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Sample records for oral morphine tablets

  1. Morphine Oral

    MedlinePlus

    ... relieve moderate to severe pain. Morphine extended-release tablets and capsules are only used to relieve severe ( ... use of other pain medications. Morphine extended-release tablets and capsules should not be used to treat ...

  2. Iron supplementation: oral tablets versus intramuscular injection.

    PubMed

    Dawson, Brian; Goodman, Carmel; Blee, Tanya; Claydon, Gary; Peeling, Peter; Beilby, John; Prins, Alex

    2006-04-01

    Non-anemic, iron depleted women were randomly assigned to an injection group (IG) or oral group (OG) to assess which method is more efficient for increasing iron stores over a short time period. IG received a course of 5 x 2 mL intramuscular injections over 10 d, and OG received one tablet daily for 30 d. Fourteen, 21 and 28 d after commencing supplementation, ferritin concentration in OG significantly increased from baseline (means +/- standard error: 27 +/- 3 to 40 +/- 5 to 41 +/- 5 to 41 +/- 5 microg/L; P < 0.01). Similarly, on days 15, 20, and 28 post the first injection, ferritin concentration in IG significantly increased from baseline (means +/- standard error: 20 +/- 2 to 71 +/- 17 to 63 +/- 11 to 63 +/- 7 microg/L; P < 0.01), and was also significantly greater than OG at day 15 and 28 (P < 0.05). Iron injections are significantly more effective (both in time and degree of increase) in improving ferritin levels over 30 d than oral tablets. PMID:16779924

  3. Morphine and Codeine in Oral Fluid after Controlled Poppy Seed Administration

    PubMed Central

    Concheiro, Marta; Newmeyer, Matthew N.; da Costa, Jose Luiz; Flegel, Ron; Gorelick, David A.; Huestis, Marilyn A.

    2014-01-01

    Opiates are an important drug class in drug testing programs. Ingestion of poppy seeds containing morphine and codeine can yield positive opiate tests and mislead result interpretation in forensic and clinical settings. Multiple publications evaluated urine opiate concentrations following poppy seed ingestion, but only 2 addressed oral fluid (OF) results; neither provided the ingested morphine and codeine dosage. We administered two 45g raw poppy seed doses, each containing 15.7mg morphine and 3.1mg codeine, 8h apart to 17 healthy adults. All OF specimens were screened by on-site OF immunoassay Draeger DrugTest 5000, and confirmed with OF collected with Oral-Eze® device and quantified by liquid chromatography tandem mass spectrometry (1μg/L morphine and codeine limits of quantification). Specimens (n=459) were collected before and up to 32h after the first dose. All specimens screened positive 0.5h after dosing and remained positive for 0.5-13h at Draeger 20μg/L morphine cutoff. Maximum OF morphine and codeine concentrations (Cmax) were 177 and 32.6μg/L, with times to Cmax (Tmax) of 0.5-1h and 0.5-2.5h post-dose, respectively. Windows of detection after the second dose extended at least 24h for morphine and to 18h for codeine. After both doses, the last morphine positive OF result was 1h with 40μg/L 2004 proposed US Substance Abuse and Mental Health Services Administration cutoff, and 0.5h with 95μg/L cutoff, recently recommended by the Driving Under the Influence of Drugs and Medicines project. Positive OF morphine results are possible 0.5-1h after ingestion of 15.7mg of morphine in raw poppy seeds, depending upon the cutoff employed. PMID:25345619

  4. Oral administration of morphine versus ibuprofen to manage postfracture pain in children: a randomized trial

    PubMed Central

    Poonai, Naveen; Bhullar, Gina; Lin, Kangrui; Papini, Adam; Mainprize, David; Howard, Jocelyn; Teefy, John; Bale, Michelle; Langford, Cindy; Lim, Rodrick; Stitt, Larry; Rieder, Michael J.; Ali, Samina

    2014-01-01

    Background: Recent warnings from Health Canada regarding codeine for children have led to increased use of nonsteroidal anti-inflammatory drugs and morphine for common injuries such as fractures. Our objective was to determine whether morphine administered orally has superior efficacy to ibuprofen in fracture-related pain. Methods: We used a parallel group, randomized, blinded superiority design. Children who presented to the emergency department with an uncomplicated extremity fracture were randomly assigned to receive either morphine (0.5 mg/kg orally) or ibuprofen (10 mg/kg) for 24 hours after discharge. Our primary outcome was the change in pain score using the Faces Pain Scale — Revised (FPS-R). Participants were asked to record pain scores immediately before and 30 minutes after receiving each dose. Results: We analyzed data from 66 participants in the morphine group and 68 participants in the ibuprofen group. For both morphine and ibuprofen, we found a reduction in pain scores (mean pre–post difference ± standard deviation for dose 1: morphine 1.5 ± 1.2, ibuprofen 1.3 ± 1.0, between-group difference [δ] 0.2 [95% confidence interval (CI) −0.2 to 0.6]; dose 2: morphine 1.3 ± 1.3, ibuprofen 1.3 ± 0.9, δ 0 [95% CI −0.4 to 0.4]; dose 3: morphine 1.3 ± 1.4, ibuprofen 1.4 ± 1.1, δ −0.1 [95% CI −0.7 to 0.4]; and dose 4: morphine 1.5 ± 1.4, ibuprofen 1.1 ± 1.2, δ 0.4 [95% CI −0.2 to 1.1]). We found no significant differences in the change in pain scores between morphine and ibuprofen between groups at any of the 4 time points (p = 0.6). Participants in the morphine group had significantly more adverse effects than those in the ibuprofen group (56.1% v. 30.9%, p < 0.01). Interpretation: We found no significant difference in analgesic efficacy between orally administered morphine and ibuprofen. However, morphine was associated with a significantly greater number of adverse effects. Our results suggest that ibuprofen remains safe and effective

  5. Morphine mouthwash for the management of oral mucositis in patients with head and neck cancer

    PubMed Central

    Sarvizadeh, Mostafa; Hemati, Simin; Meidani, Mohsen; Ashouri, Moghtada; Roayaei, Mahnaz; Shahsanai, Armindokht

    2015-01-01

    Background: Oral mucositis is a debilitating side effect of cancer treatment for which there is not much successful treatments at yet. We evaluated the effectiveness of topical morphine compared with a routine mouthwash in managing cancer treatment-induced mucositis. Materials and Methods: Thirty head and neck cancer patients with severe mucositis (World Health Organization Grade III or IV) were randomized into the morphine and magic mouthwash groups. Patients received morphine sulfate 2% or magic solution (contained magnesium aluminum hydroxide, viscous lidocaine, and diphenhydramine), 10 ml for every 3 h, six times a day, for 6 days. Both groups received same dietary and oral hygiene instructions and care. Mucositis was graded at baseline and every 3 days after treatment. Patients’ satisfaction and drug effect maintenance were also evaluated. Results: Twenty-eight patients (mean age of 49.5 ± 13.2 years, 63.3% female) completed the trial; 15 in the morphine group and 13 in the magic group. There was a decrease in mucositis severity in both of the morphine (P < 0.001) and magic (P = 0.049) groups. However, at the 6th day, more reduction was observed in mucositis severity in the morphine compared with magic group (P = 0.045). Drug effect maintenance was similar between the two groups, but patients in the morphine group were more satisfied by their treatments than those in the magic group (P = 0.008). Conclusions: Topical morphine is more effective and more satisfactory to patients than the magic mouthwash in reducing severity of cancer treatment-induced oral mucositis. More studies with larger sample size and longer follow-up are required in this regard. PMID:25789270

  6. Ginger Orally Disintegrating Tablets to Improve Swallowing in Older People.

    PubMed

    Hirata, Ayumu; Funato, Hiroki; Nakai, Megumi; Iizuka, Michiro; Abe, Noriaki; Yagi, Yusuke; Shiraishi, Hisashi; Jobu, Kohei; Yokota, Junko; Hirose, Kahori; Hyodo, Masamitsu; Miyamura, Mitsuhiko

    2016-01-01

    We previously prepared and pharmaceutically evaluated ginger orally disintegrating (OD) tablets, optimized the base formulation, and carried out a clinical trial in healthy adults in their 20 s and 50s to measure their effect on salivary substance P (SP) level and improved swallowing function. In this study, we conducted clinical trials using the ginger OD tablets in older people to clinically evaluate the improvements in swallowing function resulting from the functional components of the tablet. The ginger OD tablets were prepared by mixing the excipients with the same amount of mannitol and sucrose to a concentration of 1% ginger. Eighteen healthy older adult volunteers aged 63 to 90 were included in the swallowing function test. Saliva was collected before and 15 min after administration of the placebo and ginger OD tablets. Swallowing endoscopy was performed by an otolaryngologist before administration and 15 min after administration of the ginger OD tablets. A scoring method was used to evaluate the endoscopic swallowing. Fifteen minutes after taking the ginger OD tablets, the salivary SP amount was significantly higher than prior to ingestion or after taking the placebo (p<0.05). Among 10 subjects, one scored 1-3 using the four evaluation criteria. Overall, no aspiration occurred and a significant improvement in the swallowing function score was observed (p<0.05) after taking the ginger OD tablets. Our findings showed that the ginger OD tablets increased the salivary SP amount and improved swallowing function in older people with appreciably reduced swallowing function. PMID:27374286

  7. Morphine and codeine in oral fluid after controlled poppy seed administration.

    PubMed

    Concheiro, Marta; Newmeyer, Matthew N; da Costa, Jose Luiz; Flegel, Ron; Gorelick, David A; Huestis, Marilyn A

    2015-07-01

    Opiates are an important drug class in drug testing programmes. Ingestion of poppy seeds containing morphine and codeine can yield positive opiate tests and mislead result interpretation in forensic and clinical settings. Multiple publications evaluated urine opiate concentrations following poppy seed ingestion, but only two addressed oral fluid (OF) results; neither provided the ingested morphine and codeine dosage. We administered two 45 g raw poppy seed doses, each containing 15.7 mg morphine and 3.1 mg codeine, 8 h apart to 17 healthy adults. All OF specimens were screened by on-site OF immunoassay Draeger DrugTest 5000, and confirmed with OF collected with Oral-Eze® device and quantified by liquid chromatography-tandem mass spectrometry (1 µg/L morphine and codeine limits of quantification). Specimens (n = 459) were collected before and up to 32 h after the first dose. All specimens screened positive 0.5 h after dosing and remained positive for 0.5-13 h at Draeger 20 µg/L morphine cut-off. Maximum OF morphine and codeine concentrations (Cmax ) were 177 and 32.6 µg/L, with times to Cmax (Tmax ) of 0.5-1 h and 0.5-2.5 h post-dose, respectively. Windows of detection after the second dose extended at least 24 h for morphine and to 18 h for codeine. After both doses, the last morphine positive OF result was 1 h with 40 µg/L 2004 proposed US Substance Abuse and Mental Health Services Administration cut-off, and 0.5 h with 95 µg/L cut-off, recently recommended by the Driving under the Influence of Drugs and Medicines project. Positive OF morphine results are possible 0.5-1 h after ingestion of 15.7 mg of morphine in raw poppy seeds, depending on the cut-off employed. PMID:25345619

  8. 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. PMID:15553108

  9. The development of use of oral morphine within the last 10 years in Japan.

    PubMed

    Takeda, F

    2001-01-01

    Japan's national cancer relief programme was initiated with a field-test of the WHO guidelines for cancer pain management in 1982. It revealed in an excellent result that 87% of 156 cancer patients could be completely relieved of their persistent pain, but this result were ignored by most Japanese health professionals, because of their lack of interest in cancer pain relief. The WHO guidelines were published in 1986 and made quite an impact on those health professionals in Japan. In 1987, a special research team appointed by the Ministry of Health and Welfare of Japan (MOHW) initiated discussion on the philosophy of palliative care in Japan. According to the recommendations made by this research team, the MOHW established a new policy on palliative care, edited manuals on palliative care for terminally ill cancer patients which included guidelines on cancer pain management, and revised narcotics control measures by 1992 in order to much improve the accessibility of opioid analgesics to cancer patients who need them for effective pain relief. The annual consumption of morphine for medical purposes was only 65 kg in 1986 in Japan, but it rose to 973 kg in 1999. Currently, morphine is mostly given by mouth and two-thirds of morphine preparations consumed are MS Contin Tablets. However, the current morphine consumption per capita in Japan is still less than one-sixth of the consumption in the United States. In order to achieve further improvement, educational effort should be much emphasized. In the 1990s, approximately 70% of medical and nursing schools in Japan have initiated their educational curriculum for cancer pain relief and palliative care. There have been government-sponsored, medical, nursing and pharmaceutical societies-sponsored seminar courses on appropriate morphine use in cancer pain management, palliative care and opioid availability, all of which have increasingly strengthened postgraduate education. PMID:11798223

  10. Development of oral acetaminophen chewable tablets with inhibited bitter taste.

    PubMed

    Suzuki, Hiroyuki; Onishi, Hiraku; Takahashi, Yuri; Iwata, Masanori; Machida, Yoshiharu

    2003-01-30

    Various formulations with some matrix bases and corrigents were examined for development of oral chewable tablets which suppressed the bitter taste of acetaminophen, often used as an antipyretic for infants. Corn starch/lactose, cacao butter and hard fat (Witepsol H-15) were used for matrix bases, and sucrose, cocoa powder and commercial bitter-masking powder mixture made from lecithin (Benecoat BMI-40) were used for corrigents against bitter taste. The bitter taste intensity was evaluated using volunteers by comparison of test samples with standard solutions containing quinine at various concentrations. For the tablets made of matrix base and drug, Witepsol H-15 best inhibited the bitter taste of the drug, and the bitter strength tended to be suppressed with increase in the Witepsol H-15 amount. When the inhibitory effect on the bitter taste of acetaminophen solution was compared among the corrigents, each tended to suppress the bitter taste; especially, Benecoat BMI-40 exhibited a more inhibitory effect. Further, chewable tablets were made of one matrix base and one corrigent, and of one matrix base and two kinds of corrigents, their bitter taste intensities after chewing were compared. As a result, the tablets made of Witepsol H-15/Benecoat BMI-40/sucrose, of Witepsol H-15/cocoa powder/sucrose and of Witepsol H-15/sucrose best masked the bitter taste so that they were tolerable enough to chew and swallow. The dosage forms best masking bitter taste showed good release of the drug, indicating little change in bioavailability by masking. PMID:12527182

  11. Oral thyroxine: variation in biologic action and tablet content.

    PubMed

    Sawin, C T; Surks, M I; London, M; Ranganathan, C; Larsen, P R

    1984-05-01

    Thirty-two patients with primary hypothyroidism were given oral thyroxine as Levothroid or Synthroid to see if the two preparations had similar effects. The serum thyroxine was used as an index of bioavailability and the serum thyrotrophin as an index of biologic activity. The serum thyroxine was lower in all 32 patients when taking Synthroid than when taking Levothroid. In 15 patients the serum thyroxine level fell low enough to raise the serum thyrotrophin; in all 15 the serum thyrotrophin rose when taking Synthroid. Direct measurement of thyroxine in the tablets showed that the tablets of Synthroid contained 20% to 30% less thyroxine than their stated content. Thus, the decreased bioavailability (lower serum thyroxine) and decreased biologic action (higher serum thyrotrophin) of Synthroid were due to the lower content of thyroxine. An incidental observation is that the range of serum thyroxine in treated hypothyroid patients is 7.6 to 16.6 micrograms/dL, higher than in normal persons. Because oral thyroxine is widely used, a cooperative effort among manufacturers, the United States Pharmacopeia and Food and Drug Administration, and clinicians to ensure the potency and biologic action of oral thyroxine is in order. Meanwhile, it seems reasonable to use oral thyroxine that is close to the stated content. PMID:6546843

  12. Development of sildenafil-loaded orally disintegrating tablet with new lactate salt.

    PubMed

    Jung, Si-Young; Kim, Dong-Wuk; Seo, Youn Gee; Woo, Jong Soo; Yong, Chul Soon; Choi, Han-Gon

    2012-05-01

    To develop a sildenafil lactate-loaded orally disintegrating tablet with a faster drug effect onset and immediate action of erection, the orally disintegrating tablets were prepared with various amounts of menthol and colloidal silica using the direct compression technique followed by vacuum drying. Their tablet properties such as friability, hardness, wetting time and disintegration time were investigated. The oral bioavailability of sildenafil in the orally disintegrating tablet was then compared with the sildenafil citrate-loaded commercial tablet (Viagra(®)) in rabbits. Sildenafil lactate was a new salt form with more improved solubility and alleviated bitterness compared with commercial salt, sildenafil citrate. As the amount of menthol in the orally disintegrating tablet increased, the friability increased and hardness decreased, resulting in a shorter wetting time and disintegration time. Colloidal silica did the opposite. The sildenafil lactate-loaded orally disintegrating tablet prepared with 45 mg/tab of menthol and 1.5 mg/tab of colloidal silica gave a hardness of 3-4 KP, friability less than 0.5% and disintegration time less than 30 s, suggesting that it was a practical and commercial product with good tablet property and excellent efficacy. Furthermore, it gave higher AUC and C(max), and shorter T(max) values than did the commercial tablet, indicating that it improved the oral bioavailability of sildenafil in rabbits compared with the commercial tablet. Thus, the sildenafil lactate-loaded orally disintegrating tablet might induce a fast onset of action and immediate erection compared with the sildenafil citrate-loaded commercial tablet. PMID:22010981

  13. 77 FR 1695 - Determination That AVALIDE (Hydrochlorothiazide and Irbesartan), Oral Tablets, 25 Milligrams/300...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-11

    ...The Food and Drug Administration (FDA) has determined that AVALIDE (hydrochlorothiazide and irbesartan), oral tablets, 25 milligrams (mg)/300 mg and 12.5 mg/75 mg, were not withdrawn from sale for reasons of safety or effectiveness. This determination will allow FDA to approve abbreviated new drug applications (ANDAs) for hydrochlorothiazide and irbesartan, oral tablets, 25 mg/300 mg and 12.5......

  14. Orally disintegrating mini-tablets (ODMTs)--a novel solid oral dosage form for paediatric use.

    PubMed

    Stoltenberg, I; Breitkreutz, J

    2011-08-01

    The new European regulations on paediatric medicines and recent WHO recommendations have induced an increased need for research into novel child-appropriate dosage forms. The aim of this study was the development of orally disintegrating mini-tablets (ODMTs) as a suitable dosage form for paediatric patients. The suitability of five commercially available ready-to-use tableting excipients, Ludiflash, Parteck ODT, Pearlitol Flash, Pharmaburst 500 and Prosolv ODT, to be directly compressed into mini-tablets, with 2 mm in diameter, was examined. All of the excipients are based on co-processed mannitol. Drug-free ODMTs and ODMTs with a child-appropriate dose of hydrochlorothiazide were investigated. ODMTs could be produced with all investigated excipients. ODMTs with a sufficient crushing strength >7 N and a low friability <1% could be obtained, as well as ODMTs with a short simulated wetting test-time <5 s. ODMTs made of Ludiflash showed the best results with crushing strengths from 7.8 N up to 11.8 N and excellent simulated wetting test-times from 3.1 s to 5.0 s. For each excipient, ODMTs with accordance to the pharmacopoeial specification content uniformity could be obtained. The promising results indicate that orally disintegrating mini-tablets may serve as a novel platform technology for paediatrics in future. PMID:21324357

  15. Dynamics of breakthrough pain vs. pharmacokinetics of oral morphine: implications for management.

    PubMed

    Zeppetella, G

    2009-07-01

    Dynamics of breakthrough pain vs. pharmacokinetics of oral morphine: implications for managementBreakthrough pain is a transient exacerbation of pain that occurs either spontaneously, or in relation to a specific predictable or unpredictable trigger, despite relatively stable and adequately controlled background pain. The onset of breakthrough pain is typically fast and the duration is usually relatively short, but despite the self-limiting nature of each breakthrough pain, the repeated episodes can have a significant impact on patients' quality of life. Effective management is therefore imperative and often involves the use of supplemental doses of medication known as 'rescue medication'. The ideal rescue medication should be efficacious, have a rapid onset of action, a relatively short duration of effect and minimal adverse effects. Normal-release oral opioids have been the mainstay approach for patients who are receiving around the clock opioid regimen, but the onset and duration of action of oral opioids such as morphine may not be suitable for treating many breakthrough pains. PMID:19473378

  16. Pain control with morphine: Evaluation of prescriptions for oral morphine for outpatients at King Faisal Specialist Hospital and Research Centre.

    PubMed

    Nuessle, S; Gray, A; Lambert, G; Boyar, A; Ba-Hatheq, A; Adloni, S; Al Khayyal, M

    1996-07-01

    With the rapid improvement in living standards and health care delivery in Saudi Arabia, people are expected to live longer, patterns of illness will change, and the chronic illnesses which now dominate medical care in the West will develop here. Among these is cancer, which is already the third most common cause of death in Bahrain and Kuwait. Many cancer patients experience considerable distress, particularly pain. Management of symptoms in advanced cancer is now a medical and nursing specialty called palliative care. The most common and most feared symptom in advanced cancer is pain, which can only be effectively relieved with morphine in 60% of such patients. Prescribing narcotics such as morphine for cancer pain in Saudi Arabia has been severely restricted legally because of the fear of addiction, but there is no evidence that the medicinal use of morphine for treating cancer pain causes addiction. This paper describes a review carried out at King Faisal Specialist Hospital and Research Center, one of the few centers in the Kingdom that can prescribe morphine to outpatients, to review the appropriateness and effectiveness of morphine usage, and to monitor any misuse. The review confirms that morphine usage was appropriate and effective, but that procurement of adequate narcotic supplies from year to year causes severe problems due to the stringency of both national and international regulations. Also, better monitoring of patients on morphine and recording of their level of pain control is required. In general, this survey shows that morphine usage in this hospital is appropriate and that limitations on supplies could be improved by changes to the Ministry of Health regulations. PMID:17372444

  17. Effect of formulated ingredients on rapidly disintegrating oral tablets prepared by the crystalline transition method.

    PubMed

    Sugimoto, Masaaki; Narisawa, Shinji; Matsubara, Koji; Yoshino, Hiroyuki; Nakano, Minoru; Handa, Tetsurou

    2006-02-01

    The aim of this article was to determine the optimal ingredients for the rapidly disintegrating oral tablets prepared by the crystalline transition method (CT method). The effect of ingredients (diluent, active drug substance and amorphous sugar) on the characteristics of the tablets was investigated. The ingredients were compressed and the resultant tablets were stored under various conditions. The oral disintegration time of the tablet significantly depended on diluents, due to differences in the penetration of a small amount of water in the mouth and the viscous area formed inside the tablet. The oral disintegration time was 10-30 s for tablets with a tensile strength of approximately 1 MPa, when erythritol, mannitol or xylitol was used as the diluent. The increase in the tensile strength of tablets containing highly water-soluble active drug substances during storage was as large as that of tablets without active drug substances, while the increase in the tensile strength of tablets containing low water-soluble active drug substances was small. It was therefore found that highly water-soluble active drug substances were more suitable for the formulation prepared by the CT method than low water-soluble active drug substances. Irrespective of the type of amorphous sugar (amorphous sucrose, lactose or maltose) used, the porosity of tablets with 1 MPa of tensile strength was 30-40%, and their oral disintegration time was 10-20 s. The optimal ingredients for rapidly disintegrating oral tablets with reasonable tensile strength and disintegration time were therefore determined from these results. PMID:16462059

  18. 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. PMID:26177197

  19. Formulation development, evaluation and comparative study of effects of super disintegrants in cefixime oral disintegrating tablets.

    PubMed

    Remya, Ks; Beena, P; Bijesh, Pv; Sheeba, A

    2010-07-01

    The present work was aimed at formulation development, evaluation and comparative study of the effects of superdisintegrants in Cefixime 50 mg oral disintegrating tablets. The superdisintegrants used for the present study were sodium starch glycolate and crosscarmellose sodium. The formulated tablets were evaluated for various tableting properties, like hardness, thickness, friability, weight variation, disintegration time and dissolution rate. Comparative evaluation of the above-mentioned parameters established the superiority of the tablets formulated with crosscarmellose sodium to those formulated with sodium starch glycolate. PMID:21042477

  20. Formulation Development, Evaluation and Comparative Study of Effects of Super Disintegrants in Cefixime Oral Disintegrating Tablets

    PubMed Central

    Remya, KS; Beena, P; Bijesh, PV; Sheeba, A

    2010-01-01

    The present work was aimed at formulation development, evaluation and comparative study of the effects of superdisintegrants in Cefixime 50 mg oral disintegrating tablets. The superdisintegrants used for the present study were sodium starch glycolate and crosscarmellose sodium. The formulated tablets were evaluated for various tableting properties, like hardness, thickness, friability, weight variation, disintegration time and dissolution rate. Comparative evaluation of the above-mentioned parameters established the superiority of the tablets formulated with crosscarmellose sodium to those formulated with sodium starch glycolate. PMID:21042477

  1. The influence of formulation and manufacturing process parameters on the characteristics of lyophilized orally disintegrating tablets.

    PubMed

    Jones, Rhys J; Rajabi-Siahboomi, Ali; Levina, Marina; Perrie, Yvonne; Mohammed, Afzal R

    2011-01-01

    Gelatin is a principal excipient used as a binder in the formulation of lyophilized orally disintegrating tablets. The current study focuses on exploiting the physicochemical properties of gelatin by varying formulation parameters to determine their influence on orally disintegrating tablet (ODT) characteristics. Process parameters, namely pH and ionic strength of the formulations, and ball milling were investigated to observe their effects on excipient characteristics and tablet formation. The properties and characteristics of the formulations and tablets which were investigated included: glass transition temperature, wettability, porosity, mechanical properties, disintegration time, morphology of the internal structure of the freeze-dried tablets, and drug dissolution. The results from the pH study revealed that adjusting the pH of the formulation away from the isoelectric point of gelatin, resulted in an improvement in tablet disintegration time possibly due to increase in gelatin swelling resulting in greater tablet porosity. The results from the ionic strength study revealed that the inclusion of sodium chloride influenced tablet porosity, tablet morphology and the glass transition temperature of the formulations. Data from the milling study showed that milling the excipients influenced formulation characteristics, namely wettability and powder porosity. The study concludes that alterations of simple parameters such as pH and salt concentration have a significant influence on formulation of ODT. PMID:24310589

  2. Long-Term High-dose Oral Morphine in Phantom Limb Pain with No Addiction Risk

    PubMed Central

    Kumar, Vinod; Garg, Rakesh; Bharati, Sachidanand Jee; Gupta, Nishkarsh; Bhatanagar, Sushma; Mishra, Seema; Balhara, Yatan Pal Singh

    2015-01-01

    Chronic phantom limb pain (PLP) is a type of neuropathic pain, which is located in the missing/amputated limb. Phantom pain is difficult to treat as the exact basis of pain mechanism is still unknown. Various methods of treatment for PLP have been described, including pharmacological (NSAIDs, opioids, antiepileptic, antidepressants) and non-pharmacological (TENS, sympathectomy, deep brain stimulation and motor cortex stimulation). Opioids are used for the treatment of neuropathic pain and dose of opioid is determined based on its effect and thus there is no defined ceiling dose for opioids. We report a case where a patient receiving high-dose oral morphine for chronic cancer pain did not demonstrate signs of addiction. PMID:25709194

  3. Long-Term High-dose Oral Morphine in Phantom Limb Pain with No Addiction Risk.

    PubMed

    Kumar, Vinod; Garg, Rakesh; Bharati, Sachidanand Jee; Gupta, Nishkarsh; Bhatanagar, Sushma; Mishra, Seema; Balhara, Yatan Pal Singh

    2015-01-01

    Chronic phantom limb pain (PLP) is a type of neuropathic pain, which is located in the missing/amputated limb. Phantom pain is difficult to treat as the exact basis of pain mechanism is still unknown. Various methods of treatment for PLP have been described, including pharmacological (NSAIDs, opioids, antiepileptic, antidepressants) and non-pharmacological (TENS, sympathectomy, deep brain stimulation and motor cortex stimulation). Opioids are used for the treatment of neuropathic pain and dose of opioid is determined based on its effect and thus there is no defined ceiling dose for opioids. We report a case where a patient receiving high-dose oral morphine for chronic cancer pain did not demonstrate signs of addiction. PMID:25709194

  4. Effect of preparation method on properties of orally disintegrating tablets made by phase transition.

    PubMed

    Kuno, Yoshio; Kojima, Masazumi; Ando, Shuichi; Nakagami, Hiroaki

    2008-05-01

    In order to evaluate the effect of preparation method on the properties of orally disintegrating (OD) tablets, OD tablets were prepared by compressing a mixture of high melting point sugar alcohol (HMP-SA) and low melting point sugar alcohol (LMP-SA) and subsequent heating. In the direct compression method (DCM) where the LMP-SA was added as a powder, both hardness and disintegration time were increased by decreasing the particle size of the LMP-SA. In the wet granule compression method (WGCM), where the LMP-SA was added as an aqueous binder solution, the tablets became harder with less heating compared to tablets prepared by DCM. Using 1% xylitol as the LMP-SA provided tablets with sufficient hardness when prepared by WGCM, as opposed to DCM where 5% xylitol was necessary to prepare tablets with similar hardness. These results suggest that uniformly distributed LMP-SA on the surface of HMP-SA particles in WGCM might diffuse more easily during the heating process compared to mechanically mixed LMP-SA in DCM, resulting in an increase in tablet hardness even with a short heating time and low content of LMP-SA. In addition, disintegration and hardness stability of the tablets were affected by the LMP-SA content when prepared by WGCM, suggesting that the LMP-SA content should be regulated to assure the stability of OD tablet characteristics. PMID:18182258

  5. The Effect of Oral Morphine on Pain-Related Brain Activation - An Experimental Functional Magnetic Resonance Imaging Study.

