Objective. Objective of the present work was to develop site-specific gastroretentive drug delivery of Troxipide using polymers Pluronic F127 and Polyox 205?WSR. Troxipide is a novel gastroprotective agent with antiulcer, anti-inflammatory, and mucus secreting properties with elimination half-life of 7.4?hrs. Troxipide inhibits H. pylori-derived urease. It is mainly absorbed from stomach. Methods. 32 factorial design was applied to study the effect of independent variable. Effects of concentration of polymer on dependant variables as swelling index, hardness, and % drug release were studied. Pluronic F127 and Polyox 205?WSR were used as rate controlled polymer. Sodium bicarbonate and citric acid were used as effervescent-generating agent. Results. From the factorial batches, it was observed that formulation F5 (19% Pluronic F127 and 80% Polyox 205?WSR) showed optimum controlled drug release (98.60%?±?1.82) for 10?hrs with ability to float >12?hrs. Optimized formulation characterized by FTIR and DSC studies confirmed no chemical interactions between drug and polymer. Gastroretention for 6?hrs for optimized formulations was confirmed by in vivo X-ray placebo study. Conclusion. Results demonstrated feasibility of Troxipide in the development of gastroretentive site-specific drug delivery. PMID:25505995
Jagdale, Swati C.; Kamble, Shraddha B.; Kuchekar, Bhanudas S.; Chabukswar, Aniruddha R.
Migraine follows circadian rhythm in which headache is more painful at the awakening time. This needs administration of dosage form at night time to release drug after lag period when pain gets worse. Sumatriptan succinate is a drug of choice for migraine. Sumatriptan succinate has bitter taste, low oral bioavailability, and shorter half-life. Present work deals with application of design of experiment for polyox and xanthan gum in development of press coated floating pulsatile tablet. Floating pulsatile concept was applied to increase gastric residence of the dosage form. Burst release was achieved through immediate release tablet using crospovidone as superdisintegrant (10%). Pulse lag time was achieved using swellable polymer polyox WSR 205 and xanthan gum. 32 experimental design was applied. Optimized formulation was evaluated for physical characteristics and in-vitro and in-vivo study. From results, it can be concluded that optimized batch F8 containing polyox WSR205 (72.72%) and xanthan gum (27.27%) of total weight of polymer has shown floating lag time of 55 ± 2?sec, drug content of 100.35 ± 0.4%, hardness of 6 ± 0.1?Kg/cm2, and 98.69 ± 2% drug release in pulse manner with lag time of 7 ± 0.1?h. Optimized batch showed prolong gastric residence which was confirmed by in-vivo X-ray study. PMID:25530963
Jagdale, Swati C.; Pawar, Chandrakala R.
Polyethylene oxide (Polyox) and carrageenan based solvent cast films have been formulated as dressings for drug delivery to wounds. Films plasticised with glycerol were loaded with streptomycin (30%, w/w) and diclofenac (10%, w/w) for enhanced healing effects in chronic wounds. Blank and drug loaded films were characterised by texture analysis (for mechanical and mucoadhesive properties), scanning electron microscopy, differential scanning calorimetry, X-ray diffraction and Fourier transform infrared spectroscopy. In addition, swelling, in vitro drug release and antibacterial studies were conducted to further characterise the films. Both blank and drug loaded films showed a smooth, homogeneous surface morphology, excellent transparency, high elasticity and acceptable tensile (mechanical) properties. The drug loaded films showed a high capacity to absorb simulated wound fluid and significant mucoadhesion force which is expected to allow effective adherence to and protection of the wound. The films showed controlled release of both streptomycin and diclofenac for 72 h. These drug loaded films produced higher zones of inhibition against Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli compared to the individual drugs zones of inhibition. Incorporation of streptomycin can prevent and treat chronic wound infections whereas diclofenac can target the inflammatory phase of wound healing to relieve pain and swelling. PMID:23228898
Boateng, Joshua S; Pawar, Harshavardhan V; Tetteh, John
An experimental investigation was conducted into the behavior of water jets dosed with increasing amounts of polymer additive to produce a non-Newtonian jet fluid. As a preliminary to this investigation the properties of Newtonian jets are reviewed and compared with various semi-empirical models. The behavior of non-Newtonian fluids and drag reducing additives is also reviewed with a view to application
K. S. Nystroem; R. F. Boucher; L. Filipsson
Presents an imaginative story to be used to introduce elementary school students to the different properties and uses of "Polyox." Various ideas for using "Polyox" in elementary science are given. (MDR)
McCormack, Alan J.
