris

    2016-03-01

    The implications for patients with cancer, of the 'tablet burden' resulting from increasing use of oral anticancer drugs and medication for co-morbidities have not previously been well explored. We sought to (i) quantify tablet burden in women with metastatic breast cancer (MBC), (ii) establish which groups of drug contribute most to this burden and (iii) gain insight into patients' attitudes towards oral anti-cancer treatment. One hundred patients with MBC anonymously completed a questionnaire describing their medication histories and attitudes towards their tablets. The patients (mean age 60, range 31-95) were all female and taking a median of six tablets (range 0-31) daily; 37 patients were taking >10 tablets. Oral anticancer treatment constituted the category of treatment taken by the highest proportion of patients, followed by symptomatic cancer treatments, proton pump inhibitors and cardiovascular medication. Numerically, however, symptomatic drugs accounted for 44% of all tablets and specific anti-cancer treatment for 15%; medication not directly related to the cancer accounted for the remaining 40% of tablets. A quarter of patients reported inconvenience in taking their tablets, the main reason being tablet size and one third reported forgetting their tablets at least once a week. Nearly two thirds of patients expressing a preference favoured oral anticancer treatment, the commonest reason being greater convenience. Tablet burden is considerable for many patients with MBC and can be problematic. A significant proportion of tablets represent treatment for co-morbidities, the significance of which may be questionable in women with MBC. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. New film-coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower-risk MDS: Results of the randomized, phase II ECLIPSE study.

    PubMed

    Taher, Ali T; Origa, Raffaella; Perrotta, Silverio; Kourakli, Alexandra; Ruffo, Giovan Battista; Kattamis, Antonis; Goh, Ai-Sim; Cortoos, Annelore; Huang, Vicky; Weill, Marine; Merino Herranz, Raquel; Porter, John B

    2017-05-01

    Once-daily deferasirox dispersible tablets (DT) have a well-defined safety and efficacy profile and, compared with parenteral deferoxamine, provide greater patient adherence, satisfaction, and quality of life. However, barriers still exist to optimal adherence, including gastrointestinal tolerability and palatability, leading to development of a new film-coated tablet (FCT) formulation that can be swallowed with a light meal, without the need to disperse into a suspension prior to consumption. The randomized, open-label, phase II ECLIPSE study evaluated the safety of deferasirox DT and FCT formulations over 24 weeks in chelation-naïve or pre-treated patients aged ≥10 years, with transfusion-dependent thalassemia or IPSS-R very-low-, low-, or intermediate-risk myelodysplastic syndromes. One hundred seventy-three patients were randomized 1:1 to DT (n = 86) or FCT (n = 87). Adverse events (overall), consistent with the known deferasirox safety profile, were reported in similar proportions of patients for each formulation (DT 89.5%; FCT 89.7%), with a lower frequency of severe events observed in patients receiving FCT (19.5% vs. 25.6% DT). Laboratory parameters (serum creatinine, creatinine clearance, alanine aminotransferase, aspartate aminotransferase and urine protein/creatinine ratio) generally remained stable throughout the study. Patient-reported outcomes showed greater adherence and satisfaction, better palatability and fewer concerns with FCT than DT. Treatment compliance by pill count was higher with FCT (92.9%) than with DT (85.3%). This analysis suggests deferasirox FCT offers an improved formulation with enhanced patient satisfaction, which may improve adherence, thereby reducing frequency and severity of iron overload-related complications. © 2017 Wiley Periodicals, Inc.

  17. Tablet telerounding.

    PubMed

    Kaczmarek, Bartosz F; Trinh, Quoc-Dien; Menon, Mani; Rogers, Craig G

    2012-12-01

    To evaluate the feasibility of remote rounding using commercially available standard tablets with videoconferencing system and assess patient satisfaction. Thirty-two patients with at least 2 postoperative days of hospital stay after robotic urologic procedures were included in the study. On the first postoperative day, the physician-patient encounter was performed as telerounding with videoconferencing due to the physician's duties scheduled in another affiliated hospital. On the second day, the personal bedside encounter took place. The tablet we used was an iPad2 (Apple, iOS 5.1; Apple, Cupertino, CA) with a videoconferencing application. A telerounding satisfaction survey was fulfilled by all patients on the touchscreen of the tablet. Average time of telerounding encounter was 4.5 minutes (range, 1.0-13.5 minutes), average age of the patient was 57.7 years (range, 19-80 years), and 19 were men (59%). Patients expressed a high level of satisfaction with 91% of patients stating that their care was better using telerounding and 97% of patients stating that telerounding should be a regular part of patient care in the hospital. Additionally, 94% of patients stated that they could easily communicate with their doctor over the telerounding system, 84% of patients agreed that they would feel comfortable with telerounding daily if they were hospitalized again and 81% of patients would prefer telerounding communication with their doctor than be directly seen by another doctor. Tablet telerounding using videoconferencing can be a strong supplementing tool in doctor-patient communication. It is convenient for the physician and increases the patient's hospital stay satisfaction. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Medication administration via enteral tubes: a survey of nurses' practices.

    PubMed

    Phillips, Nicole Margaret; Endacott, Ruth

    2011-12-01

    This article is a report of a study examining the practices of acute care nurses when administering medication via enteral tubes. Administering medication via enteral tubes is predominantly a nursing responsibility across countries. It is important to establish what nurses actually do when giving enteral medication to inform policy and continuing education development. In 2007, a survey was conducted using a random sample of acute care nurses at two large metropolitan hospitals in Melbourne, Australia. There were 181 Registered Nurses who participated in the study; 92 (50.8%) practised in intensive care units, 52 (28.7%) in surgical areas, 30 (16.6%) in medical areas and 7 (3.9%) were from combined medical-surgical areas. The questionnaire was developed by the researchers and a pilot study was conducted in August 2006 to test reliability, face validity and user-friendliness of the tool. Nurses reported using a range of methods to verify enteral tube position prior to administering enteral medication; some were unreliable methods. A majority reported administering enteric-coated and slow or extended release forms of medication, and giving solid forms of medication when liquid form was available. Nearly all (96%) reported flushing a tube after giving medication, 28% before, and 12% always flushed between each medication. Enteral medication administration practices are inconsistent. Some nurses are using unsafe practices and may therefore compromise patient care. © 2011 Blackwell Publishing Ltd.

  19. NMR imaging of density distributions in tablets.

    PubMed

    Djemai, A; Sinka, I C

    2006-08-17

    This paper describes the use of (1)H nuclear magnetic resonance (NMR) for 3D mapping of the relative density distribution in pharmaceutical tablets manufactured under controlled conditions. The tablets are impregnated with a compatible liquid. The technique involves imaging of the presence of liquid which occupies the open pore space. The method does not require special calibration as the signal is directly proportional to the porosity for the imaging conditions used. The NMR imaging method is validated using uniform density flat faced tablets and also by direct comparison with X-ray computed tomography. The results illustrate (1) the effect of die wall friction on density distribution by compressing round, curved faced tablets using clean and pre-lubricated tooling, (2) the evolution of density distribution during compaction for both clean and pre-lubricated die wall conditions, by imaging tablets compressed to different compaction forces, and (3) the effect of tablet image on density distribution by compressing two complex shape tablets in identical dies to the same average density using punches with different geometries.

  20. Principles of Tablet Computing for Educators

    ERIC Educational Resources Information Center

    Katzan, Harry, Jr.

    2015-01-01

    In the study of modern technology for the 21st century, one of the most popular subjects is tablet computing. Tablet computers are now used in business, government, education, and the personal lives of practically everyone--at least, it seems that way. As of October 2013, Apple has sold 170 million iPads. The success of tablets is enormous and has…

  1. Mathematics Instruction and the Tablet PC

    ERIC Educational Resources Information Center

    Fister, K. Renee; McCarthy, Maeve L.

    2008-01-01

    The use of tablet PCs in teaching is a relatively new phenomenon. A cross between a notebook computer and a personal digital assistant (PDA), the tablet PC has all of the features of a notebook with the additional capability that the screen can also be used for input. Tablet PCs are usually equipped with a stylus that allows the user to write on…

  2. Using Tablet on Education

    ERIC Educational Resources Information Center

    Algoufi, Rateeba

    2016-01-01

    Technological advancements in digital devices have made educational methodology to adopt new strategies and procedures to suit the Mobile learning era. Mobile devices such as tablets are growing to be the focus of research studies and educational use around the globe in the present day. With the influence of handy computing tablets in the hands of…

  3. Bioequivalence of a single 400-mg dose of imatinib 100-mg oral tablets and a 400-mg tablet in healthy adult Korean volunteers.

    PubMed

    Lee, Hae Won; Seong, Sook Jin; Park, Sung Min; Lee, Joomi; Gwon, Mi-Ri; Kim, Hyun-Ju; Lim, Sung Mook; Lim, Mi-Sun; Kim, Woomi; Yang, Dong Heon; Yoon, Young-Ran

    2015-06-01

    Imatinib mesylate (IM) is a selective tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. A new once-daily 400-mg film-coated tablet of imatinib has been developed by a pharmaceutical company in Korea. The present study was designed to assess and compare the PK parameters, bioavailability, and bioequivalence of the new imatinib 400-mg formulation (test) versus the conventional 100-mg formulation (reference) administered as a single 400-mg dose in healthy adult male volunteers. This randomized, open-label, single-dose, two-way crossover study was conducted in healthy Korean male volunteers. Eligible subjects were randomly assigned in a 1 : 1 ratio to receive 400 mg of the test (one 400-mg tablet) or reference (four 100-mg tablets) formulation, followed by a 2-week washout period and administration of the alternate formulation. Serial blood samples were collected at 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 48, and 72 hours after administration. Plasma imatinib concentrations were determined using liquid chromatography coupled with tandem mass spectrometry. The formulations were to be considered bioequivalent if the 90% confidence intervals (CIs) of the adjusted geometric mean ratios for Cmax, AUC(0-t), and AUC(0-∞)ž were within the predetermined range of 0.80 - 1.25. In total, 35 subjects completed the study. No serious adverse event was reported during the study. The 90% CIs of the adjusted geometric mean ratios of the test formulation to the reference formulation for C(max), AUC(0-t) and AUC(0-∞)ž of imatinib were all within the bioequivalence criteria range of 0.8 - 1.25. The test formulation of imatinib met the Korean regulatory requirements for bioequivalence. Both imatinib formulations were well-tolerated in all subjects.

  4. 21 CFR 520.82a - Aminopropazine fumarate tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Aminopropazine fumarate tablets. 520.82a Section 520.82a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Aminopropazine fumarate tablets. (a) Specifications. The drug is in tablet form. Each tablet contains...

  5. Evaluation of tableting and tablet properties of Kollidon SR: the influence of moisture and mixtures with theophylline monohydrate.

    PubMed

    Hauschild, Karsten; Picker-Freyer, Katharina M

    2006-02-01

    The aim of the study was firstly to investigate the influence of moisture on the tableting and tablet properties of Kollidon SR and secondly to investigate the influence of theophylline monohydrate on the tableting behavior and tablet properties produced from binary mixtures with Kollidon SR. In comparison to Kollidon SR, microcrystalline cellulose (MCC) was used. The glass transition temperature (Tg) of the powder over the whole range of RH (0-90%), and in addition, the Tg of tablets of Kollidon SR were measured. Densities and flowability of the powders were analyzed. The tablets were produced at five different maximum relative densities (rho(rel), max) on an instrumented eccentric tableting machine. They were produced at three different relative humidities (RH), 30%, 45%, and 60% RH for the pure substances and binary mixtures with different ratios of drug and excipient were tableted at 45% RH. The tableting properties were analyzed by 3D modeling, force-displacement profiles, and compactibility plots. First, the Tg of the powder decreased with increasing RH and the Tg of the tablet was 4-8 K lower than the powder. The predominant deformation of Kollidon SR is plastic deformation and Kollidon SR showed a higher compactibility than MCC. The parameters of the 3D model showed an extreme change between 45 and 60% RH, and at higher RH more and more particles deformed elastically. This was confirmed by analysis of force-displacement profiles. At 60% RH, the radial tensile strength of the Kollidon SR tablets was half of the radial tensile strength at 45% RH. The reason is a higher relative energy of plastic deformation than for MCC. This results in a better utilization of the energy to deform the powder into a tablet and the exceeding of the glass transition temperature at higher RH. In conclusion, at 60% RH at the same rho(rel, max), tableting and tablet properties of Kollidon SR are extremely changed since plasticity is significantly higher. In the second part of the

  6. Tablet-Aided BehavioraL intervention EffecT on Self-management skills (TABLETS) for Diabetes.

    PubMed

    Lynch, Cheryl P; Williams, Joni S; J Ruggiero, Kenneth; G Knapp, Rebecca; Egede, Leonard E

    2016-03-22

    Multiple randomized controlled trials (RCTs) show that behavioral lifestyle interventions are effective in improving diabetes management and that comprehensive risk factor management improves cardiovascular disease (CVD) outcomes. The role of technology has been gaining strong support as evidence builds of its potential to improve diabetes management; however, evaluation of its impact in minority populations is limited. This study intends to provide early evidence of a theory-driven intervention, Tablet-Aided BehavioraL intervention EffecT on Self-management skills (TABLETS), using real-time videoconferencing for education and skills training. We examine the potential for TABLETS to improve health risk behaviors and reduce CVD risk outcomes among a low-income African American (AA) population with poorly controlled type 2 diabetes. The study is a two-arm, pilot controlled trial that randomizes 30 participants to the TABLETS intervention and 30 participants to a usual care group. Blinded outcome assessments will be completed at baseline, 2.5 months (immediate post-intervention), and 6.5 months (follow-up). The TABLETS intervention consists of culturally tailored telephone-delivered diabetes education and skills training delivered via videoconferencing on tablet devices, with two booster sessions delivered via tablet-based videoconferencing at 3 months and 5 months to stimulate ongoing use of the tablet device with access to intervention materials via videoconferencing slides and a manual of supplementary materials. The primary outcomes are physical activity, diet, medication adherence, and self-monitoring behavior, whereas the secondary outcomes are HbA1c, low-density lipoprotein cholesterol (LDL-C), BP, CVD risk, and quality of life. This study provides a unique opportunity to assess the feasibility and efficacy of a theory-driven, tablet-aided behavioral intervention that utilizes real-time videoconferencing technology for education and skills training on self

  7. Drug loss while crushing tablets: Comparison of 24 tablet crushing devices

    PubMed Central

    Thong, Min Yew; Manrique, Yady J.

    2018-01-01

    This study investigated 24 tablet crushing devices for drug loss using different methods to recover the crushed tablet. 24 devices were compared: 3 with disposable cups, 6 with disposable bags, 12 without separate vessels and 3 types of mortar and pestle. One paracetamol tablet was crushed and recovered by tapping the powder out. Where appropriate, depending on crusher size and manufacturer instructions, the powder was also recovered by mixing with water or food. Paracetamol recovery (quantity that can be delivered to a patient) and leftover (quantity remaining in the device) were measured using a validated UV method and the entire experiment was replicated 3 times. Drug recovery ranged from 86.7–98.1% when the crushed tablet was tapped out of the crushers (average loss 5.8%). Significant losses were measured for 18 crushers, particularly manually operated hand-twist crushers with a serrated crushing surface, and some devices with disposable bags or cups. Rinsing the crushed powder with water once resulted in an average of 24.2% drug loss, and this was reduced to 4.2% after a second rinse. If crushing is unavoidable, maximizing medication delivery to the patient is essential. Rinsing twice resulted in similar paracetamol recovery to tapping the powder out; however only water rinses have the potential for direct consumption by the patient, minimizing drug loss across the entire crushing and transfer process. PMID:29494695

  8. 21 CFR 520.1193 - Ivermectin tablets and chewables.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ivermectin tablets and chewables. 520.1193 Section... tablets and chewables. (a) Specifications. (1) Each tablet or chewable contains 68, 136, or 272 micrograms... tablets or chewables described in paragraph (a)(1) as in paragraph (d)(1) and chewables described in...

  9. Development of a zero-order sustained-release tablet containing mesalazine and budesonide intended to treat the distal gastrointestinal tract in inflammatory bowel disease.

    PubMed

    Gareb, Bahez; Eissens, Anko C; Kosterink, Jos G W; Frijlink, Hendrik W

    2016-06-01

    Ulcerative colitis (UC) and Crohn's disease (CD) are diseases affecting the gastrointestinal tract. Treatment depends on the severity of the disease, site of inflammation, and patient's response. The aim of this study was to develop a zero-order sustained-release tablet containing both the anti-inflammatory drugs mesalazine and budesonide as a new treatment option for ileo-colonic CD and UC. Tablets were attained by wet granulation with hydroxypropyl methylcellulose and direct compression. Our newly developed tablet core was coated with different ColoPulse® coating thicknesses and the mesalazine and budesonide release profiles were investigated in a 600-min gastrointestinal simulation system (GISS) experiment, together with commercially available MMX®-mesalazine and MMX®-budesonide. Lag-time, release rate (k0), completeness of release, and zero-order correlation coefficient (R(2)0) could be manipulated by varying ColoPulse® coating thickness. Our newly developed combination preparation (C[4.92]) complied with all conducted European Pharmacopoeia tests as well as an accelerated 6-month stability test and had a lag-time of 250min (simulated ileum targeted), a linear release profile (mesalazine R(2)0=0.9002; budesonide R(2)0=0.9481), and drug release of 100% mesalazine and 77% budesonide. Like C[4.92], MMX®-mesalazine had a linear (R(2)0=0.9883) and complete release profile (96%). However, C[4.92] lag-time was longer (250 vs. 210min), assuring simulated ileum specificity. Remarkably, MMX®-budesonide lag-time was 480min and release was only 7% with a linear character (R(2)0=0.9906). The in vitro results suggest that MMX®-budesonide effectiveness may be improved if budesonide release in the aqueous phase would be increased and that C[4.92] is a potential, new treatment option for ileo-colonic CD and UC. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Microtomographic studies of subdivision of modified-release tablets.