    PubMed

    Hansen, Tine Maria; Olesen, Anne Estrup; Graversen, Carina; Drewes, Asbjørn Mohr; Frøkjaer, Jens Brøndum

    2015-11-01

    Knowledge about cerebral mechanisms underlying pain perception and effect of analgesic drugs is important for developing methods for diagnosis and treatment of pain. The aim was to explore altered brain activation before and after morphine treatment using functional magnetic resonance imaging recorded during experimental painful heat stimulation. Functional magnetic resonance imaging data were recorded and analysed in 20 healthy volunteers (13 men and 7 women, 24.9 ± 2.6 years) in a randomized, double-blind, placebo-controlled, cross-over study. Painful stimulations were applied to the right forearm using a contact heat evoked potential stimulator (CHEPS) before and after treatment with 30 mg oral morphine and placebo. CHEPS stimulations before treatment induced activation in the anterior cingulate cortex, secondary somatosensory cortex/insula, thalamus and cerebellum (n = 16, p < 0.05). In response to morphine treatment, the spatial extent of these pain-specific areas decreased (n = 20). Reduced pain-induced activation was seen in the right insula, anterior cingulate cortex and inferior parietal cortex after morphine treatment compared to before treatment (n = 16, p < 0.05), and sensory ratings of pain perception were significantly reduced after morphine treatment (p = 0.02). No effect on pain-induced brain activation was seen after placebo treatment compared to before treatment (n = 12, p > 0.05). In conclusion, heat stimulation activated areas in the 'pain matrix' and a clinically relevant dose of orally administered morphine revealed significant changes in brain areas where opioidergic pathways are predominant. The method may be useful to investigate the mechanisms of analgesics. PMID:25924691

  6. Efficacy of oral powder compared with chewable tablets for lanthanum carbonate administration in hemodialysis patients.

    PubMed

    Sakurada, Tsutomu; Oishi, Daisuke; Shibagaki, Yugo; Yasuda, Takashi; Kimura, Kenjiro

    2013-10-01

    Lanthanum carbonate (LC) has been administered in a chewable tablet form for patients with hyperphosphatemia undergoing dialysis. However, some patients have difficulty chewing the tablets. LC oral powder has recently been released in Japan. The purpose of this study was to clarify the efficacy of LC oral powder form compared with that of chewable tablet form. The efficacy and safety of LC oral powder was retrospectively assessed in hemodialysis patients who switched from chewable tablet form to oral powder form without dose modification. Thirty-six patients (mean age, 66.8 ± 10.5 years; male, 64%; 39% with diabetes; mean duration of dialysis treatment, 99.2 ± 95.6 months) were enrolled in this study between June and July of 2012. Changes in clinical data and adverse events after the switch to oral powder form were investigated. The average dose of LC was 1180 ± 520 mg/day. Serum phosphorus levels were significantly decreased after the switch from chewable tablet form to oral powder form (5.3 ± 1.7 mg/dL at baseline vs. 4.9 ± 1.2 mg/dL at after 1 month after, P = 0.038). In contrast, no significant differences were observed in serum calcium and parathyroid hormone levels. Furthermore, no significant differences were evident in weight gain after the switch to oral powder form (2.5 ± 1.2 kg at baseline vs. 2.4 ± 1.1 kg at 1 month after the switch, P = 0.29). No serious adverse events were recorded. Our results suggest that LC is more effective in oral powder form than chewable tablet form for hemodialysis patients. PMID:24134326

  7. Oral Disintegration Tablets of Stavudine for HIV Management: A New Technological Approach.

    PubMed

    Sankar, V; Ramakrishna, B; Devi, P Shalini; Karthik, S

    2012-11-01

    Stavudine oral disintegration tablets were formulated to minimize the bitter taste and to reduce the first-pass hepatic metabolism. The various precompression parameters like the angle of repose, bulk density, compressibility index and Hausner's ratio were determined for the powder blend. In this study, 14 formulations of stavudine oral disintegration tablet were prepared by direct compression method. The tablets were evaluated for weight variation, percentage friability, disintegration time, hardness, wetting time and water absorption ratio. The in vitro dissolution study results of the batch S1 (stavudine+crospovidone+sodium starch glycollate) are encouraging as highest dissolution rate (99.2% in 100 min) and lowest time of disintegration (56 s) was achieved. The in vivo drug release studies were carried out in rabbits and the relative bioavailability of formulation S1 was found to be 2.83 times greater than that of conventional tablets. PMID:23798782

  8. Development of oral dispersible tablets containing prednisolone nanoparticles for the management of pediatric asthma

    PubMed Central

    Chen, Yi-Dan; Liang, Zhong-Yuan; Cen, Yan-Yan; Zhang, He; Han, Mei-Gui; Tian, Yun-Qiao; Zhang, Jie; Li, Shu-Jun; Yang, Da-Sheng

    2015-01-01

    The purpose of the present study was to develop oral dispersible tablets containing prednisolone (PDS)-loaded chitosan nanoparticles using microcrystalline cellulose (MCC 101), lactose, and croscarmellose sodium (CCS). The PDS-loaded chitosan nanoparticles were formulated by ionotropic external gelation technique in order to enhance the solubility of PDS in salivary pH. Prepared nanoparticles were used for the development of oral fast disintegrating tablets by direct compression method. The prepared tablets were evaluated for disintegration time (DT), in vitro drug release (DR), thickness, weight variation, drug content uniformity, friability, and hardness. The effect of concentrations of the dependent variables (MCC, lactose, CCS) on DT and in vitro DR was studied. Fast disintegrating tablets of PDS can be prepared by using MCC, CCS, and lactose with enhanced solubility of PDS. The minimum DT was found to be 15 seconds, and the maximum DR within 30 minutes was 98.50%. All independent variables selected for the study were statistically significant. Oral fast disintegrating tablets containing PDS nanoparticles could be the better choice for the pediatric patients that would result in better patient compliance. From this study, it can be concluded that fast disintegrating tablets could be a potential drug delivery technology for the management of asthma in pediatrics. PMID:26640367

  9. Development of oral dispersible tablets containing prednisolone nanoparticles for the management of pediatric asthma.

    PubMed

    Chen, Yi-Dan; Liang, Zhong-Yuan; Cen, Yan-Yan; Zhang, He; Han, Mei-Gui; Tian, Yun-Qiao; Zhang, Jie; Li, Shu-Jun; Yang, Da-Sheng

    2015-01-01

    The purpose of the present study was to develop oral dispersible tablets containing prednisolone (PDS)-loaded chitosan nanoparticles using microcrystalline cellulose (MCC 101), lactose, and croscarmellose sodium (CCS). The PDS-loaded chitosan nanoparticles were formulated by ionotropic external gelation technique in order to enhance the solubility of PDS in salivary pH. Prepared nanoparticles were used for the development of oral fast disintegrating tablets by direct compression method. The prepared tablets were evaluated for disintegration time (DT), in vitro drug release (DR), thickness, weight variation, drug content uniformity, friability, and hardness. The effect of concentrations of the dependent variables (MCC, lactose, CCS) on DT and in vitro DR was studied. Fast disintegrating tablets of PDS can be prepared by using MCC, CCS, and lactose with enhanced solubility of PDS. The minimum DT was found to be 15 seconds, and the maximum DR within 30 minutes was 98.50%. All independent variables selected for the study were statistically significant. Oral fast disintegrating tablets containing PDS nanoparticles could be the better choice for the pediatric patients that would result in better patient compliance. From this study, it can be concluded that fast disintegrating tablets could be a potential drug delivery technology for the management of asthma in pediatrics. PMID:26640367

  10. Bioavailability, pharmacokinetics, and safety of riociguat given as an oral suspension or crushed tablet with and without food

    PubMed Central

    Frey, Reiner; Becker, Corina; Unger, Sigrun; Wensing, Georg; Mück, Wolfgang

    2016-01-01

    Abstract Riociguat is approved for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Some patients have difficulty swallowing tablets; therefore, 2 randomized, nonblinded, crossover studies compared the relative bioavailability of riociguat oral suspensions and immediate-release (IR) tablet and of crushed-tablet preparations versus whole IR tablet. In study 1, 30 healthy subjects received 5 single riociguat doses: 0.3 and 2.4 mg (0.15 mg/mL suspensions), 0.15 mg (0.03 mg/mL), and 1.0 mg (whole IR tablet) under fasted conditions and 2.4 mg (0.15 mg/mL) after a high-fat, high-calorie American-style breakfast. In study 2, 25 healthy men received 4 single 2.5-mg doses: whole IR tablet and crushed IR tablet suspended in applesauce and water, respectively, under fasted conditions, and whole IR tablet after a continental breakfast. In study 1, dose-normalized pharmacokinetics of riociguat oral suspensions and 1.0-mg whole IR tablet were similar in fasted conditions; 90% confidence intervals for riociguat area under the curve (AUC) to dose and mean maximum concentration (Cmax) to dose were within bioequivalence criteria. After food, dose-normalized AUC and Cmax decreased by 15% and 38%, respectively. In study 2, riociguat exposure was similar for all preparations; AUC ratios for crushed-IR-tablet preparations to whole IR tablet were within bioequivalence criteria. The Cmax increased by 17% for crushed IR tablet in water versus whole IR tablet. Food intake decreased Cmax of the whole tablet by 16%, with unaltered AUC versus fasted conditions. Riociguat bioavailability was similar between the oral suspensions and the whole IR tablet; exposure was similar between whole IR tablet and crushed-IR-tablet preparations. Minor food effects were observed. Results suggest that riociguat formulations are interchangeable. PMID:27162630

  11. Formulation and in vivo evaluation of ondansetron orally disintegrating tablets using different superdisintegrants.

    PubMed

    Sheshala, Ravi; Khan, Nurzalina; Chitneni, Mallikarjun; Darwis, Yusrida

    2011-11-01

    The aim of this study was to formulate cost effective taste-masked orally disintegrating tablets of ondansetron, a bitter drug using different superdisintegrants by a wet granulation technique. Microcrystalline cellulose (Avicel) as a diluent and disintegrant in addition to aspartame as a sweetener were used in all formulations. The prepared tablets were evaluated for weight variation, thickness, hardness, friability, drug content, water content, in vitro disintegration time and in vitro drug release. The tablets' hardness was maintained in the range of 2-3 kg and friability was <1% for all batches. All tablet formulations disintegrated rapidly in vitro within 5.83 to 33.0 sec. The optimized formulation containing 15% Polyplasdone XL-10 released more than 90% of drug within 5 min and the release was comparable to that of a commercial product. In human volunteers, optimized formulation was found to have a pleasant taste and mouth feel and they disintegrated in the oral cavity within 12 sec. The stability results were also satisfactory. A pharmacokinetic study with the optimized formulation was performed in comparison with a reference (Zofer MD 8®) and they were found to be bioequivalent. In conclusion, a cost effective ondansetron orally disintegrating tablet was successfully prepared with acceptable hardness, desirable taste and rapid disintegration in the oral cavity. PMID:22139694

  12. Formulation and Characterization of Oral Mucoadhesive Chlorhexidine Tablets Using Cordia myxa Mucilage

    PubMed Central

    Moghimipour, Eskandar; Aghel, Nasrin; Adelpour, Akram

    2012-01-01

    Background The dilution and rapid elimination of topically applied drugs due to the flushing action of saliva is a major difficulty in the effort to eradicate infections of oral cavity. Utilization a proper delivery system for incorporation of drugs has a major impact on drug delivery and such a system should be formulated for prolonged drug retention in oral cavity. Objectives The aim of the present study was the use of mucilage of Cordia myxa as a mucoadhesive material in production of chlorhexidine buccal tablets and its substitution for synthetic polymers such as HPMC. Materials and Methods The influence of mucilage concentration on the physicochemical responses (hardness, friability, disintegration time, dissolution, swelling, and muco-adhesiveness strength) was studied and swelling of mucilage and HPMC were compared. The evaluated responses included pharmacopoeial characteristics of tablets, the force needed to separate tablets from mucosa, and the amount of water absorbed by tablets. Results In comparison to HPMC, the rise of mucilage concentration in the formulations increased disintegration time, drug dissolution rate, and reduced MDT. Also, compared to 30% HPMC, muco-adhesiveness strength of buccal tablets containing 20% mucilage was significantly higher. Conclusions It can be concluded that the presence of Cordia myxa powdered mucilage may significantly affect the tablet characteristics, and increasing in muco-adhesiveness may be achieved by using 20% w/w mucilage. PMID:24624170

  13. Latent structure analysis of the process variables and pharmaceutical responses of an orally disintegrating tablet.

    PubMed

    Hayashi, Yoshihiro; Oshima, Etsuko; Maeda, Jin; Onuki, Yoshinori; Obata, Yasuko; Takayama, Kozo

    2012-01-01

    A multivariate statistical technique was applied to the design of an orally disintegrating tablet and to clarify the causal correlation among variables of the manufacturing process and pharmaceutical responses. Orally disintegrating tablets (ODTs) composed mainly of mannitol were prepared via the wet-granulation method using crystal transition from the δ to the β form of mannitol. Process parameters (water amounts (X(1)), kneading time (X(2)), compression force (X(3)), and amounts of magnesium stearate (X(4))) were optimized using a nonlinear response surface method (RSM) incorporating a thin plate spline interpolation (RSM-S). The results of a verification study revealed that the experimental responses, such as tensile strength and disintegration time, coincided well with the predictions. A latent structure analysis of the pharmaceutical formulations of the tablet performed using a Bayesian network led to the clear visualization of a causal connection among variables of the manufacturing process and tablet characteristics. The quantity of β-mannitol in the granules (Q(β)) was affected by X(2) and influenced all granule properties. The specific surface area of the granules was affected by X(1) and Q(β) and had an effect on all tablet characteristics. Moreover, the causal relationships among the variables were clarified by inferring conditional probability distributions. These techniques provide a better understanding of the complicated latent structure among variables of the manufacturing process and tablet characteristics. PMID:22878814

  14. Stability of cilazapril in pediatric oral suspensions prepared from commercially available tablet dosage forms.

    PubMed

    Stanisz, Beata J; Paszun, Sylwia K; Zalewska, Anna

    2014-01-01

    Abstract: Cilazapril is a drug commonly used in management of heart failure in pediatric population. On pharmaceutical market it is available only in inconvenient for pediatric use tablet dosage forms. Until now, no oral liquid formulation containing cilazapril has been evaluated. Therefore, the aim of this study was to prepare easy to made and palatable 1 mg/mL oral liquid formulation with cilazapril (with consideration of original and generic cilazapril tablet and different packages) and subsequent investigation of physicochemical stability of these suspensions. Formulations were compounded using cilazapril obtained from original or generic cilazapril marketed tablet formulations and Ora-Blend" suspending agent. Stability of prepared suspensions stored in closed amber glass or amber plastic PET bottles in the temperature of 298 K was estimated throughout 28 day shelf-life period. Chemical stability was assessed by HPLC cilazapril stability indicating method. Physical stability was evaluated by appearance, taste, smell, pH and theological assessments. Cilazapril oral suspensions at concentration of 1 mg/mL demonstrated satisfactory stability over 28 day long storage at room temperature. Cilazapril concentrations remained within acceptable limit (+/- 10%) stored in closed amber bottles made of glass or PET material. Moreover, suspensions physical properties remained unaffected. Cilazapril - Ora-Blend* pediatric oral liquid is easy to made, palatable and stable when stored at room temperature for 28 days. Stability of cilazapril oral liquid remains unchanged while using cilazapril tablets produced by different manufacturers and bottles made of amber glass or PET material. PMID:25272892

  15. Lyophilized mucoadhesive-dendrimer enclosed matrix tablet for extended oral delivery of albendazole.

    PubMed

    Mansuri, Shakir; Kesharwani, Prashant; Tekade, Rakesh Kumar; Jain, Narendra Kumar

    2016-05-01

    Dendrimers are multifunctional carriers widely employed for delivering drugs in a variety of disease conditions including HIV/AIDS and cancer. Albendazole (ABZ) is a commonly used anthelmintic drug in human as well as veterinary medicine. In this investigation, ABZ was formulated as a "muco-dendrimer" based sustained released tablet. The mucoadhesive complex was synthesized by anchoring chitosan to fifth generation PPI dendrimer (Muco-PPI) and characterized by UV, FTIR, (1)H NMR spectroscopy and electron microscopy. ABZ was entrapped inside Muco-PPI followed by lyophilization and tableting as matrix tablet. A half-life (t1/2) of 8.06±0.15, 8.17±0.47, 11.04±0.73, 11.49±0.92, 12.52±1.04 and 16.9±1.18h was noted for ABZ (free drug), conventional ABZ tablet (F1), conventional ABZ matrix tablet (F2), PPI-ABZ complex, PPI-ABZ matrix tablet (F3) and Muco-PPI-ABZ matrix tablet (F4), respectively. Thus the novel mucoadhesive-PPI based formulation of ABZ (F4) increased the t1/2 of ABZ significantly by almost twofold as compared to the administration of free drug. The in vivo drug release data showed that the Muco-PPI based formulations have a significantly higher Cmax (2.40±0.02μg/mL) compared with orally administered free ABZ (0.19±0.07μg/mL) as well as conventional tablet (0.20±0.05μg/mL). In addition, the Muco-PPI-ABZ matrix tablet displayed increased mean residence time (MRT) and is therefore a potential candidate to appreciably improve the pharmacokinetic profile of ABZ. PMID:26563727

  16. Mirtazapine orally disintegrating tablet versus sertraline: a prospective onset of action study.

    PubMed

    Behnke, Kirsten; Søgaard, Jesper; Martin, Stephen; Bäuml, Josef; Ravindran, Arun V; Agren, Hans; Vester-Blokland, Estelle D

    2003-08-01

    This multinational, randomized, double-blind study was specifically designed to prospectively compare the onset of antidepressant efficacy of mirtazapine orally disintegrating tablets and sertraline at dosages commonly used in clinical practice. A total of 345 patients with major depressive episode (DSM-IV) received mirtazapine (30-45 mg/d) or sertraline (50-150 mg/d) for 8 weeks. Mirtazapine was administered in the newly developed fast dissolving, orally disintegrating tablet formulation. Assessments were performed at baseline and on days 4, 7, 10, 14, 28, 42, and 56. The primary efficacy variable (mean absolute change from baseline in the Hamilton Depression Rating Scale [HAMD] total score [17 items]) showed that mirtazapine was significantly (P < 0.05) more effective than sertraline at all assessments during the first 2 weeks of the study. After this time, HAMD total scores were similar in both groups. These findings were supported by analysis of the HAMD response rate (ie, > or =50% reduction in HAMD total score from baseline), HAMD remission rate (HAMD total score of < or =7), and the Montgomery-Asberg Depression Rating Scale (MADRS). Both treatments were well tolerated. In addition, mirtazapine had a greater effect than sertraline on sexual functioning. In conclusion, this first prospective onset of action study using the orally disintegrating tablet indicates that mirtazapine has a faster onset of therapeutic effect than sertraline. The orally disintegrating tablet formulation of mirtazapine used in this study is known to enhance the convenience and compliance by the patient. PMID:12920411

  17. Mechanistic Population Pharmacokinetics of Morphine in Neonates With Abstinence Syndrome After Oral Administration of Diluted Tincture of Opium.

    PubMed

    Liu, Tao; Lewis, Tamorah; Gauda, Estelle; Gobburu, Jogarao; Ivaturi, Vijay

    2016-08-01

    Conducting and analyzing clinical trials in vulnerable neonates are extremely challenging. The aim of this analysis is to develop a morphine population pharmacokinetics (PK) model using data collected during a randomized control trial in neonates with abstinence syndrome (NAS). A 3-compartment morphine structural PK model after intravenous (IV) administration from previously published work was utilized as prior, whereas an allometric scaling method with physiological consideration was used to extrapolate a PK profile from adults to pediatrics. The absorption rate constant and bioavailability were estimated in NAS after oral administration of diluted tincture of opium (DTO). Goodness-of-fit plots along with normalized prediction distribution error and bootstrap method were performed for model evaluation. We successfully extrapolated the PK profile from adults to pediatrics after IV administration. The estimated first-order absorption rate constant and bioavailability were 0.751 hour(-1) and 48.5%, respectively. Model evaluations showed that the model can accurately and precisely describe the observed data. The population pharmacokinetic model we derived for morphine after oral administration of DTO is reasonable and acceptable; therefore, it can be used to describe the PK and guide future studies. The integration of the previous population PK knowledge as prior information successfully overcomes the logistic and practical issue in vulnerable neonate population. PMID:26712409

  18. Hair testing in postmortem diagnosis of substance abuse: An unusual case of slow-release oral morphine abuse in an adolescent.

    PubMed

    Baillif-Couniou, Valérie; Kintz, Pascal; Sastre, Caroline; Pok, Phak-Rop Pos; Chèze, Marjorie; Pépin, Gilbert; Leonetti, Georges; Pelissier-Alicot, Anne-Laure

    2015-11-01

    Morphine sulfate misuse is essentially observed among regular heroin injectors. To our knowledge, primary addiction to morphine sulfate is exceptional, especially among young adolescents. A 13-year-old girl, with no history of addiction, was found dead with three empty blisters of Skenan(®) LP 30 mg at her side. Opiates were detected in biological fluids and hair by chromatographic methods. Blood analyses confirmed morphine overdose (free morphine: 428 ng/mL; total morphine: 584 ng/mL) and segmental hair analysis confirmed regular exposure over several months (maximum morphine concentration 250 pg/mg). Suspecting the victim's mother of recreational use of Skenan(®), the magistrate ordered analysis of her hair, with negative results. From an epidemiological viewpoint, this case of oral morphine sulfate abuse in an adolescent with no previous history suggests the emergence of a new trend of morphine sulfate consumption. From a toxicological viewpoint, it demonstrates the value of hair testing, which documented the victim's regular exposure and made an important contribution to the police investigation. PMID:26492165

  19. Comparison of Glucosamine Absorption After Administration of Oral Liquid, Chewable, and Tablet Formulations to Dogs.

    PubMed

    Maxwell, Lara K; Regier, Penny; Achanta, Satyanarayana

    2016-01-01

    Glucosamine (GS) is commonly administered as a nutritional supplement to support joint function. Although many supplements are available, the effect of formulation on oral absorption in dogs is unknown. The purpose of this study was to determine the relative bioavailability of GS for liquid, chewable, and tablet formulations containing GS sulfate or hydrochloride and chondroitin sulfate. In a randomized cross-over design, supplements were administered daily for 8 days with a 1 wk washout period between treatments. Liquid or Tablet A was administered to four dogs, whereas Liquid or Tablet B was administered to four additional dogs. When nutraceutical exposure was normalized to the administered dose of GS free base, similar relative bioavailabilities were determined for all three formulations. However, the dose-normalized maximum plasma GS concentration was higher for the liquid supplement (5.5 ± 0.5 μg/mL) than for the two tablets (3.1 ± 0.6 and 2.1 ± 0.6 μg/mL, P < 0.001). Similarly, the time at which maximal plasma GS concentrations occurred was shorter for the liquid formulation (0.7 ± 0.5 hr) than for the two tablets (4.2 ± 0.6 and 5.0 ± 0.6 hr, P < 0.001). These data show that the formulation of joint supplements affects the oral absorption of GS in dogs. PMID:26808433

  20. Formulation of cyclodextrin inclusion complex-based orally disintegrating tablet of eslicarbazepine acetate for improved oral bioavailability.

    PubMed

    Desai, Samixa; Poddar, Aditi; Sawant, Krutika

    2016-01-01

    The present investigation was aimed towards developing a beta-cyclodextrin (β-CD) solid dispersion (SD) based orally disintegrating tablet (ODT) of eslicarbazepine acetate (ESL), for improving the dissolution and providing fast onset of anti-epileptic action. Optimum ratio of ESL and β-CD was determined by Job's plot. Thereafter, solid dispersions were prepared by solvent evaporation method and evaluated for yield, assay, Differential scanning calorimetry (DSC), Fourier transform infra red spectroscopy (FTIR), X-ray diffraction (XRD), and in vitro dissolution. Optimized SD was compressed into ODT by direct compression using super disintegrants and evaluated for wetting time, drug content, in vitro drug release and in vivo studies. The results of DSC, FTIR and XRD analysis supported the formation of inclusion complex. An improved dissolution with 99.95 ± 2.80% drug release in 60 min was observed in comparison to 24.85 ± 2.96% release from a plain drug suspension. Tablets with crosspovidone as a super disintegrant showed the least disintegration time of 24.66 ± 1.52 s and higher in vitro drug release against marketed tablets. In vivo studies indicated that the formulated tablets had 2 times higher bioavailability than marketed tablets. Thus, the developed β-CD-ESL SD-ODT could provide faster onset of action and higher bioavailability, which would be beneficial in case of epileptic seizures. PMID:26478377

  1. Localization of fluconazole in oral cavity by preferential coating of buccoadhesive tablet for treatment of oral thrush

    PubMed Central

    Pathak, Kamla; Sharma, Vijay; Akhtar, Nida; Rastogi, Pragya

    2016-01-01

    Background: The present research work was aimed at localization of fluconazole in the oral cavity by preferential coating of buccoadhesive tablet for the treatment of oral thrush. Materials and Methods: In order to achieve the aim, buccoadhesive tablets were optimized using 32 full factorial design to study the influence of varying content of chitosan and carbopol 934P (input variables) on the responses. Results: Perturbation plots revealed high sensitivity of the input variables to ex vivo mucoadhesion force and percent cumulative drug release (CDR) whereas the ex vivo mucoadhesion time was less sensitive to the input variables. Based on the highest desirability factor of 0.693 the formulation F9 was identified as the optimized formulation and was preferentially coated with ethyl cellulose (3% w/v) on one tablet face to get F9C. In reference to F9, F9C showed superior mucoadhesive features (P < 0.05) but the % CDR was comparable (f2 = 50.80). The preferential coating (F9C, Jss = 0.812 μg/cm2/h) limited the permeation of fluconazole across goat buccal mucosa by almost half the value of F9 (Jss = 1.34 μg/cm2/h) that could serve as an advantage in establishing high local concentration of drug in the oral cavity, thereby facilitating faster attainment of minimum inhibitory concentration. Scanning electron microscopy and histological analysis established nonirritant potential. The developed formulation was stable and demonstrated antifungal activity against Candida albicans. Conclusion: Thus it can be concluded that preferentially coated buccoadhesive tablets of fluconazole might be considered as a precise approach to localize the drug delivery in oral cavity. PMID:27051630

  2. Formulation and evaluation of clozapine orally disintegrating tablets prepared by direct compression.

    PubMed

    Olmez, S S; Vural, I; Sahin, S; Ertugrul, A; Capan, Y

    2013-02-01

    In this study, clozapine orally disintegrating tablets (ODTs) were prepared by direct compression method. Disintegration time, resistance to crushing of tablets, porosity, friability, dissolution tests were performed and dissolution profiles of ODTs were investigated. Morphological and interaction studies were also performed. Friability values were found to be less than 1%. All tablet formulations disintegrated within 1 min and fulfilled the 3 min disintegration time required for ODTs given in the European Pharmacopoeia. More than 85% of the labeled amount of clozapine was dissolved in 15 min from the ODTs. No interaction or changes were found between active substance and excipients. As a result of the studies, ODT formulations developed in this study can be suggested as promising formulations, which assist development and manufacturing a generic product of clozapine. PMID:23469682

  3. PREPARATION AND CHARACTERIZATION OF ORALLY DISINTEGRATING LORATADINE TABLETS MANUFACTURED WITH CO-PROCESSED MIXTURES.

    PubMed

    Amelian, Aleksandra; Szekalska, Marta; Wilczewska, Agnieszka Zofia; Basa, Anna; Winnicka, Katarzyna

    2016-01-01

    The aim of this study was to develop orally disintegrated tablets (ODT) with loratadine using Parteck ODT and Ludiflash--new commercially available tableting excipients based on co-processed mannitol. ODT containing loratadine were prepared with 3% addition of various superdisintegrants (AcDiSol, Kollidon CL-F and Kollidon CL-SF) by direct compression method. Obtained tablets were characterized for friability, pore structure, and wetting and disintegration time measured by four independents methods. In order to identify possible interactions between loratadine and the excipients, differential scanning calorimetry was used. The results showed that all formulated ODT were characterized by appropriate mechanical properties (friability < 1%), the uniform content of the drug substance and pleasant mouth feeling. Disintegration time below 30 s was observed in formulations with crospovidones as disintegrant. PMID:27180438

  4. 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. PMID:25657794

  5. Sucralose as co-crystal co-former for hydrochlorothiazide: development of oral disintegrating tablets.

    PubMed

    Arafa, Mona F; El-Gizawy, Sanaa A; Osman, Mohamed A; El Maghraby, Gamal M

    2016-08-01

    Development of oral disintegrating tablets requires enhancement of drug dissolution and selection of sweetener. Co-crystallization of drugs with inert co-former is an emerging technique for enhancing dissolution rate. The benefit of this technique will become even greater if one of the sweeteners can act as co-crystal co-former to enhance dissolution and mask the taste. Accordingly, the objective of this work was to investigate the efficacy of sucralose as a potential co-crystal co-former for enhancing the dissolution rate of hydrochlorothiazide. This was extended to prepare oral disintegrating tablets. Co-crystallization was achieved after dissolving hydrochlorothiazide with increasing molar ratios of sucralose in the least amount of acetone. The co-crystallization products were characterized using Fourier transform infrared spectroscopy, differential thermal analysis and powder X-ray diffraction. These measurements indicated that co-crystallization process started at a drug sucralose molar ratio of 1:1 and completed at 1:2. The developed co-crystals exhibited faster drug dissolution compared with the control, with co-crystal containing the drug with sucralose at 1:2 molar ratio being optimum. The later was used to prepare fast disintegrating tablets. These tablets had acceptable physical characteristics and showed fast disintegration with subsequent rapid dissolution. The study introduced sucralose as co-crystal co-former for enhanced dissolution and masking the taste. PMID:26555927

  6. In vitro and in vivo evaluation of oral tablet formulations prepared with ketoconazole and hydroxypropyl-beta-cyclodextrin.