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 3˛ 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
Jagdale, Swati C; Bari, Nilesh A; Kuchekar, Bhanudas S; Chabukswar, Aniruddha R
The present study is intended to enhance gastric retention of sustained release tablet of valacyclovir hydrochloride by combined approach of floating and swelling. The tablets are prepared by direct compression method. Polyethylene oxide (Polyox WSR 303) is selected as the swelling matrix agent. Sodium starch glycolate (SSG) is used as swelling enhancer, and sodium bicarbonate is used as an effervescent agent for floating. A 3(2) full factorial design is applied to systematically optimize the formulation. The concentration of Polyox WSR 303 (X 1) and concentration of SSG (X 2) are selected as independent variables. The percentage drug release at 12 h, floating lag time, and maximum percentage swelling are selected as dependent variables. Formulations are evaluated for hardness, friability, floating lag time, total floating time, percentage swelling, in vitro drug release, and in vivo floating study. The results indicated that X 1 and X 2 significantly affected the drug release properties, floating lag times, and maximum percentage swelling. Release rate decreases as the concentration of Polyox increased. Regression analysis and numerical optimization are performed to identify the best formulation. Formulation F5 prepared with Polyox WSR 303 (15 %) and SSG (10 %) is found to be the best formulation. F5 followed zero-order release mechanism. Swelling and floating gastroretentive tablets of valacyclovir HCl are successfully formulated with controlled delivery to stomach with an aim of increasing the mean residence time in the upper part of GIT where the drug has its absorption window. PMID:25787207
Upadhyay, Pratik; Nayak, Kunal; Patel, Kaushika; Patel, Jaymin; Shah, Shreeraj; Deshpande, Jayant
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
Jagdale, Swati C.; Bari, Nilesh A.; Kuchekar, Bhanudas S.; Chabukswar, Aniruddha R.
Laser Doppler measurements of blood flow velocities in the vessels of rat mesentery have been performed to study the effect of the drag-reducing agent polyethylene oxide Polyox WSR-301 on microcirculation. These agents are capable of increasing the cardiac output and decreasing the arterial pressure. Measurements performed on spontaneously hypertensive rats anesthetized by Nembutal showed that the mean blood velocities in all groups of studied vessels are higher (by nearly two to three times) as compared to those in controls. Most likely these results reflect the effects of hypertensive raising pressure drop and the `rarefaction' phenomenon.
Polyakova, Marina S.; Sokolova, Irina A.; Priezzhev, Alexander V.; Proskurin, Sergei G.; Savchenko, Natalia B.; Shakhnazarov, Alexander A.
Anionic polymer sodium carboxymethylcellulose (CELLOGEN® HP-HS and\\/or HP-12HS) was investigated for its ability to influence\\u000a the release of three model drugs propranolol hydrochloride, theophylline and ibuprofen from polyethylene oxide (POLYOX™ WSR\\u000a 1105 and\\/or Coagulant) hydrophilic matrices. For anionic ibuprofen and non-ionic theophylline, no unusual\\/unexpected release\\u000a profiles were obtained from tablets containing a mixture of two polymers. However, for cationic propranolol
Dasha Palmer; Marina Levina; Ali Nokhodchi; Dennis Douroumis; Tom Farrell; Ali Rajabi-Siahboomi
The objective of the present study was to develop techniques for an abuse-deterrent (AD) platform utilizing hot melt extrusion (HME) process. Formulation optimization was accomplished by utilizing Box-Behnken design of experiments to determine the effect of the three formulation factors: PolyOx™ WSR301, Benecel™ K15M, and Carbopol 71G; each of which was studied at three levels on TR attributes of the produced melt extruded pellets. A response surface methodology was utilized to identify the optimized formulation. Lidocaine Hydrochloride was used as a model drug, and suitable formulation ingredients were employed as carrier matrices and processing aids. All of the formulations were evaluated for the TR attributes such as particle size post-milling, gelling, percentage of drug extraction in water and alcohol. All of the DOE formulations demonstrated sufficient hardness and elasticity, and could not be reduced into fine particles (<150µm), which is a desirable feature to prevent snorting. In addition, all of the formulations exhibited good gelling tendency in water with minimal extraction of drug in the aqueous medium. Moreover, Benecel™ K15M in combination with PolyOx™ WSR301 could be utilized to produce pellets with TR potential. HME has been demonstrated to be a viable technique with a potential to develop novel abuse-deterrent formulations. PMID:24433429
Maddineni, Sindhuri; Battu, Sunil Kumar; Morott, Joe; Majumdar, Soumyajit; Repka, Michael A.