    PubMed

    Wilczyński, Sławomir; Koprowski, Robert; Duda, Piotr; Banyś, Anna; Błońska-Fajfrowska, Barbara

    2016-09-25

    The uniformity of dosage units within a certain batch is ensured when each unit contains the active pharmaceutical ingredient (API) within a narrow range around the label claim. For tablets containing a score-line authorised for dose reductions, the European Pharmacopoeia (Ph. Eur.) considers that the uniformity of the tablet parts may be based on weight measurements regardless of the tablet type (immediate or modified release). This is because it is up to the regulatory authorities first to assess whether the tablet may contain a score-line for such use. X-ray microtomography was applied to assess the symmetry of 36 modified release tablets, containing 300mg of theophylline. The sum of the volume and surface area of the pellets in the subdivided tablets were compared. Simulations were carried out to identify the optimal amount of pellets in the tablet mass. The maximum difference in the API content between two subdivided halves was 165.18mg vs 133.83mg. If the amount of pellets in the tablet mass would drop below 13% on the basis of the pellet surface area, then the Ph. Eur. requirements would be exceeded. The amount of pellets in the tablet halves resulting in the greatest variability in API content was 38%. The results of this study indicate that the pellets were not distributed uniformly in the tablet mass. Thus, the uniformity of the dose in both halves of a tablet containing pellets cannot be based on the weight measurements i.e. it is necessary to develop further standards for tablet subdivision. Microtomographic methods are a very interesting alternative to expensive and time-consuming pharmacokinetic studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. 21 CFR 520.2150b - Stanozolol chewable tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Stanozolol chewable tablets. 520.2150b Section 520... chewable tablets. (a) Specifications. Each chewable tablet contains 2 milligrams of stanozolol. (b) Sponsor... treatment in dogs. (2) Administered orally to small breeds of dogs, 1/2 to 1 tablet twice daily for several...

  12. 21 CFR 529.400 - Chlorhexidine tablets and suspension.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Chlorhexidine tablets and suspension. 529.400... Chlorhexidine tablets and suspension. (a) Specification. Each tablet and each 28-milliliter syringe of.... 000856 in § 510.600(c) of this chapter. (c) Conditions of use—(1) Amount. Place 1 or 2 tablets deep in...

  13. Medication Errors in Patients with Enteral Feeding Tubes in the Intensive Care Unit.

    PubMed

    Sohrevardi, Seyed Mojtaba; Jarahzadeh, Mohammad Hossein; Mirzaei, Ehsan; Mirjalili, Mahtabalsadat; Tafti, Arefeh Dehghani; Heydari, Behrooz

    2017-01-01

    Most patients admitted to Intensive Care Units (ICU) have problems in using oral medication or ingesting solid forms of drugs. Selecting the most suitable dosage form in such patients is a challenge. The current study was conducted to assess the frequency and types of errors of oral medication administration in patients with enteral feeding tubes or suffering swallowing problems. A cross-sectional study was performed in the ICU of Shahid Sadoughi Hospital, Yazd, Iran. Patients were assessed for the incidence and types of medication errors occurring in the process of preparation and administration of oral medicines. Ninety-four patients were involved in this study and 10,250 administrations were observed. Totally, 4753 errors occurred among the studied patients. The most commonly used drugs were pantoprazole tablet, piracetam syrup, and losartan tablet. A total of 128 different types of drugs and nine different oral pharmaceutical preparations were prescribed for the patients. Forty-one (35.34%) out of 116 different solid drugs (except effervescent tablets and powders) could be substituted by liquid or injectable forms. The most common error was the wrong time of administration. Errors of wrong dose preparation and administration accounted for 24.04% and 25.31% of all errors, respectively. In this study, at least three-fourth of the patients experienced medication errors. The occurrence of these errors can greatly impair the quality of the patients' pharmacotherapy, and more attention should be paid to this issue.

  14. 21 CFR 520.863 - Ethylisobutrazine hydrochloride tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ethylisobutrazine hydrochloride tablets. 520.863 Section 520.863 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Ethylisobutrazine hydrochloride tablets. (a) Specifications. Each tablet contains either 10 milligrams or 50...

  15. 21 CFR 520.2582 - Triflupromazine hydrochloride tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Triflupromazine hydrochloride tablets. 520.2582 Section 520.2582 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Triflupromazine hydrochloride tablets. (a) Specifications. Each tablet contains either 10 milligrams or 25...

  16. [Bioequivalence of pyridostigmine bromide dispersible tablets in rabbits].

    PubMed

    Wang, Hong; Wang, Hong; Tan, Qun-you; Zhang, Li; Cheng, Xun-guan; Zhang, Jing-qing

    2011-10-01

    To compare the pharmacokinetic parameters of pyridostigmine bromide dispersible tablets and common tablets in rabbits. Twelve rabbits were given an oral dose (60 mg) of pyridostigmine bromide dispersible tablets or common tablets in a randomized crossover study. The plasma concentration of pyridostigmine bromide was determined by reversed-phase ion pair chromatography. The pharmacokinetic parameters were calculated using DAS2.1.1 software. The pharmacokinetic parameters showed no significant differences in rabbit plasma between pyridostigmine bromide dispersible tablets and common tablets. The two tablets had a C(max) of 1.83∓0.08 mg·L(-1) and 1.68∓0.03 mg·L(-1), tmax of 2.33∓0.41 h and 2.58∓0.20 h, AUC(0-24) of 15.50∓0.62 mg·h·L(-1) and 15.14∓0.30 mg·h·L(-1), AUC(0-∞) of 15.82∓0.70 mg·h·L(-1) and 15.57∓0.32 mg·h·L(-1), respectively. The relative bioavailability F(0-24) was 102.38% and F(0-∞) was 101.61% for the dispersible tablets. The two tablets are bioequivalent in rabbits.

  17. 21 CFR 520.2158b - Dihydrostreptomycin tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Dihydrostreptomycin tablets. 520.2158b Section 520.2158b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Dihydrostreptomycin tablets. (a) Specifications. Each tablet contains 37.5 milligrams dihydrostreptomycin (as the...

  18. 21 CFR 520.2362 - Thenium closylate tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Thenium closylate tablets. 520.2362 Section 520... tablets. (a) Chemical name. (N,N-Dimethyl-N-2-phenoxyethyl-N-2′-thenylammo-nium)-p-chlorobenzene-sulfonate. (b) Specifications. Thenium closylate tablets contain thenium closylate equivalent to 500 milligrams...

  19. 21 CFR 520.246 - Butorphanol tartrate tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Butorphanol tartrate tablets. 520.246 Section 520.246 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... tartrate tablets. (a) Specifications. Each tablet contains 1, 5, or 10 milligrams of butorphanol base...

  20. 21 CFR 520.1331 - Meclofenamic acid tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Meclofenamic acid tablets. 520.1331 Section 520.1331 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... tablets. (a) Specifications. Each tablet contains either 10 or 20 milligrams of meclofenamic acid. (b...

  1. Diclofenac and metabolite pharmacokinetics in children.

    PubMed

    van der Marel, Caroline D; Anderson, Brian J; Rømsing, Janne; Jacqz-Aigrain, Evelyne; Tibboel, Dick

    2004-06-01

    Data concerning metabolism of diclofenac in children are limited to intravenous and enteric coated oral formulations. There are no data examining diclofenac or its hydroxyl metabolite pharmacokinetics after rectal administration in children. Infants (n = 26) undergoing tonsillectomy were given diclofenac 2 mg.kg(-1) followed by 1 mg.kg(-1) 8 h as suppository formulation for postoperative analgesia. Serum was assayed for diclofenac, 4'-hydroxydiclofenac and 5'-hydroxydiclofenac concentrations during the procedure and 1, 2 and 4 h postoperatively. The formation clearances of diclofenac to hydroxyl metabolites were estimated using nonlinear mixed effects models. A single compartment, first order absorption and first order elimination model was used to describe diclofenac pharmacokinetics. Published data from 11 children given enteric-coated diclofenac tablets were used to assess relative bioavailability. Mean (sd) age and weight of the patients were 4.5 (1.5) years and 20.5 (4.1) kg. The formation clearance to 4'-hydroxydiclofenac (% CV) and to 5'-hydroxydiclofenac were 8.41 (8.1) and 3.41 (113) l.h(-1) respectively, standardized to a 70 kg person using allometric '1/4 power' models. Clearance by other routes contributed 33.0 (64) l.h(-1) 70 kg(-1). Elimination clearance of hydroxyl metabolites was fixed at 27.5 l.h(-1) 70 kg(-1). The volumes of distribution of parent diclofenac and its hydroxyl metabolite were 22.8 (19.0) and 45.3 (l.70) kg(-1). The suppository formulation had an absorption half-life of 0.613 (33.2) h with a lag time of 0.188 (24.9) h. Interoccasion variability of formation clearance to 4'-hydroxydiclofenac, diclofenac volume of distribution, absorption half-time and lag time for the suppository was 36%, 55%, 14% and 119%, respectively. The relative bioavailability of the suppository compared with an enteric-coated tablet was 1.26. The formation clearance of the active metabolite 4'-hydroxydiclofenac contributed 19% of total clearance (44.82 l.h(-1

  2. Epinephrine Use in Clinical Trials of Sublingual Immunotherapy Tablets.

    PubMed

    Nolte, Hendrik; Casale, Thomas B; Lockey, Richard F; Fogh, Bodil Svanholm; Kaur, Amarjot; Lu, Susan; Nelson, Harold S

    Allergy immunotherapy can result in systemic allergic reactions and even life-threatening anaphylaxis requiring epinephrine administration. The objective of this study was to describe epinephrine use in the clinical trial development programs of 3 rapidly dissolving sublingual immunotherapy tablets (SLIT-tablets; Merck & Co., Inc., Kenilworth, NJ/ALK, Hørsholm, Denmark/Torii Pharmaceutical Co., Ltd., Tokyo, Japan). Data on epinephrine use were collected from 13 timothy grass SLIT-tablet trials (MK-7243; ≤2800 bioequivalent allergen units/75,000 SQ-T dose, n = 2497; placebo, n = 2139), 5 short ragweed SLIT-tablet trials (MK-3641; ≤12 Amb a 1-U, n = 1725; placebo, n = 770), and 11 house dust mite (HDM) SLIT-tablet trials (MK-8237; ≤12 SQ-HDM; n = 3930; placebo, n = 2246). In grass SLIT-tablet trials, epinephrine was used 13 times (grass SLIT-tablet, n = 10; placebo, n = 3). Eight administrations were for grass SLIT-tablet-related adverse events (AEs): 4 for systemic allergic reactions and 4 for local mouth and/or throat swelling. In ragweed SLIT-tablet trials, epinephrine was used 9 times in 8 subjects (ragweed SLIT-tablet, n = 7; placebo, n = 1 [2 administrations for protracted anaphylaxis]). Four administrations were for ragweed SLIT-tablet-related AEs: 1 for systemic allergic reaction and 3 for local mouth and/or pharynx/throat swelling. In HDM SLIT-tablet trials, epinephrine was administered 13 times (HDM SLIT-tablet, n = 8; placebo, n = 5). Four administrations were for HDM SLIT-tablet-related AEs: 1 for systemic allergic reaction and 3 for local events. Of the 16 epinephrine administrations for events related to SLIT-tablet treatment, 11 occurred within the first week of treatment (7 administrations on day 1) and 5 were subject self-administered. Epinephrine administrations in response to SLIT-tablet-related reactions in clinical trials are uncommon, typically occur within the first week of treatment, and are rarely self-administered. All

  3. 21 CFR 520.1157 - Iodinated casein tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Iodinated casein tablets. 520.1157 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1157 Iodinated casein tablets. (a) Specifications. Each 1-gram tablet contains 25 milligrams of iodinated casein. (b) Sponsor...

  4. 21 CFR 520.1157 - Iodinated casein tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Iodinated casein tablets. 520.1157 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1157 Iodinated casein tablets. (a) Specifications. Each 1-gram tablet contains 25 milligrams of iodinated casein. (b) Sponsor...

  5. 21 CFR 520.1341 - Megestrol acetate tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Megestrol acetate tablets. 520.1341 Section 520.1341 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... tablets. (a) Specifications. Each tablet contains 5 or 20 milligrams of megestrol acetate. (b) Sponsor. No...

  6. 21 CFR 520.784 - Doxylamine succinate tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Doxylamine succinate tablets. 520.784 Section 520.784 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... succinate tablets. (a) Specifications. The drug is in tablet form and contains doxylamine succinate as the...

  7. 21 CFR 520.2042 - Pyrantel pamoate tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Pyrantel pamoate tablets. 520.2042 Section 520.2042 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... tablets. (a) Specifications. Each tablet contains pyrantel pamoate equivalent to 22.7, 45.4, or 113.5...

  8. 21 CFR 520.1331 - Meclofenamic acid tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Meclofenamic acid tablets. 520.1331 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1331 Meclofenamic acid tablets. (a) Specifications. Each tablet contains either 10 or 20 milligrams of meclofenamic acid. (b...

  9. 21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Methylprednisolone, aspirin tablets. 520.1409... Methylprednisolone, aspirin tablets. (a) Specifications. Each tablet contains 0.5 milligram of methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No. 000009 in § 510.600(c) of this chapter. (c) NAS/NRC...

  10. 21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Methylprednisolone, aspirin tablets. 520.1409... Methylprednisolone, aspirin tablets. (a) Specifications. Each tablet contains 0.5 milligram of methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No. 000009 in § 510.600(c) of this chapter. (c) NAS/NRC...

  11. 21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Methylprednisolone, aspirin tablets. 520.1409... Methylprednisolone, aspirin tablets. (a) Specifications. Each tablet contains 0.5 milligram of methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No. 000009 in § 510.600(c) of this chapter. (c) NAS/NRC...

  12. 21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Methylprednisolone, aspirin tablets. 520.1409... Methylprednisolone, aspirin tablets. (a) Specifications. Each tablet contains 0.5 milligram of methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No. 000009 in § 510.600(c) of this chapter. (c) NAS/NRC...

  13. 21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Methylprednisolone, aspirin tablets. 520.1409... Methylprednisolone, aspirin tablets. (a) Specifications. Each tablet contains 0.5 milligram of methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No. 000009 in § 510.600(c) of this chapter. (c) NAS/NRC...

  14. Reduction of tablet weight variability by optimizing paddle speed in the forced feeder of a high-speed rotary tablet press.

    PubMed

    Peeters, Elisabeth; De Beer, Thomas; Vervaet, Chris; Remon, Jean-Paul

    2015-04-01

    Tableting is a complex process due to the large number of process parameters that can be varied. Knowledge and understanding of the influence of these parameters on the final product quality is of great importance for the industry, allowing economic efficiency and parametric release. The aim of this study was to investigate the influence of paddle speeds and fill depth at different tableting speeds on the weight and weight variability of tablets. Two excipients possessing different flow behavior, microcrystalline cellulose (MCC) and dibasic calcium phosphate dihydrate (DCP), were selected as model powders. Tablets were manufactured via a high-speed rotary tablet press using design of experiments (DoE). During each experiment also the volume of powder in the forced feeder was measured. Analysis of the DoE revealed that paddle speeds are of minor importance for tablet weight but significantly affect volume of powder inside the feeder in case of powders with excellent flowability (DCP). The opposite effect of paddle speed was observed for fairly flowing powders (MCC). Tableting speed played a role in weight and weight variability, whereas changing fill depth exclusively influenced tablet weight. The DoE approach allowed predicting the optimum combination of process parameters leading to minimum tablet weight variability. Monte Carlo simulations allowed assessing the probability to exceed the acceptable response limits if factor settings were varied around their optimum. This multi-dimensional combination and interaction of input variables leading to response criteria with acceptable probability reflected the design space.

  15. Relationship between Age and the Ability to Break Scored Tablets

    PubMed Central

    Notenboom, Kim; Vromans, Herman; Schipper, Maarten; Leufkens, Hubert G. M.; Bouvy, Marcel L.

    2016-01-01

    Background: Practical problems with the use of medicines, such as difficulties with breaking tablets, are an often overlooked cause for non-adherence. Tablets frequently break in uneven parts and loss of product can occur due to crumbling and powdering. Health characteristics, such as the presence of peripheral neuropathy, decreased grip strength and manual dexterity, can affect a patient's ability to break tablets. As these impairments are associated with aging and age-related diseases, such as Parkinson's disease and arthritis, difficulties with breaking tablets could be more prevalent among older adults. The objective of this study was to investigate the relationship between age and the ability to break scored tablets. Methods: A comparative study design was chosen. Thirty-six older adults and 36 young adults were systematically observed with breaking scored tablets. Twelve different tablets were included. All participants were asked to break each tablet by three techniques: in between the fingers with the use of nails, in between the fingers without the use of nails and pushing the tablet downward with one finger on a solid surface. It was established whether a tablet was broken or not, and if broken, whether the tablet was broken accurately or not. Results: The older adults experienced more difficulties to break tablets compared to the young adults. On average, the older persons broke 38.1% of the tablets, of which 71.0% was broken accurately. The young adults broke 78.2% of the tablets, of which 77.4% was broken accurately. Further analysis by mixed effects logistic regression revealed that age was associated with the ability to break tablets, but not with the accuracy of breaking. Conclusions: Breaking scored tablets by hand is less successful in an elderly population compared to a group of young adults. Health care providers should be aware that tablet breaking is not appropriate for all patients and for all drugs. In case tablet breaking is unavoidable, a

  16. Carnauba wax as a promising excipient in melt granulation targeting the preparation of mini-tablets for sustained release of highly soluble drugs.