    PubMed

    Taneri, Filiz; Ozcan, Ipek; Guneri, Tamer

    2010-04-01

    The objective of this study was to enhance the solubility, dissolution rate, and oral bioavailability of a very poorly water-soluble anti-fungal agent, ketoconazole (KET), by inclusion complexation with a highly-soluble cyclodextrin derivative, hydroxypropyl-beta cyclodextrin (HP-beta-CD). Two groups of tablets containing KET alone and KET:HP-beta-CD (1:2) kneaded product (KP) including magnesium stearate and lactopress (anhydrous and spray-dried) as excipients were prepared by direct compression method. After the characterization studies, the in vitro dissolution studies of these tablets in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) were carried out. To evaluate the in vivo bioavailability, the tablets were administered orally to rabbits and drug levels in serum were determined by HPLC. Tablets containing the cyclodextrin complex showed a higher in vitro dissolution rate and bioavailability compared to the tablets containing KET alone. PMID:20148713

  7. Iron supplement tablet embedded in the oral cavity mimicking neoplasm: a case report

    PubMed Central

    2016-01-01

    The detection of foreign bodies in the upper-aerodigestive tract is a fairly frequent event and can occur in various areas and for various reasons. In rare cases, foreign bodies can simulate a neoplasia. We evaluated similar cases during emergency regimen with an oral cavity mucosal lesion, causing lockjaw, sore throat, dysphagia, and swelling of the submandibular and laterocervical region. Physical examination revealed an extensive mucosal ulceration in the floor of the mouth and the lateral surface of the tongue, comparable to oral cancer. During a second, more accurate assessment, a partially deteriorated iron supplement tablet was found embedded in a mucosal pocket. After removing the tablet, gradual normalization of the tissue was observed without any sequelae. This is one of the many reasons why it is advisable and useful in cases of oral lesions to collect a detailed medical history and to perform an accurate clinical evaluation, including inspection and palpation of the lesion, before proceeding to further diagnostic assessments, especially in elderly patients taking many medications. However unlikely, it is possible that difficulty in swallowing pills or tablets could generate tumorlike lesions. PMID:27162752

  8. New Generation of Orally Disintegrating Tablets for Sustained Drug Release: A Propitious Outlook.

    PubMed

    Elwerfalli, Arwa Matoug; Ghanchi, Zabir; Rashid, Fatema; Alany, Raid G; ElShaer, Amr

    2015-01-01

    Orally disintegrating tablets (ODTs) or orodispersible tablets are solid dosage forms that disintegrate within 3 minutes in the mouth into a paste that can be easily swallowed. ODTs have improved over the past years, in an attempt to produce a safe and efficient substitute to the conventional oral dosage forms, particularly for dysphagia patients. Since its introduction in the market in the 1980s, ODTs expanded rapidly and achieved revenues over $3 billion in 2006 and sustaining 20% annual growth. It is therefore evident that ODTs carry good commercial value, however there is potential for improvement. Current sustained-release technologies may be exploited and incorporated into an ODT to provide greater therapeutic value by reducing the need for multiple daily dosing regimens and improving patient adherence. A number of technologies such as polymer coated nanoparticles, stimuli-responsive polymers and ion-exchange resins have emerged to produce robust, sustained release orally disintegrating tablets (SR-ODT). The purpose of this review is to highlight these various approaches and techniques and how they have been utilised in an ODT formulation to extend differentiated line, market exclusivity and patent life. The review also explores future perspective and the potential challenges that SR-ODTs will face. PMID:25760951

  9. Relative bioavailability of diclofenac potassium from softgel capsule versus powder for oral solution and immediate-release tablet formulation.

    PubMed

    Bende, Girish; Biswal, Shibadas; Bhad, Prafulla; Chen, Yuming; Salunke, Atish; Winter, Serge; Wagner, Robert; Sunkara, Gangadhar

    2016-01-01

    The oral bioavailability of diclofenac potassium 50 mg administered as a soft gelatin capsule (softgel capsule), powder for oral solution (oral solution), and tablet was evaluated in a randomized, open-label, 3-period, 6-sequence crossover study in healthy adults. Plasma diclofenac concentrations were measured using a validated liquid chromatography-mass spectrometry/mass spectrometry method, and pharmacokinetic analysis was performed by noncompartmental methods. The median time to achieve peak plasma concentrations of diclofenac was 0.5, 0.25, and 0.75 hours with the softgel capsule, oral solution, and tablet formulations, respectively. The geometric mean ratio and associated 90%CI for AUCinf, and Cmax of the softgel capsule formulation relative to the oral solution formulation were 0.97 (0.95-1.00) and 0.85 (0.76-0.95), respectively. The geometric mean ratio and associated 90%CI for AUCinf and Cmax of the softgel capsule formulation relative to the tablet formulation were 1.04 (1.00-1.08) and 1.67 (1.43-1.96), respectively. In conclusion, the exposure (AUC) of diclofenac with the new diclofenac potassium softgel capsule formulation was comparable to that of the existing oral solution and tablet formulations. The peak plasma concentration of diclofenac from the new softgel capsule was 67% higher than the existing tablet formulation, whereas it was 15% lower in comparison with the oral solution formulation. PMID:27119581

  10. Determination of the in vitro disintegration profile of rapidly disintegrating tablets and correlation with oral disintegration.

    PubMed

    Abdelbary, G; Eouani, C; Prinderre, P; Joachim, J; Reynier, Jp; Piccerelle, Ph

    2005-03-23

    The assessment of the in vitro disintegration profile of rapidly disintegrating tablets (RDT) is very important in the evaluation and the development of new formulations of this type. So far neither the US Pharmacopoeia nor the European Pharmacopoeia has defined a specific disintegration test for RDT; currently, it is only possible to refer to the tests on dispersible or effervescent tablets for the evaluation of RDT's disintegration capacity. In the present study, we have evaluated the disintegration profile of RDT manufactured by main commercialised technologies, using the texture analyser (TA). In order to simulate as much as possible the oral disintegration of these dosage forms, a new operating structure was developed. This structure mimics the situation in the patient's mouth and provides a gradual elimination of the detached particles during the disintegration process. The obtained time-distance profiles or disintegration profiles enabled the calculation of certain quantitative values as the disintegration onset (t1) and the total disintegration time (t2). These values were used in the characterisation of the effect of test variables as the disintegration medium and temperature on the disintegration time of RDT. Moreover, the oral disintegration time of the same products was evaluated by 14 healthy volunteers. Results obtained when artificial saliva at 37 degrees C was employed as disintegration medium were used to correlate the in vitro (t2) and oral disintegration times. Excellent correlation was found and in addition, we were able to achieve a qualitative measure of the mouthfeel by comparing the thickness of the tablets and the penetration distance obtained from the disintegration profile. This method also permitted the discrimination between different RDT, where differences in the disintegration mechanism were reflected on the disintegration profile achieved for each tablet. PMID:15725551

  11. Sufentanil Sublingual Tablet System vs. Intravenous Patient-Controlled Analgesia with Morphine for Postoperative Pain Control: A Randomized, Active-Comparator Trial

    PubMed Central

    Melson, Timothy I; Boyer, David L; Minkowitz, Harold S; Turan, Alparslan; Chiang, Yu-Kun; Evashenk, Mark A; Palmer, Pamela P

    2014-01-01

    Background Problems with intravenous patient-controlled analgesia (IV PCA) are well known, including invasive route of delivery and pump programming errors. The primary objective of this study was to evaluate patient satisfaction with a novel sublingual sufentanil PCA system (sufentanil sublingual tablet system 15 mcg with a 20-minute lockout interval; SSTS) to IV PCA morphine sulfate 1 mg with a 6-minute lockout interval (IV PCA MS) for the management of acute postoperative pain. Methods This was a randomized, open-label, 48-hour non-inferiority study with optional extension to 72 hours at 26 U.S. sites enrolling patients scheduled for elective major open abdominal or orthopedic (hip or knee replacement) surgery. The primary outcome measure was the proportion of patients who responded “good” or “excellent” (collectively “success”) at the 48-hour timepoint on the Patient Global Assessment of method of pain control (PGA48). Results A total of 357 patients received study drug and 78.5% vs. 65.6% of patients achieved PGA48 “success” for SSTS vs. IV PCA MS, respectively, demonstrating non-inferiority (P < 0.001 using the one-side Z-test against the non-inferiority margin) as well as statistical superiority for treatment effect (P = 0.007). Patients using SSTS reported more rapid onset of analgesia and patient and nurse ease of care and satisfaction scores were higher than IV PCA MS. Adverse events were similar between the 2 groups; however, SSTS had fewer patients experiencing oxygen desaturations below 95% compared to IV PCA MS (P = 0.028). Conclusions Sufentanil sublingual tablet system is a promising new analgesic technology that may address some of the concerns with IV PCA. PMID:25155134

  12. [Technical scheme of real-time evaluation of traditional Chinese medicine orally disintegrating tablets].

    PubMed

    Qin, Dong; Chen, Xu-dong; Feng, Liang; Gu, Jun-fei; Yuan, Jia-rui; Jia, Xiao-bin

    2014-12-01

    Orally disintegrating tablets (ODT), a kind of new solid tablet that rapidly disintegrates to work in the mouth, has became the hot form of new drug research in recent years with many advantages, such as the convenient taking, a widely applicable people, fast acting, high bioavailability, good compliance, and so on. ODT has been widely used in chemical medicines, while the application of it in traditional Chinese medicines (TCMs) is still in the stage of development The development of TCMs ODT provides a new direction for the research of Chinese medicine new dosage, accelerates the pace of connecting to the world and modernization of Chinese medicine. This dosage has a broad market prospect, and its quality control and assessment standards, taste, the disintegration time in vitro and evaluation method are the key factors that affect the industrialization, standardization of Chinese medicine ODT. Therefore, this paper reviewed the characteristics, preparation, taste masking technology and quality evaluation with new technology of ODT. Meantime, numerous application examples of ODT used in traditional Chinese medicine were described. We expect to provide the reference and utilization for the development of traditional Chinese medicine orally disinteeratine tablets. PMID:25898566

  13. A new modified wetting test and an alternative disintegration test for orally disintegrating tablets.

    PubMed

    Hooper, Patrick; Lasher, Jason; Alexander, Kenneth S; Baki, Gabriella

    2016-02-20

    Industrial manufacturing of solid oral dosage forms require quality tests, such as friability, hardness, and disintegration. The United States Pharmacopeia (USP) disintegration test uses 900mL of water. However, recent studies of orally disintegrating tablets (ODTs) have shown that this volume does not accurately portray the oral environment. In our study, various tests were conducted with a more moderate amount of water that accurately resembles the oral environment. A simulated wetting test was performed to calculate the water absorption ratio. Results showed that wetting was comparable to disintegration. Although the wetting test worked for most types of ODTs, it had limitations that produced inaccurate results. This led to the use of a modified shaking water bath test. This test was found to work for all types of ODT products and was not subject to the limitations of the wetting test. The shake test could provide disintegration times rather than water permeation times; however, it could not be used to calculate the water absorption ratio. A strong correlation was observed between the standardized shake test and the USP disintegration times for the tablets. This shake test could be used during the development stages and quality tests for ODTs with relative ease. PMID:26774944

  14. Bioequivalence of ondansetron oral soluble film 8 mg (ZUPLENZ) and ondansetron orally disintegrating tablets 8 mg (ZOFRAN) in healthy adults.

    PubMed

    Dadey, Eric

    2015-01-01

    Oral formulations of ondansetron are used to prevent nausea and vomiting associated with chemotherapy, radiotherapy, and surgery. An oral soluble film formulation of ondansetron (OND OSF) was developed using MonoSol Rx's proprietary PharmFilm technology and was formulated to dissolve rapidly on the tongue, without the need for water. This product provides an oral antiemetic treatment option for patients who experience difficulty swallowing. The purpose of this study was to compare the bioequivalence of OND OSF 8 mg (ZUPLENZ, Monosol Rx, Warren, NJ) with ondansetron orally disintegrating tablets (OND ODT) 8 mg (ZOFRAN, GlaxoSmithKline, Research Triangle Park). In 3 individual open-label, randomized studies, healthy adult subjects received a single dose of OND OSF 8 mg and a single dose of OND ODT 8 mg, under fasted conditions (study 1, n = 48), fed conditions (study 2, n = 48), and fasted with and without water (study 3, n = 18). Each dosing period was followed by a 3- or 7-day washout period. Ondansetron pharmacokinetics were assessed predose to 24 hours postdose for the single 8-mg doses of OND OSF and OND ODT. All analyses were conducted on natural log-transformed pharmacokinetic parameters for OND OSF and OND ODT. Under both fasted and fed conditions, the 90% confidence interval for the comparisons of OND OSF and OND ODT plasma ondansetron area under the curve from time 0 to the last measured concentration (AUC0-t), area under the concentration vs. time curve from time 0 to infinity (AUC0-∞), and maximum plasma concentration (Cmax) were within the 80%-125% range, indicating bioequivalence between the formulations. With features designed to make it portable and easy to take, OND OSF 8 mg provides an alternative treatment option, particularly for patients with dysphagia and others who find it difficult to take oral tablets. PMID:25581856

  15. Design, development, and optimization of orally disintegrating tablets of etoricoxib using vacuum-drying approach.

    PubMed

    Patel, Dharmesh; Shah, Mohit; Shah, Sunny; Shah, Tejal; Amin, Avani

    2008-01-01

    Etoricoxib is a cyclooxygenase 2 (COX-2) inhibitor that selectively inhibits the COX-2 enzyme and decreases the incidences of side effects associated with these agents. It is commonly prescribed for acute pain, gouty arthritis, and rheumatoid arthritis. Conventional tablets of etoricoxib are not capable of rapid action, which is required for faster drug effect onset and immediate relief from pain. Thus, the aim of the present investigation is to formulate orally disintegrating tablets (ODTs) of etoricoxib. A combination of the superdisintegrants with a sublimation technique was used to prepare the tablets. Tablets were prepared using a direct compression method employing superdisintegrants such as low substituted hydroxylpropyl methyl cellulose (L-HPMC), low substituted hydroxyl-propyl cellulose (L-HPC), crospovidone, croscarmellose sodium, and sodium starch glycolate. Tablets of etoricoxib prepared using L-HPC exhibited the least friability and disintegration time (approximately 65 s). To decrease the disintegration time further, a sublimation technique was used along with the superdisintegrants for the preparation of ODTs. The use of sublimating agents including camphor, menthol, and thymol was explored. The addition of camphor lowered the disintegration time (approximately 30 s) further, but the percent friability was increased. A 3(2) full factorial design was employed to study the joint influence of the amount of superdisintegrant (L-HPC) and the amount of sublimating agent (camphor) on the percent of friability and the disintegration time. The results of multiple linear regression analysis revealed that for obtaining an effective ODT of etoricoxib, higher percentages of L-HPC and camphor should be used. Checkpoint batches were prepared to validate the evolved mathematical model. A response surface plot is also presented to graphically represent the effect of the independent variables on the percent of friability and the disintegration time. The approach using

  16. Formulation design for orally disintegrating tablets containing enteric-coated particles.

    PubMed

    Okuda, Yutaka; Okamoto, Yasunobu; Irisawa, Yosuke; Okimoto, Kazuto; Osawa, Takashi; Yamashita, Shinji

    2014-01-01

    The purpose of this study was to investigate the applicability of our newly developed technology (RACTAB® technology) for preparing orally disintegrating tablets (ODTs) containing enteric-coated particles. Tamsulosin hydrochloride (TAM) was used as a model drug contained in the enteric-coated particles. Enteric-coated particles containing TAM (ECP-T) were prepared by spray coating a mixture of TAM with controlled-release materials. ECP-T was then mixed with rapidly disintegrating granules (RDGs), which were prepared using the suspension spray-coating method, and was tableted to form ODTs (ODTRAC). ODTRAC was evaluated for its hardness, thickness, internal structure (X-ray-CT scanning), functional properties (controlled-release profile), and in vivo disintegration time. Since RDGs with micronized ethylcellulose (MEC) increased tablet hardness by increasing the contact frequency between granules, ODTRAC containing ECP-T exhibited high hardness (>50 N) and low friability (<0.5%) with a relatively low compression force. After tableting, the structure of ECP-T in ODTRAC remained intact and no damage was observed on the surface. ECP-T recovered from ODTRAC showed the same dissolution profile of TAM in Japanese Pharmacopoeia (JP) 1st and JP 2nd media as that of intact ECP-T, which indicated that the tableting process did not affect the acid-resistibility of the particle. In addition, ODTRAC rapidly disintegrated in vivo (< 30 s), even at a high compression force (at 9 kN). These findings clearly suggest that RACTAB® technology is a useful approach to prepare ODTs containing enteric-coated particles. PMID:24789923

  17. Effects of Orally Administered Lactoferrin and Lactoperoxidase-Containing Tablets on Clinical and Bacteriological Profiles in Chronic Periodontitis Patients

    PubMed Central

    Shimizu, Eiju; Kobayashi, Tetsuo; Wakabayashi, Hiroyuki; Yamauchi, Koji; Iwatsuki, Keiji; Yoshie, Hiromasa

    2011-01-01

    This study was undertaken to evaluate the effect of oral administration of lactoferrin (LF) and lactoperoxidase-(LPO-)containing tablet on periodontal condition. Seventy-two individuals with chronic periodontitis were randomly assigned to take either bovine LF and LPO-containing tablets (test group, n = 37) or control tablets (control group, n = 35) every day for 12 weeks. Periodontal parameters and levels of subgingival plaque bacteria, human and bovine LF, and endotoxin in gingival crevicular fluid (GCF) were evaluated at baseline, 1 week, 4 weeks, and 12 weeks. Significant differences were observed in GCF levels of bovine LF between the test and control groups throughout the study (P < .05). However, clinical and bacteriological parameter values proved comparable between the two groups at 1 week to 12 weeks. Therefore, the effect of oral administration of LF and LPO-containing tablets might be weak on periodontal and bacteriological profile in this study. PMID:21747858

  18. Morphine Rectal

    MedlinePlus

    Rectal morphine is used to relieve moderate to severe pain. Morphine is in a class of medications called opiate ( ... Rectal morphine comes as a suppository to insert in the rectum. It is usually inserted every 4 hours. Use ...

  19. Acute kidney injury in a preterm infant homozygous for the C3435T polymorphism in the ABCB1 gene given oral morphine

    PubMed Central

    Pogliani, Laura; Mameli, Chiara; Cattaneo, Dario; Clementi, Emilio; Meneghin, Fabio; Radice, Sonia; Bruno, Simona; Zuccotti, Gian Vincenzo

    2012-01-01

    A 34-week infant born from a mother with a history of drug abuse developed neonatal abstinence syndrome (NAS) in the first hours of life. Urine drug screening was positive for cocaine and heroin. The infant developed acute kidney injury and bilateral hydronephrosis while receiving oral morphine for control of NAS. Cessation of morphine therapy and urinary catheterization resulted in a rapid and complete resolution of the symptoms. Our patient was homozygous for the C3435T polymorphism in the ABCB1 gene, a polymorphism previously associated with impaired P-glycoprotein activity. We hypothesize that acute renal toxicity was related to accumulation of morphine within urothelial cells due to genetically determined impaired P-glycoprotein activity. PMID:26019822

  20. The efficacy and safety of clotrimazole vaginal tablet vs. oral fluconazole in treating severe vulvovaginal candidiasis.

    PubMed

    Zhou, Xiaofang; Li, Ting; Fan, Shangrong; Zhu, Yuxia; Liu, Xiaoping; Guo, Xuedong; Liang, Yiheng

    2016-07-01

    To compare the efficacy and safety of two doses of clotrimazole vaginal tablet 500 mg with two doses of oral fluconazole 150 mg in treating severe vulvovaginal candidiasis (SVVC), 240 consecutive patients with SVVC were studied at the Department of Obstetrics and Gynaecology of Peking University Shenzhen Hospital between June 2014, and September 2015. Patients were randomly assigned in a 1 : 1 ratio to receive treatment with either two doses of clotrimazole vaginal tablet or two doses of oral fluconazole. The clinical cure rates in the clotrimazole group and the fluconazole group at days 7-14 follow-up were 88.7% (102/115) and 89.1% (98/110) respectively; the clinical cure rates at days 30-35 in the two groups were 71.9% (82/114) and 78.0% (85/109) respectively. The mycological cure rates at days 7-14 follow-up in the two groups were 78.3% (90/115) and 73.6% (81/110) respectively. The mycological cure rates of the patients at days 30-35 in the two groups were 54.4% (62/114) and 56.0% (61/109) respectively (P > 0.05). The adverse events of clotrimazole were mainly local. This study demonstrated that two doses of clotrimazole vaginal tablet 500 mg were as effective as two doses of oral fluconazole 150 mg in the treatment of patients with SVVC and could be an appropriate treatment for this disorder. PMID:27073145

  1. Coated dextrin microcapsules of amlodipine incorporable into orally disintegrating tablets for geriatric patients.

    PubMed

    Jang, Dong-Jin; Bae, Soo Kyung; Oh, Euichaul

    2014-10-01

    To improve oral absorption and patient compliance when using amlodipine, novel coated dextrin microcapsules incorporable into orally disintegrating tablets (ODT's) were investigated. Amlodipine-loaded dextrin microcapsules (ADM) were prepared by spray-drying a mixture of amlodipine free base dissolved in ethanol and aqueous dextrin solution. The ADM were suspended in Eudragit(®) EPO solution in ethanol and subsequently spray-dried to collect coated ADM (CADM). The ADM or CADM were blended with ODT excipients and then directly compressed into ODTs. The ADM and CADM used were both spherical with smooth surfaces and had mean particle sizes of 13.3 and 18.5μm, respectively. Amlodipine was dispersed in an amorphous state and was readily encapsulated within ADM or CADM. Unlike the ADM, the tableted CADM remained intact without rupture during tableting, which was consistent with no loss of ethanol (0.82%) entrapped in the ODTs containing the CADM (ODTs-CADM). The amlodipine content appeared to be uniformly maintained as designed in all the dextrin microcapsules and ODTs. The ODTs-CADM compressed with 3kp of hardness showed acceptable ODT characteristics: fast disintegration time (29.8s) and low friability (0.1%). Drug dissolution from the ODTs-CADM was much faster than that of amlodipine free base itself at both pH 1.2 and 6.8 over the tested time. CADM demonstrated significantly higher plasma concentrations (2.7 fold in AUC0-24h and 2.5 fold in Cmax) in SD rats than did amlodipine free base. These results indicate that CADM substantially increased the oral absorption of amlodipine and can be incorporated into ODTs while maintaining their original physicochemical features. The dextrin microcapsules coated using Eudragit(®) EPO may be applied to the development of an amlodipine ODT formulation for improving geriatric patient compliance. PMID:25458788

  2. The simultaneous determination of codeine, morphine, hydrocodone, hydromorphone, 6-acetylmorphine, and oxycodone in hair and oral fluid.

    PubMed

    Jones, Joseph; Tomlinson, Kimberly; Moore, Christine

    2002-04-01

    Recently, the abuse of prescription opiates as alternatives to heroin has become a national concern. The determination of a six-drug opiate panel, codeine, morphine, 6-acetylmorphine, hydrocodone, hydromorphone, and oxycodone, in hair and oral fluid using solid-phase extraction and capillary gas chromatography-mass spectrometry (GC-MS) is described. Oral fluid was obtained from the donor by insertion of absorptive collectors into the mouth. Hair was collected from the patient and powdered using stainless steel ball bearings in a mini bead-beater apparatus. Opiates present in the samples were extracted from a buffered, aqueous matrix using a solid-phase cartridge. The extracts were concentrated and the methoxime/BSTFA derivatives prepared in order to eliminate interference from the keto-opiates. The extracts were separated by GC-MS in electron impact mode. By utilizing methoxyamine, we were able to produce the methoxime derivatives required for single derivative production and chromatographically separate all six opiates. The routine analysis of these opiates in hair and oral fluid using GC-MS is described for the first time. PMID:11991534

  3. Maltodextrin: a novel excipient used in sugar-based orally disintegrating tablets and phase transition process.

    PubMed

    Elnaggar, Yosra Shaaban R; El-Massik, Magda A; Abdallah, Ossama Y; Ebian, Abd Elazim R

    2010-06-01

    The recent challenge in orally disintegrating tablets (ODT) manufacturing encompasses the compromise between instantaneous disintegration, sufficient hardness, and standard processing equipment. The current investigation constitutes one attempt to fulfill this challenge. Maltodextrin, in the present work, was utilized as a novel excipient to prepare ODT of meclizine. Tablets were prepared by both direct compression and wet granulation techniques. The effect of maltodextrin concentrations on ODT characteristics--manifested as hardness and disintegration time--was studied. The effect of conditioning (40 degrees C and 75% relative humidity) as a post-compression treatment on ODT characteristics was also assessed. Furthermore, maltodextrin-pronounced hardening effect was investigated using differential scanning calorimetry (DSC) and X-ray analysis. Results revealed that in both techniques, rapid disintegration (30-40 s) would be achieved on the cost of tablet hardness (about 1 kg). Post-compression conditioning of tablets resulted in an increase in hardness (3 kg), while keeping rapid disintegration (30-40 s) according to guidance of the FDA for ODT. However, direct compression-conditioning technique exhibited drawbacks of long conditioning time and appearance of the so-called patch effect. These problems were, yet, absent in wet granulation-conditioning technique. DSC and X-ray analysis suggested involvement of glass-elastic deformation in maltodextrin hardening effect. High-performance liquid chromatography analysis of meclizine ODT suggested no degradation of the drug by the applied conditions of temperature and humidity. Overall results proposed that maltodextrin is a promising saccharide for production of ODT with accepted hardness-disintegration time compromise, utilizing standard processing equipment and phenomena of phase transition. PMID:20405257

  4. Concentrations of Morphine and Codeine in Paired Oral Fluid and Urine Specimens Following Ingestion of a Poppy Seed Roll and Raw Poppy Seeds.