The present study deals with the inclusion or incorporation of hot-melts into buccoadhesive patches. Our aim is to develop a patient-friendly dosage form that is capable of extending release of short elimination half-life drugs so to decrease dosing frequency and to increase the bioavailability of highly-metabolized drugs with the ultimate aim of dose reduction. Tizanidine hydrochloride (TIZ) was used as a model drug.TIZ was incorporated into Compritol-based hot-melts, and then further formulated into buccal patches prepared using HPMC, PVA and Polyox. A Central Composite Face-centered Design was employed to statistically optimize the formulation variables; HPMC solution/PVA solution weight ratio, Compritol/TIZ ratio in the hot-melts and percentage Polyox. The optimized formula suggested by the software was successful in controlling drug release, where 85% of TIZ was released after 4 h and the patch showed acceptable mucoadhesion properties. Pharmacokinetic parameters of TIZ from the optimized formula were compared to those of the immediate release tablet, Sirdalud®, as reference in human volunteers using a randomized crossover design. Significant increase was observed for Cmax, Tmax, AUC(0-12) and AUC(0-1). The increase in relative bioavailability of TIZ from the optimized formula was 2.57 folds. PMID:25460150
El Mahrouk, Galal M; ElGazayerly, Omaima N; Aboelwafa, Ahmed A; Taha, Maie S
A hydraulic capsule pipeline (HCP) drag reduction study is being conducted using a 210 mm inner diameter, 131 m long steel pipe loop located at the Research Park of the University of Missouri-Columbia (UMC). Polyox (trade name for polyethylene oxide) was tested alone and in combination with fiber for the first time for drag reduction investigations in such a large diameter HCP flow. A novel design of vacuum-aided Polyox dissolution and injection system was also tested for the first time in this pipeline. The injected polymer concentration present was determined on the basis of average concentration over the entire pipeline loop. Subsequently, more detailed data reduction will be presented based upon local polymer concentration in the test section determined by a dispersion model, which is being developed and will be calibrated to the experimental system using a fluorescent dye additive for experimental measurement. In addition, abrasion-resistant resin logs with cement additives for density control were employed to simulate coal logs. Results of this study not only answered some basic questions about drag reduction in HCP flow, it is also beneficial and important to HCP commercial applications.
Wu, Gangwei; Miles, J. [Univ. of Missouri, Columbia, MO (United States); Xu, Jihuai [Central Coal Mining Research Institute, Hebei (China)
This study investigated the processing parameters and formulation factors on the bioadhesive properties, temperature stability properties, and drug release properties of miconazole in PolyOx® and Klucel® matrix systems produced by Hot-melt Extrusion (HME) technology. Miconazole incorporated into these matrix systems were found to be stable for 8 months by X-ray diffraction (XRD). The addition of miconazole increased area under the curve (AUC) at contact time intervals of 30 and 60 sec, while the bioadhesion decreased with an increase in processing temperatures. The release profiles suggest that a sustained release of miconazole was observed from all of the tested HME film formulations for approximately 10 h. The release from the optimal HME film extruded at 205°C was found to be significantly different than that extruded at 190°C. Therefore, this matrix system may address the present shortcomings of currently available therapy for oral and pharyngeal candidiasis. PMID:24550099
Chen, Meiwan; Lu, Jiannan; Deng, Weibin; Singh, Abhilasha; Mohammed, Noorullah Naqvi; Repka, Michael A; Wu, Chuanbin
Abstract Context: Conventional sustained dosage form of ranitidine hydrochloride (HCl) does not prevent frequent administration due to its degradation in colonic media and limited absorption in the upper part of GIT. Objectives: Ranitidine HCl floating tablet was formulated with sublimation method to overcome the stated problem. Methods: Compatibility study for screening potential excipients was carried out using Fourier transform infrared spectroscopy (FT-IR) and differential scanning chromatography (DSC). Selected excipients were further evaluated for optimizing the formulation. Preliminary screening of binder, polymer and sublimating material was based on hardness and drug release, drug release with release kinetics and floating lag time with total floatation time, respectively. Selected excipients were subjected to 3(2) factorial design with polymer and sublimating material as independent factors. Matrix tablets were obtained by using 16/32" flat-faced beveled edges punches followed by sublimation. Results: FT-IR and DSC indicated no significant incompatibility with selected excipients. Klucel-LF, POLYOX WSR N 60?K and l-menthol were selected as binder, polymer and sublimating material, respectively, for factorial design batches after preliminary screening. From the factorial design batches, optimum concentration to release the drug within 12?h was found to be 420?mg of POLYOX and 40?mg of l-menthol. Stability studies indicated the formulation as stable. Conclusion: Ranitidine HCl matrix floating tablets were formulated to release 90% of drug in stomach within 12?h. Hence, release of the drug could be sustained within narrow absorption site. Moreover, the dosage form was found to be floating within a fraction of second independent of the pH of media ensuring a robust formulation. PMID:25243639