    PubMed

    Nart, Viviane; Beringhs, André O'Reilly; França, Maria Terezinha; de Espíndola, Brenda; Pezzini, Bianca Ramos; Stulzer, Hellen Karine

    2017-01-01

    Mini-tablets are a new tendency in solid dosage form design for overcoming therapeutic obstacles such as impaired swallowing and polypharmacy therapy. Among their advantages, these systems offer therapeutic benefits such as dose flexibility and combined drug release patterns. The use of lipids in the formulation has also drawn considerable interest as means to modify the drug release from the dosage form. Therefore, this paper aimed at developing sustained release mini-tablets containing the highly soluble drugs captopril and metformin hydrochloride. Carnauba wax was used as a lipid component in melt granulation, targeting the improvement of the drugs poor flowability and tabletability, as well as to sustain the drug release profiles in association with other excipients. To assist sustaining the drug release, Ethocel™ (EC) and Kollicoat® SR 30D associated with Opadry® II were employed as matrix-forming and reservoir-forming materials, respectively. The neat drugs, granules and the bulk formulations were evaluated for their angle of repose, compressibility index, Hausner ratio and tabletability. Mini-tablets were evaluated for their weight variation, hardness, friability, drug content and in-vitro drug release. The results indicated that melt granulation with carnauba wax improved the flow and the tabletability of the drugs, allowing the preparation of mini-tablets with adequate tensile strength under reduced compaction pressures. All mini-tablet formulations showed acceptable hardness (within the range of 1.16 to 3.93Kp) and friability (<0.1%). The melt-granulated captopril in matrix systems containing 50% EC (45P, 100P or 100FP) and the melt-granulated metformin hydrochloride in reservoir systems coated with Kollicoat® SR 30D and Opadry® II (80:20 with 10% weight gain or 70:30 with 20% weight gain) exhibited release profiles adequate to sustained release formulations, for over 450min. Therefore, carnauba wax proved to be a promising excipient in melt

  17. [Modern polymers in matrix tablets technology].

    PubMed

    Zimmer, Łukasz; Kasperek, Regina; Poleszak, Ewa

    2014-01-01

    Matrix tablets are the most popular method of oral drug administration, and polymeric materials have been used broadly in matrix formulations to modify and modulate drug release rate. The main goal of the system is to extend drug release profiles to maintain a constant in vivo plasma drug concentration and a consistent pharmacological effect. Polymeric matrix tablets offer a great potential as oral controlled drug delivery systems. Cellulose derivatives, like hydroxypropyl methylcellulose (HPMC) are often used as matrix formers. However, also other types of polymers can be used for this purpose including: Kollidon SR, acrylic acid polymers such as Eudragits and Carbopols. Nevertheless, polymers of natural origin like: carragens, chitosan and alginates widely used in the food and cosmetics industry are now coming to the fore of pharmaceutical research and are used in matrix tablets technology. Modern polymers allow to obtain matrix tablets by 3D printing, which enables to develop new formulation types. In this paper, the polymers used in matrix tablets technology and examples of their applications were described.

  18. Tablet splitting: is it worthwhile? Analysis of drug content and weight uniformity for half tablets of 16 commonly used medications in the outpatient setting.

    PubMed

    Helmy, Sally A

    2015-01-01

    Tablet splitting is a well-established medical practice in clinical settings for multiple reasons, including cost savings and ease of swallowing. However, it does not necessarily result in weight-uniform half tablets. To (a) investigate the effect of tablet characteristics on weight and content uniformity of half tablets, resulting from splitting 16 commonly used medications in the outpatient setting and (b) provide recommendations for safe tablet-splitting prescribing practices. Ten random tablets from each of the selected medications were weighed and split by 5 volunteers (2 men and 3 women aged 25-44 years) using a knife. The selected medications were mirtazapine 30 mg, bromazepam 3 mg, oxcarbazepin 150 mg, sertraline 50 mg, carvedilol 25 mg, bisoprolol fumarate 10 mg, losartan 50 mg, digoxin 0.25 mg, amiodarone HCl 200 mg, metformin HCl 1,000 mg, glimepiride 4 mg, montelukast 10 mg, ibuprofen 600 mg, celecoxib 200 mg, meloxicam 15 mg, and sildenafil citrate 50 mg. The resulting half tablets were evaluated for weight and drug content uniformity in accordance with proxy United States Pharmacopeia (USP) specification (95%-105% for digoxin and 90%-110% for the other 15 drugs). Weight and drug content uniformity were assessed by comparing weight or drug content of the half tablets with one-half of the mean weight or drug content for all whole tablets in the sample. The percentages by which the weight and drug content of each whole tablet or half tablet differed from sample mean values were calculated. Other relevant physical characteristics of the 16 products were measured. A total of 52 of 320 half tablets (16.2%) and 48 of 320 half tablets (15.0%) fell outside of the proxy USP specification for weight and drug content, respectively. Bromazepam, carvedilol, bisoprolol, losartan, digoxin, and meloxicam half tablets failed the weight and content uniformity test; however, the half tablets for the rest of the medications passed the test. Mean percent weight loss after

  19. Continuous manufacturing of tablets with PROMIS-line - Introduction and case studies from continuous feeding, blending and tableting.

    PubMed

    Simonaho, Simo-Pekka; Ketolainen, Jarkko; Ervasti, Tuomas; Toiviainen, Maunu; Korhonen, Ossi

    2016-07-30

    Drug manufacturing technology is in the midst of modernization and continuous manufacturing of drug products is especially the focus of great interest. The adoption of new manufacturing approaches requires extensive cooperation between industry, regulatory bodies, academics and equipment manufacturers. In this paper we introduce PROMIS-line which is a continuous tableting line built at the University of Eastern Finland, School of Pharmacy, PROMIS-centre. PROMIS-line is modular and tablets can be produced via dry granulation or direct compression. In three case studies, continuous feeding, blending and tablet performance is studied to illustrate some basic features of PROMIS-line. In conclusion, the PROMIS-line is an excellent tool for studying the fundamentals of continuous manufacturing of tablets. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Scaffolding Equals Success in Teaching Tablet PCs

    ERIC Educational Resources Information Center

    Dickerson, Jeremy; Williams, Scott; Browning, J. B.

    2009-01-01

    After many years of using the mouse and keyboard as the primary means of computer input, people are seeing a strong surge into a new generation of input technologies such as tablet PCs. As more professionals adopt tablet PCs for use in the workplace, there is a subsequent increased demand for tablet PC instruction in the classroom. Examples of…

  1. 21 CFR 520.2150a - Stanozolol tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... chapter. (c) Conditions of use. (1) Used as an anabolic steroid treatment in dogs and cats. (2) Administered orally to cats and small breeds of dogs, 1/2 to 1 tablet twice daily for several weeks; to large breeds of dogs, 1 to 2 tablets twice daily for several weeks. The tablets may be crushed and administered...

  2. 21 CFR 520.2150a - Stanozolol tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... chapter. (c) Conditions of use. (1) Used as an anabolic steroid treatment in dogs and cats. (2) Administered orally to cats and small breeds of dogs, 1/2 to 1 tablet twice daily for several weeks; to large breeds of dogs, 1 to 2 tablets twice daily for several weeks. The tablets may be crushed and administered...

  3. 21 CFR 520.2150a - Stanozolol tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... chapter. (c) Conditions of use. (1) Used as an anabolic steroid treatment in dogs and cats. (2) Administered orally to cats and small breeds of dogs, 1/2 to 1 tablet twice daily for several weeks; to large breeds of dogs, 1 to 2 tablets twice daily for several weeks. The tablets may be crushed and administered...

  4. 21 CFR 520.2150a - Stanozolol tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... chapter. (c) Conditions of use. (1) Used as an anabolic steroid treatment in dogs and cats. (2) Administered orally to cats and small breeds of dogs, 1/2 to 1 tablet twice daily for several weeks; to large breeds of dogs, 1 to 2 tablets twice daily for several weeks. The tablets may be crushed and administered...

  5. 21 CFR 520.903e - Febantel tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Febantel tablets. 520.903e Section 520.903e Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.903e Febantel tablets. (a) Specifications. Each scored tablet contains 27.2 milligrams of febantel for use in dogs, puppies, cats, and...

  6. 21 CFR 520.2150a - Stanozolol tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Stanozolol tablets. 520.2150a Section 520.2150a... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2150a Stanozolol tablets. (a) Specifications. Each tablet contains 2 milligrams of stanozolol. (b) Sponsor. No. 000009 in § 510.600(c) of this...

  7. 21 CFR 520.1872 - Praziquantel, pyrantel pamoate, and febantel tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... tablets. 520.1872 Section 520.1872 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.1872 Praziquantel, pyrantel pamoate, and febantel tablets. (a) Specifications. Each tablet or chewable tablet contains either: (1) Tablet No. 1: 22.7 milligrams praziquantel, 22.7 milligrams pyrantel...

  8. Orodispersible tablets containing taste-masked solid lipid pellets with metformin hydrochloride: Influence of process parameters on tablet properties.

    PubMed

    Petrovick, Gustavo Freire; Kleinebudde, Peter; Breitkreutz, Jörg

    2018-01-01

    Compaction of multiparticulates into tablets, particularly into orodispersible tablets (ODTs), is challenging. The compression of pellets, made by solid lipid extrusion/spheronization processes, presents peculiar difficulties since solid lipids usually soften or melt at relatively low temperature ranges and due to applied mechanical forces. Until now, there are no reports in literature about the development of ODTs based on solid lipid pellets. To investigate the feasibility of producing such tablets, a design of experiment (DoE) approach was performed to elucidate the influence of compression force and amount of two co-processed excipients (Ludiflash ® and Parteck ® ODT) on properties of the tablets (friability, tensile strength, and disintegration time). ODTs (15 mm, flat-faced) with solid lipid pellets (250-1000 µm in diameter) containing 500 mg of metformin HCl, presenting immediate drug release profile and taste-masked properties, were targeted. During compression, a strong lamination of the tablets containing Parteck ® ODT was observed. This phenomenon was prominently observed when high compression forces (≥5 kN) and high excipient amounts (≥40%; w/w) were used. On the other hand, the DoE focused on tablets with Ludiflash ® showed better results regarding the production of ODTs. A positive influence of the compression force on the tensile strength and disintegration time of the tablets, regarding specifications of the Ph. Eur., was observed. The increase in the amount of this excipient resulted in fast disintegrating tablets, however, a negative influence on the tensile strength was noticed. After optimization of the parameters and formulation, based on the DoE results and considering the Ph. Eur. specifications for tablets, ODTs based on lipid pellets containing metformin HCl presenting immediate release profile (85% drug release in less than 30 min) and taste-masked properties (determined by an electronic tongue) were successfully

  9. [Consideration of drug absorption in customizing drug therapy].

    PubMed

    Walter-Sack, I; Haefeli, W E

    2000-09-01

    The rate and extent of drug absorption from the small intestine are related to the release of the active ingredient from a dosage form, its solubility in the liquid phase of gastrointestinal contents, and the transport of the dissolved compound or the intact dosage form from the stomach into the duodenum. With pharmaceutical preparations releasing the active compound within the stomach, and enteric-coated "micro"-formulations (micropellets), gastric emptying is possible during the interdigestive and the digestive period. Potential differences of drug absorption between fasting administration and intake during the digestive period are unpredictable, because they are related to the release characteristics of the dosage form. However, larger enteric-coated preparations like tablets can leave the stomach only with a phase 3 contraction of fasting motility; intake during the digestive period will result in gastric retention of this type of dosage form until all food has left the stomach and fasting motility is restored. Consequently the onset of drug absorption is delayed. This interaction between food and large enteric-coated dosage forms is predictable from pyloric function in relation to the gastric motility. As it occurs regularly, it can be taken into account when prescribing enteric-coated dosage forms. If concomitant intake of food and enteric-coated drugs is unavoidable, but a rapid onset of drug absorption is necessary, micropellets are the dosage form of choice. When the therapeutic effect is insufficient, drug dosage form and timing of drug administration should be checked before prescribing a different active compound.

  10. Enhancement of the Oral Bioavailability of Fexofenadine Hydrochloride via Cremophor® El-Based Liquisolid Tablets

    PubMed Central

    Yehia, Soad Ali; El-Ridi, Mohamed Shafik; Tadros, Mina Ibrahim; El-Sherif, Nolwa Gamal

    2015-01-01

    Purpose: The current work aimed to develop promising Fexofenadine hydrochloride (FXD) liquisolid tablets able to increase its oral bioavailability and shorten time to reach maximum plasma concentrations (Tmax). Methods: Eighteen liquisolid powders were developed based on 3 variables; (i) vehicle type [Propylene glycol (PG) or Cremophor® EL (CR)], (ii) carrier [Avicel® PH102] to coat [Aerosil® 200] ratio (15, 20, 25) and (iii) FXD concentration in vehicle (30, 35, 40 %, w/w). Pre-compression studies involved identification of physicochemical interactions and FXD crystallinity (FT-IR, DSC, XRD), topographic visualization (SEM) and estimation of flow properties (angle of repose, Carr’s index, Hausner’s ratio). CR-based liquisolid powders were compressed as liquisolid tablets (LST 9 – 18) and evaluated for weight-variation, drug-content, friability-percentage, disintegration-time and drug-release. The pharmacokinetics of LST-18 was evaluated in healthy volunteers relative to Allegra® tablets. Results: Pre-compression studies confirmed FXD dispersion in vehicles, conversion to amorphous form and formation of liquisolid powders. CR-based liquisolid powders showed acceptable-to-good flow properties suitable for compaction. CR-based LSTs had appropriate physicochemical properties and short disintegration times. Release profile of LST-18 showed a complete drug release within 5 min. Conclusion: LST-18 succeeded in increasing oral FXD bioavailability by 62% and reducing Tmax to 2.16 h. PMID:26819931

  11. Systematic evaluation of common lubricants for optimal use in tablet formulation.

    PubMed

    Paul, Shubhajit; Sun, Changquan Calvin

    2018-05-30

    As an essential formulation component for large-scale tablet manufacturing, the lubricant preserves tooling by reducing die-wall friction. Unfortunately, lubrication also often results in adverse effects on tablet characteristics, such as prolonged disintegration, slowed dissolution, and reduced mechanical strength. Therefore, the choice of lubricant and its optimal concentration in a tablet formulation is a critical decision in tablet formulation development to attain low die-wall friction while minimizing negative impact on other tablet properties. Three commercially available tablet lubricants, i.e., magnesium stearate, sodium stearyl fumerate, and stearic acid, were systematically investigated in both plastic and brittle matrices to elucidate their effects on reducing die-wall friction, tablet strength, tablet hardness, tablet friability, and tablet disintegration kinetics. Clear understanding of the lubrication efficiency of commonly used lubricants as well as their impact on tablet characteristics would help future tablet formulation efforts. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. 21 CFR 520.1199 - Ivermectin, pyrantel, and praziquantel tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ivermectin, pyrantel, and praziquantel tablets... Ivermectin, pyrantel, and praziquantel tablets. (a) Specifications. Each chewable tablet contains: (1) 34...) Amount. Administer monthly according to body weight as follows: (i) 6 to 12 lb: one tablet as described...

  13. 21 CFR 520.1200 - Ivermectin, fenbendazole, and praziquantel tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ivermectin, fenbendazole, and praziquantel tablets... Ivermectin, fenbendazole, and praziquantel tablets. (a) Specifications. Each chewable tablet contains either... § 510.600(c) of this chapter. (c) Conditions of use in dogs—(1) Amount. Administer tablets to provide 6...

  14. In vitro dissolution of proton-pump inhibitor products intended for paediatric and geriatric use in physiological bicarbonate buffer.

    PubMed

    Liu, Fang; Shokrollahi, Honaz

    2015-05-15

    Proton-pump inhibitor (PPI) products based on enteric coated multiparticulates are design to meet the needs of patients who cannot swallow tablets such as children and older adults. Enteric coated PPI preparations exhibit delays in in vivo absorption and onset of antisecretory effects, which is not reflected by the rapid in vitro dissolution in compendial pH 6.8 phosphate buffer commonly used for assessment of these products. A more representative and physiological medium, pH 6.8 mHanks bicarbonate buffer, was used in this study to evaluate the in vitro dissolution of enteric coated multiparticulate-based PPI products. Commercially available omeprazole, lansoprazole and esomeprazole products were subject to dissolution tests using USP-II apparatus in pH 4.5 phosphate buffer saline for 45 min (acid stage) followed by pH 6.8 phosphate buffer or pH 6.8 mHanks bicarbonate buffer. In pH 6.8 phosphate buffer, all nine tested products displayed rapid and comparable dissolution profiles meeting the pharmacopeia requirements for delayed release preparations. In pH 6.8 mHanks buffer, drug release was delayed and failed the pharmacopeia requirements from most enteric coated preparations. Despite that the same enteric polymer, methacrylic acid-ethyl acrylate copolymer (1:1), was applied to all commercial multiparticulate-based products, marked differences were observed between dissolution profiles of these preparations. The use of pH 6.8 physiological bicarbonate (mHanks) buffer can serve as a useful tool to provide realistic and discriminative in vitro release assessment of enteric coated PPI preparations and to assist rational formulation development of these products. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Continuous direct tablet compression: effects of impeller rotation rate, total feed rate and drug content on the tablet properties and drug release.

    PubMed

    Järvinen, Maiju A; Paaso, Janne; Paavola, Marko; Leiviskä, Kauko; Juuti, Mikko; Muzzio, Fernando; Järvinen, Kristiina

    2013-11-01

    Continuous processing is becoming popular in the pharmaceutical industry for its cost and quality advantages. This study evaluated the mechanical properties, uniformity of dosage units and drug release from the tablets prepared by continuous direct compression process. The tablet formulations consisted of acetaminophen (3-30% (w/w)) pre-blended with 0.25% (w/w) colloidal silicon dioxide, microcrystalline cellulose (69-96% (w/w)) and magnesium stearate (1% (w/w)). The continuous tableting line consisted of three loss-in-weight feeders and a convective continuous mixer and a rotary tablet press. The process continued for 8 min and steady state was reached within 5 min. The effects of acetaminophen content, impeller rotation rate (39-254 rpm) and total feed rate (15 and 20 kg/h) on tablet properties were examined. All the tablets complied with the friability requirements of European Pharmacopoeia and rapidly released acetaminophen. However, the relative standard deviation of acetaminophen content (10% (w/w)) increased with an increase in impeller rotation rate at a constant total feed rate (20 kg/h). A compression force of 12 kN tended to result in greater tablet hardness and subsequently a slower initial acetaminophen release from tablets when compared with those made with the compression force of about 8 kN. In conclusion, tablets could be successfully prepared by a continuous direct compression process and process conditions affected to some extent tablet properties.

  16. 21 CFR 520.2280 - Sulfamethizole and methenamine mandelate tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sulfamethizole and methenamine mandelate tablets... Sulfamethizole and methenamine mandelate tablets. (a) Specifications. Each tablet contains 250 milligrams of... urethra and bladder. (2) It is administered at a dosage level of one tablet for each 20 pounds of body...