    PubMed

    Samano, Kimberly L; Clouette, Randal E; Rowland, Barbara J; Sample, R H Barry

    2015-10-01

    Interpretation of opiate drug test results can be challenging due to casual dietary consumption of poppy seeds, which may contain variable opiate content. Opiate concentrations in paired oral fluid (OF), collected with the Oral-Eze(®) Oral Fluid Collection System, and urine were analyzed after ingestion of poppy seeds from the same source, consumed raw or contained in a roll. In Part 1, 12 individuals consumed equal portions of a poppy seed roll. For Part 2, the same individuals consumed an equivalent quantity of raw poppy seeds, containing ∼3.2 mg of morphine and 0.6 mg of codeine. Specimens were analyzed both by enzyme immunoassay (opiates) and by GC-MS (morphine/codeine). Urinary morphine was between 155-1,408 (roll) and 294-4,213 ng/mL (raw), measured at 2, 4, 6 and 20 h post-ingestion. Urinary codeine concentrations between 140-194 (roll) and 121-664 ng/mL (raw) were observed up to 6 h post-ingestion. Following consumption of raw poppy seeds, OF specimens were positive, above LOQ, from 0.25 to 3.0 h with morphine ranging from 7 to 600 ng/mL and codeine from 8 to 112 ng/mL. After poppy seed roll consumption, morphine concentrations of 7-143 ng/mL were observed up to 1.5 h with codeine detected in only 5.5% of OF specimens and ranging from 8 to 28 ng/mL. Combined with the existing poppy seed literature, these results support previous findings and provide guidance for interpretation of OF opiate testing. PMID:26378141

  5. Concentrations of Morphine and Codeine in Paired Oral Fluid and Urine Specimens Following Ingestion of a Poppy Seed Roll and Raw Poppy Seeds

    PubMed Central

    Samano, Kimberly L.; Clouette, Randal E.; Rowland, Barbara J.; Sample, R.H. Barry

    2015-01-01

    Interpretation of opiate drug test results can be challenging due to casual dietary consumption of poppy seeds, which may contain variable opiate content. Opiate concentrations in paired oral fluid (OF), collected with the Oral-Eze® Oral Fluid Collection System, and urine were analyzed after ingestion of poppy seeds from the same source, consumed raw or contained in a roll. In Part 1, 12 individuals consumed equal portions of a poppy seed roll. For Part 2, the same individuals consumed an equivalent quantity of raw poppy seeds, containing ∼3.2 mg of morphine and 0.6 mg of codeine. Specimens were analyzed both by enzyme immunoassay (opiates) and by GC–MS (morphine/codeine). Urinary morphine was between 155–1,408 (roll) and 294–4,213 ng/mL (raw), measured at 2, 4, 6 and 20 h post-ingestion. Urinary codeine concentrations between 140–194 (roll) and 121–664 ng/mL (raw) were observed up to 6 h post-ingestion. Following consumption of raw poppy seeds, OF specimens were positive, above LOQ, from 0.25 to 3.0 h with morphine ranging from 7 to 600 ng/mL and codeine from 8 to 112 ng/mL. After poppy seed roll consumption, morphine concentrations of 7–143 ng/mL were observed up to 1.5 h with codeine detected in only 5.5% of OF specimens and ranging from 8 to 28 ng/mL. Combined with the existing poppy seed literature, these results support previous findings and provide guidance for interpretation of OF opiate testing. PMID:26378141

  6. Effects of Food Thickeners on the Inhibitory Effect of Voglibose Oral-disintegrating Tablets on Post-prandial Elevation of Blood Sugar Levels.

    PubMed

    Tomita, Takashi; Goto, Hidekazu; Sumiya, Kenji; Yoshida, Tadashi; Tanaka, Katsuya; Kohda, Yukinao

    2016-01-01

    The aim of this study was to examine the effects of food thickeners on the pharmacodynamics of voglibose, an α-glucosidase inhibitor. The pharmacodynamics of voglibose were examined in an open-label study in 9 healthy participants after the ingestion of a single oral dose of a voglibose oral-disintegrating tablet, with and without food thickener immersion. The area under the incremental blood sugar concentration-time curve was larger and the rate of increments in the blood sugar concentration was higher with the voglibose oral-disintegrating tablets immersed in the food thickener than with the tablets that were not immersed. Immersing the voglibose oral-disintegrating tablets in the food thickener possibly delayed their disintegration rate. This suggests that commercially available food thickeners may be associated with changes in the disintegration of voglibose oral-disintegrating tablets and should therefore be used carefully in certain clinical situations. PMID:27477734

  7. Development and optimization of taste-masked orally disintegrating tablets (ODTs) of clindamycin hydrochloride.

    PubMed

    Cantor, Stuart L; Khan, Mansoor A; Gupta, Abhay

    2015-01-01

    The purpose of this research was to develop an orally disintegrating tablet (ODT) dosage form containing taste-masked beads of clindamycin HCl. Several formulation strategies were evaluated and a taste-masked ODT of clindamycin HCl was prepared without the use of a waxy cushioning agent. Clindamycin HCl (ca. 46% w/w) was coated onto microcrystalline cellulose beads (Cellets® 200) followed by the addition of a taste-masking layer of amino methacrylate copolymer, NF (Eudragit EPO® (EPO)) coating suspension. The efficiency of both the drug coating process and the taste-masking polymer coating process, as well as the taste masking ODTs was determined using potency and drug release analysis. Magnesium stearate was found to be advantageous over talc in improving the efficiency of the EPO coating suspension. A response surface methodology using a Box-Behnken design for the tablets revealed compression force and levels of both disintegrant and talc to be the main factors influencing the ODT properties. Blending of talc to the EPO-coated beads was found to be the most critical factor in ensuring that ODTs disintegrate within 30 s. The optimized ODTs formulation also showed negligible (<0.5%) drug release in 1 min using phosphate buffer, pH 6.8 (which is analogous to the residence time and pH in the oral cavity). By carefully adjusting the levels of coating polymers, the amounts of disintegrant and talc, as well as the compression force, robust ODTs can be obtained to improve pediatric and geriatric patient compliance for clindamycin oral dosage forms. PMID:25000481

  8. Formulation and Evaluation of a Novel Matrix-Type Orally Disintegrating Ibuprofen Tablet

    PubMed Central

    Tayebi, Hoda; Mortazavi, Seyed Alireza

    2011-01-01

    Orally disintegrating tablets (ODTs) are capable of turning quickly into a liquid dosage form in contact with the saliva, thus possessing the advantages of both the solid dosage forms particularly stability and liquid dosage forms specially ease of swallowing and pre-gastric absorption of drug. The aim of this study was to prepare a novel matrix-type buccal fast disintegrating ibuprofen tablet formulation using special polymers, water soluble excipients, super-disintegrants and quickly soluble granules. For this purpose different tablet formulations of ibuprofen were prepared. The amount of ibuprofen in each formulation was 100 mg. Eight groups of formulation were prepared (A-H series), accounting for a total number of 45 formulations. Formulations prepared were examined in terms of different physicochemical tests including powder/granule flowability, appearance, thickness, uniformity of weight, hardness, friability and disintegration time. Results of formulation F22a (in series F), was found to be acceptable, making it the chosen formulation for further studies. Then, by adding various flavorants and sweeteners to this formulation, complementary series of formulations, named G and H, were prepared. Following the comparison of their taste with each other through asking 10 volunteers, the most suitable formulation regarding the taste, being formulation F22s, was chosen as the ultimate formulation. This formulation had PVP, ibuprofen and croscarmellose as the intra-granular components and xylitol and saccharin as the extra-granular ingredients. Formulation F22s was found to be acceptable in terms of physicochemical tests conducted, showing quick disintegration within the buccal cavity, appropriate hardness and rather low friability. Hence formulation F22s was selected as the final formulation. PMID:24250378

  9. Evidence-Based Nanoscopic and Molecular Framework for Excipient Functionality in Compressed Orally Disintegrating Tablets

    PubMed Central

    Al-khattawi, Ali; Alyami, Hamad; Townsend, Bill; Ma, Xianghong; Mohammed, Afzal R.

    2014-01-01

    The work investigates the adhesive/cohesive molecular and physical interactions together with nanoscopic features of commonly used orally disintegrating tablet (ODT) excipients microcrystalline cellulose (MCC) and D-mannitol. This helps to elucidate the underlying physico-chemical and mechanical mechanisms responsible for powder densification and optimum product functionality. Atomic force microscopy (AFM) contact mode analysis was performed to measure nano-adhesion forces and surface energies between excipient-drug particles (6-10 different particles per each pair). Moreover, surface topography images (100 nm2–10 µm2) and roughness data were acquired from AFM tapping mode. AFM data were related to ODT macro/microscopic properties obtained from SEM, FTIR, XRD, thermal analysis using DSC and TGA, disintegration testing, Heckel and tabletability profiles. The study results showed a good association between the adhesive molecular and physical forces of paired particles and the resultant densification mechanisms responsible for mechanical strength of tablets. MCC micro roughness was 3 times that of D-mannitol which explains the high hardness of MCC ODTs due to mechanical interlocking. Hydrogen bonding between MCC particles could not be established from both AFM and FTIR solid state investigation. On the contrary, D-mannitol produced fragile ODTs due to fragmentation of surface crystallites during compression attained from its weak crystal structure. Furthermore, AFM analysis has shown the presence of extensive micro fibril structures inhabiting nano pores which further supports the use of MCC as a disintegrant. Overall, excipients (and model drugs) showed mechanistic behaviour on the nano/micro scale that could be related to the functionality of materials on the macro scale. PMID:25025427

  10. Evidence-based nanoscopic and molecular framework for excipient functionality in compressed orally disintegrating tablets.

    PubMed

    Al-Khattawi, Ali; Alyami, Hamad; Townsend, Bill; Ma, Xianghong; Mohammed, Afzal R

    2014-01-01

    The work investigates the adhesive/cohesive molecular and physical interactions together with nanoscopic features of commonly used orally disintegrating tablet (ODT) excipients microcrystalline cellulose (MCC) and D-mannitol. This helps to elucidate the underlying physico-chemical and mechanical mechanisms responsible for powder densification and optimum product functionality. Atomic force microscopy (AFM) contact mode analysis was performed to measure nano-adhesion forces and surface energies between excipient-drug particles (6-10 different particles per each pair). Moreover, surface topography images (100 nm2-10 µm2) and roughness data were acquired from AFM tapping mode. AFM data were related to ODT macro/microscopic properties obtained from SEM, FTIR, XRD, thermal analysis using DSC and TGA, disintegration testing, Heckel and tabletability profiles. The study results showed a good association between the adhesive molecular and physical forces of paired particles and the resultant densification mechanisms responsible for mechanical strength of tablets. MCC micro roughness was 3 times that of D-mannitol which explains the high hardness of MCC ODTs due to mechanical interlocking. Hydrogen bonding between MCC particles could not be established from both AFM and FTIR solid state investigation. On the contrary, D-mannitol produced fragile ODTs due to fragmentation of surface crystallites during compression attained from its weak crystal structure. Furthermore, AFM analysis has shown the presence of extensive micro fibril structures inhabiting nano pores which further supports the use of MCC as a disintegrant. Overall, excipients (and model drugs) showed mechanistic behaviour on the nano/micro scale that could be related to the functionality of materials on the macro scale. PMID:25025427

  11. Effect of granule properties on rough mouth feel and palatability of orally disintegrating tablets.

    PubMed

    Kimura, Shin-Ichiro; Uchida, Shinya; Kanada, Ken; Namiki, Noriyuki

    2015-04-30

    In this study, we evaluated the palatability of orally disintegrating tablets (ODTs) containing core granules with different particle sizes, coating, and types of materials using visual analog scales (VAS). Tableting the core granules into ODTs reduced rough mouth feel and improved overall palatability compared to the ingestion of core granules alone. Moreover, the evaluation performed immediately after spitting out ODTs demonstrated differences in rough mouth feel between ODTs containing placebo and core granules. Rough mouth feel was found to be significantly more intense with core granules with particle sizes ≥ 200 μm. Since ODTs may contain taste-masked particles, palatability of ODTs containing coated core granules was also evaluated. Although coating with polymers impairs palatability, it was improved by coating the outer layer with d-mannitol. The effects on palatability of materials constituting core granules were also evaluated, with reduced rough mouth feel observed with core granules composed of water-soluble additives. Based on these data, receiver operating characteristic analysis was performed to determine the threshold VAS scores at which the subjects felt roughness and discomfort. In addition, the threshold particle size of the core granule contained within the ODT required for feeling roughness was determined to be 244 μm. This study elucidated the effect of the properties of masking particles on the rough mouth feel and palatability of ODTs. PMID:25681720

  12. Bioequivalence assay between orally disintegrating and conventional tablet formulations in healthy volunteers.

    PubMed

    Armando, Yara Popst; Schramm, Simone Grigoleto; Silva, Marina de Freitas; Kano, Eunice Kazue; Koono, Eunice Emiko Mori; Porta, Valentina; Serra, Cristina Helena dos Reis

    2009-01-21

    The purpose of this study was to evaluate bioequivalence of two commercial 8 mg tablet formulations of ondansetrona available in the Brazilian market. In this study, a simple, rapid, sensitive and selective liquid chromatography-tandem mass spectrometry method is described for the determination of ondansetron in human plasma samples. The method was validated over a concentration range of 2.5-60 ng/ml and used in a bioequivalence trial between orally disintegrating and conventional tablet ondansetron formulations, to assess its usefulness in this kind of study. Vonau flash (Biolab Sanus Farmacêutica, Brazil, as test formulations) and Zofran (GlaxoSmithKline, Brazil, as reference formulation) were evaluated following a single 8 mg dose to 23 healthy volunteers of both genders. The dose was administered after an overnight fast according to a two-way crossover design. Bioequivalence between the products was determinated by calculating 90% confidence interval (90% CI) for the ratio of C(max), AUC(0-t) and AUC(0-infinity) values for the test and reference products, using logarithmically transformed data. The 90% confidence interval for the ratio of C(max) (87.5-103.8%), AUC(0-t) (89.3-107.2%) and AUC(0-infinity) (89.7-106.0%) values for the test and reference products is within the 80-125% interval, proposed by FDA, EMEA and ANVISA. It was concluded that two ondansetron formulations are bioequivalent in their rate and extent of absorption. PMID:18848869

  13. Increased dissolution rate and oral bioavailability of hydrophobic drug glyburide tablets produced using supercritical CO₂ silica dispersion technology.

    PubMed

    Guan, Jibin; Han, Jihong; Zhang, Dong; Chu, Chunxia; Liu, Hongzhuo; Sun, Jin; He, Zhonggui; Zhang, Tianhong

    2014-04-01

    The aim of this study was to design a silica-supported solid dispersion of a water-insoluble drug, glyburide, to increase its dissolution rate and oral absorption using supercritical fluid (SCF) technology. DSC and PXRD results indicated that the encapsulated drug in the optimal solid dispersion was in an amorphous state and the product was stable for 6 months. Glyburide was adsorbed onto the porous silica, as confirmed by the SEM images and BET analysis. Furthermore, FT-IR spectroscopy confirmed that there was no change in the chemical structure of glyburide after the application of SCF. The glyburide silica-based dispersion could also be compressed into tablet form. In vitro drug release analysis of the silica solid dispersion tablets demonstrated faster release of glyburide compared with the commercial micronized tablet. In an in vivo test, the AUC of the tablets composed of the new glyburide silica-based solid dispersion was 2.01 times greater than that of the commercial micronized glyburide tablets. In conclusion, SCF technology presents a promising approach to prepare silica-based solid dispersions of hydrophobic drugs because of its ability to increase their release and oral bioavailability. PMID:24184803

  14. Mucoadhesive elementary osmotic pump tablets of trimetazidine for controlled drug delivery and reduced variability in oral bioavailability.

    PubMed

    Alam, Naushad; Beg, Sarwar; Rizwan, Mohammad; Ahmad, Akifa; Ahmad, Farhan Jalees; Ali, Asgar; Aqil, Mohammad

    2015-04-01

    The objectives of this work was preparation and evaluation of the mucoadhesive elementary osmotic pump tablets of trimetazidine hydrochloride to achieve desired controlled release action and augmentation of oral drug absorption. The drug-loaded core tablets were prepared employing the suitable tableting excipients and coated with polymeric blend of ethyl cellulose and hydroxypropyl methylethylcellulose E5 (4:1). The prepared tablets were characterized for various quality control tests and in vitro drug release. Evaluation of drug release kinetics through model fitting suggested the Fickian mechanism of drug release, which was regulated by osmosis and diffusion as the predominant mechanism. Evaluation of mucoadhesion property using texture analyzer suggested good mucoadhesion potential of the developed osmotic systems. Solid state characterization using Fourier-transform infrared spectroscopy, differential scanning calorimetry and powder X-ray diffraction spectroscopy confirmed the absence of any physiochemical incompatibilities between drug and excipients. Scanning electron microscopy analysis showed the smooth surface appearance of the coated tablets with intact polymeric membrane without any fracture. In vivo pharmacokinetic studies in rabbits revealed 3.01-fold enhancement in the oral bioavailability vis-à-vis the marketed formulation (Vastarel MR®). These studies successfully demonstrate the bioavailability enhancement potential of the mucoadhesive elementary osmotic pumps as novel therapeutic systems for other drugs too. PMID:24669975

  15. Effect of food on the comparative pharmacokinetics of modified-release morphine tablet formulations: Oramorph SR and MST Continus

    PubMed Central

    DRAKE, J.; KIRKPATRICK, C. T.; ALIYAR, C. A.; CRAWFORD, F. E.; GIBSON, P.; HORTH, C. E.

    1996-01-01

    The relative bioavailability and pharmacokinetic profiles of Oramorph SR (OSR) and MST Continus (MST), were evaluated by a randomized, four-way cross-over study in 24 healthy, male volunteers given single oral (30 mg) doses whilst fasting or after a high-fat breakfast. Mean Cmax, tmax, AUC(0,24h), AUC and tlag were significantly greater in fed compared with fasting subjects. Overall relative bioavailability of the two formulations (log AUC), was within the acceptable 80–125% limits for bioequivalence both fed and fasting. Mean fasting Cmax for OSR was greater than MST (P<0.05) but there was no difference between formulations in mean fed Cmax. No statistically significant difference between OSR and MST was found for other parameters nor in the incidence of adverse events. These results suggest that OSR and MST are bioequivalent and that if patients were to transfer between formulations, dosage adjustment would be unnecessary, irrespective of their meal schedules or food intake. PMID:8735684

  16. Oral liquid L-thyroxine (L-t4) may be better absorbed compared to L-T4 tablets following bariatric surgery.

    PubMed

    Pirola, Ilenia; Formenti, Anna M; Gandossi, Elena; Mittempergher, Francesco; Casella, Claudio; Agosti, Barbara; Cappelli, Carlo

    2013-09-01

    Drug malabsorption is a potential concern after bariatric surgery. We present four case reports of hypothyroid patients who were well replaced with thyroxine tablets to euthyroid thyrotropin (TSH) levels prior to Roux-en-Y gastric bypass surgery. These patients developed elevated TSH levels after the surgery, the TSH responded reversibly to switching from treatment with oral tablets to a liquid formulation. PMID:23824980

  17. Formulation and In-vitro Evaluation of Orally Disintegrating Tablets of Olanzapine-2-Hydroxypropyl-β-Cyclodextrin Inclusion Complex

    PubMed Central

    Ajit Shankarrao, Kulkarni; Dhairysheel Mahadeo, Ghadge; Pankaj Balavantrao, Kokate

    2010-01-01

    The aim of this study was to design orally disintegrating tablets of Olanzapine and to complex Olanzapine with 2-hydroxypropyl-β- cyclodextrin with special emphasis on disintegration and dissolution studies. Phase solubility studies demonstrated the formation of 1:1 molar inclusion complex by kneading method. Tablets were prepared by using superdisintegrants namely, sodium starch glycolate, croscarmellose sodium, crospovidone, tulsion 339, and indion 414. Complex was characterized using infrared spectroscopy, drug content estimation, saturated solubility study, diffrerential scanning calorimetry and X-ray diffractometry. 5% w/w croscarmellose sodium showed the minimum disintegration time 39 ± 1.76 sec and in-vitro drug release 99.19 ± 0.18% within 6 min. In general, solubility of Olanzapine can be improved by complexing with 2-hydroxypropyl-β- cyclodextrin. Croscarmellose sodium can be used for faster disintegration of tablets. PMID:24381598

  18. Intra-gastric performance and bioavailability study of a new per-oral bioadhesive Verapamil HCl matrix tablet in dogs.

    PubMed

    Yassin, Alaa Eldeen B; Alkhaled, F; al-Suwayeh, S; Elkheshen, S

    2003-09-01

    In a previous study, we developed a per-oral extended--release bioadhesive matrix tablet for verapamil HCl (VP). The system combined both strong bioadhesion and sustained release properties in vitro. The purpose of this study is to evaluate the in vivo performance of the prepared bioadhesive tablets (B). The conduction of a periodic X-ray imaging of the abdomen of beagle dogs, after administration of B containing 12% barium sulfate, was used to evaluate the intra-gastric performance. The VP concentrations in blood samples taken at specified times after oral administration of B to fasted beagle dogs were determined and compared with those obtained after administration of a commercial sustained release VP tablets (Manidon 120 R). The X-ray images showed that bioadhesive tablets remained almost at the same place in the stomach for at least 6 hours while it disappeared after 1 hour in case of the control tablets. No statistical difference was seen between the Cmax, tmax, AUC, t1/2, and MRT for B compared to Manidon. The Cmax was found to be 51.4 +/- 15.5 and 48.6 +/- 17.9 (ng/ml) for Manidon and B, respectively and the corresponding tmax were 7.0 +/- 1.9 and 6.0 +/- 0, respectively. The AUCO-. for Manidon and B were 949.84 +/- 245.11 and 722.92 +/- 144.42 ng.h/ml, respectively. So, the prepared B tablets can be considered bioequivalent to the commercial Manidon Retard product. PMID:14677272

  19. Per-oral extended-release bioadhesive tablet formulation of verapamil HCl.

    PubMed

    Elkheshen, Seham; Yassin, Alaa Eldeen B; Alkhaled, Fayza

    2003-06-01

    The objective of this study was to formulate a hydrogel-forming bioadhesive drug delivery system for oral administration of verapamil HCl (VP). This system is a non-distintegrating gastro-retentive tablet to allow continuous slow release of VP in the stomach medium where it is more soluble. Different formulate of VP tablets were prepared by compression using various proportions of hydroxypropyl cellulose (HPC) and carbopol 934p (CP). The effect of polymer concentration on the release profile, water uptake and in vitro bioadhesion was studied. Five formulae (F3-F7) exhibited slow release profiles. Formulations F6 (40% HPC and 30% CP) and F7 (40% HPC and 40% CP) had the slowest. They showed 63.6 and 52.2% drug release, respectively, after 12 hours. The kinetic analysis of the release data demonstrated that the bigbest linearity were achieved when data fitted in Higuchi equation rather than zero or first order equations. They had n values close to 0.5 that confirming their Higuchi diffusion. F3 showed the highest swelling index (101.2%), however, the detachment force was intermediate (1.427 N/cm2). Formulae (F4-F7) showed relatively strong in-vitro bioadhesive force. They had detachment forces higher than 1 N/cm2. In general, a delay in drug release and an increase in the in-vitro bioadhesion was seen with the increase in both polymer concentrations. The in vitro data revealed that Formulae F4-F7 served the dual purpose of bioadhesion and sustained release. PMID:14526657

  20. Effect of a high-fat meal on the pharmacokinetics of 300-milligram posaconazole in a solid oral tablet formulation.

    PubMed

    Kersemaekers, Wendy M; Dogterom, Peter; Xu, Jialin; Marcantonio, Eugene E; de Greef, Rik; Waskin, Hetty; van Iersel, Marlou L P S

    2015-01-01

    Posaconazole in oral suspension must be taken multiple times a day with food (preferably a high-fat meal) to ensure adequate exposure among patients. We evaluated the effect of food on the bioavailability of a new delayed-release tablet formulation of posaconazole at the proposed clinical dose of 300 mg once daily in a randomized, open-label, single-dose, two-period crossover study with 18 healthy volunteers. When a single 300-mg dose of posaconazole in tablet form (3 tablets × 100 mg) was administered with a high-fat meal, the posaconazole area under the concentration-time curve from 0 to 72 h (AUC0-72) and maximum concentration in plasma (Cmax) increased 51% and 16%, respectively, compared to those after administration in the fasted state. The median time to Cmax (Tmax) shifted from 5 h in the fasted state to 6 h under fed conditions. No serious adverse events were reported, and no subject discontinued the study due to an adverse event. Six of the 18 subjects reported at least one clinical adverse event; all of these events were mild and short lasting. The results of this study demonstrate that a high-fat meal only modestly increases the mean posaconazole exposure (AUC), ∼1.5-fold, after administration of posaconazole tablets, in contrast to the 4-fold increase in AUC observed previously for a posaconazole oral suspension given with a high-fat meal. PMID:25824210

  1. A Pharmacokinetic Study Comparing Eslicarbazepine Acetate Administered Orally as a Crushed or Intact Tablet in Healthy Volunteers.

    PubMed

    Sunkaraneni, Soujanya; Kharidia, Jahnavi; Schutz, Ralph; Blum, David; Cheng, Hailong

    2016-07-01

    The relative bioequivalence of crushed versus intact eslicarbazepine acetate (ESL) tablets (800 mg) administered orally in healthy adults was evaluated in an open-label, randomized, 2-period crossover study with a 5-day washout between treatments. Sample blood levels of eslicarbazepine and (R)-licarbazepine were determined; pharmacokinetic parameters were derived for eslicarbazepine. Bioequivalence was established if the 90% confidence intervals (CIs) for the geometric mean treatment ratios of eslicarbazepine AUC(0-∞) and Cmax were within the prespecified 80%-125% range. Twenty-seven subjects in the intent-to-treat population (n = 28) completed both treatment periods. Eslicarbazepine exposure measures were similar for crushed versus intact ESL tablets: average Cmax , 11 700 versus 11 500 ng/mL; AUC(0-∞) , 225 000 versus 234 000 ng·h/mL; AUC(0-last) , 222 000 versus 231 000 ng·h/mL, respectively. Geometric least squares mean ratios (90%CIs) comparing eslicarbazepine exposure measures were within the 80%-125% range (Cmax , 102.63% [97.07%-108.51%]; AUC(0-∞) , 96.72% [94.36%-99.13%]; AUC0-last , 96.69% [94.24%-99.21%]). In conclusion, ESL administered orally as a crushed tablet sprinkled on applesauce, or intact were bioequivalent in healthy subjects. Eslicarbazepine bioavailability was not significantly altered by crushing, indicating that ESL tablets can be administered intact or crushed. PMID:27249205

  2. Metabolism and pharmacokinetics of major polyphenol components in rat plasma after oral administration of total flavonoid tablet from Anemarrhenae Rhizoma.

    PubMed

    Xie, Yuan-Yuan; Wang, Xiu-Ming; Wang, Si-Huan; Wang, Yi-Ming; Tian, Hui-Fang; Yuan, Yong-Sheng; Li, Hong-Yan; Liang, Qiong-Lin; Luo, Guo-An

    2016-07-15

    Total flavonoid tablet from Anemarrhenae Rhizoma (Zhimu tablet), which was made of total polyphenol components extracted from the dried rhizome of Anemarrhena asphodeloides Bge. (Zhimu in Chinese), is a novel traditional Chinese medicine prescribed for the treatment of diabetes. Mangiferin (MF) and neomangiferin (NMF) are the two main components detected and determined in Zhimu tablet, accounting for 8.9% of the total weight of each tablet. In the present study, high performance liquid chromatography (HPLC) coupled with time-of-flight (TOF) tandem mass spectrometry (MS) was applied to characterize the metabolites of MF and NMF in rat plasmas collected at different time points after oral administration of Zhimu tablet at a dose of 3.63g/kg (corresponding to 270mg/kg MF). Accurate mass measurement was used to determine the elemental composition of metabolites and thus to confirm the proposed structures of identified metabolites. Time points of appearance of some metabolites, such as isomers, were also taken into account during the structure confirmation. A total of 21 potential metabolites were found in rat plasma at different time points, and the metabolic pathways in vivo were involved in hydrolysis, methylation, glucuronide conjugation, glycoside conjugation, sulphation, dehydration and isomerisation. Furthermore, a selective and accurate LC-MS assay method was developed and validated for the quantification of MF in plasma. Semi-quantification of main conjugated metabolites was also performed in order to describe the dynamic metabolism profiles of polyphenol components in Zhimu tablet. MF concentration in plasma reached 1.36±0.47μgmL(-1) about 5.0h after oral administration of Zhimu tablet, which showed a 3.24- and 4.91-fold increase in plasma maximum concentration and area under the concentration-time curve (AUC) from 0 to 24h of MF compared with those for rats administered with free MF, respectively. The results indicated that the pharmacokinetic processes and

  3. Combination effect of physical and gustatory taste masking for propiverine hydrochloride orally disintegrating tablets on palatability.