Kesarla, Rajesh S; Vora, Pratik Ashwinbhai; Sridhar, B K; Patel, Gunvant; Omri, Abdelwahab
Wafers combining weight ratios of Polyox with carrageenan (75/25) or sodium alginate (50/50) containing streptomycin and diclofenac were prepared to improve chronic wound healing. Gels were freeze-dried using a lyophilisation cycle incorporating an annealing step. Wafers were characterised for morphology, mechanical and in vitro functional (swelling, adhesion, drug release in the presence of simulated wound fluid) characteristics. Both blank (BLK) and drug-loaded (DL) wafers were soft, flexible, elegant in appearance and non-brittle in nature. Annealing helped to improve porous nature of wafers but was affected by the addition of drugs. Mechanical characterisation demonstrated that the wafers were strong enough to withstand normal stresses but also flexible to prevent damage to newly formed skin tissue. Differences in swelling, adhesion and drug release characteristics could be attributed to differences in pore size and sodium sulphate formed because of the salt forms of the two drugs. BLK wafers showed relatively higher swelling and adhesion than DL wafers with the latter showing controlled release of streptomycin and diclofenac. The optimised dressing has the potential to reduce bacterial infection and can also help to reduce swelling and pain associated with injury due to the anti-inflammatory action of diclofenac and help to achieve more rapid wound healing. PMID:24700434
Pawar, Harshavardhan V; Boateng, Joshua S; Ayensu, Isaac; Tetteh, John
This study was aimed to develop an ascending release push-pull osmotic pump (APOP) system with a novel mechanism and an easy manufacture process. Theoretical analysis showed that the key to obtain the non-zero order drug release was to break the balance between the drug suspension release rate in the drug layer and the swelling rate of the core, and an ascending drug release rate was achieved when the former was slower than the latter. A polymer (Polyox WSR N-12K) was introduced as a suspension agent in drug layer to slow down the hydration rate of drug layer. Influence of the composition of drug layer (PEO category, total amount, drug loading and fraction of NaCl), push layer (NaCl amount), and also the level of coating weight gain on the drug release profiles was investigated. Observation of hydration state was estimated by taking photos, and also was confirmed by the theories. Paliperidone was delivered successfully by APOP at an ascending release rate up to 20 h in vitro. The in vivo plasma concentration of paliperidone in beagle dogs increased gradually up to 19 h. The APOP with an easy manufacture process was a promising strategy to deliver drug at an ascending rate. PMID:24095815
Xu, Heming; Li, Zhao; Pan, Hao; Zhang, Zhihong; Liu, Dandan; Tian, Baocheng; Ma, Shilin; Song, Shilong; Pan, Weisan
Streptomycin (STP) and diclofenac (DLF) loaded film dressings were prepared by blending Polyox(®) (POL) with four hydrophilic polymers [hydroxypropylmethylcellulose (HPMC), carrageenan (CAR), sodium alginate (SA) or chitosan (CS)] using glycerol (GLY) as plasticiser. The films were characterised by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy, texture analysis (tensile and swelling characteristics) and in vitro dissolution profiles using Franz diffusion cell. SEM showed homogeneous morphology for both blank (BLK) and drug loaded (DL) films. Films prepared by blending of POL with the other polymers showed a reduction in the crystallisation of POL in descending order of SA>CS>HPMC>CAR respectively. DSC and XRD showed no crystalline peaks of STP and DLF suggesting molecular dispersion of both drugs as well as possible drug interaction with negatively charged sulphate ions present in CAR. The DL films did not show any IR bands of both drugs, confirming the DSC and XRD results. POL-CAR-BLK films showed higher tensile strength (12.32±1.40 MPa) than the POL-CAR-DL films (9.52±1.12 MPa). DL films plasticised with 25%w/w GLY revealed soft and tough (tensile strength 1.02±0.28 MPa, % elongation 1031.33±16.23) formulations. The swelling capacities of POL-CAR-BLK and POL-CAR-DL films were (733.17±25.78%) and (646.39±40.39%), increasing to (1072.71±80.30%) and (1051±86.68%) for POL-CAR-BLK-25% GLY and POL-CAR-DL-25% GLY respectively. POL-CAR-DL films showed significantly (n=3, p<0.0318) lower cumulative release of STP and DLF (52.11±1.34, 55.26±2.25) compared to POL-CAR-DL-25% GLY films (60.07±1.56, 63.39±1.92) respectively. PMID:23006557
Pawar, H V; Tetteh, J; Boateng, J S