  17. 21 CFR 520.1446 - Milbemcyin oxime and lufenuron tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Milbemcyin oxime and lufenuron tablets. 520.1446... oxime and lufenuron tablets. (a) Specifications—(1) Tablets containing: 2.3 milligrams (mg) milbemycin... 230 mg lufenuron, or 23 mg milbemycin oxime and 460 mg lufenuron. (2) Flavored tablets containing: 2.3...

  18. Enalapril maleate orally disintegrating tablets: tableting and in vivo evaluation in hypertensive rats.

    PubMed

    Tawfeek, Hesham M; Faisal, Waleed; Soliman, Ghareb M

    2018-06-01

    The aim of this study was to develop orally disintegrating tablets (ODTs) for enalapril maleate (EnM) to facilitate its administration to the elderly or other patients having dysphagia. Compatibility between EnM and various excipients was studied using differential scanning calorimetry. ODTs of EnM were prepared by direct compression of EnM mixtures with various superdisintegrants. The tablets were evaluated for physical properties including drug content, hardness, friability, disintegration time, wetting time, and drug release. The antihypertensive effect of the optimum EnM ODTs was evaluated in vivo in hypertensive rats and compared with commercial EnM formulation. EnM ODTs had satisfactory results in terms of drug content and friability. Tablet wetting and disintegration were fast and dependent on the used superdisintegrant where croscarmellose showed the fastest wetting and disintegration time of ∼7 s. EnM release from the tablets was rapid where complete release was obtained in 10-15 min. Selected EnM ODTs rapidly and efficiently reduced the rat's blood pressure to its normal value within 1 h, compared with 4 h for EnM commercial formulation. These results confirm that EnM ODTs could find application in the management of hypertension in the elderly or other patients having dysphagia.

  19. Composition profiling of seized ecstasy tablets by Raman spectroscopy.

    PubMed

    Bell, S E; Burns, D T; Dennis, A C; Matchett, L J; Speers, J S

    2000-10-01

    Raman spectroscopy with far-red excitation has been investigated as a simple and rapid technique for composition profiling of seized ecstasy (MDMA, N-methyl-3,4-methylenedioxyamphetamine) tablets. The spectra obtained are rich in vibrational bands and allow the active drug and excipient used to bulk the tablets to be identified. Relative band heights can be used to determine drug/excipient ratios and the degree of hydration of the drug while the fact that 50 tablets per hour can be analysed allows large numbers of spectra to be recorded. The ability of Raman spectroscopy to distinguish between ecstasy tablets on the basis of their chemical composition is illustrated here by a sample set of 400 tablets taken from a large seizure of > 50,000 tablets that were found in eight large bags. The tablets are all similar in appearance and carry the same logo. Conventional analysis by GC-MS showed they contained MDMA. Initial Raman studies of samples from each of the eight bags showed that despite some tablet-to-tablet variation within each bag the contents could be classified on the basis of the excipients used. The tablets in five of the bags were sorbitol-based, two were cellulose-based and one bag contained tablets with a glucose excipient. More extensive analysis of 50 tablets from each of a representative series of sample bags have distribution profiles that showed the contents of each bag were approximately normally distributed about a mean value, rather than being mixtures of several discrete types. Two of the sorbitol-containing sample sets were indistinguishable while a third was similar but not identical to these, in that it contained the same excipient and MDMA with the same degree of hydration but had a slightly different MDMA/sorbitol ratio. The cellulose-based samples were badly manufactured and showed considerable tablet-to-tablet variation in their drug/excipient ratio while the glucose-based tablets had a tight distribution in their drug/excipient ratios

  20. 21 CFR 520.622c - Diethylcarbamazine citrate chewable tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Diethylcarbamazine citrate chewable tablets. 520... Diethylcarbamazine citrate chewable tablets. (a) Specifications. Each chewable tablet contains 30, 45, 60, 120, 150... tablets as in paragraph (c)(2)(i) of this section. (2) For 000069, use of 60, 120, or 180 milligram...

  1. [Production and assessing release of imipramine and magnesium from tablets].

    PubMed

    Kasperek, Regina; Zimmer, Łukasz; Szalast-Pietrzak, Agnieszka; Marzec, Zbigniew; Poleszak, Ewa

    2014-01-01

    In the pharmaceutical technology there is a trend to produce tablets composed of several medicinal substances to increase therapeutic effect and reduce the frequency of drug administration. In the literature there are reports concerning pharmacological studies in which a potentiation of the effects has been observed after a co-administration of antidepressant imipramine and magnesium. Currently, there is no formulation on the market comprising imipramine and magnesium, therefore, it was decided to produce uncoated tablets. In order to prepare the tablets by direct compression, it was necessary to select suitable excipients. The aim of the study was to elaborate the composition and to prepare the tablets with imipramine and magnesium, as well as to assess the quality of the tablets by physical characteristics and by the release study of the active substances. In order to prepare the tablets, compositions of different polymers and other excipients were added. The tablets were produced by direct compression method in a tablet press. Physical properties of the obtained tablets and the release of the active substances into an acidic medium in a paddle apparatus were tested. The contents of imipramine and magnesium were determined by different methods: spectrophotometrically and atomic absorption spectrometry, respectively. The composition of excipients necessary to produce tablets comprising imipramine and magnesium was established. All of prepared tablets were in compliance with the pharmacopoeial requirements. The release tests showed that above 80% of imipramine was released within 20-35 min and 80-76% of magnesium up to 45 min from the composed tablets and one-ingredient tablets, respectively. The compositions of excipients for tablets consisting of imipramine and magnesium were presented. The active substances were released within 45 min in the acidic medium, and the administration of these substances in the composed tablets did not affect pharmaceutical

  2. Near-infrared spectroscopy monitoring and control of the fluidized bed granulation and coating processes-A review.

    PubMed

    Liu, Ronghua; Li, Lian; Yin, Wenping; Xu, Dongbo; Zang, Hengchang

    2017-09-15

    The fluidized bed granulation and pellets coating technologies are widely used in pharmaceutical industry, because the particles made in a fluidized bed have good flowability, compressibility, and the coating thickness of pellets are homogeneous. With the popularization of process analytical technology (PAT), real-time analysis for critical quality attributes (CQA) was getting more attention. Near-infrared (NIR) spectroscopy, as a PAT tool, could realize the real-time monitoring and control during the granulating and coating processes, which could optimize the manufacturing processes. This article reviewed the application of NIR spectroscopy in CQA (moisture content, particle size and tablet/pellet thickness) monitoring during fluidized bed granulation and coating processes. Through this review, we would like to provide references for realizing automated control and intelligent production in fluidized bed granulation and pellets coating of pharmaceutical industry. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. 21 CFR 520.82b - Aminopropazine fumarate, neomycin sulfate tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Aminopropazine fumarate, neomycin sulfate tablets... Aminopropazine fumarate, neomycin sulfate tablets. (a) Specifications. The drug is in tablet form. Each tablet... administered at a dosage level of one to two tablets per 10 pounds of body weight twice daily for 3 days.1 (3...

  4. How do roll compaction/dry granulation affect the tableting behaviour of inorganic materials? Microhardness of ribbons and mercury porosimetry measurements of tablets.

    PubMed

    Freitag, Franziska; Reincke, Katrin; Runge, Jürgen; Grellmann, Wolfgang; Kleinebudde, Peter

    2004-07-01

    The effect of roll compaction/dry granulation on the ribbon and tablet properties produced using different magnesium carbonates was evaluated. The ribbon microhardness and the pore size distribution of tablets were used as evaluation factors. Increasing the specific compaction force resulted in higher microhardness for ribbons prepared with all four magnesium carbonates accompanied with decreased part of fine. Consequently, the corresponding produced tablets displayed a lower tensile strength. A possible correlation between the particle shape, surface area and the resulting pore structure of tablets produced with the four different types of magnesium carbonate was observed. The tensile strength of tablets prepared using granules was lower than tensile strength of tablets produced using starting materials. The partial loss of compactibility resulted in a demand of low loads during roll compaction. However, the impact of changes in the material properties during the roll compaction depended greatly on the type of magnesium carbonate, the specific compaction force and the tableting pressure applied.

  5. 21 CFR 520.581 - Dichlorophene tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...) Specifications. Each tablet contains 1 gram of dichlorophene. (b) Sponsor. See 023851 in § 510.600(c) of this.... Dogs—(1) Amount. Single dose of 1 tablet (1 gram of dichlorophene) for each 10 pounds of body weight...

  6. 21 CFR 520.581 - Dichlorophene tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) Specifications. Each tablet contains 1 gram of dichlorophene. (b) Sponsor. See 023851 in § 510.600(c) of this.... Dogs—(1) Amount. Single dose of 1 tablet (1 gram of dichlorophene) for each 10 pounds of body weight...

  7. 21 CFR 520.581 - Dichlorophene tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) Specifications. Each tablet contains 1 gram of dichlorophene. (b) Sponsor. See 023851 in § 510.600(c) of this.... Dogs—(1) Amount. Single dose of 1 tablet (1 gram of dichlorophene) for each 10 pounds of body weight...

  8. The accuracy, precision and sustainability of different techniques for tablet subdivision: breaking by hand and the use of tablet splitters or a kitchen knife.

    PubMed

    van Riet-Nales, Diana A; Doeve, Myrthe E; Nicia, Agnes E; Teerenstra, Steven; Notenboom, Kim; Hekster, Yechiel A; van den Bemt, Bart J F

    2014-05-15

    Tablets are frequently subdivided to lower the dose, to facilitate swallowing by e.g. children or older people or to save costs. Splitting devices are commonly used when hand breaking is difficult or painful. Three techniques for tablet subdivision were investigated: hand breaking, tablet splitter, kitchen knife. A best case drug (paracetamol), tablet (round, flat, uncoated, 500 mg) and operator (24-year student) were applied. Hundred tablets were subdivided by hand and by three devices of each of the following types: Fit & Healthy, Health Care Logistics, Lifetime, PillAid, PillTool, Pilomat tablet splitter; Blokker kitchen knife. The intra and inter device accuracy, precision and sustainability were investigated. The compliance to (adapted) regulatory requirements was investigated also. The accuracy and precision of hand broken tablets was 104/97% resp. 2.8/3.2% (one part per tablet considered; parts right/left side operator). The right/left accuracies of the splitting devices varied between 60 and 133%; the precisions 4.0 and 29.6%. The devices did not deteriorate over 100-fold use. Only hand broken tablets complied with all regulatory requirements. Health care professionals should realize that tablet splitting may result in inaccurate dosing. Authorities should undertake appropriate measures to assure good function of tablet splitters and, where feasible, to reduce the need for their use. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Solventless visible light-curable coating: I. Critical formulation and processing parameters.

    PubMed

    Bose, Sagarika; Bogner, Robin H

    2010-06-30

    Film coating is generally accomplished by spraying polymers dissolved in solvents onto a cascading bed of tablets. The limitations associated with the use of solvents (both aqueous and organic) can be overcome by the use of solventless coating technologies. In this proposed solventless photocurable film coating system, each layer of coating onto the pellets (non-pareil beads) was formed using liquid photocurable monomer, powdered pore-forming agents, photosensitizers and photoinitiators in a mini-coating pan and later cured by visible light. Yield, coating efficiency, variation in color, diameter and roundness were determined for each batch to evaluate process efficiency and coating quality. It was found that the ratio (S/L ratio) of the amount of solid (S) pore-forming agent to volume of liquid (L) monomer, particle size and type of the pore-forming agent, concentration of initiator, and total exposure (light intensity x exposure time) of light were critical formulation and processing parameters for the process. Using lactose as a pore-forming agent, an optimum ratio of pore-forming agent to photocurable polymer was 1.8-3.0 to achieve good process efficiency and uniformity. The ratio was sensitive to particle size and type of pore-forming agent. 2010 Elsevier B.V. All rights reserved.

  10. Assessing Student Writing on Tablets

    ERIC Educational Resources Information Center

    Davis, Laurie Laughlin; Orr, Aline; Kong, Xiaojing; Lin, Chow-Hong

    2015-01-01

    There is increasing expectation that schools should be able to use tablets for a range of instructional and assessment purposes. This article considers the comparability of student writing on tablets and laptops to ensure that writing assessment is conducted in a way that is fair to all students. Data were collected from a sample of 826 students…

  11. Tablet PCs: The Write Approach

    ERIC Educational Resources Information Center

    Milner, Jacob

    2006-01-01

    This article discusses the transforming effects of tablet PCs in the classroom. As 1-to-1 computing becomes the goal on K-12 campuses, school districts are turning to this newer, pen-based technology. Saint Mary's School's new Lenovo ThinkPad X41 tablet PCs had transformed the way Saint Mary's teachers did their jobs. Teachers created outlines for…

  12. Comparative bioavailability study of cefuroxime axetil (equivalent to 500 mg cefuroxime/tablet) tablets (Zednad® versus Zinnat®) in healthy male volunteers.

    PubMed

    Asiri, Y A; Al-Hadiya, B M; Kadi, A A; Al-Khamis, K I; Mowafy, H A; El-Sayed, Y M

    2011-09-01

    This study was performed to investigate the bioequivalence of cefuroxime axetil tablets between a generic test product (A) Zednad® Tablet (500 mg cefuroxime/ tablet, Diamond Pharma, Syria), and the Reference Product (B) Zinnat® Tablet (500 mg cefuroxime/tablet, GlaxoSmithKline, Saudi Arabia). The bioavailability study was carried out for 24 healthy male volunteers. The subjects received 1 Zednad® Tablet (500 mg/ tablet) and 1 Zinnat® Tablet (500 mg/tablet) in a randomized, two-way crossover design fashion on 2 treatment days, after an overnight fast of at least 10 h, with a washout period of 7 days. 24 volunteers plus 2 alternatives completed the crossover. The bioanalysis of clinical plasma samples was accomplished by HPLC method, which was developed and validated in accordance with international guidelines. Pharmacokinetic parameters, determined by standard non-compartmental methods, and ANOVA statistics were calculated using SAS Statistical Software. The significance of a sequence effect was tested using the subjects nested in sequence as the error term. The 90% confidence intervals for the ratio between the test and reference product pharmacokinetic parameters of AUC0→t, AUC0→∞, and Cmax were calculated and found to be within the confidence limits of 80.00 - 125.00% for AUC0→t, AUC0→∞ and Cmax. The study demonstrated that the test product (A) was found bioequivalent to the reference product (B) following an oral dose of 500 mg tablet. Therefore, the two formulations were considered to be bioequivalent.

  13. Controlled-release tablet formulation of isoniazid.

    PubMed

    Jain, N K; Kulkarni, K; Talwar, N

    1992-04-01

    Guar (GG) and Karaya gums (KG) alone and in combination with hydroxy-propylmethylcellulose (HPMC) were evaluated as release retarding materials to formulate a controlled-release tablet dosage form of isoniazid (1). In vitro release of 1 from tablets followed non-Fickian release profile with rapid initial release. Urinary excretion studies in normal subjects showed steady-state levels of 1 for 13 h. In vitro and in vivo data correlated (r = 0.9794). The studies suggested the potentiality of GG and KG as release retarding materials in formulating controlled-release tablet dosage forms of 1.

  14. 21 CFR 520.1720a - Phenylbutazone tablets and boluses.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Phenylbutazone tablets and boluses. 520.1720a... Phenylbutazone tablets and boluses. (a) Specifications. Each tablet contains 100, 200, or 400 milligrams (mg), or...-mg or 1-g tablets, or 2- or 4-g boluses, in dogs and horses. (2) Nos. 000010 and 059130 for use of...

  15. 21 CFR 520.581 - Dichlorophene tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) Specifications. Each tablet contains 1 gram of dichlorophene. (b) Sponsor. See 023851 in § 510.600(c) of this.... Dogs(1) Amount. Single dose of 1 tablet (1 gram of dichlorophene) for each 10 pounds of body weight. (2...

  16. The influence of plasticizers on the release of theophylline from microporous-controlled tablets.

    PubMed

    Lin, W J; Lee, H K; Wang, D M

    2004-10-19

    The aim of present work was to investigate the influence of plasticizer on the release of theophylline from microporous-controlled tablets. Three plasticizers, acetyltributyl citrate (ATBC), castor oil, and triacetin, were included in this study. These plasticizers reduced the crystallinity of poly(epsilon-caprolactone) (PCL)/poly(ethylene glycol) (PEG)-blended films, and the most prominent change of enthalpy of fusion was the film plasticized by triacetin. This might be due to triacetin penetrating into both PCL and PEG domains. However, the lipophilic property of castor oil only allowed it to alter the crystallization of hydrophobic PCL domain. The Young's modulus and the tensile strength of films showed a decreased tendency while increasing the amount of plasticizer. The change of elongation of plasticized blended films was irregular and was dependent of the type of plasticizer. The size of micropores formed in the presence of plasticizer was larger than those micropores formed in its absence. The fatty plasticizer, castor oil, altered the thermal and mechanical performance and pore size of films via soluble in PCL domain, which resulted in the release of theophylline from castor oil plasticized-coated tablets, which in turn enhanced and closed to a constant release pattern.

  17. Stability of dry coated solid dosage forms.

    PubMed

    Kablitz, Caroline Désirée; Urbanetz, Nora Anne

    2009-01-01

    The dry coating process was evaluated in terms of storage stability investigating drug release and agglomeration tendency of the different coated oral dosage forms; hydroxypropyl methylcellulose acetate succinate (HPMCAS) was used with triethylcitrate (TEC) as plasticizer and acetylated monoglyceride (Myvacet) as wetting agent. Talc or colloidal silicon dioxide (Aerosil) was used as anti-tacking agents. In contrast to coating formulations consisting of HPMCAS and Myvacet all formulations containing TEC showed enteric resistance and no agglomeration tendency after preparation. After storage at 10% RH +/- 5% enteric resistance is increased slightly. This increase is more pronounced at 60% RH +/- 5%. The formulations without anti-tacking agents showed higher drug releases after 12 and 24 months due to the damage of the film's integrity during sample preparation caused by the high tackiness of the film. Tackiness is not affected by storing if samples are stored at low relative humidity. At high relative humidity tackiness increases upon storage especially for formulations without anti-tacking agents. The sieving results of the agglomeration measurements after storage can be confirmed by ring shear measurements performed immediately after preparation and approved to be a tool, which is able to predict the agglomeration during storage.