    PubMed

    Matsui, Rakan; Uchida, Shinya; Namiki, Noriyuki

    2015-01-01

    Orally disintegrating tablets (ODTs) containing propiverine hydrochloride (which is extremely bitter and leaves a feeling of numbness in the mouth) were prepared with a combined use of physical and organoleptic taste masking. Propiverine-loaded masking particles (PLMPs) were prepared with different amounts of gastric-soluble coatings as physical masking. ODTs without organoleptic masking were prepared by mixing each group of PLMPs with Ludiflash®, crospovidone, and magnesium stearate. ODTs with organoleptic masking were also prepared by addition of L-menthol, aspartame, thaumatin, and cinnamon. Fifteen-minute dissolution of propiverine in solutions with pH 1.2 was ≥ 85% for all ODTs, whereas that in pH 6.8 solutions was ≤ 85% and increased with physical masking. A single blind randomized crossover trial was conducted. Ten healthy volunteers were asked to quantify the bitterness, numbness, and overall palatability using a 100-mm visual analog scale (VAS) at the period of disintegration as well as 1 and 5 min later. VAS scores of bitterness, numbness, and overall palatability improved along with increasing amounts of physical masking, and the effects persisted for 5 min. VAS scores for numbness increased over time regardless of the amount of physical masking. Bitterness, numbness, and overall palatability were significantly improved by organoleptic masking if the amount of physical masking was small. Combined use of physical and organoleptic masking is useful for improving palatability of ODTs containing propiverine. PMID:25744453

  4. Orally disintegrating vardenafil tablets for the treatment of erectile dysfunction: efficacy, safety, and patient acceptability

    PubMed Central

    Green, Roger; Hicks, Rodney W

    2011-01-01

    Background: Erectile dysfunction (ED) is a well-documented medical condition that is expected to increase significantly over the next several decades, especially as men live longer and the prevalence of diabetes and cardiovascular diseases increase. Pharmacology agents are often the first line treatment approach. Newer solid dosage forms, known as orally disintegrating tablets (ODT), are now available as one treatment option. Objectives: To review the drug delivery mechanisms of ODTs in general and to review safety and efficacy of vardenafil ODT (a PDE-5 inhibitor) as a treatment option for management of ED. Method: Literature reviews were performed of pharmaceutical dosage forms and the POTENT I (n = 358 subjects) and POTENT II (n = 337 subjects) studies that investigated vardenafil ODT. Results: Vardenafil ODT has been successfully used in multiple age groups and in multiple settings with men from various ethnic backgrounds. Efficacy of vardenafil ODT, as measured using the International Index of Erectile Function (IIEF-EF) and from the Sexual Encounter Profile (SEP) was significantly greater than placebo (P < 0.0001) at 12 weeks. Safety profiles were similar to film-coated dosage forms with no patient deaths reported. Conclusion: Vardenafil ODT offers a convenient, ready-to-use approach for combating ED. Safety concerns are similar to other PDE-5 inhibitors and practitioners should counsel patients accordingly. PMID:21573049

  5. Biopharmaceutical characterization of oral theophylline and aminophylline tablets. Quantitative correlation between dissolution and bioavailability studies.

    PubMed

    Varshosaz, J; Ghafghazi, T; Raisi, A; Falamarzian, M

    2000-09-01

    Considering the narrow therapeutic index of theophylline and the low range between the safe and toxic serum concentrations of this drug, the study of its pharmacokinetic properties is necessary. However, considering the time consuming and expensive in vivo tests, quantitative correlation between in vivo bioavailability and in vitro dissolution tests can be used routinely in quality control tests of these drug products to predict the in vivo pharmacokinetic parameters. For this reason healthy human volunteers were used for in vivo studies and serum samples were analyzed by a fluorescence polarization immunoassay analysis (FPIA) method. The results showed that an open one compartmental model could best describe the pharmacokinetic properties of orally administered theophylline and aminophylline tablets. Linear regression analysis by least-square method showed a good correlation between some in vivo and in vitro parameters obtained from dissolution studies by rotating basket and paddle methods. D(30)% (percentage of drug dissolved in vitro after 30 min) and F(0.5)% (drug absorbed in vivo after half an hour calculated by Wagner-Nelson equation) showed best correlation (r=0. 99036). C(max) (maximum serum concentration) of this drug also correlates well with t(25%) (time required to dissolve 25% of the drug). The calculated correlation coefficients could best predict the actual values of some pharmacokinetic parameters; AUC(0-->infinity), AUC(0-->1), F(0.5)% and C(max). PMID:10962242

  6. The prediction of the palatability of orally disintegrating tablets by an electronic gustatory system.

    PubMed

    Nakamura, Hideshi; Uchida, Shinya; Sugiura, Takeshi; Namiki, Noriyuki

    2015-09-30

    In this study, the human gustatory palatability sensation of taste-masked famotidine and amlodipine orally disintegrating tablets (ODTs) was quantitatively predicted by an electronic gustatory system (α-Astree e-Tongue). Furthermore, its use in formulation design was evaluated. The famotidine- and amlodipine-containing ODTs, which were bitter- and highly bitter-tasting, respectively, were prepared using a physical (granules spray-coated with ethyl cellulose) or organoleptic (the addition of a sweetener and a flavor) masking method and combinations thereof. The taste-masking effects of different masking methods on the ODTs were investigated in a human gustatory sensation test. In the test, volunteers scored the overall palatability using a 100mm visual analog scale (VAS). The electronic gustatory system was evaluated using the Euclidean distance (the distance between each drug-containing ODT and its corresponding placebo) and partial least squares (PLS) regression analysis of the sensor response values. A good linear relationship was observed between each ODT's Euclidean distance analysis, PLS regression analysis, and clinical VAS scores. Cross-validation verification of each analysis confirmed the model's predictive power. This study suggests that the α-Astree can quantitatively evaluate physical and organoleptic taste masking and that the palatability of unknown formulations can be predicted by Euclidean distance and PLS regression data analysis. PMID:26216412

  7. Day-to-day variations during clinical drug monitoring of morphine, morphine-3-glucuronide and morphine-6-glucuronide serum concentrations in cancer patients. A prospective observational study

    PubMed Central

    Klepstad, Pål; Hilton, Priscilla; Moen, Jorunn; Kaasa, Stein; Borchgrevink, Petter C; Zahlsen, Kolbjørn; Dale, Ola

    2004-01-01

    Background The feasibility of drug monitoring of serum concentrations of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) during chronic morphine therapy is not established. One important factor relevant to drug monitoring is to what extent morphine, M6G and M3G serum concentrations fluctuate during stable morphine treatment. Methods We included twenty-nine patients admitted to a palliative care unit receiving oral morphine (n = 19) or continuous subcutaneous (sc) morphine infusions (n = 10). Serum concentrations of morphine, M6G and M3G were obtained at the same time on four consecutive days. If readmitted, the patients were followed for another trial period. Day-to-day variations in serum concentrations and ratios were determined by estimating the percent coefficient of variation (CV = (mean/SD) ×100). Results The patients' median morphine doses were 90 (range; 20–1460) mg/24 h and 135 (range; 30–440) mg/24 h during oral and sc administration, respectively. Intraindividual fluctuations of serum concentrations estimated by median coefficients of day-to-day variation were in the oral group for morphine 46%, for M6G 25% and for M3G 18%. The median coefficients of variation were lower in patients receiving continuous sc morphine infusions (morphine 10%, M6G 13%, M3G 9%). Conclusion These findings indicate that serum concentrations of morphine and morphine metabolites fluctuate. The fluctuations found in our study are not explained by changes in morphine doses, administration of other drugs or by time for collection of blood samples. As expected the day-to-day variation was lower in patients receiving continuous sc morphine infusions compared with patients receiving oral morphine. PMID:15461818

  8. Application of water-insoluble polymers to orally disintegrating tablets treated by high-pressure carbon dioxide gas.

    PubMed

    Ito, Yoshitaka; Maeda, Atsushi; Kondo, Hiromu; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

    2016-09-10

    The phase transition of pharmaceutical excipients that can be induced by humidifying or heating is well-known to increase the hardness of orally disintegrating tablets (ODTs). However, these conditions are not applicable to drug substances that are chemically unstable against such stressors. Here, we describe a system which enhances the hardness of tablets containing water-insoluble polymers by using high-pressure carbon dioxide (CO2). On screening of 26 polymeric excipients, aminoalkyl methacrylate copolymer E (AMCE) markedly increased tablet hardness (+155N) when maintained in a high-pressure CO2 environment. ODTs containing 10% AMCE were prepared and treatment with 4.0MPa CO2 gas at 25°C for 10min increased the hardness to +30N, whose level corresponded to heating at 70°C for 720min. In addition, we confirmed the effects of CO2 pressure, temperature, treatment time, and AMCE content on the physical properties of ODTs. Optimal pressure of CO2 gas was considered to be approximately 3.5MPa for an AMCE formula, as excessive pressure delayed the disintegration of ODTs. Combination of high-pressure CO2 gas and AMCE is a prospective approach for increasing the tablet hardness for ODTs, and can be conducted without additional heat or moisture stress using a simple apparatus. PMID:27374202

  9. High-amylose sodium carboxymethyl starch matrices: development and characterization of tramadol hydrochloride sustained-release tablets for oral administration.

    PubMed

    Nabais, Teresa; Leclair, Grégoire

    2014-01-01

    Substituted amylose (SA) polymers were produced from high-amylose corn starch by etherification of its hydroxyl groups with chloroacetate. Amorphous high-amylose sodium carboxymethyl starch (HASCA), the resulting SA polymer, was spray-dried to obtain an excipient (SD HASCA) with optimal binding and sustained-release (SR) properties. Tablets containing different percentages of SD HASCA and tramadol hydrochloride were produced by direct compression and evaluated for dissolution. Once-daily and twice-daily SD HASCA tablets containing two common dosages of tramadol hydrochloride (100 mg and 200 mg), a freely water-soluble drug, were successfully developed. These SR formulations presented high crushing forces, which facilitate further tablet processing and handling. When exposed to both a pH gradient simulating the pH variations through the gastrointestinal tract and a 40% ethanol medium, a very rigid gel formed progressively at the surface of the tablets providing controlled drug-release properties. These properties indicated that SD HASCA was a promising and robust excipient for oral, sustained drug-release, which may possibly minimize the likelihood of dose dumping and consequent adverse effects, even in the case of coadministration with alcohol. PMID:25006518

  10. A bioequivalence study of levothyroxine tablets versus an oral levothyroxine solution in healthy volunteers.

    PubMed

    Yannovits, N; Zintzaras, E; Pouli, A; Koukoulis, G; Lyberi, S; Savari, E; Potamianos, S; Triposkiadis, F; Stefanidis, I; Zartaloudis, E; Benakis, A

    2006-01-01

    Probably for genetic reasons a substantial part of the Greek population requires Levothyroxine treatment. Since commercially available Levothyroxine was first marketed, the manufacture and storage of the drug in tablet form has been complicated and difficult; and as cases of therapeutic failure have frequently been reported following treatment with this medicinal agent, quality control is an essential factor. Due to the unreliability of Levothyroxine-based commercial products, in the present study we decided to follow the Food and Drug Administration (FDA) guidelines*, and use a Levothyroxine solution as reference product. The bioavailability of the Levothyroxine sodium tablet formulation THYROHORMONE/Ni-The Ltd (0.2 mg/tab) and that of a reference oral solution (0.3 mg/100 ml) under fasting conditions were compared in an open, randomized, single-dose two-way crossover study. Twenty four healthy Caucasian volunteers (M/F=15/9, mean age=32.9+/-7.4yr) participated in the study. Bioavailability was assessed by pharmacokinetic parameters such as the area under plasma concentration-time curve from time zero up to the measurable last time point (AUC(last)) and the maximum plasma concentration (Cmax). Heparinized venous blood samples were collected pre-dose and up to a 48-hour period post-dose. Levothyroxine sodium in plasma samples was assayed by a validated electrochemiluninescent immunoassay technique. Statistical analysis showed that the post-dose thyrotropin-stimulating hormone (TSH) levels decreased significantly (p<0.05). Regarding Levothyroxine (T4), the point estimate of the test formulation to the reference formulation ratios (T/R) for AUC(last) and Cmax was 0.92 with 90% confidence limits (0.90, 0.94) and 0.93 with 90% confidence limits (0.91, 0.94), respectively. Regarding triiodo-L-thyronine (T3), the point estimate for the T/R ratios of AUC(last) and Cmax was 0.92 with 90% confidence limits (0.90, 0.95) and 0.94 with 90% confidence limits (0.92, 0

  11. Influence of Prosolv and Prosolv:Mannitol 200 direct compression fillers on the physicomechanical properties of atorvastatin oral dispersible tablets.

    PubMed

    Gowda, Veeran; Pabari, Ritesh M; Kelly, John G; Ramtoola, Zebunnissa

    2015-06-01

    The objective of the present study was to evaluate the influence of Prosolv® and Prosolv®: Mannitol 200 direct compression (DC) fillers on the physicomechanical characteristics of oral dispersible tablets (ODTs) of crystalline atorvastatin calcium. ODTs were formulated by DC and were analyzed for weight uniformity, hardness, friability, drug content, disintegration and dissolution. Three disintegration time (DT) test methods; European Pharmacopoeia (EP) method for conventional tablets (Method 1), a modification of this method (Method 2) and the EP method for oral lyophilisates (Method 3) were compared as part of this study. All ODTs showed low weight variation of <2.5%. Prosolv® only ODTs showed the highest tablet hardness of ∼ 73 N, hardness decreased with increasing mannitol content. Friability of all formulations was <1% although friability of Prosolv®:Mannitol ODTs was higher than for pure Prosolv®. DT of all ODTs was <30 s. Method 2 showed the fastest DT. Method 3 was non-discriminatory giving a DT of 13-15 s for all formulations. Atorvastatin dissolution from all ODTs was >60% within 5 min despite the drug being crystalline. Prosolv® and Prosolv®:Mannitol-based ODTs are suitable for ODT formulations by DC to give ODTs with high mechanical strength, rapid disintegration and dissolution. PMID:24397821

  12. 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

  13. Formulation and bioequivalence of two Valsartan/Amlodipine immediate release tablets after a single oral administration.

    PubMed

    Zaid, Abdel Naser; Natur, Salam; Qaddomi, Aiman; Abualhasan, Murad; Al-Ramahi, Rowa; Shraim, Naser; Khammash, Saed; Jaradat, Nidal

    2014-07-01

    The aim of this study was to formulate a film-coated Valsartan/Amlodipine (VS/AM) immediate release tablets and to evaluate their in vivo release profile. VS/AM core tablets were manufactured using dry granulation method. Opadry aqueous coating dispersion was used as film coating material. Dissolution of the film coated tablets was tested in 900 ml of 0.5% SLS media, bioequivalence of tablets was tested by comparisons against the reference brand product. The ICH guidelines were used to evaluate the stability of the obtained tablets. The coated tablets were subjected to gastric pH, and drug release was analyzed using HPLC system to evaluate the efficiency of the film coat. The coated tablets had no defects. VS/AM release met the FDA guidelines for bioequivalence studies. Statistical comparison of the main pharmacokinetic parameters showed no significant difference between test and reference. These findings suggest that aqueous film coating with Opadry system is an easy and economical approach for preparing stable film coated VS/AM tablets without compromising their in vivo drugs release. PMID:25015436

  14. Pharmacokinetic profile of rizatriptan 10-mg tablet and 10-mg orally disintegrating tablet administered with or without water in healthy subjects: an open-label, randomized, single-dose, 3-period crossover study.

    PubMed

    Swan, Suzanne K; Alcorn, Harry; Rodgers, Anthony; Hustad, Carolyn M; Ramsey, Karen E; Woll, Susan; Skobieranda, Franck

    2006-02-01

    This open-label, 3-period crossover study compared the plasma concentration profiles of rizatriptan tablet, orally disintegrating tablet with water (ODTc), and ODT without water (ODTs) in 24 healthy volunteers aged 18 to 45 years. At each period, subjects received a single dose of either 10-mg rizatriptan tablet, 10-mg rizatriptan ODTs, or 10-mg rizatriptan ODTc. The authors hypothesized that ODTc has a greater geometric mean AUC(0-2h) than ODTs and that ODTc has a greater geometric mean AUC(0-1h) than tablet. A secondary end point was to compare the time of occurrence of the maximum rizatriptan plasma concentration (t(max)) of each dosing method. ODTc had a statistically significantly greater geometric mean AUC(0-2h) compared with ODTs (33.84 h x ng/mL vs 18.83 h x ng/mL; P < .001). ODTc had a slightly, but not statistically significantly, greater geometric mean AUC(0-1h) compared with rizatriptan tablet (17.07 h x ng/mL vs 13.32 h x ng/mL). The median t(max) was 0.67 hours for ODTc and tablet and 1.33 hours for ODTs. ODTc showed a slightly, but not significantly, faster rate of absorption compared with tablet. ODTs with water had a faster rate of absorption than ODTc. Future studies are needed to determine whether this pharmacokinetic difference produces differential efficacy in a clinical setting. PMID:16432269

  15. Population pharmacokinetics of levodopa in subjects with advanced Parkinson's disease: levodopa-carbidopa intestinal gel infusion vs. oral tablets

    PubMed Central

    Othman, Ahmed A; Dutta, Sandeep

    2014-01-01

    Aims Levodopa-carbidopa intestinal gel (LCIG) provides continuous levodopa-carbidopa delivery through intrajejunal infusion. This study characterized the population pharmacokinetics of levodopa following a 16 h jejunal infusion of LCIG or frequent oral administration of levodopa-carbidopa tablets (LC-oral) in subjects with advanced Parkinson's disease (PD). Methods A non-linear mixed-effects model of levodopa pharmacokinetics was developed using serial plasma concentrations from an LCIG phase 1 study and a phase 3 double-blind, double-dummy study of the efficacy and safety of LCIG compared with LC-oral in advanced PD patients (n = 68 for model development; 45 on LCIG and 23 on LC-oral). The final model was internally evaluated using stochastic simulations and bootstrap and externally evaluated using sparse pharmacokinetic data from 311 subjects treated in a long term safety study of LCIG. Results The final model was a two compartment model with a transit compartment for absorption, first order elimination, bioavailability for LCIG (97%; confidence interval = 95% to 98%) relative to LC-oral, different first order transit absorption rate constants (LCIG = 9.2 h–1 vs. LC-oral = 2.4 h–1; corresponding mean absorption time of 7 min for LCIG vs. 25 min for LC-oral) and different residual (intra-subject) variability for LCIG (15% proportional error, 0.3 μg ml−1 additive error) vs. LC-oral (29% proportional error, 0.59 μg ml−1 additive error). Estimated oral clearance and steady-state volume of distribution for levodopa were 24.8 l h−1 and 131 l, respectively. Conclusions LCIG administration results in faster absorption, comparable levodopa bioavailability and significantly reduced intra-subject variability in levodopa concentrations relative to LC-oral administration. PMID:24433449

  16. Preparation and characterisation of Kolliphor® P 188 and P 237 solid dispersion oral tablets containing the poorly water soluble drug disulfiram.

    PubMed

    Ramadhani, Nisrina; Shabir, Mehwish; McConville, Christopher

    2014-11-20

    The oral route of administration is the most common and preferred route of drug delivery due to its ease of administration, cost-effectiveness and flexibility in design. However, limited aqueous solubility of the active pharmaceutical ingredient can result in poor bioavailability, which is a major issue for the pharmaceutical industry. Increasing numbers of new drugs are falling into class II of the Biopharmaceutical Classification System (BCS), where they have a low solubility and high tissue permeability, meaning that bioavailability is solubility dependent. Here we demonstrate the development and characterisation of solid dispersion oral tablets, containing the poorly water-soluble drug disulfiram, prepared using both the hot melt and solvent evaporation methods and manufactured from two different polymers, Kolliphor(®) P 188 and P 237, specifically designed for the manufacture of solid dispersions. This paper demonstrates that the disulfiram solid dispersions tablets have an enhanced release rate of disulfiram compared to the control tablets. The Kolliphor(®) P 188 polymer control tablets released approximately 48.8% of their disulfiram content over 8h, with the solvent evaporated tablets releasing approximately 65.8%, while the 60 and 80 °C hot melt tablets released approximately 73.2 and 100% of their disulfiram content respectively. A similar trend was seen with Kolliphor(®) P 237 as the control tablets released approximately 50.5% of their disulfiram content over 8h, while the solvent evaporated tablets released approximately 79.5% and the 60 and 80 °C hot melt tablets released 100.2 and 100.3% respectively. Depending on what method and polymer is used to manufacture the solid dispersions the disulfiram is either maintained completely or partially in its amorphous state and it is this which enhances its solubility and release rate from the tablets. The disulfiram in the Kolliphor(®) P 188 solvent evaporated and 60 °C hot melt tablets retained 50

  17. Preparation of Orally Disintegrating Tablets Containing Powdered Tea Leaves with Enriched Levels of Bioactive Compounds by Means of Microwave Irradiation Technique.

    PubMed

    Tanaka, Hironori; Iwao, Yasunori; Izumikawa, Masahiro; Sano, Syusuke; Ishida, Hitoshi; Noguchi, Shuji; Itai, Shigeru

    2016-01-01

    In the present study, a microwave treatment process has been applied to prepare orally disintegrating tablets (ODTs) containing powdered tea leaves with enriched levels of the anti-inflammatory compounds such as chafuroside A (CFA) and chafuroside B (CFB). The use of distilled water as the adsorbed and granulation solvents in this preparation process afforded tablets with a long disintegration time (more than 120 s). The CFA and CFB contents of these tablets did not also change after 4 min of microwave irradiation due to the tablet temperature, which only increased to 100°C. In contrast, the tablet temperature increased up to 140°C after 3 min of microwave irradiation when a 1.68 M Na2HPO4 solution instead of distilled water. Notably, the disintegration time of these tablets was considerably improved (less than 20 s) compared with the microwave-untreated tablets, and there were 7- and 11-fold increases in their CFA and CFB contents. In addition, the operational conditions for the preparation of the tablets were optimized by face-centered composite design based on the following criteria: tablet hardness greater than 13 N, disintegration time less than 30 s and friability less than 0.5%. The requirements translated into X1 (the amount of granulation solvent), X2 (tableting pressure) and X3 (content of the powdered tea leaves) values of 45%, 0.43 kN and 32%, respectively, and the ODTs containing powdered tea leaves prepared under these optimized conditions were found to show excellent tablet properties and contain enriched levels of CFA and CFB. PMID:27581633

  18. [Pharmacokinetic study on peoniflorin, astilbin, rosmarinic acid, isofraxidin and liquiritin in rat blood after oral administration of shaolin xiaoyin tablets].

    PubMed

    Zhao, Rui-Zhi; Wang, Yin-Jie; Feng, Li-Min; Lu, Chuan-Jian

    2014-07-01

    To establish a method for the determination of astilbin, peoniflorin, rasmarinci acid, isofraxidin and liquiritin contained in Shaolin Xiaoyin tablets, in order to lay a foundation for designing late-stage dosage forms and clinical medication schemes. In this paper, efforts were made to establish a method for the determination of the blood concentration of the five components and study the in vivo pharmacokinetics in rats. The blood concentration was determined by HPLC. Phenomenex C18 column (4.6 mm x 250 mm, 5 microm) was adopted and eluted with methanol-acetonitrile-0.05% formic acid, the flow rate was 0.8 mL x min(-1), and the wavelength was 275 nm. The samples were processed by the solid phase extraction method. After oral administration of Shaoling Xiaoyin tablets, the rat bloods were collected at different time points to determine the blood concentrations. The experimental results showed that the baseline separation could be adopted for the five components, and astilbin, peoniflorin, rasmarinci acid, isofraxidin and liquiritin showed good linear relations within ranges of 2.48-248, 0.213 6-21.36, 0.531-53.1, 0.704-70.4, 0.253-25.3 mg x L(-1). All the five components could be absorbed in blood and excreted quickly. The method established in this paper is rapid and accurate, and could be used for in vivo analysis on preparations containing similar components. The main components in Shaoling Xiaoyin tablets could be absorbed and excreted quickly, and thus suitable to be made into sustained release tablets. Common preparations are required to be taken for 4-6 times a day. PMID:25276982

  19. Differential pharmacokinetics and the brain distribution of morphine and ephedrine constitutional isomers in rats after oral administration with Keke capsule using rapid-resolution LC-MS/MS.

    PubMed

    Song, Yonggui; Su, Dan; Lu, Tulin; Mao, Chunqin; Ji, De; Liu, Yali; Wei, Binbin; Fan, Ronghua

    2014-02-01

    Opioid and ephedra alkaloids known as the active ingredients for Keke capsule, which is used to treat coughs and bronchial asthma, could have potential adverse effects on the central nervous system. Therefore, an efficient, sensitive rapid-resolution LC-MS/MS method for the simultaneous determination of morphine, ephedrine, and pseudoephedrine in rat plasma and brain tissue homogenate has been developed. The method was validated in the plasma and brain tissue samples, showed good linearity over a wide concentration range (r(2) > 0.99). The intra- and interday assay variability was less than 15% for all analytes, and the accuracy was between -8.8 and 5.7%. The study provided the pharmacokinetics profiles and the brain regional distribution of the three active alkaloids after oral administration of Keke capsule. The results also indicated that significant difference in pharmacokinetics parameters of the epimers was observed between ephedrine and pseudoephedrine. PMID:24318005

  20. Albizia procera gum as an excipient for oral controlled release matrix tablet.

    PubMed

    Pachuau, Lalduhsanga; Mazumder, Bhaskar

    2012-09-01

    The purpose of this research was to develop and evaluate controlled release matrix tablets of paracetamol based on natural gum exudates of Albizia procera. Procera gum was characterized of its properties like compressibility index, angle of repose, viscosity and moisture content. The interaction between the gum and paracetamol was also studied through differential scanning calorimetry (DSC) and FTIR spectroscopy. Matrix tablets were then prepared by wet granulation method with different concentrations of procera gum and hydroxypropyl methylcellulose (HPMC) and evaluated for their physical properties like weight variation, hardness, friability and content uniformity. Dissolution study was conducted to characterize release mechanism from the matrix system and data were fitted to various kinetic models. The mechanism of drug release from both types of matrix tablets was found to be anomalous type. Results from various evaluations suggested that A. procera gum could be used as drug release retardant in controlled release matrix systems. PMID:24751043

  1. 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. PMID:26212139

  2. Development and characterisation of sustained release solid dispersion oral tablets containing the poorly water soluble drug disulfiram.