  18. The variability of ecstasy tablets composition in Brazil.

    PubMed

    Togni, Loraine R; Lanaro, Rafael; Resende, Rodrigo R; Costa, Jose L

    2015-01-01

    The content of ecstasy tablets has been changing over the years, and nowadays 3,4-methylenedioxymethamphetamine (MDMA) is not always present in the tablets. The aim of this study was to investigate the chemical composition in the seized tablets labeled as ecstasy. We analyzed samples from 150 different seizures made by Sao Paulo's State Police by gas chromatography-mass spectrometry. MDMA was present in 44.7% of the analyzed samples, and another twenty different active substances were identified in these tablets, such as caffeine, 2C-B, piperazines, amphetamines, phencyclidine, and others. Methamphetamine was present in 22% of these samples. The results demonstrate a huge shift in the pattern of trafficking of synthetic drugs, where MDMA has been replaced in tablets mostly by illicit psychoactive substances, in a clear attempt to bypass the law. The great variability in the tablets composition may lead to an increased risk of drug poisoning. © 2014 American Academy of Forensic Sciences.

  19. Optimization studies on compression coated floating-pulsatile drug delivery of bisoprolol.

    PubMed

    Jagdale, Swati C; Bari, Nilesh A; Kuchekar, Bhanudas S; Chabukswar, Aniruddha R

    2013-01-01

    The purpose of the present work was to design and optimize compression coated floating pulsatile drug delivery systems of bisoprolol. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. The prepared system consisted of two parts: a core tablet containing the active ingredient and an erodible outer shell with gas generating agent. The rapid release core tablet (RRCT) was prepared by using superdisintegrants with active ingredient. Press coating of optimized RRCT was done by polymer. A 3² full factorial design was used for optimization. The amount of Polyox WSR205 and Polyox WSR N12K was selected as independent variables. Lag period, drug release, and swelling index were selected as dependent variables. Floating pulsatile release formulation (FPRT) F13 at level 0 (55 mg) for Polyox WSR205 and level +1 (65 mg) for Polyox WSR N12K showed lag time of 4 h with >90% drug release. The data were statistically analyzed using ANOVA, and P < 0.05 was statistically significant. Release kinetics of the optimized formulation best fitted the zero order model. In vivo study confirms burst effect at 4 h in indicating the optimization of the dosage form.

  20. Optimization Studies on Compression Coated Floating-Pulsatile Drug Delivery of Bisoprolol

    PubMed Central

    Jagdale, Swati C.; Bari, Nilesh A.; Kuchekar, Bhanudas S.; Chabukswar, Aniruddha R.

    2013-01-01

    The purpose of the present work was to design and optimize compression coated floating pulsatile drug delivery systems of bisoprolol. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. The prepared system consisted of two parts: a core tablet containing the active ingredient and an erodible outer shell with gas generating agent. The rapid release core tablet (RRCT) was prepared by using superdisintegrants with active ingredient. Press coating of optimized RRCT was done by polymer. A 32 full factorial design was used for optimization. The amount of Polyox WSR205 and Polyox WSR N12K was selected as independent variables. Lag period, drug release, and swelling index were selected as dependent variables. Floating pulsatile release formulation (FPRT) F13 at level 0 (55 mg) for Polyox WSR205 and level +1 (65 mg) for Polyox WSR N12K showed lag time of 4 h with >90% drug release. The data were statistically analyzed using ANOVA, and P < 0.05 was statistically significant. Release kinetics of the optimized formulation best fitted the zero order model. In vivo study confirms burst effect at 4 h in indicating the optimization of the dosage form. PMID:24367788

  1. Enteric glia.

    PubMed

    Rühl, A; Nasser, Y; Sharkey, K A

    2004-04-01

    The enteric nervous system is composed of both enteric neurones and enteric glia. Enteric glial cells were first described by Dogiel and are now known to outnumber neurones approximately 4 : 1. In the past, these cells were assumed to subserve a largely supportive role; however, recent evidence indicates that enteric glial cells may play a more active role in the control of gut function. In transgenic mouse models, where enteric glial cells are selectively ablated, the loss of glia results in intestinal inflammation and disruption of the epithelial barrier. Enteric glia are activated specifically by inflammatory insults and may contribute actively to inflammatory pathology via antigen presentation and cytokine synthesis. Enteric glia also express receptors for neurotransmitters and so may serve as intermediaries in enteric neurotransmission. Thus, enteric glia may serve as a link between the nervous and immune systems of the gut and may also have an important role in maintaining the integrity of the mucosal barrier and in other aspects of intestinal homeostasis.

  2. Smartphones and tablets: Reshaping radiation oncologists’ lives

    PubMed Central

    Gomez-Iturriaga, Alfonso; Bilbao, Pedro; Casquero, Francisco; Cacicedo, Jon; Crook, Juanita

    2012-01-01

    Background Smartphones and tablets are new handheld devices always connected to an information source and capable of providing instant updates, they allow doctors to access the most updated information and provide decision support at the point of care. Aim The practice of radiation oncology has always been a discipline that relies on advanced technology. Smartphones provide substantial processing power, incorporating innovative user interfaces and applications. Materials and methods The most popular smartphone and tablet app stores were searched for “radiation oncology” and “oncology” related apps. A web search was also performed searching for smartphones, tablets, oncology, radiology and radiation oncology. Results Smartphones and tablets allow rapid access to information in the form of podcasts, apps, protocols, reference texts, recent research and more. Conclusion With the rapidly changing advances in radiation oncology, the trend toward accessing resources via smartphones and tablets will only increase, future will show if this technology will improve clinical care. PMID:24669308

  3. Electronic acquisition of OSCE performance using tablets

    PubMed Central

    Hochlehnert, Achim; Schultz, Jobst-Hendrik; Möltner, Andreas; Tımbıl, Sevgi; Brass, Konstantin; Jünger, Jana

    2015-01-01

    Background: Objective Structured Clinical Examinations (OSCEs) often involve a considerable amount of resources in terms of materials and organization since the scores are often recorded on paper. Computer-assisted administration is an alternative with which the need for material resources can be reduced. In particular, the use of tablets seems sensible because these are easy to transport and flexible to use. Aim: User acceptance concerning the use of tablets during OSCEs has not yet been extensively investigated. The aim of this study was to evaluate tablet-based OSCEs from the perspective of the user (examiner) and the student examinee. Method: For two OSCEs in Internal Medicine at the University of Heidelberg, user acceptance was analyzed regarding tablet-based administration (satisfaction with functionality) and the subjective amount of effort as perceived by the examiners. Standardized questionnaires and semi-standardized interviews were conducted (complete survey of all participating examiners). In addition, for one OSCE, the subjective evaluation of this mode of assessment was gathered from a random sample of participating students in semi-standardized interviews. Results: Overall, the examiners were very satisfied with using tablets during the assessment. The subjective amount of effort to use the tablet was found on average to be “hardly difficult”. The examiners identified the advantages of this mode of administration as being in particular the ease of use and low rate of error. During the interviews of the examinees, acceptance for the use of tablets during the assessment was also detected. Discussion: Overall, it was found that the use of tablets during OSCEs was well accepted by both examiners and examinees. We expect that this mode of assessment also offers advantages regarding assessment documentation, use of resources, and rate of error in comparison with paper-based assessments; all of these aspects should be followed up on in further studies

  4. Electronic acquisition of OSCE performance using tablets.

    PubMed

    Hochlehnert, Achim; Schultz, Jobst-Hendrik; Möltner, Andreas; Tımbıl, Sevgi; Brass, Konstantin; Jünger, Jana

    2015-01-01

    Objective Structured Clinical Examinations (OSCEs) often involve a considerable amount of resources in terms of materials and organization since the scores are often recorded on paper. Computer-assisted administration is an alternative with which the need for material resources can be reduced. In particular, the use of tablets seems sensible because these are easy to transport and flexible to use. User acceptance concerning the use of tablets during OSCEs has not yet been extensively investigated. The aim of this study was to evaluate tablet-based OSCEs from the perspective of the user (examiner) and the student examinee. For two OSCEs in Internal Medicine at the University of Heidelberg, user acceptance was analyzed regarding tablet-based administration (satisfaction with functionality) and the subjective amount of effort as perceived by the examiners. Standardized questionnaires and semi-standardized interviews were conducted (complete survey of all participating examiners). In addition, for one OSCE, the subjective evaluation of this mode of assessment was gathered from a random sample of participating students in semi-standardized interviews. Overall, the examiners were very satisfied with using tablets during the assessment. The subjective amount of effort to use the tablet was found on average to be "hardly difficult". The examiners identified the advantages of this mode of administration as being in particular the ease of use and low rate of error. During the interviews of the examinees, acceptance for the use of tablets during the assessment was also detected. Overall, it was found that the use of tablets during OSCEs was well accepted by both examiners and examinees. We expect that this mode of assessment also offers advantages regarding assessment documentation, use of resources, and rate of error in comparison with paper-based assessments; all of these aspects should be followed up on in further studies.

  5. 21 CFR 520.763a - Dithiazanine iodide tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Dithiazanine iodide tablets. 520.763a Section 520... iodide tablets. (a) Chemical name. 3-Ethyl-2-[5-(3-ethyl - 2 - benzothiazolinylidene) - 1,3 - pentadienyl]-benzothiazolium iodide. (b) Specifications. Dithiazanine iodide tablets contain 10 milligrams, 50 milligrams, 100...

  6. 21 CFR 520.2220d - Sulfadimethoxine-ormetoprim tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sulfadimethoxine-ormetoprim tablets. 520.2220d Section 520.2220d Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Sulfadimethoxine-ormetoprim tablets. (a) Specifications. Each tablet contains 120 milligrams (100 milligrams of...

  7. 21 CFR 520.2041 - Pyrantel pamoate chewable tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Pyrantel pamoate chewable tablets. 520.2041 Section 520.2041 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... pamoate chewable tablets. (a) Specifications. Each tablet contains pyrantel pamoate equivalent to 22.7 or...

  8. Sodium lauryl sulfate impedes drug release from zinc-crosslinked alginate beads: switching from enteric coating release into biphasic profiles.

    PubMed

    Taha, Mutasem O; Nasser, Wissam; Ardakani, Adel; Alkhatib, Hatim S

    2008-02-28

    The aim of this research is to investigate the effects of sodium lauryl sulfate (SLS) on ionotropically cross-linked alginate beads. Different levels of SLS were mixed with sodium alginate and chlorpheniramine maleate (as loaded model drug). The resulting viscous solutions were dropped onto aqueous solutions of zinc or calcium ions for ionotropic curing. The generated beads were assessed by their drug releasing profiles, infrared and differential scanning colorimetery (DSC) traits. SLS was found to exert profound concentration-dependent impacts on the characteristics of zinc-crosslinked alginate beads such that moderate modifications in the levels of SLS switched drug release from enteric coating-like behavior to a biphasic release modifiable to sustained-release by the addition of minute amounts of xanthan gum. Calcium cross-linking failed to reproduce the same behavior, probably due to the mainly ionic nature of calcium-carboxylate bonds compared to the coordinate character of their zinc-carboxylate counterparts. Apparently, moderate levels of SLS repel water penetration into the beads, and therefore minimize chlorpheniramine release. However, higher SLS levels seem to discourage polymeric cross-linking and therefore allow biphasic drug release.

  9. Organic-aqueous crossover coating process for the desmopressin orally disintegrating microparticles.

    PubMed

    Kim, Ju-Young; Hwang, Kyu-Mok; Park, Chun-Woong; Rhee, Yun-Seok; Park, Eun-Seok

    2015-02-01

    The purpose of the present study was to prepare desmopressin orally disintegrating microparticles (ODMs) using organic-aqueous crossover coating process which featured an organic sub-coating followed by an aqueous active coating. Sucrose beads and hydroxypropyl cellulose (HPC) were used as inert cores and a coating material, respectively. Characterizations including size distribution analysis, in-vitro release studies and in-vitro disintegration studies were performed. A pharmacokinetic study of the ODMs was also conducted in eight beagle dogs. It was found that sucrose beads should be coated using organic solvents to preserve their original morphology. For the active coating, the aqueous coating solution should be used for drug stability. When sucrose beads were coated using organic-aqueous crossover coating process, double-layer ODMs with round shapes were produced with detectable impurities below limit of US Pharmacopeia. The median size of ODMs was 195.6 μm, which was considered small enough for a good mouthfeel. The ODMs dissolved in artificial saliva within 15 s because of hydrophilic materials including sucrose and HPC in the ODMs. Because of its fast-dissolving properties, 100% release of the drug was reached within 5 min. Pharmacokinetic parameters including Cmax and AUC24 indicated bioequivalence of the ODMs and the conventional immediate release tablets. Therefore, by using the organic-aqueous crossover coating process, double-layer ODMs were successively prepared with small size, round shapes and good drug stability.

  10. Frosta: a new technology for making fast-melting tablets.

    PubMed

    Jeong, Seong Hoon; Fu, Yourong; Park, Kinam

    2005-11-01

    The fast-melting tablet (FMT) technology, which is known to be one of the most innovated methods in oral drug delivery systems, is a rapidly growing area of drug delivery. The initial success of the FMT formulation led to the development of various technologies. These technologies, however, still have some limitations. Recently, a new technology called Frosta (Akina) was developed for making FMTs. The Frosta technology utilises the conventional wet granulation process and tablet press for cost-effective production of tablets. The Frosta tablets are mechanically strong with friability of < 1% and are stable in accelerated stability conditions when packaged into a bottle container. They are robust enough to be packaged in multi-tablet vials. Conventional rotary tablet presses can be used for the production of the tablets and no other special instruments are required. Thus, the cost of making FMTs is lower than that of other existing technologies. Depending on the size, Frosta tablets can melt in < 10 s after placing them in the oral cavity for easy swallowing. The Frosta technology is ideal for wide application of FMTs technology to various drug and nutritional formulations.

  11. Magnetic resonance imaging for the in vivo evaluation of gastric-retentive tablets.

    PubMed

    Steingoetter, Andreas; Weishaupt, Dominik; Kunz, Patrick; Mäder, Karsten; Lengsfeld, Hans; Thumshirn, Miriam; Boesiger, Peter; Fried, Michael; Schwizer, Werner

    2003-12-01

    To develop a magnetic resonance imaging (MRI) technique for assessing in vivo properties of orally ingested gastric-retentive tablets under physiologic conditions. Tablets with different floating characteristics (tablet A-C) were marked with superparamagnetic Fe3O4 particles to analyze intragastric tablet position and residence time in human volunteers. Optimal Fe3O4 concentration was determined in vitro. Intragastric release characteristic of one slow-release tablet (tablet D) was analyzed by embedding gadolinium chelates (Gd-DOTA) as a drug model into the tablet. All volunteers underwent MRI in the sitting position. Tablet performance was analyzed in terms of relative position of tablet to intragastric meal level (with 100% at meal surface), intragastric residence time (min) and Gd-DOTA distribution volume (% of meal volume). Intragastric tablet floating performance and residence time of tablets (tablet A-D) as well as the intragastric Gd-DOTA distribution of tablet D could be monitored using MRI. Tablet floating performance was different between the tablets (A, 93%(95 - 9%); B, 80%(80 - 68%): C, 38%(63 - 32%); p < 0.05). The intragastric distribution volume of Gd-DOTA was 19.9% proximally and 35.5% distally. The use of MRI allows the assessment of galenic properties of orally ingested tablets in humans in seated position.

  12. Eudragit-coated dextran microspheres of 5-fluorouracil for site-specific delivery to colon.

    PubMed

    Rai, Gopal; Yadav, Awesh K; Jain, Narendra K; Agrawal, Govind P

    2016-01-01

    Objective of the present investigation was to prepare and evaluate the potential of enteric coated dextran microspheres for colon targeting of 5-fluorouracil (5-FU). Dextran microspheres were prepared by emulsification-crosslinking method and the formulation variables studied included different molecular weights of dextran, drug:polymer ratio, volume of crosslinking agent, stirring speed and time. Enteric coating (Eudragit S-100) of dextran microspheres was performed by oil-in-oil solvent evaporation method using different coat:core ratios (4:1 or 8:1). Uncoated and coated dextran microspheres were characterized by particle size, surface morphology, entrapment efficiency, DSC, in vitro drug release in the presence of dextranase and 2% rat cecal contents. The release study of 5-FU from coated dextran microspheres was pH dependent. No release was observed at acidic pH; however, the drug was released quickly where Eudragit starts solublizing there was continuous release of drug from the microspheres. Organ distribution study was suggested that coated dextran microspheres retard the release of drug in gastric and intestinal pH environment and released of drug from microspheres in colon due to the degradation of dextran by colonic enzymes.

  13. [Study on preparation of phenols gastric floating tablet].

    PubMed

    Zhai, Xiao-Ling; Ni, Jian; Gu, Yu-Long

    2008-01-01

    To study the preparation of phenols gastric floating tablet. The tablets which were prepared using Eudragit IV, HPMC(K4M), MCC101 and Octadecanol as excipients were evaluated by vitro floatation and releasing performance. The pressure of preparationg was also study to select the optimal preparation. The tablets were successfully prepared in which the drug, Eudragit IV, Octadecanol were 31% respectively,and MCC101 was 7%. And 3-4 kg was found to be the eligible pressure. The study was found to be effective in the process of phenols gastric floating tablet.

  14. Site Targeted Press Coated Delivery of Methylprednisolone Using Eudragit RS 100 and Chitosan for Treatment of Colitis.