    PubMed

    Shergill, Mandip; Patel, Mina; Khan, Siraj; Bashir, Ayesha; McConville, Christopher

    2016-01-30

    Administration of drugs via the oral route is the most common and preferred route due to its ease of administration, cost-effectiveness and flexibility in design. However, if the drug being administered has limited aqueous solubility it can result in poor bioavailability. Furthermore, the low pH of the stomach as well as enzymatic activity can result in drugs delivered via the oral route being rapidly metabolised and degraded. Here we demonstrate the development and characterisation of sustained release solid dispersion oral tablets, containing the poorly water-soluble drug disulfiram (DSF). The tablets, which are manufactured from two different polymers (Kolliphor(®) P 188 and P 237) specifically designed for the manufacture of solid dispersions and two different polymers (Kollidon(®) SR and HPMC) specifically designed to provide sustained release, can enhance the solubility of DSF, sustain its release, while protecting it from degradation in simulated gastric fluid (SGF). The paper demonstrates that when using the hot melt method at 80°C the DSF loading capacity of the Kolliphor(®) P 188 and P 237 polymers is approximately 43 and 46% respectively, with the DSF completely in an amorphous state. The addition of 80% Kollidon(®) SR to the formulation completely protected the DSF in SGF for up to 70 min with 16% degradation after 120 min, while 75% degradation occurred after 120 min with the addition of 80% HPMC. The release rate of DSF can be manipulated by both the loading and type of sustained release polymer used, with HPMC providing for a much faster release rate compared to Kollidon(®) SR. PMID:26608620

  3. In vitro effect of fluoride oral hygiene tablets on artificial caries lesion formation and remineralization in human enamel

    PubMed Central

    Gängler, Peter; Kremniczky, Thomas; Arnold, Wolfgang H

    2009-01-01

    Background Aim of this in-vitro-study was to assess the remineralization potential of a tooth cleaning tablet with different fluoride content. Methods Twenty three caries free impacted third molars were examined, enamel surfaces were wax coated leaving two 3 × 4 mm windows for exposure to demineralization/remineralization cycles. The teeth were randomly assigned to 4 groups of 5 control and 6 experimental teeth. Demineralization by standardised HEC-gel, pH 4.7 at 37°C for 72 h, was alternated by rinsing in remineralization solution, pH 7.0 at 37°C for 72 h, total challenge time 432 h. The negative control group N was treated during remineralization cycles with saline; positive control group P was treated with remineralization solution; experimental group D1 was exposed to remineralization solution containing Denttabs®-tablets with 1450 ppm F; experimental group D2 was exposed to remineralization solution and Denttabs®-tablets with 4350 ppm F. Each tooth was cut into serial sections and analyzed by polarized light microscopy for assessment of the different zones of white-spot lesions in 3 representative sections. Statistical analysis was based on the Mann-Whitney-Test. Results Both control groups N(-) and P(+) exhibited characteristic white-spot lesions. The remineralization and the demineralization inhibition of the lesions increased considerably from N

    oral hygiene product and the remineralization is correlated to the fluoride content. PMID:19799785

  4. Morphine withdrawal dramatically reduces lymphocytes in morphine-dependent macaques.

    PubMed

    Weed, Michael R; Carruth, Lucy M; Adams, Robert J; Ator, Nancy A; Hienz, Robert D

    2006-09-01

    The immune effects of chronic opiate exposure and/or opiate withdrawal are not well understood. The results of human studies with opiate abusers are variable and may not be able to control for important factors such as subjects' drug histories, health and nutritional status. Nonhuman primate models are necessary to control these important factors. A model of opiate dependence in macaques was developed to study the effects of opiate dependence and withdrawal on measures of immune function. Four pigtailed macaques drank a mixture of morphine (20 mg/kg/session) and orange-flavored drink every 6 h for several months. During stable morphine dependence, absolute numbers of neutrophils, monocytes and lymphocytes did not change relative to pre-morphine levels. However, there was a significant decrease in the absolute number and percentage of natural killer (NK) cells in morphine dependence. Either precipitated withdrawal or abstinence for 24 h resulted in behavioral withdrawal signs in all animals. Absolute lymphocyte counts decreased and absolute netrophil counts increased significantly in withdrawal, relative to levels during morphine dependence. Lymphocyte subset (CD4+, CD8+, CD20+) cells were also decreased in absolute numbers with little change in their percentage distributions. There was, however, a significant increase in the percentage of NK cells in withdrawal relative to levels during morphine dependence. This study demonstrates the usefulness of voluntary oral self-dosing procedures for maintaining morphine dependence in nonhuman primates and demonstrates that the morphine withdrawal syndrome includes large alterations in blood parameters of immune system function, including nearly 50% reduction in numbers of CD4+, CD8+ and CD20+ cells. PMID:18040802

  5. A clinical evaluation of amlexanox oral adhesive pellicles in the treatment of recurrent aphthous stomatitis and comparison with amlexanox oral tablets: a randomized, placebo controlled, blinded, multicenter clinical trial

    PubMed Central

    Meng, Wenxia; Dong, Yi; Liu, Jie; Wang, Zhi; Zhong, Xiaobo; Chen, Ruiyang; Zhou, Hongmei; Lin, Mei; Jiang, Lu; Gao, Feng; Xu, Tao; Chen, Qianming; Zeng, Xin

    2009-01-01

    Background Amlexanox has been developed as a 5 percent topical oral paste for the treatment of patients with recurrent aphthous stomatitis (RAS) in most European countries. However, it is not yet available in China and has not been generally accepted in clinical treatment. The aim of this study was to explore the effectiveness of amlexanox oral adhesive pellicles in the treatment of minor recurrent aphthous ulcers, and compare the results with those of amlexanox oral adhesive tablets in order to analyse the difference between the two dosage forms of amlexanox. Methods We performed a randomized, blinded, placebo-controlled, parallel, multicenter clinical study. A total of 216 patients with minor recurrent aphthous ulcers (MiRAU) were recruited and randomized to amlexanox pellicles or placebo pellicles. Pellicles were consecutively applied four times per day, for five days. The size and pain level of ulcers were measured and recorded on treatment days 0, 4 and 6. Finally, the results were compared with those of our previous 104 cases treated with amlexanox tablets. Results Amlexanox oral adhesive pellicles significantly reduced ulcer size (P= 0.017 for day 4, P=0.038 for day 6) and alleviated ulcer pain (P=0.021 for day 4, P=0.036 for day 6). No significant difference was observed in the treatment effectiveness between the pellicle and tablet form of amlexanox. Conclusions Amlexanox oral adhesive pellicles are as effective and safe as amlexanox oral adhesive tablets in the treatment of MiRAU for this Chinese cohort. However, pellicles seem to be more comfortable to use when compared with the dosage form of tablets. Therefore, in clinical practice, amlexanox oral adhesive pellicles may be a better choice for RAS patients. Trials registration Nederlands Trial Register NTR1727. PMID:19419555

  6. Preparation and evaluation of orally disintegrating tablets of taste masked phencynonate HCl using ion-exchange resin.

    PubMed

    Ge, Zhenzhong; Yang, Meiyan; Wang, Yuli; Shan, Li; Gao, Chunsheng

    2015-06-01

    This study was intended to design an orally disintegrating tablet (ODT) formulation that can mask the extremely bitter and metallic taste of phencynonate HCl by novel ion-exchange resins. The drug-resin complexes (DRCs) were prepared and characterized by scanning electron microscopy, X-ray powder diffraction and differential scanning calorimetry. In vitro properties (dissolution, wetting time and disintegration time) and in vivo behavior (disintegration time and taste-masking effect) in healthy volunteers of the prepared ODTs were also investigated. The drug was changed from the crystal structure to the amorphous form in the DRC. Compared with commercial tablets, the in vitro and in vivo disintegration of optimized DRC-loaded ODTs with a drug-resin ratio of 1:1 was greatly improved and better palatability with a low bitterness index (0.33) was obtained. The current DRC-loaded ODT could promise a good way to mask the unpleasant taste of certain drugs and accordingly improve the patient compliance. PMID:24785576

  7. Oral L-thyroxine liquid versus tablet in patients with hypothyroidism without malabsorption: a prospective study.

    PubMed

    Fallahi, Poupak; Ferrari, Silvia Martina; Antonelli, Alessandro

    2016-06-01

    No consistent data are present in literature about the effectiveness of levothyroxine (L-T4) liquid formulation in patients without malabsorption. The aim of this study is to compare the effectiveness of L-T4 liquid formulation, with L-T4 tablets, in hypothyroid patients without malabsorption or drug interference. One hundred and fifty two patients were recruited. Patients were switched from the L-T4 therapy in tablets, to liquid L-T4 at the same dosage, 30 min before breakfast. Serum thyrotropic hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were re-evaluated after 1-3 months (first control) and 5-7 months (second control) from the switch. TSH values significantly declined with respect to the basal value after the switch to liquid L-T4 both at the first control (P < 0.05) and at the second control (P < 0.01); FT4 and FT3 levels were not significantly changed. We show that liquid L-T4 is more effective than L-T4 tablet in controlling TSH levels in hypothyroid patients without malabsorption, gastric disorders, or drug interference. PMID:26721663

  8. Enteric-coated tablet of risedronate sodium in combination with phytic acid, a natural chelating agent, for improved oral bioavailability.

    PubMed

    Kim, Jeong S; Jang, Sun W; Son, Miwon; Kim, Byoung M; Kang, Myung J

    2016-01-20

    The oral bioavailability (BA) of risedronate sodium (RS), an antiresorptive agent, is less than 1% due to its low membrane permeability as well as the formation of non-absorbable complexes with multivalent cations such as calcium ion (Ca(2+)) in the gastrointestinal tract. In the present study, to increase oral BA of the bisphosphonate, a novel enteric-coated tablet (ECT) dosage form of RS in combination with phytic acid (IP6), a natural chelating agent recognized as safe, was formulated. The chelating behavior of IP6 against Ca(2+), including a stability constant for complex formulation was characterized using the continuous variation method. Subsequently, in vitro dissolution profile and in vivo pharmacokinetic profile of the novel ECT were evaluated comparatively with that of the marketed product (Altevia, Sanofi, US), an ECT containing ethylenediaminetetraacetic acid (EDTA) as a chelating agent, in beagle dogs. The logarithm of stability constant for Ca(2+)-IP6 complex, an equilibrium constant approximating the strength of the interaction between two chemicals to form complex, was 19.05, which was 3.9-fold (p<0.05) and 1.7-fold (p<0.05) higher than those of Ca(2+)-RS and Ca(2+)-EDTA complexes. The release profile of RS from both enteric-coated dosage forms was equivalent, regardless of the type of chelating agent. An in vivo absorption study in beagle dogs revealed that the maximum plasma concentration and area under the curve of RS after oral administration of IP6-containing ECT were approximately 7.9- (p<0.05) and 5.0-fold (p<0.05) higher than those of the marketed product at the same dose (35mg as RS). Therefore, our study demonstrates the potential usefulness of the ECT system in combination with IP6 for an oral therapy with the bisphosphonate for improved BA. PMID:26594027

  9. Safety of fluralaner chewable tablets (BravectoTM), a novel systemic antiparasitic drug, in dogs after oral administration

    PubMed Central

    2014-01-01

    Background Fluralaner is a novel systemic insecticide and acaricide that provides long acting efficacy in dogs after a single oral treatment. This study investigated the safety of oral administration of fluralaner in chewable tablets to dogs at the highest recommended treatment dose and at multiples of this dose. Methods Thirty-two (16 male and 16 female) healthy 8-week old Beagle dogs weighing 2.0 - 3.6 kg at first administration were included in the study. Fluralaner was administered on three occasions at 8-week intervals at doses of up to 56, 168, and 280 mg fluralaner/kg body weight, equivalent to 1, 3, and 5 times the highest recommended treatment dose of fluralaner; sham dosed dogs served as controls. During the study, all dogs were clinically observed, and their health was carefully monitored including body weight development, food consumption and measurement of hematology, coagulation, clinical chemistry (including measurement of levels of ACTH and C-reactive protein) and urinalysis. Following euthanasia of the dogs, complete gross post mortem examination, including organ weight determination, and histopathological examination of multiple tissues were conducted. Results There were no clinical findings related to fluralaner treatment. Statistically significant differences between the treated groups and the control group were observed for some clinical pathology parameters and organ weights; none of these findings were considered to be of clinical relevance. Conclusions Oral administration of fluralaner at the highest recommended treatment dose (56 mg/kg) at 8-week intervals is well tolerated and has a safety margin of more than five in healthy dogs eight weeks of age or older and weighing at least 2 kg. PMID:24606886

  10. Formulation Optimization of Hydrodynamically Balanced Oral Controlled Release Bioadhesive Tablets of Tramadol Hydrochloride

    PubMed Central

    Singh, Bhupinder; Rani, Ashu; Babita; Ahuja, Naveen; Kapil, Rishi

    2010-01-01

    The directly compressible floating-bioadhesive tablets of tramadol were formulated using varying amounts Carbopol 971P (CP) and hydroxy-propylmethyl cellulose (HPMC), along with other requisite excipients. In vitro drug release profile, floatational characteristics and ex vivo bioadhesive strength using texture analyzer were determined, and systematically optimized using a 32 central composite design (CCD). The studies indicated successful formulation of gastroretentive compressed matrices with excellent controlled release, mucoadhesion and hydrodynamic balance. Comparison of the dissolution profiles of the optimized formulation, with optimal composition of CP:HPMC :: 80.0:125.0, with that of the marketed controlled release formulation other indicated analogy of drug release performance with each other. Validation of optimization study using eight confirmatory experimental runs indicated very high degree of prognostic ability of CCD with mean ± SEM of −0.06% ± 0.37. Further, the study successfully unravels the effect of the polymers on the selected response variables. PMID:21179349

  11. [Method for the evaluation of the stability and usability after opening packages of orally disintegrating tablets: case of amlodipine besilate products].

    PubMed

    Hori, Katsuhito; Yoshida, Naoko; Okumura, Tomonori; Okamura, Yasufumi; Kawakami, Junichi

    2010-08-01

    Orally disintegrating (OD) tablets are widely used in clinical practice. However, drug information on the choice and dispensing based on their stability after opening packages and usability in patients and dispensaries is not sufficient. The aim of this study was to investigate possible evaluation methods of the stability and usability of amlodipine OD tablets. Additives of the brand were changed in April 2009, and therefore the previous and current forms and two generics, current and newly marketed (in November 2009) products of different firms, were used. OD tablets were stored at 25 degrees C and 75% relative humidity for 3 months after opening the packages, and their physicochemical properties were evaluated. Their weight, diameter, thickness, and color difference increased slightly from the initial state. The extent of the change in their hardness, disintegration time, and friability was different among products. These physicochemical changes were acceptable in dispensary practice. Storage after opening the packages did not affect their dissolution rate. The dissolution rate at the initial state of the current brand was slower than that of the previous one. All products used were able to be dispensed by an automatic tablet-packing machine and applied to the so-called simple suspension method for intubational administration. Sensory evaluation tests revealed no major difference in the oral disintegration time, taste, impression, and preference among products. In conclusion, the stability and usability of amlodipine OD tablets used in this study were examined using several methods, and they can be used equivalently from the stability and usability viewpoints. PMID:20686207

  12. Comparison of the effect of a single oral L-thyroxine dose (150 micrograms) in tablet and in solution on serum thyroxine and TSH concentrations.

    PubMed

    Carpi, A; De Gaudio, C; Cirigliano, G; Toni, M G

    1993-04-01

    150 micrograms of L-thyroxine were administered to each of 14 euthyroid goitrous patients orally between 7:30 and 8:30 a.m. after fasting overnight. The L-T4 dose given was one and half tablets of the drug "Eutirox" (L-T4 tablet of 100 micrograms distributed by Bracco, Milan, Italy) or one and half ml of the solution "Tiroxen" (solution containing 100 micrograms/ml of L-T4 distributed by Laboratori Baldacci, Pisa, Italy). Two studies (one with tablet and one with solution) were performed on each patient. The tablet or the liquid form of L-T4 were administered in random order. In each study a blood sample for serum hormone determination was drawn immediately before L-T4 administration, then 30 minutes later and every hour up to the fifth hour after. The second study was performed in similar fashion later. The mean serum TT4 concentration value at any time was very similar in the two studies, thus showing the same time course after the administration of solution and the tablet formulation. The mean basal TT4 value (9.07 +/- 0.56 and 8.90 +/- 0.73 micrograms/dl respectively) increased significantly at the first and second hours. The highest value was reached at the second and at the third hour after the solution (11.15 +/- 0.58 micrograms/dl) and the tablet (11.81 +/- 0.78 micrograms/dl) respectively. Subsequently, the mean TT4 values remained significantly higher than basally over the entire 5 hours. The FT4 mean serum concentration at all times were very similar in the two studies and showed the same time course.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7508742

  13. Bioequivalence study of two oral tablet formulations containing tenofovir disoproxil fumarate in healthy volunteers.

    PubMed

    Yerino, Gustavo A; Halabe, Emilia K; Zini, Elvira; Feleder, Ethel C

    2011-01-01

    Tenofovir disoproxil fumarate (TDF, CAS 147127-20-6) is a nucleotide reverse transcriptase inhibitor which is indicated in combination with other antiretroviral agents for the management of HIV-1 infection. The objective of this study was to compare the rate and extent of absorption and to assess the bioequivalence between a new pharmaceutical equivalent tablet formulation containing 300 mg of TDF and the innovator product. A randomized, single-center, open-label, single-dose, two-way crossover bioequivalence study in 40 healthy adult subjects was conducted. Dosing was separated by a wash-out period of 14 days. Blood samples were collected over 48 h and plasma levels of tenofovir (TFV) were determined by a validated HPLC assay. Rate and extent of absorption were similar between products. The 90% confidence interval (CI) of the ratio of the geometric means for log-transformed C(max), AUC(last) and AUC(inf) values were used to assess bioequivalence between the two formulations using the equivalence interval of 80 and 125%. In healthy subjects, the point estimate and 90% CI of the ratios of C(max), AUC(last) and AUC(inf) values were 0.99 (0.92-1.02), 0.99 (0.95-1.03) and 0.93 (0.85-1.02), respectively. Both treatments exhibited similar tolerability and safety. It was concluded that the new pharmaceutical product was bioequivalent to the innovator. PMID:21355446

  14. The practical approach to the evaluation of methods used to determine the disintegration time of orally disintegrating tablets (ODTs).

    PubMed

    Brniak, Witold; Jachowicz, Renata; Pelka, Przemyslaw

    2015-09-01

    Even that orodispersible tablets (ODTs) have been successfully used in therapy for more than 20 years, there is still no compendial method of their disintegration time evaluation other than the pharmacopoeial disintegration test conducted in 800-900 mL of distilled water. Therefore, several alternative tests more relevant to in vivo conditions were described by different researchers. The aim of this study was to compare these methods and correlate them with in vivo results. Six series of ODTs were prepared by direct compression. Their mechanical properties and disintegration times were measured with pharmacopoeial and alternative methods and compared with the in vivo results. The highest correlation with oral disintegration time was found in the case of own-construction apparatus with additional weight and the employment of the method proposed by Narazaki et al. The correlation coefficients were 0.9994 (p < 0.001), and 0.9907 (p < 0.001) respectively. The pharmacopoeial method correlated with the in vivo data much worse (r = 0.8925, p < 0.05). These results have shown that development of novel biorelevant methods of ODT's disintegration time determination is eligible and scientifically justified. PMID:27134547

  15. Formulation, preparation, and evaluation of novel orally disintegrating tablets containing taste-masked naproxen sodium granules and naratriptan hydrochloride.

    PubMed

    Stange, Ulrike; Führling, Christian; Gieseler, Henning

    2014-04-01

    The purpose of this study was to develop and manufacture novel freeze-dried orally disintegrating tablets (ODTs) for migraine therapy containing taste-masked naproxen sodium and naratriptan hydrochloride. The formulation was optimized based on freeze-drying of sucrose solutions with different binders (hydroxyethylstarch, sodium alginate, methylcellulose, and gelatin) and varying amounts of Eudragit® E-coated naproxen sodium granules. Excellent product performance of the ODTs in terms of hardness and disintegration time (<10 s) independent of the mass of particles embedded was found for the solution consisting of sucrose and hydroxyethylstarch. Poloxamer 188, menthol flavor, naratriptan hydrochloride, and taste-masked naproxen sodium granules corresponding to 200 mg of naproxen were then added, and the final batches of ODTs for migraine therapy were produced. The ODTs were fully characterized, and subsequently stored for 1 month at room temperature and at 40°C. The amount of free naproxen sodium after freeze-drying and storage was below the threshold bitterness value, and the coating remained intact. Additionally, the particle size distribution of taste-masked granules was preserved, and more than 90 % naproxen sodium was released after 30 min. Naratriptan hydrochloride was dissolved immediately after disintegration, hence facilitating buccal absorption of the active pharmaceutical ingredient. PMID:24532095

  16. Mefenamic acid taste-masked oral disintegrating tablets with enhanced solubility via molecular interaction produced by hot melt extrusion technology

    PubMed Central

    Alshehri, Sultan M.; Park, Jun-Bom; Alsulays, Bader B.; Tiwari, Roshan V.; Almutairy, Bjad; Alshetaili, Abdullah S.; Morott, Joseph; Shah, Sejal; Kulkarni, Vijay; Majumdar, Soumyajit; Martin, Scott T.; Mishra, Sanjay; Wang, Lijia; Repka, Michael A.

    2015-01-01

    The objective of this study was to enhance the solubility as well as to mask the intensely bitter taste of the poorly soluble drug, Mefenamic acid (MA). The taste masking and solubility of the drug was improved by using Eudragit® E PO in different ratios via hot melt extrusion (HME), solid dispersion technology. Differential scanning calorimetry (DSC) studies demonstrated that MA and E PO were completely miscible up to 40% drug loads. Powder X-ray diffraction analysis indicated that MA was converted to its amorphous phase in all of the formulations. Additionally, FT-IR analysis indicated hydrogen bonding between the drug and the carrier up to 25% of drug loading. SEM images indicated aggregation of MA at over 30% of drug loading. Based on the FT-IR, SEM and dissolution results for the extrudates, two optimized formulations (20% and 25% drug loads) were selected to formulate the orally disintegrating tablets (ODTs). ODTs were successfully prepared with excellent friability and rapid disintegration time in addition to having the desired taste-masking effect. All of the extruded formulations and the ODTs were found to be physically and chemically stable over a period of 6 months at 40°C/75% RH and 12 months at 25°C/60% RH, respectively. PMID:25914727

  17. Comparative Studies on the Dissolution Profiles of Oral Ibuprofen Suspension and Commercial Tablets using Biopharmaceutical Classification System Criteria

    PubMed Central

    Rivera-Leyva, J. C.; García-Flores, M.; Valladares-Méndez, A.; Orozco-Castellanos, L. M.; Martínez-Alfaro, M.

    2012-01-01

    In vitro dissolution studies for solid oral dosage forms have recently widened the scope to a variety of special dosage forms such as suspensions. For class II drugs, like Ibuprofen, it is very important to have discriminative methods for different formulations in physiological conditions of the gastrointestinal tract, which will identify different problems that compromise the drug bioavailability. In the present work, two agitation speeds have been performed in order to study ibuprofen suspension dissolution. The suspensions have been characterised relatively to particle size, density and solubility. The dissolution study was conducted using the following media: buffer pH 7.2, pH 6.8, 4.5 and 0.1 M HCl. For quantitative analysis, the UV/Vis spectrophotometry was used because this methodology had been adequately validated. The results show that 50 rpm was the adequate condition to discriminate the dissolution profile. The suspension kinetic release was found to be dependent on pH and was different compared to tablet release profile at the same experimental conditions. The ibuprofen release at pH 1.0 was the slowest. PMID:23626386

  18. Pharmaceutical development of an oral tablet formulation containing a spray dried amorphous solid dispersion of docetaxel or paclitaxel.

    PubMed

    Sawicki, Emilia; Beijnen, Jos H; Schellens, Jan H M; Nuijen, Bastiaan

    2016-09-25

    Previously, it was shown in Phase I clinical trials that solubility-limited oral absorption of docetaxel and paclitaxel can be drastically improved with a freeze dried solid dispersion (fdSD). These formulations, however, are unfavorable for further clinical research because of limitations in amorphicity of SD and scalability of the production process. To resolve this, a spray drying method for an SD (spSD) containing docetaxel or paclitaxel and subsequently drug products were developed. Highest saturation solubility (Smax), precipitation onset time (Tprecip), amorphicity, purity, residual solvents, yield/efficiency and powder flow of spSDs were studied. Drug products were monitored for purity/content and dissolution during 24 months at +15-25°C. Docetaxel spSD Smax was equal to that of fdSD but Tprecip was 3 times longer. Paclitaxel spSD Smax was 30% increased but Tprecip was equal to fdSD. spSDs were fully amorphous, >99% pure, <5% residual solvents, mean batch yield was 100g and 84%. spSDs had poor powder flow characteristics, which could not be resolved by changing settings, but by using 75% lactose as diluent. The drug product was a tablet with docetaxel or paclitaxel spSD and was stable for at least 24 months. Spray drying is feasible for the production of SD of docetaxel or paclitaxel for upcoming clinical trials. PMID:27480397

  19. Enhancement of Solubility of Lamotrigine by Solid Dispersion and Development of Orally Disintegrating Tablets Using 32 Full Factorial Design

    PubMed Central

    Singh, Jatinderpal; Garg, Rajeev; Gupta, Ghanshyam Das

    2015-01-01

    Present investigation deals with the preparation and evaluation of orally disintegrating tablets (ODTs) of lamotrigine using β-cyclodextrin and PVP-K30 as polymers for the preparation of solid dispersion which help in enhancement of aqueous solubility of this BCS CLASS-II drug and sodium starch glycolate (SSG) and crospovidone as a superdisintegrating agent, to reduce disintegration time. The ODTs were prepared by direct compression method. Nine formulations were developed with different ratios of superdisintegrating agents. All the formulations were evaluated for disintegration time, weight variation, hardness, friability, drug content uniformity, wetting time, and in vitro drug release study. In vitro drug release study was performed using United States Pharmacopoeia (USP) type 2 dissolution test apparatus employing paddle stirrer at 50 rpm using 900 mL of 0.1 N HCl maintained at 37°C ± 0.5°C as the dissolution medium. On the basis of evaluation parameters formulations were prepared using β-CD 1 : 1 solid dispersion. Then 32 full factorial design was applied using SSG and crospovidone in different ratios suggested by using design expert 8.0.7.1 and optimized formulation was prepared using amount of SSG and crospovidone as suggested by the software. The optimized formulation prepared had disintegrating time of 15 s, wetting time of 24 s, and % friability of 0.55. PMID:26634173

  20. The practical approach to the evaluation of methods used to determine the disintegration time of orally disintegrating tablets (ODTs)

    PubMed Central

    Brniak, Witold; Jachowicz, Renata; Pelka, Przemyslaw

    2015-01-01

    Even that orodispersible tablets (ODTs) have been successfully used in therapy for more than 20 years, there is still no compendial method of their disintegration time evaluation other than the pharmacopoeial disintegration test conducted in 800–900 mL of distilled water. Therefore, several alternative tests more relevant to in vivo conditions were described by different researchers. The aim of this study was to compare these methods and correlate them with in vivo results. Six series of ODTs were prepared by direct compression. Their mechanical properties and disintegration times were measured with pharmacopoeial and alternative methods and compared with the in vivo results. The highest correlation with oral disintegration time was found in the case of own-construction apparatus with additional weight and the employment of the method proposed by Narazaki et al. The correlation coefficients were 0.9994 (p < 0.001), and 0.9907 (p < 0.001) respectively. The pharmacopoeial method correlated with the in vivo data much worse (r = 0.8925, p < 0.05). These results have shown that development of novel biorelevant methods of ODT’s disintegration time determination is eligible and scientifically justified. PMID:27134547

  1. Preliminary buprenorphine sublingual tablet pharmacokinetic data in plasma, oral fluid and sweat during treatment of opioid-dependent pregnant women

    PubMed Central

    Concheiro, Marta; Jones, Hendreé E.; Johnson, Rolley E.; Choo, Robin; Huestis, Marilyn A.

    2011-01-01

    Background Buprenorphine is currently under investigation as a pharmacotherapy to treat pregnant women for opioid dependence. This research evaluates buprenorphine (BUP), norbuprenophine (NBUP), buprenorphine-glucuronide (BUP-Gluc) and norbuprenorphine-glucuronide (NBUP-Gluc) pharmacokinetics after high dose (14–20 mg) BUP sublingual tablet administration in three opioid-dependent pregnant women. Methods Oral fluid and sweat specimens were collected in addition to plasma specimens for 24 h during gestation weeks 28 or 29 and 34, and 2 months after delivery. Tmax was not affected by pregnancy; however, BUP and NBUP Cmax and AUC0–24h tended to be lower during pregnancy compared to postpartum levels. Results Statistically significant but weak positive correlations were found for BUP plasma and OF concentrations, and BUP/NBUP ratios in plasma and OF. Conclusion Statistically significant negative correlations were observed for times of specimen collection and BUP and NBUP OF/plasma ratios. BUP-Gluc and NBUP-Gluc were detected in only 5% of OF specimens. In sweat, BUP and NBUP were detected in only 4 of 25 (12 or 24 h) specimens in low concentrations (<2.4 ng/patch). These preliminary data describe BUP and metabolite pharmacokinetics in pregnant women and suggest that, like methadone, upward dose adjustments may be needed with advancing gestation. PMID:21860340

  2. Bioequivalence assessment of ambroxol tablet after a single oral dose administration to healthy male volunteers.

    PubMed

    Lee, Hee Joo; Joung, Sun Koung; Kim, Yoon Gyoon; Yoo, Jeong-Yeon; Han, Sang Beom

    2004-01-01

    A bioequivalence study of the ambroxol hydrochloride tablets was conducted. Twenty-four healthy male Korean volunteers received each medicine at the ambroxol hydrochloride dose of 30 mg in a 2 x 2 cross-over study. There was a 1-week washout period between the doses. Plasma concentrations of ambroxol were monitored by a high-performance liquid chromatography (HPLC) for over a period of 24h after the administration. AUC(t) (the area under the plasma concentration-time curve from time 0 to last sampling time, 24h) was calculated by the linear-log trapezoidal rule method. C(max) (maximum plasma drug concentration) and T(max) (time to reach C(max)) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUC(t) and C(max), and untransformed T(max). The geometric mean of AUC(t) was 495.8 ng ml(-1)h(-1) (test medication) and 468.3 ng ml(-1)h(-1) (reference medication). C(max) of 61.5 and 57.3 ng ml(-1) were achieved for the test and the reference medication, respectively. The point estimates and 90% confidence intervals for AUC(t) (parametric) and C(max) (parametric) were, in point estimate (90% confidence interval), 1.058 (0.989-1.134) and 1.073 (1.007-1.142), respectively, satisfying the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration Guidelines. The corresponding value of T(max) was 0.229 (0.015-0.444). These results indicate that the two medications of ambroxol hydrochloride are bioequivalent and, thus, may be prescribed interchangeably. PMID:14597158

  3. 21 CFR 520.2150a - Stanozolol tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) 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...

  4. Effect of food on the oral bioavailability of amlodipine/valsartan and amlodipine/valsartan/hydrochlorothiazide fixed dose combination tablets in healthy subjects.

    PubMed

    Sunkara, Gangadhar; Jiang, Xuemin; Reynolds, Christine; Serra, Denise; Zhang, Yiming; Ligueros-Saylan, Monica; Ayalasomayajula, Surya; Winter, Serge; Jarugula, Venkateswar

    2014-11-01

    A double fixed dose combination of amlodipine/valsartan and triple fixed dose combination of amlodipine/valsartan/HCTZ tablets have been developed to treat patients with moderate-to-severe hypertension. Here, we present the effect of food on the oral bioavailability of these two fixed dose combination tablets from two separate clinical studies in healthy subjects. Single oral doses of amlodipine/valsartan (10/160 mg) and amlodipine/valsartan/HCTZ (10/320/25 mg were administered under fasted or fed conditions. Blood samples were collected in both studies to determine the pharmacokinetic parameters of amlodipine, valsartan, and/or HCTZ using non-compartmental analysis. Following amlodipine/valsartan administration, the geometric mean ratios (GMRs, 90% CI) of AUC0-∞ and Cmax were 1.09 (1.05-1.13) and 1.03 (0.97-1.09) for amlodipine, and 0.94 (0.81-1.10) and 0.86 (0.73-1.02) for valsartan, respectively. Following amlodipine/valsartan/HCTZ administration, the GMRs (90%CI) of AUC0-∞ and Cmax were 1.09 (1.04-1.15) and 1.11 (1.05-1.08) for amlodipine, 1.14 (0.99-1.31) and 1.12 (0.98-1.29) for valsartan, and 1.09 (1.02-1.16) and 0.86 (0.79-0.93) for HCTZ, respectively. Considering the sample size and pharmacokinetic variability associated with analytes, these study results indicate that food effect is minimal or none when fixed dose combination tablets are administered with food. In conclusion, both fixed dose combination tablets can be administered without regards to meals. PMID:27129123

  5. 21 CFR 520.1284 - Sodium liothyronine tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Sodium liothyronine tablets. 520.1284 Section 520... liothyronine tablets. (a) Specifications. Sodium liothyronine tablets consist of tablets intended for oral administration which contain liothyronine at 60 or 120 micrograms per tablet, as the sodium salt. (b)...

  6. 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... liothyronine tablets. (a) Specifications. Sodium liothyronine tablets consist of tablets intended for oral administration which contain liothyronine at 60 or 120 micrograms per tablet, as the sodium salt. (b)...

  7. 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... liothyronine tablets. (a) Specifications. Sodium liothyronine tablets consist of tablets intended for oral administration which contain liothyronine at 60 or 120 micrograms per tablet, as the sodium salt. (b)...

  8. Mice with neuropathic pain exhibit morphine tolerance due to a decrease in the morphine concentration in the brain.

    PubMed

    Ochiai, Wataru; Kaneta, Mitsumasa; Nagae, Marina; Yuzuhara, Ami; Li, Xin; Suzuki, Haruka; Hanagata, Mika; Kitaoka, Satoshi; Suto, Wataru; Kusunoki, Yoshiki; Kon, Risako; Miyashita, Kazuhiko; Masukawa, Daiki; Ikarashi, Nobutomo; Narita, Minoru; Suzuki, Tsutomu; Sugiyama, Kiyoshi

    2016-09-20

    The chronic administration of morphine to patients with neuropathic pain results in the development of a gradual tolerance to morphine. Although the detailed mechanism of this effect has not yet been elucidated, one of the known causes is a decrease in μ-opioid receptor function with regard to the active metabolite of morphine, M-6-G(morphine-6-glucuronide), in the ventrotegmental area of the midbrain. In this study, the relationship between the concentration of morphine in the brain and its analgesic effect was examined after the administration of morphine in the presence of neuropathic pain. Morphine was orally administered to mice with neuropathic pain, and the relationship between morphine's analgesic effect and its concentration in the brain was analysed. In addition, the expression levels of the conjugation enzyme, UGT2B (uridine diphosphate glucuronosyltransferase), which has morphine as its substrate, and P-gp, which is a transporter involved in morphine excretion, were examined. In mice with neuropathic pain, the concentration of morphine in the brain was significantly decreased, and a correlation was found between this decrease and the decrease in the analgesic effect. It was considered possible that this decrease in the brain morphine concentration may be due to an increase in the expression level of P-gp in the small intestine and to an increase in the expression level and binding activity of UGT2B in the liver. The results of this study suggest the possibility that a sufficient analgesic effect may not be obtained when morphine is administered in the presence of neuropathic pain due to a decrease in the total amount of morphine and M-6-G that reach the brain. PMID:27102159

  9. Morphine: Myths and Reality

    MedlinePlus

    ... and Families Take the Quiz Morphine: Myths and Reality February, 2013 The mere mention of “Morphine” can ... due to misinformation and lack of training. The reality is that Morphine (and other opiates that work ...

  10. [Involvement of zinc in taste disturbance occurring during treatment for malignant tumor in the chest and the effects of polaprezinc oral disintegrating tablets (a retrospective study)].

    PubMed

    Nakata, Yoko; Hirashima, Tomonori; Kondou, Yoko; Tokuoka, Yoshie; Imazato, Hitomi; Iwata, Kaori; Oomori, Yukari; Yamato, Akihiro; Shimizu, Saburou; Nagao, Sadako; Matsui, Kaoru; Abe, Noriko

    2008-06-01

    We analyzed the correlation between serum zinc levels and taste disturbance, and between patient backgrounds and serum zinc levels or taste disturbance, and evaluated the effects of polaprezinc oral disintegrating tablets on taste disturbance in 29 patients with lung cancer and one patient with malignant pleural mesothelioma who were receiving chemotherapy. Taste disturbance developed in 11 (36.7%) out of 30 patients. Serum zinc levels significantly correlated with taste disturbance (p=0.0227). Serum zinc levels were significantly lower (p=0.0235) and taste disturbance tended to be more frequent (p=0.0625) in males. Polaprezinc improved taste disturbance in 5 of 8 patients. PMID:18633224

  11. The effects of screw configuration and polymeric carriers on hot-melt extruded taste-masked formulations incorporated into orally disintegrating tablets.

    PubMed

    Morott, Joseph T; Pimparade, Manjeet; Park, Jun-Bom; Worley, Chelsea P; Majumdar, Soumyajit; Lian, Zhuoyang; Pinto, Elanor; Bi, Yunxia; Durig, Thomas; Repka, Michael A

    2015-01-01

    The primary aim of this research was to produce successfully taste masked formulations of Sildenafil Citrate (SC) using hot-melt extrusion (HME) technology. Multiple screw configurations and polymeric carriers were evaluated for their effects on taste masking efficiency, which was assessed by both E-tongue analysis and in vitro dissolution in simulated salivary fluid (SSF, pH 6.8 artificial saliva). The screw configurations were further assessed for their effects on the morphology of the API using PXRD, FT-IR and mid-infrared chemical imaging. It was determined that the screw configuration had a profound effect on the taste masking efficiency of the formulations as a result of altering the physical state of the API. Selected extruded formulations using ethylcellulose (EC) with a pore former were further formulated into orally disintegrating tablets (ODTs), which were optimized by varying the grade and percentage of the superdisintegrant used. An optimized disintegration time of approximately 8 seconds was achieved. The final ODT formulation exhibited excellent taste masking properties with over 85% drug release in gastric media as well as physical tablet properties. Interestingly, friability, which tends to be a common concern when formulating ODTs, was well within the acceptable limits (<1%) for common tablets. PMID:25410968

  12. The Effects of Screw Configuration and Polymeric Carriers on Hot-Melt Extruded Taste-Masked Formulations Incorporated into Orally Disintegrating Tablets

    PubMed Central

    Morott, Joseph T.; Pimparade, Manjeet; Park, Jun-Bom; Worley, Chelsea P.; Majumdar, Soumyajit; Lian, Zhuoyang; Pinto, Elanor; Bi, Yunxia; Durig, Thomas; Repka, Michael A.

    2015-01-01

    The primary aim of this research was to produce successfully taste masked formulations of Sildenafil Citrate (SC) using hot-melt extrusion (HME) technology. Multiple screw configurations and polymeric carriers were evaluated for their effects on taste masking efficiency, which was assessed by both E-tongue analysis and in vitro dissolution in simulated salivary fluid (SSF, pH 6.8 artificial saliva). The screw configurations were further assessed for their effects on the morphology of the API using PXRD, FT-IR and mid-infrared chemical imaging. It was determined that the screw configuration had a profound effect on the taste masking efficiency of the formulations as a result of altering the physical state of the API. Selected extruded formulations using ethylcellulose (EC) with a pore former were further formulated into orally disintegrating tablets (ODTs), which were optimized by varying the grade and percentage of the superdisintegrant used. An optimized disintegration time of approximately 8 seconds was achieved. The final ODT formulation exhibited excellent taste masking properties with over 85% drug release in gastric media as well as physical tablet properties. Interestingly, friability, which tends to be a common concern when formulating ODTs, was well within the acceptable limits (<1%) for common tablets. PMID:25410968

  13. Pharmacokinetic Comparative Study of Gastrodin and Rhynchophylline after Oral Administration of Different Prescriptions of Yizhi Tablets in Rats by an HPLC-ESI/MS Method

    PubMed Central

    Ge, Zhaohui; Liang, Qionglin; Wang, Yiming; Luo, Guoan

    2014-01-01

    Pharmacokinetic characters of rhynchophylline (RIN), gastrodin (GAS), and gastrodigenin (p-hydroxybenzyl alcohol, HBA) were investigated after oral administration of different prescriptions of Yizhi: Yizhi tablets or effective parts of tianma (total saponins from Gastrodiae, EPT) and gouteng (rhynchophylla alkaloids, EPG). At different predetermined time points after administration, the concentrations of GAS, HBA, and RIN in rat plasma were determined by an HPLC-ESI/MS method, and the main pharmacokinetic parameters were investigated. The results showed that the pharmacokinetic parameters Cmax and AUC0–∞ (P < 0.05) were dramatically different after oral administration of different prescriptions of Yizhi. The data indicated that the pharmacokinetic processes of GAS, HBA, and RIN in rats would interact with each other or be affected by other components in Yizhi. The rationality of the compatibility of Uncaria and Gastrodia elata as a classic “herb pair” has been verified from the pharmacokinetic viewpoint. PMID:25610474

  14. Pharmacokinetic Comparative Study of Gastrodin and Rhynchophylline after Oral Administration of Different Prescriptions of Yizhi Tablets in Rats by an HPLC-ESI/MS Method.

    PubMed

    Ge, Zhaohui; Xie, Yuanyuan; Liang, Qionglin; Wang, Yiming; Luo, Guoan

    2014-01-01

    Pharmacokinetic characters of rhynchophylline (RIN), gastrodin (GAS), and gastrodigenin (p-hydroxybenzyl alcohol, HBA) were investigated after oral administration of different prescriptions of Yizhi: Yizhi tablets or effective parts of tianma (total saponins from Gastrodiae, EPT) and gouteng (rhynchophylla alkaloids, EPG). At different predetermined time points after administration, the concentrations of GAS, HBA, and RIN in rat plasma were determined by an HPLC-ESI/MS method, and the main pharmacokinetic parameters were investigated. The results showed that the pharmacokinetic parameters C max and AUC0-∞ (P < 0.05) were dramatically different after oral administration of different prescriptions of Yizhi. The data indicated that the pharmacokinetic processes of GAS, HBA, and RIN in rats would interact with each other or be affected by other components in Yizhi. The rationality of the compatibility of Uncaria and Gastrodia elata as a classic "herb pair" has been verified from the pharmacokinetic viewpoint. PMID:25610474

  15. Simultaneous LC-MS/MS determination of five tripterygium pyridine alkaloids in dog plasma and its application to their pharmacokinetic study after oral administration of tripterygium glycosides tablets.

    PubMed

    Su, Meng-xiang; Song, Min; Yang, Da-song; Shi, Jin-fang; Di, Bin; Hang, Tai-jun

    2015-05-15

    A sensitive and selective liquid chromatography tandem mass spectrometric method was developed and validated for the simultaneous determination of five pyridine alkaloids contained in tripterygium glycosides tablets (triptolide, wilforine, wilforgine, wilfording and wilfortrine) in dog plasma. The analysis was carried out on a Sepax GP-Phenyl column using a mixture of methanol and 10mmol/L ammonium formate buffer solution containing 0.1% formic acid (75:25, v/v) as the mobile phase pumped at a flow-rate of 1.0mL/min. All MS data were obtained in the positive ESI mode with selective multiple reaction monitoring of ion transitions. The method was fully validated to be accurate and precise with a linear range of 0.2-1000ng/mL for triptolide and 0.05-1000ng/mL for the other four pyridine alkaloids. The intra-day and inter-day precisions (relative standard deviation, RSD, %) were within 10.6% and 14.0%, respectively, and the relative error (RE, %) were all less than 13.1%. The method was successfully applied to multi-components pharmacokinetic study of the five pyridine alkaloids in beagle dogs after a single oral administration of 3mg/kg and 30mg/kg tripterygium glycosides tablets, respectively, and a multiple oral administration of 30mg/kg for 6 consecutive days. PMID:25855315

  16. Development and potential application of an oral ColoPulse infliximab tablet with colon specific release: A feasibility study.

    PubMed

    Maurer, Jacoba M; Hofman, Susan; Schellekens, Reinout C A; Tonnis, Wouter F; Dubois, Annelien O T; Woerdenbag, Herman J; Hinrichs, Wouter L J; Kosterink, Jos G W; Frijlink, Henderik W

    2016-05-30

    The monoclonal antibody infliximab is one of the cornerstones in the treatment of Crohn's disease. Local delivery of infliximab would be an alternative to overcome the inherent disadvantages of intravenous therapy. For this purpose 5mg infliximab tablets were developed. To stabilize the antibody during production and storage it was incorporated in a sugar glass containing the oligosaccharide inulin. To obtain colon-specific release a ColoPulse coating was applied. The tablets were stored for 16 months under different conditions based on ICH climatic zone I. PMID:26997425

  17. 21 CFR 520.1451 - Moxidectin tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Moxidectin tablets. 520.1451 Section 520.1451 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 § 520.1451 Moxidectin tablets. (a) Specifications. Each tablet contains 30,...

  18. 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....

  19. 21 CFR 520.1310 - Marbofloxacin tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 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....

  20. 21 CFR 520.1310 - Marbofloxacin tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 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....

  1. 21 CFR 520.1310 - Marbofloxacin tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 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....

  2. 21 CFR 520.1310 - Marbofloxacin tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 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....

  3. 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 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) Specifications. Each tablet...

  4. 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) Specifications. Each tablet contains either...

  5. 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) Specifications. Each tablet...

  6. 21 CFR 520.1880 - Prednisolone tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Prednisolone tablets. 520.1880 Section 520.1880... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1880 Prednisolone tablets. (a) Specifications. Each tablet contains 5 or 20 milligrams prednisolone. (b) Sponsor. See No. 061690 in §...

  7. 21 CFR 520.1880 - Prednisolone tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Prednisolone tablets. 520.1880 Section 520.1880... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1880 Prednisolone tablets. (a) Specifications. Each tablet contains 5 or 20 milligrams prednisolone. (b) Sponsor. See No. 061690 in §...

  8. 21 CFR 520.1880 - Prednisolone tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Prednisolone tablets. 520.1880 Section 520.1880... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1880 Prednisolone tablets. (a) Specifications. Each tablet contains 5 or 20 milligrams prednisolone. (b) Sponsor. See No. 061690 in §...

  9. 21 CFR 520.1880 - Prednisolone tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Prednisolone tablets. 520.1880 Section 520.1880... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1880 Prednisolone tablets. (a) Specifications. Each tablet contains 5 or 20 milligrams prednisolone. (b) Sponsor. See No. 061690 in §...

  10. 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) Specifications. Each tablet...

  11. 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) Specifications. Each tablet...

  12. 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... 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)...

  13. 21 CFR 520.816 - Epsiprantel tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 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...

  14. 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... 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...

  15. 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... 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)...

  16. 21 CFR 520.1616 - Orbifloxacin tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Orbifloxacin tablets. 520.1616 Section 520.1616... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1616 Orbifloxacin tablets. (a) Specifications. Each tablet contains 5.7, 22.7, or 68 milligrams (mg) orbifloxacin. (b) Sponsor. See No....

  17. 21 CFR 520.581 - Dichlorophene tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Dichlorophene tablets. 520.581 Section 520.581... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.581 Dichlorophene tablets. (a) Specifications. Each tablet contains 1 gram of dichlorophene. (b) Sponsor. See 023851 in § 510.600(c) of...

  18. 21 CFR 520.1900 - Primidone tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 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 §...

  19. 21 CFR 520.812 - Enrofloxacin tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 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...

  20. 21 CFR 520.816 - Epsiprantel tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 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...

  1. 21 CFR 520.1870 - Praziquantel tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 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....

  2. 21 CFR 520.1510 - Nitenpyram tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 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 §...

  3. 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)...

  4. 21 CFR 520.1510 - Nitenpyram tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 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 §...

  5. 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... 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)...

  6. 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... 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)...

  7. 21 CFR 520.1870 - Praziquantel tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 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....

  8. 21 CFR 520.1870 - Praziquantel tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 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....

  9. 21 CFR 520.816 - Epsiprantel tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 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...

  10. 21 CFR 520.1510 - Nitenpyram tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 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 §...

  11. 21 CFR 520.1900 - Primidone tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 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. 054628 in §...

  12. 21 CFR 520.1870 - Praziquantel tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 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....

  13. 21 CFR 520.1616 - Orbifloxacin tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Orbifloxacin tablets. 520.1616 Section 520.1616... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1616 Orbifloxacin tablets. (a) Specifications. Each tablet contains 5.7, 22.7, or 68 milligrams (mg) orbifloxacin. (b) Sponsor. See No....

  14. 21 CFR 520.816 - Epsiprantel tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 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...

  15. 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... 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)...

  16. 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... 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)...

  17. 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... 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)...

  18. 21 CFR 520.1900 - Primidone tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 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 §...

  19. 21 CFR 520.812 - Enrofloxacin tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 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...

  20. 21 CFR 520.581 - Dichlorophene tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Dichlorophene tablets. 520.581 Section 520.581... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.581 Dichlorophene tablets. (a) Specifications. Each tablet contains 1 gram of dichlorophene. (b) Sponsor. See 023851 in § 510.600(c) of...

  1. 21 CFR 520.1616 - Orbifloxacin tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Orbifloxacin tablets. 520.1616 Section 520.1616... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1616 Orbifloxacin tablets. (a) Specifications. Each tablet contains 5.7, 22.7, or 68 milligrams (mg) orbifloxacin. (b) Sponsor. See No....

  2. 21 CFR 520.1510 - Nitenpyram tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 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 §...

  3. 21 CFR 520.312 - Carnidazole tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 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)...

  4. 21 CFR 520.1900 - Primidone tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 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 §...

  5. 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... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.581 Dichlorophene tablets. (a) Specifications. Each tablet contains 1 gram of dichlorophene. (b) Sponsor. See 023851 in § 510.600(c) of...

  6. 21 CFR 520.1616 - Orbifloxacin tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Orbifloxacin tablets. 520.1616 Section 520.1616... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1616 Orbifloxacin tablets. (a) Specifications. Each tablet contains 5.7, 22.7, or 68 milligrams (mg) orbifloxacin. (b) Sponsor. See No....

  7. 21 CFR 520.581 - Dichlorophene tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Dichlorophene tablets. 520.581 Section 520.581... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.581 Dichlorophene tablets. (a) Specifications. Each tablet contains 1 gram of dichlorophene. (b) Sponsor. See 023851 in § 510.600(c) of...

  8. 21 CFR 520.370 - Cefpodoxime tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 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) Specifications. Each tablet...

  9. 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 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 § 520.1510 Nitenpyram tablets. (a) Specifications. Each tablet contains 11.4...

  10. 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 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) Specifications. Each tablet contains...

  11. 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 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 § 520.816 Epsiprantel tablets. (a) Specifications. Each tablet contains...

  12. 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...

  13. 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...

  14. Interchangeability of two 500 mg amoxicillin capsules with one 1000 mg amoxicillin tablet after a single oral administration.

    PubMed

    Zaid, A N; Cortesi, R; Kort, J; Sweileh, W

    2010-07-01

    The aim of the study was to evaluate if two capsules (Amoxil(®) capsules, 500 mg/capsule) and one tablet (Amoxicare(®) tablets, 1000 mg/tablet) of amoxicillin have similar bioequivalence parameters. For this purpose a randomized, two-way, crossover, bioequivalence study was performed in 24 healthy, male volunteers, divided into two groups of 12 subjects each. One group was treated with the reference standard (Amoxil(®)) and the other one with the generic tablet Amoxicare(®), with a crossover after a wash-out period of 7 days. Blood samples were collected at fixed time intervals and amoxicillin was determined by a validated HPLC method. The pharmacokinetic parameters AUC(0-8), AUC(0-∞), C(max), T(max), K(e) and T(1/2) were determined for both formulations and statistically compared to evaluate the bioequivalence between the two brands of amoxicillin, using the statistical model recommended by the FDA. C(max) and AUC(0-∞) were statistically analyzed using analysis of variance (ANOVA); no statistically significant difference was observed between the two formulations. The 90% confidence intervals between the mean values of C(max) and AUC(0-∞) fall within the FDA specified bioequivalent limits (80-125%) suggesting that the two products are bioequivalent and the two formulations are interchangeable. Based on these findings it was concluded that the practice of interchangeability between the above formulations to achieve better patient compliance could be followed without compromising the extent of amoxicillin absorption. PMID:21218049

  15. Pre-exposure Prophylaxis Adherence Measured by Plasma Drug Level in MTN-001: Comparison Between Vaginal Gel and Oral Tablets in Two Geographic Regions.

    PubMed

    Minnis, Alexandra M; van der Straten, Ariane; Salee, Parichat; Hendrix, Craig W

    2016-07-01

    Despite strong evidence that daily oral pre-exposure prophylaxis (PrEP) reduces HIV risk, effectiveness across studies has varied. Inconsistent adherence constitutes one explanation. Efforts to examine adherence are limited when they rely on self-reported measures. We examined recent adherence as measured by plasma tenofovir (TFV) concentration in participants of MTN-001, a phase 2 cross-over trial comparing oral tablet and vaginal gel formulations of TFV among 144 HIV-uninfected women at sites in the United States (U.S.) and sub-Saharan Africa (SSA). Adherence to daily product use was higher in the U.S. than in the SSA sites. Within region, however, adherence was similar between products. In the U.S., gel adherence was higher among married women, and lower among women using male condoms and injectable contraceptives. At the SSA sites, gel adherence was lower for younger women. Inconsistent adherence points to challenges in use of daily PrEP, even during a trial of short duration. PMID:25969178

  16. The influence of morphine on the absorption of paracetamol from various formulations in subjects in the supine position, as assessed by TDx measurement of salivary paracetamol concentrations.

    PubMed

    Kennedy, Julia M; Tyers, Nicola M; Davey, Andrew K

    2003-10-01

    The aim of this study was to determine the influence of the type of paracetamol formulation on the rate of absorption when subjects are in the supine position, with or without taking concomitant morphine. Two groups of healthy volunteers were used, who were in the fasting state and remained in the supine position during the study. One group took 1,500 mg of paracetamol on three occasions as conventional tablets, dispersible tablets or a suspension in a randomized crossover design. Seventeen saliva samples per subject were obtained (time zero to 360 min post-dose), which were then centrifuged and kept at -20 degrees C prior to analysis. The second group repeated the study following four doses of morphine syrup (10 mg 4 hourly) in the 12 h preceding paracetamol ingestion. In this phase of the study, paracetamol absorption from suspension was not investigated. A TDx assay was used to determine salivary paracetamol concentrations. The tmax for conventional tablets when taken concomitantly with morphine was 160 (+/- 81) min compared to 51 (+/- 58) min for subjects not taking morphine. For dispersible tablets the tmax in the morphine group was 14 (+/- 9) min compared to 15 (+/- 12) min without morphine. The results suggest that patients who are confined to bed and taking morphine will have an unacceptably long delay between taking conventional paracetamol tablets and the paracetamol reaching therapeutic plasma concentrations. Conversely, there is little effect on the absorption of dispersible paracetamol under the same conditions. PMID:14607015

  17. 21 CFR 520.2150b - Stanozolol chewable tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... treatment in dogs. (2) Administered orally to 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. (3) Federal law...

  18. 21 CFR 520.2150b - Stanozolol chewable tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... treatment in dogs. (2) Administered orally to 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. (3) Federal law...

  19. 21 CFR 520.2150b - Stanozolol chewable tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... treatment in dogs. (2) Administered orally to 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. (3) Federal law...

  20. 21 CFR 520.2150b - Stanozolol chewable tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... treatment in dogs. (2) Administered orally to 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. (3) Federal law...

  1. Self-intoxication with morphine obtained from an infusion pump.

    PubMed

    Gock, S B; Wong, S H; Stormo, K A; Jentzen, J M

    1999-01-01

    A 36-year-old Caucasian male was found unresponsive by his wife. He had white foam around his mouth and was pronounced dead shortly thereafter. He had a history of back pain and was treated with intrathecal morphine because of his previous addiction to oral opiate medications. Because of crimping of the pump catheter, it was replaced 4 days before his death. Toxicological findings included urine screen positive for amitriptyline, nortriptyline, opiates, hydrocodone metabolites, ibuprofen, acetaminophen, caffeine, nicotine, and metabolite. Drug concentrations were as follows: blood, 0.260 mg/L amitriptyline, 0.160 mg/L nortriptyline, 0.460 mg/L unconjugated morphine, and 0.624 mg/L total morphine; vitreous humor, 0.034 mg/L unconjugated morphine and 0.080 mg/L total morphine; and cerebrospinal fluid, 0.099 mg/L unconjugated morphine and 0.095 mg/L total morphine. Shortly after death, the volume of the residual pump reservoir was only 8 mL instead of the expected 17 mL. Testing by the FDA showed that the pump was functional. The residual content of the pump accounted for only 230 mg instead of the expected 488 mg. The high blood-morphine concentrations did not correlate with the intrathecal infusion dose. The symptoms were consistent with opiate overdose, possibly by injection of morphine withdrawn from the pump reservoir. The cause of death was determined to be fatal morphine self-intoxication, and the manner of death was accidental. This case is intended to alert regulatory agencies, pain management health professionals, pathologists, and toxicologists to the abuse potential of one of the newer analgesic-delivery systems. PMID:10192419

  2. 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. PMID:24370841

  3. Morphine: Myths and Reality

    MedlinePlus

    ... ve heard that Morphine has lots of side effects, and I feel bad enough already.” All opiates can cause nausea, drowsiness and constipation. However, all side effects will generally stop after a few days, as ...

  4. Bioequivalence study of two oral tablet formulations containing saquinavir mesylate boosted with ritonavir in healthy male subjects.