    PubMed

    Jagdale, Swati; Chandekar, Apoorva

    2016-01-01

    Inflammatory bowel disease (IBD) is one of the five most prevalent gastrointestinal disease burdens which commonly require lifetime care. Worldwide incidence rate of ulcerative colitis and Crohn's disease is about 16.8% and 13.4% respectively. Colitis is an inflammation of the colon. Colon targeted drug delivery will direct the drug to the colon. The drug will reach at the site of action and hence its side effects as well as dose can be reduced. Recent patent describes treatment of ulcerative colitis using anti CD3 antibodies, with nicotine and anti-depressant drugs, budesonide foam etc. Present study deals with optimization of site targeted methylprednisolone delivery for treatment of colitis. Chitosan and Eudragit RS 100 were used as coating polymers. Tablets were prepared by press coated technology. The core tablets contain drug, avicel as binder, croscarmellose sodium as super disintegrant and dicalcium phosphate as diluent. Drug excipient compatibility was carried out using FTIR, UV and DSC. Design of experiment was used to optimize the formulation. Tablets were evaluated for thickness, weight variation, hardness, swelling index, in-vitro drug release and release of drug in simulated media. Optimized batch (B2) contained chitosan 40% and eudragit RS 100 17.5%. B2 showed in-vitro drug release 85.65 ± 7.6% in 6.8 pH phosphate buffer and 96.7 ±9.1% in simulated media after 7.5 hours. In-vivo x-ray placebo study for formulation B2 had shown that the tablet reached to the ascending colon after 5 hours. This indicated a potential site targeted delivery of optimized batch B2.

  15. Galileo's Telescopy and Jupiter's Tablet

    NASA Astrophysics Data System (ADS)

    Usher, P. D.

    2003-12-01

    A previous paper (BAAS 33:4, 1363, 2001) reported on the dramatic scene in Shakespeare's Cymbeline that features the descent of the deity Jupiter. The paper suggested that the four ghosts circling the sleeping Posthumus denote the four Galilean moons of Jupiter. The god Jupiter commands the ghosts to lay a tablet upon the prone Posthumus, but says that its value should not be overestimated. When Posthumus wakens he notices the tablet, which he calls a "book." Not only has the deity's "tablet" become the earthling's "book," but it appears that the book has covers which Posthumus evidently recognizes because without even opening the book he ascribes two further properties to it: rarity, and the very property that Jupiter had earlier attributed, viz. that one must not read too much into it. The mystery deepens when the Jovian gift undergoes a second metamorphosis, to "label." With the help of the OED, the potentially disparate terms "tablet," "book," and "label," may be explained by terms appropriate either to supernatural or worldly beings. "Tablet" may recognize the Mosaic artifact, whereas "book" and "label" are probably mundane references to Galileo's Sidereus Nuncius which appeared shortly before Cymbeline. The message of the Olympian god indicates therefore that the book is unique even as its contents have limited value. The first property celebrates the fact that Galileo's book is the first of its kind, and the second advises that all results except the discovery of Jupiter's moons have been reported earlier, in Hamlet.

  16. 21 CFR 520.1696d - Penicillin V tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Penicillin V tablets. 520.1696d Section 520.1696d... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696d Penicillin V tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to 125 milligrams (200,000...

  17. 21 CFR 520.1696d - Penicillin V tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Penicillin V tablets. 520.1696d Section 520.1696d... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696d Penicillin V tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to 125 milligrams (200,000...

  18. Enteric-coated budesonide for the induction and maintenance of remission of Crohn's disease in children.

    PubMed

    Cohen, Stanley A; Aloi, Marina; Arumugam, Ramalingam; Baker, Robert; Bax, Kevin; Kierkuś, Jaroslaw; Koletzko, Sibylle; Lionetti, Paolo; Persson, Tore; Eklund, Stefan

    2017-07-01

    These studies evaluated the safety and efficacy of enteric-coated budesonide for the induction and maintenance of remission of mild-to-moderate Crohn's disease (CD) in children. The consecutive, multicenter, open-label, non-comparative studies enrolled patients aged 6-17 years. In the induction study, patients with active CD of the ileum and/or ascending colon received budesonide 9 mg or 6 mg once daily for 8 weeks; in the maintenance study, patients in remission received budesonide 6 mg once daily for 12 weeks. The primary objective was assessment of safety, including glucocorticosteroid-related side effects and serum cortisol levels. Efficacy was assessed using the Pediatric Crohn's Disease Activity Index (PCDAI), and health-related quality of life (HRQoL) using the IMPACT-III questionnaire. In the induction study (n = 108), most adverse events were related to CD, commonly abdominal pain; possible glucocorticosteroid-related effects included acne and increased appetite but without significant weight gain. Subnormal morning cortisol levels were observed in 32 of 103 patients after 8 weeks. Budesonide reduced disease activity from baseline (mean ± standard deviation, 9.1 ± 8.5 vs. 19.1 ± 10.1, p < .001) with 58.1% of patients reaching remission (PCDAI <10); HRQoL improved (p < .001). In the maintenance study (n = 50), mean disease activity worsened (p = .047) with HRQoL unchanged (p = .33). Budesonide treatment was generally well tolerated, although the potential for adrenal suppression was noted. Budesonide was effective for induction of remission in children with mild-to-moderate CD but not for maintaining remission (ClinicalTrials.gov identifiers: NCT01444092, NCT01453946).

  19. Efficacy of Flocculating and Other Emergency Water Purification Tablets

    DTIC Science & Technology

    1993-05-01

    iodine tablet {1). The deficiencies identified with iodine tablets included slaw kill of Giardia cysts at law temperatures, medicinal taste and odor ...and the fact that undissolved solids, color and odor in field water ~e not rerroved. A market search for a new emergency water purification...tablet, or compound , was undertaken. The tablet had to be cOITll!Ercially available, nondevelopmental and satisfy the new military requirements. The

  20. Does the performance of wet granulation and tablet hardness affect the drug dissolution profile of carvedilol in matrix tablets?

    PubMed

    Košir, Darjan; Ojsteršek, Tadej; Vrečer, Franc

    2018-06-14

    Wet granulation is mostly used process for manufacturing matrix tablets. Compared to the direct compression method, it allows for a better flow and compressibility properties of compression mixtures. Granulation, including process parameters and tableting, can influence critical quality attributes (CQAs) of hydrophilic matrix tablets. One of the most important CQAs is the drug release profile. We studied the influence of granulation process parameters (type of nozzle and water quantity used as granulation liquid) and tablet hardness on the drug release profile. Matrix tablets contained HPMC K4M hydrophilic matrix former and carvedilol as a model drug. The influence of selected HPMC characteristics on the drug release profile was also evaluated using two additional HPMC batches. For statistical evaluation, partial least square (PLS) models were generated for each time point of the drug release profile using the same number of latent factors. In this way, it was possible to evaluate how the importance of factors influencing drug dissolution changes in dependence on time throughout the drug release profile. The results of statistical evaluation show that the granulation process parameters (granulation liquid quantity and type of nozzle) and tablet hardness significantly influence the release profile. On the other hand, the influence of HPMC characteristics is negligible in comparison to the other factors studied. Using a higher granulation liquid quantity and the standard nozzle type results in larger granules with a higher density and lower porosity, which leads to a slower drug release profile. Lower tablet hardness also slows down the release profile.

  1. [The effects of various factors on the in vitro velocity of drug release from repository tablets. Part 4: Isoniazid (Rimicid) respository tablets (author's transl)].

    PubMed

    Tomassini, L; Michailova, D; Naplatanova, D; Slavtschev, P

    1979-12-01

    The authors investigated the release of isoniazid from repository tablets as related to form, processing technology, strength constant and storage for 5 years. On determining the diffusion coefficient (D), the initial dissolution rate (Vo) and the time required for the diffusion of the releasing medium to the middle of the tablet (t1/2), it was found that the difference in release rate between the flat and the biconvex tablets is small. Furthermore, it was stated that the three-layer tablets have very high D and Vo values and very low t1/2 values, for what reason they are unsuited for repository tablets of the composition under investigation. Moreover, it was found that an increase of the strength constant does not affect the D, t1/2 and Vo values, and that the release of isoniazid is retarded only in flat tablets with the highest strength constant. Storage exerts no effect on the drug release from these tablets. The industrial production of these tablets is under way.

  2. To Study Capping or Lamination Tendency of Tablets Through Evaluation of Powder Rheological Properties and Tablet Mechanical Properties of Directly Compressible Blends.

    PubMed

    Dudhat, Siddhi M; Kettler, Charles N; Dave, Rutesh H

    2017-05-01

    Air entrapment efficiency of the powders is one of the main factors leading to occurrence of capping or lamination tendency of tablets manufactured from the directly compressible powder blends. The purpose of the current research was to study this underlying cause leading to occurrence of capping or lamination of tablets through evaluation of powder rheological properties. Powder blends were prepared by addition of 0% w/w to 100% w/w of individual active pharmaceutical ingredient (API) [two model API: acetaminophen (APAP) and ibuprofen (IBU)] with microcrystalline cellulose without and with 0.5% w/w Magnesium Stearate as lubricant. Powder rheological properties were analyzed using FT4 Powder Rheometer for dynamic, bulk, and shear properties. Tablet mechanical properties of the respective blends were studied by determining the ability of the material to form tablet of specific strength under applied compaction pressure through tabletability profile. The results showed that powder rheometer distinguished the powder blends based on their ability to relieve entrapped air along with the distinctive flow characteristics. Powder blend prepared with increasing addition of APAP displayed low powder permeability as compared to IBU blends with better powder permeability, compressibility and flow characteristics. Also, lubrication of the APAP blends did not ease their ability to relieve air. Tabletability profiles revealed the potential occurrence of capping or lamination in tablets prepared from the powder blends with high APAP content. This study can help scientist to understand tableting performance at the early-developmental stages and can avoid occurrence capping and lamination of tablets.

  3. 21 CFR 520.1805 - Piperazine phosphate with thenium closylate tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... tablets. 520.1805 Section 520.1805 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.1805 Piperazine phosphate with thenium closylate tablets. (a) Specifications. Each scored tablet... chapter. (c) Conditions of use—(1) Amount. Administer orally to dogs as follows: Number of Tablets at Each...

  4. 21 CFR 520.622a - Diethylcarbamazine citrate tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Diethylcarbamazine citrate tablets. 520.622a... Diethylcarbamazine citrate tablets. (a) Sponsors. (1) See 015579 in § 510.600(c) of this chapter for use of 50, 200, and 400 milligram tablets for prevention of heartworm disease in dogs and as an aid in the treatment...

  5. Solid dispersion tablets of breviscapine with polyvinylpyrrolidone K30 for improved dissolution and bioavailability to commercial breviscapine tablets in beagle dogs.

    PubMed

    Cong, Wenjuan; Shen, Lan; Xu, Desheng; Zhao, Lijie; Ruan, Kefeng; Feng, Yi

    2014-09-01

    Breviscapine, one of cardiovascular drugs extracted from a Chinese herb Erigeron breviscapinus, has been frequently used to treat cardiovascular diseases such as hypertension, angina pectoris, coronary heart disease and stroke. However, its poor water solubility and low bioavailability in vivo severely restrict the clinical application. To overcome these drawbacks, breviscapine solid dispersion tablets consisting of breviscapine, polyvinylpyrrolidone K30 (PVP K30), microcrystalline cellulose and crospovidone were appropriately prepared. In vitro dissolution profiles showed that breviscapine released percentage of solid dispersion tablets reached 90 %, whereas it was only 40 % for commercial breviscapine tablets. Comparative pharmacokinetic study between solid dispersion tablets and commercial products was investigated on the normal beagle dogs after oral administration. Results showed that the bioavailability of breviscapine was greatly increased by 3.45-fold for solid dispersion tablets. The greatly improved dissolution rate and bioavailability might be attributed to intermolecular hydrogen bonding reactions between PVP K30 and scutellarin. These findings suggest that our solid dispersion tablets can greatly improve the bioavailability as well as the dissolution rate of breviscapine.

  6. 21 CFR 520.1900 - Primidone tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... for use of 50 and 250 milligram tablets. (c) Conditions of use in dogs—(1) Amount. Twenty-five..., epileptiform convulsions, viral encephalitis, distemper, and hardpad disease that occurs as a clinically recognizable lesion in certain entities in dogs.1 (3) Limitations. The tablets may be administered whole or...

  7. 21 CFR 520.2088 - Roxarsone tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... period. Withdraw 5 days before slaughter. Use as sole source of organic arsenic. (ii) Growing chickens—(a.... Withdraw 5 days before slaughter. Use as sole source of organic arsenic. (b)(1) Specifications. Each tablet... slaughter. Use as sole source of organic arsenic. (ii) [Reserved] (c)(1) Specifications. Each tablet...

  8. The Impact of Granule Density on Tabletting and Pharmaceutical Product Performance.

    PubMed

    van den Ban, Sander; Goodwin, Daniel J

    2017-05-01

    The impact of granule densification in high-shear wet granulation on tabletting and product performance was investigated, at pharmaceutical production scale. Product performance criteria need to be balanced with the need to deliver manufacturability criteria to assure robust industrial scale tablet manufacturing processes. A Quality by Design approach was used to determine in-process control specifications for tabletting, propose a design space for disintegration and dissolution, and to understand the permitted operating limits and required controls for an industrial tabletting process. Granules of varying density (filling density) were made by varying water amount added, spray rate, and wet massing time in a design of experiment (DoE) approach. Granules were compressed into tablets to a range of thicknesses to obtain tablets of varying breaking force. Disintegration and dissolution performance was evaluated for the tablets made. The impact of granule filling density on tabletting was rationalised with compressibility, tabletability and compactibility. Tabletting and product performance criteria provided competing requirements for porosity. An increase in granule filling density impacted tabletability and compactability and limited the ability to achieve tablets of adequate mechanical strength. An increase in tablet solid fraction (decreased porosity) impacted disintegration and dissolution. An attribute-based design space for disintegration and dissolution was specified to achieve both product performance and manufacturability. The method of granulation and resulting granule filling density is a key design consideration to achieve both product performance and manufacturability required for modern industrial scale pharmaceutical product manufacture and distribution.

  9. Urinary excretion of ciprofloxacin after administration of extended release tablets in healthy volunteers. Swellable drug-polyelectrolyte matrix versus bilayer tablets.

    PubMed

    Guzmán, M L; Romañuk, C B; Sanchez, M F; Luciani Giacobbe, L C; Alarcón-Ramirez, L P; Battistini, F D; Alovero, F L; Jimenez-Kairuz, A F; Manzo, R H; Olivera, María Eugenia

    2018-02-01

    This paper builds on a previous paper in which new ciprofloxacin extended-release tablets were developed based on a ciprofloxacin-based swellable drug polyelectrolyte matrix (SDPM-CIP). The matrix contains a molecular dispersion of ciprofloxacin ionically bonded to the acidic groups of carbomer, forming the polyelectrolyte-drug complex CB-CIP. This formulation showed that the release profile of the ciprofloxacin bilayer tablets currently commercialised can be achieved with a simpler strategy. Thus, since ciprofloxacin urine concentrations are associated with the clinical cure of urinary tract infections, the goal of this work was to compare the urinary excretion of SDPM-CIP tablets with those of the CIPRO XR® bilayer tablets. A batch of SDPM-CIP tablets was manufactured by the wet granulation method and the CB-CIP ionic complex was obtained in situ. Fasted healthy volunteers received a single oral dose of 500 mg ciprofloxacin of either formulation in a randomised crossover study. Urinary concentrations were assessed by HPLC at intervals up to 36 h. Pharmacokinetic parameters (rate of urinary excretion, maximum urine excretion rate, t max , area under the curve, amount and percentage of the ciprofloxacin dose excreted in urine) showed no statistical differences between both formulations at any of the time intervals of collection. The processing conditions to obtain SDPM-CIP tablets are easy to scale up since they involve technology currently employed in the pharmaceutical industry and the process is less challenging to implement. In addition, SDPM-CIP tablets met pharmacopoeial quality specifications.

  10. Compounded Apixaban Suspensions for Enteral Feeding Tubes.

    PubMed

    Caraballo, Maria L; Donmez, Seda; Nathan, Kobi; Zhao, Fang

    2017-07-01

    Objective: There is limited information on compounded apixaban formulations for administration via enteral feeding tubes. This study was designed to identify a suitable apixaban suspension formulation that is easy to prepare in a pharmacy setting, is compatible with commonly used feeding tubes, and has a beyond-use date of 7 days. Methods: Apixaban suspensions were prepared from commercially available 5-mg Eliquis tablets. Several vehicles and compounding methods were screened for ease of preparation, dosage accuracy, and tube compatibility. Two tubing types, polyurethane and polyvinyl chloride, with varying lengths and diameters, were included in the study. They were mounted on a peg board during evaluation to mimic the patient body position. A 7-day stability study of the selected formulation was also conducted. Results: Vehicles containing 40% to 60% Ora-Plus in water all exhibited satisfactory flowability through the tubes. The mortar/pestle compounding method was found to produce more accurate and consistent apixaban suspensions than the pill crusher or crushing syringe method. The selected formulation, 0.25 mg/mL apixaban in 50:50 Ora-Plus:water, was compatible with both tubing types, retaining >98% drug in posttube samples. The stability study also confirmed that this formulation was stable physically and chemically over 7 days of storage at room temperature. Conclusions: A suitable apixaban suspension formulation was identified for administration via enteral feeding tubes. The formulation consisted of 0.25 mg/mL apixaban in 50:50 Ora-Plus:water. The stability study results supported a beyond-use date of 7 days at room temperature.

  11. 21 CFR 520.82b - Aminopropazine fumarate, neomycin sulfate tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Aminopropazine fumarate, neomycin sulfate tablets... Aminopropazine fumarate, neomycin sulfate tablets. (a) Specifications. The drug is in tablet form. Each tablet... sulfate equivalent to 50 milligrams of neomycin base. (b) Sponsor. See No. 000061 in § 510.600(c) of this...

  12. Understanding the Delamination Risk of a Trilayer Tablet Using Minipiloting Tools.

    PubMed

    Tao, Jing; Robertson-Lavalle, Sophia; Pandey, Preetanshu; Badawy, Sherif

    2017-11-01

    A multilayer tablet is one of the formulation options used to mitigate chemical and physical incompatibility between different drug substances. Feasibility studies of multilayer tablets are often conducted using round flat-faced punch tooling. However, the link between different tooling designs and multilayer tablet performance is not well established. This study uses a prototype trilayer tablet and examines tooling design considerations when conducting small-scale studies to gauge the risk of interfacial defects. The impact of tablet weight and dimensions was evaluated to gain understanding of the effect of scale-up/down of tablet size. The factors in tooling selection, including tablet shape, cup depth, and size of embossing were evaluated to gain insight on the impact of tooling design on the interfacial strength of the trilayer tablet. It was found that tablet weight and dimensions can significantly affect the interfacial strength due to their impact on force transmission during compression and the retardation force from the die wall during ejection. Round flat-faced tooling generated trilayer tablets of the strongest interfacial strength compared to typical commercial tablets-oval shaped with concave surfaces. These factors should be accounted for when using round flat compacts to assess the interface risks of a multilayer tablet. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  13. 21 CFR 520.370 - Cefpodoxime tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Cefpodoxime tablets. 520.370 Section 520.370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.370 Cefpodoxime tablets. (a...

  14. 21 CFR 520.455 - Clomipramine tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Clomipramine tablets. 520.455 Section 520.455 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.455 Clomipramine tablets. (a...

  15. 21 CFR 520.804 - Enalapril tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Enalapril tablets. 520.804 Section 520.804 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.804 Enalapril tablets. (a...

  16. 21 CFR 520.455 - Clomipramine tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Clomipramine tablets. 520.455 Section 520.455 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.455 Clomipramine tablets. (a...

  17. 21 CFR 520.370 - Cefpodoxime tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Cefpodoxime tablets. 520.370 Section 520.370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.370 Cefpodoxime tablets. (a...

  18. 21 CFR 520.312 - Carnidazole tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Carnidazole tablets. 520.312 Section 520.312 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.312 Carnidazole tablets. (a...

  19. 21 CFR 520.370 - Cefpodoxime tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Cefpodoxime tablets. 520.370 Section 520.370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.370 Cefpodoxime tablets. (a...

  20. 21 CFR 520.812 - Enrofloxacin tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Enrofloxacin tablets. 520.812 Section 520.812 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.812 Enrofloxacin tablets. (a...

  1. 21 CFR 520.455 - Clomipramine tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Clomipramine tablets. 520.455 Section 520.455 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.455 Clomipramine tablets. (a...

  2. 21 CFR 520.312 - Carnidazole tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Carnidazole tablets. 520.312 Section 520.312 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.312 Carnidazole tablets. (a...

  3. 21 CFR 520.581 - Dichlorophene tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Dichlorophene tablets. 520.581 Section 520.581 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.581 Dichlorophene tablets. (a...

  4. 21 CFR 520.455 - Clomipramine tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Clomipramine tablets. 520.455 Section 520.455 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.455 Clomipramine tablets. (a...

  5. 21 CFR 520.804 - Enalapril tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Enalapril tablets. 520.804 Section 520.804 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.804 Enalapril tablets. (a...

  6. 21 CFR 520.312 - Carnidazole tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Carnidazole tablets. 520.312 Section 520.312 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.312 Carnidazole tablets. (a...

  7. Enhancing Student Performance Using Tablet Computers

    ERIC Educational Resources Information Center

    Enriquez, Amelito G.

    2010-01-01

    Tablet PCs have the potential to change the dynamics of classroom interaction through wireless communication coupled with pen-based computing technology that is suited for analyzing and solving engineering problems. This study focuses on how tablet PCs and wireless technology can be used during classroom instruction to create an Interactive…

  8. Development of potential novel cushioning agents for the compaction of coated multi-particulates by co-processing micronized lactose with polymers.

    PubMed

    Lin, Xiao; Chyi, Chin Wun; Ruan, Ke-feng; Feng, Yi; Heng, Paul Wan Sia

    2011-10-01

    This work aimed to explore the potential of lactose as novel cushioning agents with suitable physicomechanical properties by micronization and co-spray drying with polymers for protecting coated multi-particulates from rupture when they are compressed into tablets. Several commercially available lactose grades, micronized lactose (ML) produced by jet milling, spray-dried ML (SML), and polymer-co-processed SMLs, were evaluated for their material characteristics and tableting properties. Hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC), and polyvinylpyrrolidone (PVP) at three different levels were evaluated as co-processed polymers for spray drying. Sugar multi-particulates layered with chlorpheniramine maleate followed by an ethylcellulose coat were tableted using various lactose types as fillers. Drug release from compacted multi-particulate tablets was used to evaluate the cushioning effect of the fillers. The results showed that the cushioning effect of lactose principally depended on its particle size. Micronization can effectively enhance the protective action of lactose. Although spray drying led to a small reduction in the cushioning effect of ML, it significantly improved the physicomechanical properties of ML. Co-spray drying with suitable polymers improved both the cushioning effect and the physicomechanical properties of SML to a certain degree. Among the three polymers studied, HPC was the most effective in terms of enhancing the cushioning effect of SML. This was achieved by reducing yield pressure, and enhancing compressibility and compactibility. The combination of micronization and co-spray drying with polymers is a promising method with which new applications for lactose can be developed. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Are multisource levothyroxine sodium tablets marketed in Egypt interchangeable?

    PubMed

    Abou-Taleb, Basant A; Bondok, Maha; Nounou, Mohamed Ismail; Khalafallah, Nawal; Khalil, Saleh

    2018-02-01

    A clinical study was initiated in response to patients' complaints, supported by the treating physicians, of suspected differences in efficacy among multisource levothyroxine sodium tablets marketed in Egypt. The study design was a multiple dose (100μg levothyroxine sodium tablet once daily for 6 months) and involved 50 primary hypothyroidism female patients (5 equal groups). Tablets administered included five tablet batches (two brands, three origin locations) purchased from local pharmacies in Alexandria. Assessment parameters (measured on consecutive visits) included the thyroid stimulating hormone, total and free levothyroxine. Tablet dissolution rate was determined (BP/EP 2014 & USP 2014). In vitro vs in vivovs correlations were developed. Clinical and pharmaceutical data confirmed inter-brand and inter-source differences in efficacy. Correlations examined indicated potential usefulness of in vitro dissolution test in detecting poor performing levothyroxine sodium tablets during shelf life. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Genuine sildenafil tablets sold in Brazil disguised as MDMA.

    PubMed

    Coelho Neto, José; Faraco, Renata F P; Alves, Cíntia F; Castro, Stela M M; Machado, Yuri

    2018-02-01

    MDMA and sildenafil are two examples among many substances consumed in "raves", as well as in other types of "recreative" social events nowadays. During the first six months of 2017, five cases of supposedly MDMA tablets seized by local law enforcement forces in the state of Minas Gerais, Brazil, and brought to our forensic laboratory for examination, attracted our attention among dozens of others, as the tablets apprehended in these cases were, in fact, colorfully painted versions of genuine, pentagon-shaped, sildenafil tablets, freely available for sale in local pharmacies and drugstores. Physical profiling, together with ATR-FTIR spectral matching, multi-component/deconvolution analysis and correlation were employed to prove that these tablets were genuine sildenafil tablets from a specific manufacturer, painted in a colorful way so that they could be marketed as MDMA tablets to unsuspecting buyers. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Bioavailability and stability of erythromycin delayed release tablets.

    PubMed

    Ogwal, S; Xide, T U

    2001-12-01

    Erythromycin is available as the free base, ethylsuccinate, estolate, stearate, gluceptate, and lactobionate derivatives. When given orally erythromycin and its derivatives except the estolate are inactivated to some extent by the gastric acid and poor absorption may result. To establish whether delayed release erythromycin tablets meet the bioequivalent requirement for the market. Sectrophotometric analysis was used to determine the dissolution percentage of the tablets in vitro. High performance liquid chromatography and IBM/XT microcomputer was used to determine the bioavailability and pharmacokinetic parameters in vivo. Dissolution percentage in thirty minutes reached 28.9% and in sixty minutes erythromycin was completely released. The parameters of the delayed release tablets were Tlag 2.3 hr, Tmax.4.5 hr, and Cmax 2.123 g/ml Ka 0.38048 hr(-1) T (1/2) 1.8 hr, V*C/F 49.721 AUC 12.9155. The relative bioavailability of erythromycin delayed release tablet to erythromycin capsules was 105.31% The content, appearance, and dissolution bioavailability of delayed release erythromycin tablets conforms to the United States pharmacopoeia standards. The tablets should be stored in a cool and dry place in airtight containers and the shelf life is temporarily assigned two years.

  12. 21 CFR 520.623 - Diethylcarbamazine citrate, oxibendazole chewable tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Diethylcarbamazine citrate, oxibendazole chewable tablets. 520.623 Section 520.623 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.623 Diethylcarbamazine citrate, oxibendazole chewable tablets. (a) Specifications. Each tablet...

  13. Novel platens to measure the hardness of a pentagonal shaped tablet.

    PubMed

    Malladi, Jaya; Sidik, Kurex; Wu, Sutan; McCann, Ryan; Dougherty, Jeffrey; Parab, Prakash; Carragher, Thomas

    2017-03-01

    Tablet hardness, a measure of the breaking force of a tablet, is based on numerous factors. These include the shape of the tablet and the mode of the application of force. For instance, when a pentagonal-shaped tablet was tested with a traditional hardness tester with flat platens, there was a large variation in hardness measurements. This was due to the propensity of vertices of the tablet to crush, referred to as an "improper break". This article describes a novel approach to measure the hardness of pentagonal-shaped tablets using modified platens. The modified platens have more uniform loading than flat platens. This is because they reduce loading on the vertex of the pentagon and apply forces on tablet edges to generate reproducible tablet fracture. The robustness of modified platens was assessed using a series of studies, which included feasibility and Gauge Repeatability & Reproducibility (R&R) studies. A key finding was that improper breaks, generated frequently with a traditional hardness tester using flat platens, were eliminated. The Gauge R&R study revealed that the tablets tested with novel platens generated consistent values in hardness measurements, independent of batch, hardness level, and day of testing, operator and tablet dosage strength.

  14. An index for evaluating difficulty of Chewing Index for chewable tablets.

    PubMed

    Gupta, Abhay; Chidambaram, Nallaperumal; Khan, Mansoor A

    2015-02-01

    Chewing difficulty index, a potential measure of difficulty in chewing the chewable tablets, has been described herein as the product of tablet thickness and tablet hardness measured under the diametral loading. The proposed index was evaluated by measuring the dimensions and mechanical strength of commercial and in-house prepared chewable tablets. Data collected on tablets with different thickness but same hardness or tensile strength suggests that the proposed index provides a good assessment of the force needed to chew the chewable tablets. Influence of brief exposure to salivary fluid during chewing on the mechanical strength of the chewable tablets was also evaluated. Thirty seconds exposure to the simulated salivary fluid was also found to significantly reduce (p < 0.05) the hardness and the chewing difficulty index of a number of evaluated chewable tablet drug products.

  15. Application of face centred central composite design to optimise compression force and tablet diameter for the formulation of mechanically strong and fast disintegrating orodispersible tablets.

    PubMed

    Pabari, Ritesh M; Ramtoola, Zebunnissa

    2012-07-01

    A two factor, three level (3(2)) face centred, central composite design (CCD) was applied to investigate the main and interaction effects of tablet diameter and compression force (CF) on hardness, disintegration time (DT) and porosity of mannitol based orodispersible tablets (ODTs). Tablet diameters of 10, 13 and 15 mm, and CF of 10, 15 and 20 kN were studied. Results of multiple linear regression analysis show that both the tablet diameter and CF influence tablet characteristics. A negative value of regression coefficient for tablet diameter showed an inverse relationship with hardness and DT. A positive value of regression coefficient for CF indicated an increase in hardness and DT with increasing CF as a result of the decrease in tablet porosity. Interestingly, at the larger tablet diameter of 15 mm, while hardness increased and porosity decreased with an increase in CF, the DT was resistant to change. The optimised combination was a tablet of 15 mm diameter compressed at 15 kN showing a rapid DT of 37.7s and high hardness of 71.4N. Using these parameters, ODTs containing ibuprofen showed no significant change in DT (ANOVA; p>0.05) irrespective of the hydrophobicity of the ibuprofen. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. 21 CFR 520.1660c - Oxytetracycline hydrochloride tablets/boluses.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride tablets/boluses. 520....1660c Oxytetracycline hydrochloride tablets/boluses. (a) Specifications. Each tablet or bolus contains 250, 500, or 1,000 milligrams of oxytetracycline hydrochloride. (b) Sponsors. For sponsors in § 510...

  17. [Cost-effective analysis of rotation from sustained-release morphine tablet to transdermal fentanyl of matrix type or sustained-release oxycodone tablet].

    PubMed

    Ise, Yuya; Wako, Tetsuya; Miura, Yoshihiko; Katayama, Shirou; Shimizu, Hisanori

    2009-12-01

    The present study was undertaken to determine the pharmacoeconomics of switching from sustained-release morphine tablet to matrix type (MT) of transdermal fontanel or sustained-release Oxycodone tablet. Cost-effective analysis was performed using a simulation model along with decision analysis. The analysis was done from the payer's perspective. The cost-effective ratio/patient of transdermal MT fontanel (22, 539 yen)was lower than that of sustained -release Oxycodone tablet (23, 630 yen), although a sensitivity analysis could not indicate that this result was reliable. These results suggest the possibility that transdermal MT fontanel was much less expensive than a sustained-release Oxycodone tablet.

  18. Cyclodextrins as excipients in tablet formulations.

    PubMed

    Conceição, Jaime; Adeoye, Oluwatomide; Cabral-Marques, Helena Maria; Lobo, José Manuel Sousa

    2018-04-22

    This paper aims to provide a critical review of cyclodextrins as excipients in tablet formulations, highlighting: (i) the principal pharmaceutical applications of cyclodextrins; (ii) the most relevant technological aspects in pharmaceutical formulation development; and (iii) the actual regulatory status of cyclodextrins. Moreover, several illustrative examples are presented. Cyclodextrins can be used as complexing excipients in tablet formulations for low-dose drugs. By contrast, for medium-dose drugs and/or when the complexation efficiency is low, the methods to enhance the complexation efficiency play a key part in reducing the cyclodextrin quantity. In addition, these compounds are used as fillers, disintegrants, binders and multifunctional direct compression excipients of the tablets. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Damage-tolerance strategies for nacre tablets.

    PubMed

    Wang, Shengnan; Zhu, Xinqiao; Li, Qiyang; Wang, Rizhi; Wang, Xiaoxiang

    2016-05-01

    Nacre, a natural armor, exhibits prominent penetration resistance against predatory attacks. Unraveling its hierarchical toughening mechanisms and damage-tolerance design strategies may provide significant inspiration for the pursuit of high-performance artificial armors. In this work, relationships between the structure and mechanical performance of nacre were investigated. The results show that other than their brick-and-mortar structure, individual nacre tablets significantly contribute to the damage localization of nacre. Affected by intracrystalline organics, the tablets exhibit a unique fracture behavior. The synergistic action of the nanoscale deformation mechanisms increases the energy dissipation efficiency of the tablets and contributes to the preservation of the structural and functional integrity of the shell. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Interfacial elastic relaxation during the ejection of bi-layered tablets.

    PubMed

    Anuar, M S; Briscoe, B J

    2010-03-15

    The predilection of a bi-layered tablet to fail in the interface region after its initial formation in the compaction process reduces its practicality as a choice for controlled release solid drug delivery system. Hence, a fundamental appreciation of the governing mechanism that causes the weakening of the interfacial bonds within the bi-layered tablet is crucial in order to improve the overall bi-layered tablet mechanical integrity. This work has shown that the occurrence of the elastic relaxation in the interface region during the ejection stage of the compaction process decreases with the increase in the bi-layered tablet interface strength. This is believed to be due to the increase in the plastic bonding in the interface region. The tablet diametrical elastic relaxation affects the tablet height elastic relaxation, where the impediment of the tablet height expansion is observed when the interface region experiences a diametrical expansion. 2009 Elsevier B.V. All rights reserved.

  1. Design, development, and optimization of polymeric based-colonic drug delivery system of naproxen.

    PubMed

    Sharma, Pooja; Chawla, Anuj; Pawar, Pravin

    2013-01-01

    The aim of present investigation deals with the development of time-dependent and pH sensitive press-coated tablets for colon specific drug delivery of naproxen. The core tablets were prepared by wet granulation method then press coated with hydroxypropyl cellulose (HPC) or Eudragit RSPO : RLPO mixture and further coated with Eudragit S-100 by dip immerse method. The in vitro drug release study was conducted in different dissolution media such as pH 1.2, 6.8, and 7.4 with or without rat caecal content to simulate GIT conditions. Surface morphology and cross-sectional view of the tablets were visualized by scanning electron microscopy (SEM). All prepared batches were in compliance with the pharmacopoeial standards. The tablets which are compression coated with HPC followed by Eudragit S-100 coated showed highest in vitro drug release of 98.10% in presence of rat caecal content. The SEM of tablets suggested that the number of pores got increased in pH 7.4 medium followed by dissolution of coating layer. The tablets coat erosion study suggested that the lag time depends upon the coating concentrations of polymers. A time-dependent hydrophilic polymer and pH sensitive polymer based press-coated tablets of naproxen were promising delivery for colon targeting.

  2. Design, Development, and Optimization of Polymeric Based-Colonic Drug Delivery System of Naproxen

    PubMed Central

    Sharma, Pooja; Chawla, Anuj; Pawar, Pravin

    2013-01-01

    The aim of present investigation deals with the development of time-dependent and pH sensitive press-coated tablets for colon specific drug delivery of naproxen. The core tablets were prepared by wet granulation method then press coated with hydroxypropyl cellulose (HPC) or Eudragit RSPO : RLPO mixture and further coated with Eudragit S-100 by dip immerse method. The in vitro drug release study was conducted in different dissolution media such as pH 1.2, 6.8, and 7.4 with or without rat caecal content to simulate GIT conditions. Surface morphology and cross-sectional view of the tablets were visualized by scanning electron microscopy (SEM). All prepared batches were in compliance with the pharmacopoeial standards. The tablets which are compression coated with HPC followed by Eudragit S-100 coated showed highest in vitro drug release of 98.10% in presence of rat caecal content. The SEM of tablets suggested that the number of pores got increased in pH 7.4 medium followed by dissolution of coating layer. The tablets coat erosion study suggested that the lag time depends upon the coating concentrations of polymers. A time-dependent hydrophilic polymer and pH sensitive polymer based press-coated tablets of naproxen were promising delivery for colon targeting. PMID:24198725

  3. Embolic stroke associated with injection of buprenorphine tablets.

    PubMed

    Lim, C C Tchoyoson; Lee, Sze Haur; Wong, Yee-Choon; Hui, Francis

    2009-09-15

    Drug users who crush, dissolve, and inject buprenorphine tablets parenterally may be at risk of severe thromboembolic complications or death. We describe patients with neurologic complications after injecting buprenorphine tablets. Brain MRI including diffusion-weighted imaging (DWI) in patients admitted to the neurologic department after injecting buprenorphine tablets were reviewed. Seven men had neurologic complications after buprenorphine tablet injection. In 5 patients, multiple small scattered hyperintense lesions were detected on DWI in the cortex, white matter, and basal ganglia of the cerebral hemisphere; one patient had a single small lesion. The side of MRI abnormality corresponded to the side of needle marks on the neck except in one patient who had bilateral injections. One patient, who denied injecting into the neck, had DWI abnormalities in the middle cerebral artery territory on one side and occlusion of the ipsilateral internal carotid artery. Buprenorphine tablets can be intentionally or inadvertently injected into the carotid artery, causing a characteristic appearance on diffusion-weighted imaging, consistent with embolic cerebral infarction.

  4. Tensile and shear methods for measuring strength of bilayer tablets.

    PubMed

    Chang, Shao-Yu; Li, Jian-Xin; Sun, Changquan Calvin

    2017-05-15

    Both shear and tensile measurement methods have been used to quantify interfacial bonding strength of bilayer tablets. The shear method is more convenient to perform, but reproducible strength data requires careful control of the placement of tablet and contact point for shear force application. Moreover, data obtained from the shear method depend on the orientation of the bilayer tablet. Although more time-consuming to perform, the tensile method yields data that are straightforward to interpret. Thus, the tensile method is preferred in fundamental bilayer tableting research to minimize ambiguity in data interpretation. Using both shear and tensile methods, we measured the mechanical strength of bilayer tablets made of several different layer combinations of lactose and microcrystalline cellulose. We observed a good correlation between strength obtained by the tensile method and carefully conducted shear method. This suggests that the shear method may be used for routine quality test of bilayer tablets during manufacturing because of its speed and convenience, provided a protocol for careful control of the placement of the tablet interface, tablet orientation, and blade is implemented. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Portable Tablets in Science Museum Learning: Options and Obstacles

    ERIC Educational Resources Information Center

    Gronemann, Sigurd Trolle

    2017-01-01

    Despite the increasing use of portable tablets in learning, their impact has received little attention in research. In five different projects, this media-ethnographic and design-based analysis of the use of portable tablets as a learning resource in science museums investigates how young people's learning with portable tablets matches the…

  6. 21 CFR 520.1696d - Penicillin V potassium tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin V potassium tablets. 520.1696d Section... Penicillin V potassium tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to 125 milligrams (200,000 units) or 250 milligrams (400,000 units) of penicillin V. (b) Sponsors. See...

  7. 21 CFR 520.1696d - Penicillin V potassium tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Penicillin V potassium tablets. 520.1696d Section... Penicillin V potassium tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to 125 milligrams (200,000 units) or 250 milligrams (400,000 units) of penicillin V. (b) Sponsors. See...

  8. 21 CFR 520.1696d - Penicillin V potassium tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Penicillin V potassium tablets. 520.1696d Section... Penicillin V potassium tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to 125 milligrams (200,000 units) or 250 milligrams (400,000 units) of penicillin V. (b) Sponsors. See...

  9. Characterization of the Roman curse tablet

    NASA Astrophysics Data System (ADS)

    Liu, Wen; Zhang, Boyang; Fu, Lin

    2017-08-01

    The Roman curse tablet, produced in ancient Rome period, is a metal plate that inscribed with curses. In this research, several techniques were used to find out the physical structure and chemical composition of the Roman curse tablet, and testified the hypothesis that whether the tablet is made of pure lead or lead alloy. A sample of Roman Curse Tablet from the Johns Hopkins Archaeological Museum was analyzed using several different characterization techniques to determine the physical structure and chemical composition. The characterization techniques used were including optical microscopy, scanning electron microscopy (SEM), atomic force microscopy (AFM), and differential scanning calorimetry (DSC). Because of the small sample size, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and X-ray fluorescence (XRF) cannot test the sample. Results from optical microscopy and SEM, enlarged images of the sample surface were studied. The result revealed that the sample surface has a rough, non-uniform, and grainy surface. AFM provides three-dimensional topography of the sample surface, studying the sample surface in atomic level. DSC studies the thermal property, which is most likely a lead-alloy, not a pure lead. However, none of these tests indicated anything about the chemical composition. Future work will be required due to the lack of measures finding out its chemical composition. Therefore, from these characterization techniques above, the Roman curse tablet sample is consisted of lead alloy, not pure lead.

  10. Placing wireless tablets in clinical settings for patient education.

    PubMed

    Stribling, Judy C; Richardson, Joshua E

    2016-04-01

    The authors explored the feasibility and possible benefit of tablet-based educational materials for patients in clinic waiting areas. We distributed eight tablets preloaded with diagnosis-relevant information in two clinic waiting areas. Patients were surveyed about satisfaction, usability, and effects on learning. Technical issues were resolved. Thirty-seven of forty patients completed the survey. On average, the patients were satisfied in all categories. Placing tablet-based educational materials in clinic waiting areas is relatively easy to implement. Patients using tablets reported satisfaction across three domains: usability, education, and satisfaction.

  11. Axial strength test for round flat faced versus capsule shaped bilayer tablets.

    PubMed

    Franck, Jason; Abebe, Admassu; Keluskar, Rekha; Martin, Kyle; Majumdar, Antara; Kottala, Niranjan; Stamato, Howard

    2015-03-01

    There has been increasing interest in fixed dose combination (FDC) therapy. Multi-layer tablets are a popular choice among various technologies to deliver FDCs. In most cases, round flat faced tooling is used in testing tablets as they have the simplest geometry. However, shaped tooling is more common for commercial products and may have an effect on bilayer tablet strength. Capsule shaped bilayer tablets, similar to a commercial image, and holders conforming to the tablet topology, were compared with similar round flat faced bilayer tablets and their corresponding holders. Bilayer tablets were subjected to an axial test device, until fracture and the quantitative breaking force value was recorded. As the second layer compression force increases, regardless of holder design, an increase in breaking force occurs as expected. This consistent trend provides insight regarding the breaking force of capsule shaped bilayer tablets. The results of this study show that at lower second layer compression forces, tablet geometry does not significantly impact the results. However, at higher compression forces, a significant difference in breaking force between tablet geometries exists. Therefore, using a test geometry close to the final commercial tablet image is recommended to have the most accurate prediction for tablet breakage.

  12. Formulation and characterization of cetylpyridinium chloride bioadhesive tablets.

    PubMed

    Akbari, Jafar; Saeedi, Majid; Morteza-Semnani, Katayoun; Kelidari, Hamidreza; Lashkari, Maryam

    2014-12-01

    Bioadhesive polymers play an important role in biomedical and drug delivery applications. The aim of this study is to develop a sustained- release tablet for local application of Cetylpyridinium Chloride (CPC). This delivery system would supply the drug at an effective level for a long period of time, and thereby overcome the problem of the short retention time of CPC and could be used for buccal delivery as a topical anti-infective agent. CPC bioadhesive tablets were directly prepared using 7 mm flat-faced punches on a hydraulic press. The materials for each tablet were weighted, introduced into the die and compacted at constant compression pressure. The dissolution tests were performed to the rotation paddle method and the bioadhesive strength of the tablets were measured. The results showed that as the concentration of polymer increased, the drug release rate was decreased. Also the type and ratio of polymers altered the release kinetic of Cetylpyridinium Chloride from investigated tablets. The bioadhesion strength increased with increasing the concentration of polymer and maximum bioadhesion strength was observed with HPMC K100M. The selected formulation of CPC bioadhesive tablet can be used as a suitable preparation for continuous release of CPC with appropriate bioadhesion strength.

  13. 21 CFR 520.2260c - Sulfamethazine sustained-release tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sulfamethazine sustained-release tablets. 520....2260c Sulfamethazine sustained-release tablets. (a) Sponsor. See No. 053501 in § 510.600(c) of this chapter for use of an 8-gram sulfamethazine sustained-release tablet. (b) Conditions of use—(1) Amount. 8...

  14. Relative bioavailability of iron and folic acid from a new powdered supplement compared to a traditional tablet in pregnant women

    PubMed Central

    Hartman-Craven, Brenda; Christofides, Anna; O'Connor, Deborah L; Zlotkin, Stanley

    2009-01-01

    Background Deficiencies of iron and folic acid during pregnancy can lead to adverse outcomes for the fetus, thus supplements are recommended. Adherence to current tablet-based supplements is documented to be poor. Recently a powdered form of micronutrients has been developed which may decrease side-effects and thus improve adherence. However, before testing the efficacy of the supplement as an alternate choice for supplementation during pregnancy, the bioavailability of the iron needs to be determined. Our objective was to measure the relative bioavailability of iron and folic acid from a powdered supplement that can be sprinkled on semi-solid foods or beverages versus a traditional tablet supplement in pregnant women. Methods Eighteen healthy pregnant women (24 – 32 weeks gestation) were randomized to receive the supplements in a crossover design. Following ingestion of each supplement, the changes (over baseline) in serum iron and folate over 8 hours were determined. The powdered supplement contained 30 mg of iron as micronized dispersible ferric pyrophosphate with an emulsifier coating and 600 μg folic acid; the tablet contained 27 mg iron from ferrous fumarate and 1000 μg folic acid. Results Overall absorption of iron from the powdered supplement was significantly lower than the tablet (p = 0.003). There was no difference in the overall absorption of folic acid between supplements. Based on the differences in the area under the curve and doses, the relative bioavailability of iron from powdered supplement was lower than from the tablet (0.22). Conclusion The unexpected lower bioavailability of iron from the powdered supplement is contrary to previously published reports. However, since pills and capsules are known to be poorly accepted by some women during pregnancy, it is reasonable to continue to explore alternative micronutrient delivery systems and forms of iron for this purpose. Trial Registration ClinicalTrials.gov NCT00789490 PMID:19635145

  15. Bioequivalence of saxagliptin/dapagliflozin fixed-dose combination tablets compared with coadministration of the individual tablets to healthy subjects.

    PubMed

    Vakkalagadda, Blisse; Vetter, Marion L; Rana, Jignasa; Smith, Charles H; Huang, Jian; Karkas, Jennifer; Boulton, David W; LaCreta, Frank

    2015-12-01

    Saxagliptin and dapagliflozin are individually indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. The bioequivalence of saxagliptin/dapagliflozin 2.5/5 mg and 5/10 mg fixed-dose combination (FDC) tablets compared with coadministration of the individual tablets and the food effect on both strengths of saxagliptin/dapagliflozin FDCs were evaluated in this open-label, randomized, single-dose crossover study. Healthy subjects were randomized to saxagliptin 2.5 mg + dapagliflozin 5 mg fasted, 2.5/5 mg FDC fasted, 2.5/5 mg FDC fed (Cohort 1) or saxagliptin 5 mg + dapagliflozin 10 mg fasted, 5/10 mg FDC fasted, 5/10 mg FDC fed (Cohort 2). Serial blood samples for pharmacokinetics of saxagliptin and dapagliflozin were obtained predose and up to 60 h postdose. Bioequivalence of FDC tablets versus individual components was concluded if the 90% CIs for FDC to individual component geometric mean ratios of C max, AUC 0-T, and AUC inf of both analytes were between 0.80 and 1.25. Seventy-two subjects were randomized; 71 (98.6%) completed the study. Saxagliptin/dapagliflozin 2.5/5 mg and 5/10 mg FDC tablets were bioequivalent to the individual tablets administered concomitantly. Food had no clinically meaningful effect on saxagliptin or dapagliflozin overall systemic exposure. Saxagliptin/dapagliflozin FDC tablets were bioequivalent to coadministration of the individual components in healthy subjects under fasted conditions and food had no clinically meaningful effect on bioavailability.

  16. Replacing Smartphones With Mini Tablet Technology: An Evaluation.

    PubMed

    Maneval, Rhonda; Mechtel, Marci

    Handheld technology allows students to access point-of-care resources throughout the clinical experience. To assess the viability of replacing student smartphones with tablets, an evaluation project was undertaken. Overall, students were equally dissatisfied with the 2 types of tablets that were evaluated. Students saw the potential usefulness of tablets to manage clinical assignments, interact with the learning management system, and communicate with faculty, but not for retrieving information currently accessible on their phones.

  17. A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects.

    PubMed

    Park, Sang-In; Lee, Howard; Oh, Jaeseong; Lim, Kyoung Soo; Jang, In-Jin; Kim, Jeong-Ae; Jung, Jong Hyuk; Yu, Kyung-Sang

    2015-01-01

    In type 2 diabetes mellitus, fixed-dose combination (FDC) can provide the complementary benefits of correction of multiple pathophysiologic defects such as dysfunctions in glycemic or metabolic control while improving compliance compared with separate tablets taken together. The objective of the study reported here was to compare the pharmacodynamic (PD), pharmacokinetic (PK), and tolerability profiles of gemigliptin and extended-release metformin (metformin XR) between FDC and separate tablets. A randomized, open-label, single-dose, two-way, two-period, crossover study was conducted in 28 healthy male volunteers. Two FDC tablets of gemigliptin/metformin 25/500 mg or separate tablets of gemigliptin (50 mg ×1) and metformin XR (500 mg ×2) were orally administered in each period. Serial blood samples were collected up to 48 hours post-dose to determine dipeptidyl peptidase 4 (DPP-4) activity using spectrophotometric assay and concentrations of gemigliptin and metformin using tandem mass spectrometry. Geometric mean ratios (GMRs) of FDC to separate tablet formulations and their 90% confidence intervals (CIs) were calculated to compare the PD and PK parameters between the two formulations. Tolerability was assessed throughout the study. The plasma DPP-4 activity-time curves of the FDC and the separate tablets almost overlapped, leading to a GMR (90% CI) of the FDC to separate tablets for the plasma DPP-4 activity and its maximum inhibition of 1.00 (0.97-1.04) and 0.92 (0.82-1.05), respectively. Likewise, all of the GMRs (90% CIs) of FDC to separate tablets for the area under the plasma concentration-time curve and maximum plasma concentration of gemigliptin and metformin fell entirely within the conventional bioequivalence range of 0.80-1.25. Both the FDC and separate tablets were well tolerated. The PD, PK, and tolerability profiles of gemigliptin and metformin XR in FDC and separate tablets were found to be comparable. The FDC tablet of gemigliptin and metformin

  18. Transforming the Classroom With Tablet Technology.

    PubMed

    Sargent, Lana; Miles, Elizabeth

    Identifying the most effective models for integrating new technology into the classroom and understanding its effects on educational outcomes are essential for nurse educators. This article describes an educational intervention with tablet technology (iPads) using an innovative case-based learning model in a nursing program. Students reported positive learning outcomes when using the tablet technology for learning course content.

  19. Enhanced oral bioavailability of felodipine by novel solid self-microemulsifying tablets.

    PubMed

    Jing, Boyu; Wang, Zhiyuan; Yang, Rui; Zheng, Xia; Zhao, Jia; Tang, Si; He, Zhonggui

    2016-01-01

    The novel self-microemulsifying (SME) tablets were developed to enhance the oral bioavailability of a poor water-soluble drug felodipine (FDP). Firstly, FDP was dissolved in the optimized liquid self-microemusifying drug delivery systems (SMEDDS) containing Miglyol® 812, Cremophor® RH 40, Tween 80 and Transcutol® P, and the mixture was solidified with porous silicon dioxide and crospovidone as adsorbents. Then after combining the solidified powders with other excipients, the solid SME tablets were prepared by wet granulation-compression method. The prepared tablets possessed satisfactory characterization; the droplet size of the SME tablets following self-emulsification in water was nearly equivalent to the liquid SMEDDS (68.4 ± 14.0 and 64.4 ± 12.0 nm); differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) analysis demonstrated that FDP in SME tablets had undergone a polymorphism transition from a crystal form to an amorphous state, which was further confirmed by transmission electron microscopy (TEM). A similar dissolution performance of SME tablets and liquid SMEDDS was also obtained under the sink condition (85% within 10 min), both significantly higher than commercial tablets. The oral bioavailability was evaluated for the SME tablets, liquid SMEDDS and commercial conventional tablets in the fasted beagle dogs. The AUC of FDP from the SME tablets was about 2-fold greater than that of conventional tablets, but no significant difference was found when compared with the liquid SMEDDS. Accordingly, these preliminary results suggest that this formulation approach offers a useful large-scale producing method to prepare the solid SME tablets from the liquid SMEDDS for oral bioavailability equivalent enhancement of poorly soluble FDP.

  20. Chewability testing in the development of a chewable tablet for hyperphosphatemia.

    PubMed

    Lanz, Michael; Baldischweiler, Jan; Kriwet, Burkhard; Schill, Jutta; Stafford, John; Imanidis, Georgios

    2014-12-01

    The official Pharmacopeia does not include a test procedure for the in vitro estimation of the chewability of tablets and publications in the scientific literature on this subject are rare. The purpose of this study was to evaluate a number of different test procedures for assessing chewability, starting from standard breaking force and strength testing and progressing to develop new procedures that simulate the actual chewing action on tablets. A further goal was to apply these test procedures to characterize the chewability of the novel phosphate binder PA21 in comparison with a commercially available phosphate binder chewable tablet product based on lanthanum (Fosrenol®) and a chewable tablet product containing calcium (Calcimagon®) - the latter being used as a standard for its very good chewability. For this purpose, a number of development formulations (different batches of PA21) were tested. The radial or diametrical tablet breaking force offers a poor means of assessing chewability while the axial breaking force was concluded to better reflect the effect of chewing on the tablet. Measurement of tablet behavior upon repeated loading afforded the best simulation of the actual chewing action and was found to have a good discriminating power with respect to chewability of the tested tablets, especially when the tablet was moistened with artificial saliva. The developed tests are shown to be more suitable for evaluating chewing properties of tablets than currently used Pharmacopeial tests. Following ICHQ6, which calls for specification of hardness for chewable tablets, these test procedures enabled the optimal chewability features of PA21 tablets in development to be confirmed whilst still maintaining capabilities for robust production and transportation processes.