    PubMed

    Yerino, Gustavo A; Halabe, Emilia K; Zini, Elvira; Feleder, Ethel C

    2011-01-01

    Saquinavir (SAQ) mesylate (CAS 149845-06-7) is a potent inhibitor of the HIV-1 protease indicated in combination with other antiretrovirals for the management of HIV-1 infection. The objective of this study was to compare rate and extent of absorption and to assess the bioequivalence between a new pharmaceutical equivalent tablet formulation containing 500 mg of SAQ mesylate and the innovator film coated tablet formulation. A randomized, single-center, open-label, two-treatment, two-sequence, three-period, replicated crossover bioequivalence study in 40 healthy male subjects was conducted. All subjects received 100 mg ritonavir (CAS 155213-67-5) twice daily for a run-in period of 3 days before treatment. Dosing was separated by a wash-out period of 14 days. Blood samples were collected over 72 h and plasma levels of SAQ were determined by a validated HPLC/UV assay. The 90% confidence interval (CI) of the ratio of the geometric means for log-transformed C(max), AUC(last) and AUC(inf) values were used to assess bioequivalence using the equivalence interval of 80-125%. Point estimate and 90% CI of the ratios of C(max), AUC(last) and AUC(inf) values were 94.9 (80.9-111.3), 97.4 (82.4-115.4) and 97.4 (82.5-115.0), respectively. Both treatments exhibited similar tolerability and safety. It was concluded that the new pharmaceutical product was bioequivalent to the innovator. PMID:21950153

  5. Safety of an oral anticancer agent (trifluridine/tipiracil combination tablet) in patients with advanced and recurrent colorectal cancer.

    PubMed

    Kimura, M; Go, M; Iwai, M; Ito, D; Asano, H; Usami, E; Teramachi, H; Yoshimura, T

    2016-04-01

    We retrospectively studied the safety of trifluridine/tipiracil combination tablet (TAS-102) monotherapy in patients with advanced and recurrent colorectal cancer. Adverse events to TAS-102 monotherapy were observed in 22 out of 23 cases (95.7%). The most frequent adverse events were neutropenia (69.6%), nausea (53.2%), and malaise (30.4%). Treatment was postponed in 54 (59.3%) out of 91 courses, and in 34 (66.7%) of these 54 courses, the delay in treatment was due to bone marrow suppression. Seven patients with peritoneal metastases suffered from nausea, whilst none of the patients without peritoneal metastases had nausea (p = 0.0139). Nausea and vomiting during a previous chemotherapy cycle was significantly associated with nausea after TAS-102 treatment (p = 0.0007), and the treatment cycles were significantly longer in patients with grade 3 or 4 neutropenia (p = 0.0061). Our results suggest that the incidence of nausea was higher in patients treated with TAS-102. Therefore, it is important to inform patients of the risk of these toxicities and to provide enhanced supportive care. Moreover, we recommend that, for patients with repeated treatment postponement due to neutropenia, the dosage should be fixed based on therapeutic efficacy and prognosis. PMID:27209703

  6. An in vitro evaluation of fenugreek mucilage as a potential excipient for oral controlled-release matrix tablet.

    PubMed

    Nokhodchi, Ali; Nazemiyeh, Hossein; Khodaparast, Afagh; Sorkh-Shahan, Tarifeh; Valizadeh, Hadi; Ford, J L

    2008-03-01

    A polysaccharide mucilage derived from the seeds of fenugreek, Trigonella foenum-graceum L (family Fabaceae) was investigated for use in matrix formulations containing propranolol hydrochloride. Methocel hypomellose K4M was used as a standard controlled release polymer for comparison purposes. In this study the effect of lactose on the release behaviour of propranolol hydrochloride from matrices formulated to contain the fenugreek mucilage also was investigated. An increase in concentration of the mucilage in matrices resulted in a reduction in the release rate of propranolol hydrochloride comparable to that observed with hypomellose matrices. The rate of release of propranolol hydrochloride from fenugreek mucilage matrices was mainly controlled by the drug:mucilage ratio. However, the mechanism of release from matrices containing drug:mucilage ratios of 1:1, 1:1.25, 1:1.5, and 1:2 remained the same. The kinetics of release, utilising the release exponent n, showed that the values of n were between 0.46-0.57 indicating that the release from fenugreek mucilage matrices was predominantly by diffusion. The presence of lactose in matrices containing mucilage increased the release rate of propranolol hydrochloride. This is due to a reduction in tortuoisity and increased pore size of channels caused by lactose through which propranolol diffuses and therefore diffusion of water into the tablet is facilitated. PMID:18363148

  7. Efficacy and safety of desmopressin orally disintegrating tablet in patients with central diabetes insipidus: results of a multicenter open-label dose-titration study.

    PubMed

    Arima, Hiroshi; Oiso, Yutaka; Juul, Kristian Vinter; Nørgaard, Jens Peter

    2013-01-01

    Central diabetes insipidus (CDI) is associated with arginine vasopressin (AVP) deficiency with resultant polyuria and polydipsia. Intranasal desmopressin provides physiological replacement but oral formulations are preferred for their ease of administration. This study aimed to demonstrate the efficacy and safety of desmopressin orally disintegrating tablet (ODT) in the treatment of Japanese patients with CDI, and confirm that antidiuresis is maintained on switching from intranasal desmopressin to desmopressin ODT. A total of 20 patients aged 6-75 years with CDI were included in this 4-week multicenter, open-label study. Following observation, patients switched from intranasal desmopressin to desmopressin ODT with titration to optimal dose over ≤5 days at the study site. Following three consecutive doses with stable patient fluid balance, patients were discharged with visits at Weeks 2 and 4. Following titration from intranasal desmopressin to ODT, the mean 24-hour urine volume was unchanged, indicating similar antidiuresis with both formulations. The proportion of patients with endpoint measurements (urine osmolality, 24-hour urine volume, hourly diuresis rate and urine-specific gravity) within normal range at Days 1-2 (intranasal desmopressin) and Week 4 (desmopressin ODT) was similar. The mean daily dose ratio of intranasal desmopressin to desmopressin ODT (Week 4) was 1:24 but a wide range was observed across individuals to maintain adequate antidiuretic effect. Hyponatraemia was generally mild and managed by dose titration. Desmopressin ODT achieved sufficient antidiuretic control compared to intranasal therapy and was well tolerated over long-term treatment. The wide range of intranasal:ODT dose ratios underline the importance of individual titration. PMID:23811987

  8. LC-MS/MS determination and urinary excretion study of seven alkaloids in healthy Chinese volunteers after oral administration of Shuanghua Baihe tablets.

    PubMed

    Cheng, Minlu; Liu, Ruijuan; Wu, Yao; Gu, Pan; Zheng, Lu; Liu, Yujie; Ma, Pengcheng; Ding, Li

    2016-01-25

    An LC-MS/MS method was developed and validated for the simultaneous determination of magnoflorine, berberrubine, jatrorrhizine, coptisine, epiberberine, palmatine and berberine in human urine. The sample preparation procedure involved the four-fold dilution of the urine samples with acetonitrile/water (1:3, v/v). The chromatographic separation was achieved on a Hedera ODS-2 column under gradient elution at a flow rate of 0.4 mL/min with acetonitrile and water containing 0.5% formic acid as the mobile phase. The mass detection was performed in the positive mode. Calibration curves of the seven alkaloids showed good linearity (correlation coefficients>0.9973) over their concentration ranges. To meet the requirements of urinary excretion study for each alkaloid in human, the lower limit of quantification was set at different values from 0.05063 ng/mL to 2.034 ng/mL for the seven alkaloids, respectively. The intra- and inter-batch precision and accuracy were all within ± 15%. No matrix effect was observed for the analytes. The validated method was applied to the excretion study for the seven alkaloids in healthy Chinese volunteers after oral administration of Shuanghua Baihe tablets. The average 72 h cumulative urinary excretion of magnoflorine, berberrubine, jatrorrhizine, coptisine, epiberberine, palmatine and berberine accounted for 1.81%, 0.27%, 0.29%, 0.046%, 0.027%, 0.010% and 0.021% of the respective administered dose. PMID:26519688

  9. Patient-controlled oral analgesia versus nurse-controlled parenteral analgesia after caesarean section: a randomised controlled trial.

    PubMed

    Bonnal, A; Dehon, A; Nagot, N; Macioce, V; Nogue, E; Morau, E

    2016-05-01

    We assessed the effectiveness of early patient-controlled oral analgesia compared with parenteral analgesia in a randomised controlled non-inferiority trial of women undergoing elective caesarean section under regional anaesthesia. Seventy-seven women received multimodal paracetamol, ketoprofen and morphine analgesia. The woman having patient-controlled oral analgesia were administered four pillboxes on the postnatal ward containing tablets and instructions for self-medication, the first at 7 h after the spinal injection and then three more at 12-hourly intervals. Pain at rest and on movement was evaluated using an 11-point verbal rating scale at 2 h and then at 6-hourly intervals for 48 h. The pre-defined non-inferiority limit for the difference in mean pain scores (patient-controlled oral analgesia minus parenteral) was one. The one-sided 95% CI of the difference in mean pain scores was significantly lower than one at all time-points at rest and on movement, demonstrating non-inferiority of patient-controlled oral analgesia. More women used morphine in the patient-controlled oral analgesia group (22 (58%)) than in the parenteral group (9 (23%); p = 0.002). The median (IQR [range]) number of morphine doses in the patient-controlled oral analgesia group was 2 (1-3 [1-7]) compared with 1 (1-1 [1-2]); p = 0.006) in the parenteral group. Minor drug errors or omissions were identified in five (13%) women receiving patient-controlled oral analgesia. Pruritus was more frequent in the patient-controlled oral analgesia group (14 (37%) vs 6 (15%) respectively; p = 0.03), but no differences were noted for other adverse events and maternal satisfaction. After elective caesarean section, early patient-controlled oral analgesia is non-inferior to standard parenteral analgesia for pain management, and can be one of the steps of an enhanced recovery process. PMID:26931110

  10. Effect of hydrophilic natural gums in formulation of oral-controlled release matrix tablets of propranolol hydrochloride.

    PubMed

    Rajesh, K S; Venkataraju, M P; Gowda, D V

    2009-04-01

    In order to develop a controlled delivery of highly water-soluble propranolol hydrochloride (PPHCl) using hydrophilic natural gums (xanthan gum [X] and locust bean gum [LBG]) as cost-effective, nontoxic, easily available. The granules of PPHCl were prepared by wet granulation method using a different ratios drug: gum ratios of X, LBG and XLBG(X and LBG in 1:1 ratios). To increase the flowability and compressibility of the granules, and to prevent its adhesion to punch and die, magnesium stearate and talc were added to the granules in 1:2 ratios before punching. The tablet was analysed to determine hardness, friability, % assay and invitro release study was carried out. The release of PPHCl from a gelatinous swollen mass, which controls the diffusion of drug molecules through the polymeric material into aqueous medium. The XLBG matrice shows precise controlled release than the X and LBG matrice because of burst effect and fast release in case of X and LBG matrice respectively and there was no chemical interaction between drug and polymer in XLBG formulation as confirmed by FTIR studies. First pass effect of PPHCl can be avoided by these formulations. Matrices with XLBG show zero-order release via swelling, diffusion and relaxation mechanism. The XLBG matrice leads to more precise result than X and LBG alone by the utilization of synergistic interaction between two biopolymers and uniformity in the hydration layer in dissolution media. However, according to the similarity factor (f(2)) XLBG3 were the most similar formulations to Lol-SR as the reference standard. PMID:19339235

  11. 21 CFR 520.804 - Enalapril tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 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....

  12. 21 CFR 520.804 - Enalapril tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 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....

  13. 21 CFR 520.531 - Cythioate tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Cythioate tablets. 520.531 Section 520.531 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.531 Cythioate tablets. (a) (b) Sponsors. See No. 000859 in § 510.600(c) of this chapter for use of 30- and 90-milligram (mg) tablets...

  14. 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....

  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... 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....

  16. 21 CFR 520.531 - Cythioate tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Cythioate tablets. 520.531 Section 520.531 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.531 Cythioate tablets. (a) (b) Sponsors. See No. 000859 in § 510.600(c) of this chapter for use of 30- and 90-milligram (mg) tablets...

  17. 21 CFR 520.1380 - Methocarbamol tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 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...

  18. 21 CFR 520.1380 - Methocarbamol tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 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...

  19. 21 CFR 520.1380 - Methocarbamol tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 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...

  20. 21 CFR 520.2150a - Stanozolol tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Stanozolol tablets. 520.2150a Section 520.2150a 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 § 520.2150a Stanozolol tablets. (a) Specifications. Each tablet contains...

  1. 21 CFR 520.246 - Butorphanol tartrate tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Butorphanol tartrate tablets. 520.246 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.246 Butorphanol tartrate tablets. (a) Specifications. Each tablet contains 1, 5, or 10 milligrams of butorphanol...

  2. 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...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.246 Butorphanol tartrate tablets. (a) Specifications. Each tablet contains 1, 5, or 10 milligrams of butorphanol...

  3. 21 CFR 520.246 - Butorphanol tartrate tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Butorphanol tartrate tablets. 520.246 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.246 Butorphanol tartrate tablets. (a) Specifications. Each tablet contains 1, 5, or 10 milligrams of butorphanol...

  4. 21 CFR 520.246 - Butorphanol tartrate tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Butorphanol tartrate tablets. 520.246 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.246 Butorphanol tartrate tablets. (a) Specifications. Each tablet contains 1, 5, or 10 milligrams of butorphanol...

  5. 21 CFR 520.246 - Butorphanol tartrate tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Butorphanol tartrate tablets. 520.246 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.246 Butorphanol tartrate tablets. (a) Specifications. Each tablet contains 1, 5, or 10 milligrams of butorphanol...

  6. 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... susceptible to penicillin V potassium. (3) Limitations. Administer orally 1 to 2 hours prior to feeding...

  7. 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... susceptible to penicillin V potassium. (3) Limitations. Administer orally 1 to 2 hours prior to feeding...

  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... susceptible to penicillin V potassium. (3) Limitations. Administer orally 1 to 2 hours prior to feeding...

  9. 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....

  10. 21 CFR 520.1331 - Meclofenamic acid tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 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....

  11. 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...) 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....

  12. 21 CFR 520.1331 - Meclofenamic acid tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 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....

  13. 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...

  14. 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...

  15. 21 CFR 520.2123a - Spectinomycin tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Spectinomycin tablets. 520.2123a Section 520.2123a... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2123a Spectinomycin tablets. (a) Specifications. Each tablet contains spectinomycin dihydrochloride pentahydrate equivalent to...

  16. 21 CFR 520.2123a - Spectinomycin tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Spectinomycin tablets. 520.2123a Section 520.2123a... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2123a Spectinomycin tablets. (a) Specifications. Each tablet contains spectinomycin dihydrochloride pentahydrate equivalent to...

  17. 21 CFR 520.390a - Chloramphenicol tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Chloramphenicol tablets. 520.390a Section 520.390a... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.390a Chloramphenicol tablets. (a) Specifications. Each tablet contains 50, 100, 250, or 500 milligrams (mg); 1 or 2.5 grams (g)...

  18. 21 CFR 520.2123a - Spectinomycin tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Spectinomycin tablets. 520.2123a Section 520.2123a... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2123a Spectinomycin tablets. (a) Specifications. Each tablet contains spectinomycin dihydrochloride pentahydrate equivalent to...

  19. 21 CFR 520.2123a - Spectinomycin tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Spectinomycin tablets. 520.2123a Section 520.2123a... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2123a Spectinomycin tablets. (a) Specifications. Each tablet contains spectinomycin dihydrochloride pentahydrate equivalent to...

  20. 21 CFR 520.390a - Chloramphenicol tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Chloramphenicol tablets. 520.390a Section 520.390a... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.390a Chloramphenicol tablets. (a) Specifications. Each tablet contains 50, 100, 250, or 500 milligrams (mg); 1 or 2.5 grams (g)...

  1. Sucrose esters with various hydrophilic-lipophilic properties: novel controlled release agents for oral drug delivery matrix tablets prepared by direct compaction.

    PubMed

    Chansanroj, K; Betz, G

    2010-08-01

    Sucrose esters (SE) are esters of sucrose and fatty acids with various hydrophilic-lipophilic properties which have attracted interest from being used in pharmaceutical applications. This study aimed to gain insight into the use of SE as controlled release agents for direct compacted matrix tablets. The study focused on the effect of hydrophilic-lipophilic properties on tableting properties and drug release. Sucrose stearate with hydrophilic-lipophilic balance (HLB) values ranging from 0 to 16 was systematically tested. Tablet formulations contained SE, metoprolol tartrate as a highly soluble model drug and dibasic calcium phosphate dihydrate as a tablet formulation filler in the ratio 1:1:2. The compaction behaviour of matrix tablets was compared with the compacts of individual starting materials as reference. SE incorporation improved the plasticity, compressibility and lubricating property of powder mixtures. The hydrophilic-lipophilic properties of SE affected tableting properties, drug release rate and release mechanism. Increasing hydrophilicity corresponding to the increased monoesters in SE composition increased the relative porosity, elastic recovery and tensile strength of the tablets due to the increased hydrogen bonding between the monoesters. This also facilitated the swelling behaviour of SE, which sustained the drug release rate. A sustained release effect prevailed in tablets containing SE with HLB values of 3-16. The ability to improve the tableting properties as well as sustain the drug release rate of the highly soluble model drug via gelation of SE highlights SE as promising controlled release regulators for direct compacted matrix tablets comprising drugs with various solubilities according to the Biopharmaceutics Classification System. PMID:20132913

  2. Mirtazapine orally disintegrating tablets versus venlafaxine extended release: a double-blind, randomized multicenter trial comparing the onset of antidepressant response in patients with major depressive disorder.

    PubMed

    Benkert, Otto; Szegedi, Armin; Philipp, Michael; Kohnen, Ralf; Heinrich, Claus; Heukels, Anja; van der Vegte-Senden, Monique; Baker, Ross A; Simmons, John H; Schutte, Albert-Jan

    2006-02-01

    This randomized, multicenter, double-blind study was designed to compare specifically the onset of antidepressant action of mirtazapine orally disintegrating tablets (ODT) with venlafaxine extended-release (XR) formulation in outpatients with major depression. Both treatments were administered in a rapidly escalating dosing regimen. Target doses (mirtazapine ODT, 45 mg OD; venlafaxine XR, 225 mg OD) were reached by day 6 of treatment. On the primary efficacy parameter [the average of the change in HAM-D (17-item) total score on days 5, 8, 11, and 15], mirtazapine ODT was significantly superior to venlafaxine XR (P = 0.008). In addition, calculating the HAM-D score without the sleep items resulted in significant reductions in favor of mirtazapine ODT on days 8 (P = 0.006) and 11 (P = 0.037). The proportion of responders (HAM-D decrease of > or =50% from baseline) was higher in the mirtazapine ODT group on all assessment days, being significant on days 8 (P = 0.002), 11 (P = 0.004), and 22 (P = 0.027). More patients in the mirtazapine ODT group achieved remission (HAM-D total score of < or =7) up to day 29, and the difference was statistically significant on day 15 (P = 0.016). Significant differences in favor of mirtazapine ODT were evident in the CGI of change on days 8 (P = 0.019), 11 (P = 0.004), and 15 (P = 0.031), and the CGI of severity on days 8 (P = 0.014) and 11 (P = 0.033). Both treatments were well tolerated. These results indicate that mirtazapine ODT has a faster onset of antidepressant efficacy than venlafaxine XR in patients with major depressive disorder, and that this effect is independent of its sleep-improving properties. PMID:16415711

  3. Single- and multiple-dose pharmacokinetics of a novel tetramethylpyrazine reservoir-type transdermal patch versus tetramethylpyrazine phosphate oral tablets in healthy normal volunteers, and in vitro/in vivo correlation.

    PubMed

    Shen, Teng; Xu, Huinan; Weng, Weiyu; Zhang, Jianfang

    2013-01-01

    A novel reservoir-type transdermal system of 2,3,5,6-tetramethylpyrazine (TMP) was developed containing eucalyptus oil as a penetration enhancer. The single and multiple-dose pharmacokinetic profiles of TMP administrated by TMP transdermal patch were characterized in healthy volunteers using an in vivo, randomized, open-label, two-way crossover design. 2,3,5,6-Tetramethylpyrazine phosphate (TMPP) oral tablets were chosen as reference. Following single/multiple oral administration of 200/100 mg TMPP tablets, a TMP C(max) of 1284/613.5 ng/mL was observed within 0.75 h. Single/multiple applications of the TMP patch yielded mean C(max) of 309/325 ng/mL at a median T(max) of 5/4 h, with steady state achieved at second application. The mean C(min) of the patch was 131±30.38 ng/mL, contrasting to nearly zero for the tablet. Multiple applications of patch produced an accumulative effect over single application. At steady state 250 mg/20 cm(2) TMP patch given daily provided comparable exposure to 100 mg TMPP tablets three times daily (3753.91 versus 3563.67 ng·h/mL). TMP tablets and patch yielded similar steady-state plasma concentrations: C(av) (148.48±51.27, 156.41±40.31 ng/mL). The results demonstrated that TMP patch can achieve a therapeutic effect that is comparable to oral administration, exhibited prolonged and sustained plasma levels, fewer drug fluctuations, lower adverse effects, more convenience, and improved patient compliance. In-vitro permeation through human skin demonstrated zero-order kinetics with the flux of 364 µg/cm(2)/h. The predicted C(av) (163.9 ng/mL) was in agreement with the observed C(av) (156.4 ng/mL). PMID:23514701

  4. Tablet Weaving

    ERIC Educational Resources Information Center

    Kren, Margo

    1976-01-01

    Article described a weaving technique called tablet weaving, an ancient textile process that provides opportunity for making a variety of items, such as guitar straps, belts, and decorative bands. (Author/RK)

  5. Pooled post hoc analysis of population pharmacokinetics of oxycodone and acetaminophen following a single oral dose of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets

    PubMed Central

    Franke, Ryan M; Morton, Terri; Devarakonda, Krishna

    2015-01-01

    This analysis evaluated the single-dose population pharmacokinetics (PK) of biphasic immediate-release (IR)/extended-release (ER) oxycodone (OC)/acetaminophen (APAP) 7.5/325 mg tablets administered under fasted conditions and the effects of a meal on their single-dose population PK. Data were pooled from four randomized, single-dose crossover trials enrolling healthy adult (18–55 years old) participants (three trials) and nondependent recreational users of prescription opioids (one trial) with a body weight of ≥59 kg. Participants received IR/ER OC/APAP 7.5/325 mg tablets in single doses of 7.5/325 mg (one tablet), 15/650 mg (two tablets), or 30/1,300 mg (four tablets) under fasted or fed conditions. Six variables were examined: sex, race, age, weight, height, and body mass index. Single-dose population PK was analyzed using first-order conditional estimation methods. A total of 151 participants were included in the analysis under fasted conditions, and 31 participants were included in the fed analysis. Under fasted conditions, a 10% change in body weight was accompanied by ~7.5% change in total body clearance (CL/F) and volume of distribution (V/F) of OC and APAP. Black participants had 17.3% lower CL/F and a 16.9% lower V/F of OC compared with white participants. Under fed conditions, the absorption rate constant of OC and APAP decreased significantly, although there was no effect on CL/F and V/F. Considering that the recommended dose for IR/ER OC/APAP 7.5/325 mg tablets is two tablets every 12 hours, adjustments of <50% are not clinically relevant. Dose adjustment may be necessary for large deviations from average body weight, but the small PK effects associated with race and consumption of a meal are not clinically relevant. PMID:26316698

  6. Pooled post hoc analysis of population pharmacokinetics of oxycodone and acetaminophen following a single oral dose of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets.

    PubMed

    Franke, Ryan M; Morton, Terri; Devarakonda, Krishna

    2015-01-01

    This analysis evaluated the single-dose population pharmacokinetics (PK) of biphasic immediate-release (IR)/extended-release (ER) oxycodone (OC)/acetaminophen (APAP) 7.5/325 mg tablets administered under fasted conditions and the effects of a meal on their single-dose population PK. Data were pooled from four randomized, single-dose crossover trials enrolling healthy adult (18-55 years old) participants (three trials) and nondependent recreational users of prescription opioids (one trial) with a body weight of ≥59 kg. Participants received IR/ER OC/APAP 7.5/325 mg tablets in single doses of 7.5/325 mg (one tablet), 15/650 mg (two tablets), or 30/1,300 mg (four tablets) under fasted or fed conditions. Six variables were examined: sex, race, age, weight, height, and body mass index. Single-dose population PK was analyzed using first-order conditional estimation methods. A total of 151 participants were included in the analysis under fasted conditions, and 31 participants were included in the fed analysis. Under fasted conditions, a 10% change in body weight was accompanied by ~7.5% change in total body clearance (CL/F) and volume of distribution (V/F) of OC and APAP. Black participants had 17.3% lower CL/F and a 16.9% lower V/F of OC compared with white participants. Under fed conditions, the absorption rate constant of OC and APAP decreased significantly, although there was no effect on CL/F and V/F. Considering that the recommended dose for IR/ER OC/APAP 7.5/325 mg tablets is two tablets every 12 hours, adjustments of <50% are not clinically relevant. Dose adjustment may be necessary for large deviations from average body weight, but the small PK effects associated with race and consumption of a meal are not clinically relevant. PMID:26316698

  7. Where there is no morphine: The challenge and hope of palliative care delivery in Tanzania

    PubMed Central

    Dean, Mervyn; Hartwig, Kari; Mmbando, Paul Z.; Sayed, Abduraoof; de Vries, Elma

    2014-01-01

    Abstract Background In Tanzania, a country of 42 million, access to oral morphine is rare. Aim To demonstrate the effectiveness of palliative care teams in reducing patients’ pain and in increasing other positive life qualities in the absence of morphine; and to document the psychological burden experienced by their clinical providers, trained in morphine delivery, as they observed their patients suffering and in extreme pain. Setting One hundred and forty-five cancer patients were included from 13 rural hospitals spread across Tanzania. Method A mixed method study beginning with a retrospective quantitative analysis of cancer patients who were administered the APCA African POS tool four times. Bivariate analyses of the scores at time one and four were compared across the domains. The qualitative arm included an analysis of interviews with six nurses, each with more than five years’ palliative care experience and no access to strong opioids. Results Patients and their family caregivers identified statistically significant (p < 0.001) improvements in all of the domains. Thematic analysis of nurse interviews described the patient and family benefits from palliative care but also their great distress when ‘bad cases’ arose who would likely benefit only from oral morphine. Conclusion People living with chronic cancer-related pain who receive palliative care experience profound physical, spiritual and emotional benefits even without oral morphine. These results demonstrate the need for continued advocacy to increase the availability of oral morphine in these settings in addition to palliative care services. PMID:26245417

  8. Evaluation of NK and LAK cell activities in neoplastic patients during treatment with morphine.

    PubMed

    Provinciali, M; Di Stefano, G; Raffaeli, W; Pari, G; Desiderio, F; Fabris, N

    1991-07-01

    The cytotoxic activity of Natural Killer (NK) and Lymphokine Activated Killer (LAK) cells in neoplastic patients with or without antalgic treatment was studied. NK cell activity was found reduced in untreated neoplastic patients when compared to healthy subjects. The atalgic treatment with morphine (orally or intrathecally administered) was able to significantly reduce the mean values of NK cell activity found in cancer patients. In three patients the cytotoxicity of NK cells significantly decreased during transfer from oral to intrathecal administration of morphine. In contrast to the NK cell function, the development of LAK cell activity significantly increased in neoplastic patients when compared to healthy controls. Further increments were obtained during treatment with morphine. The oral treatment with morphine was able to determine a higher induction of LAK cells than the intrathecal administration of the drug. Besides providing new knowledge on the effect of morphine on immune system our findings suggest that, in order to include neoplastic patients in clinical trials of adoptive immunotherapy with LAK cells and interleukin-2 (IL-2), the antalgic therapy with oral administration of morphine may represent a better solution than the intrathecal administration of the drug. PMID:1774133

  9. Use of sedation and ropivacaine-morphine epidural for femoral head and neck ostectomy in a dog.

    PubMed

    Aarnes, T K; Hubbell, J A E; Hildreth, B E

    2014-06-01

    A five-year-old male German shepherd dog presented with traumatic craniodorsal luxation of the right coxofemoral joint with pre-existing moderate hip dysplasia. A femoral head and neck ostectomy was performed. The patient was sedated with acepromazine and morphine administered intramuscularly. A lumbosacral epidural was performed using a combination of morphine and ropivacaine. Intraoperatively, an infusion of medetomidine, morphine, lidocaine, and ketamine was administered intravenously, and oxygen was administered via facemask. Heart rate, respiratory rate and oscillometric arterial blood pressures were monitored. Postoperatively, carprofen was administered once subcutaneously. On the day of hospital discharge, carprofen and tramadol were administered orally every 12 hours. Twenty-one days later, the dog was doing well and the surgical staples were removed. Sedation with acepromazine and morphine, administration of an epidural containing morphine and ropivacaine, and intraoperative sedation with medetomidine, morphine, lidocaine and ketamine were suitable for femoral head and neck ostectomy. PMID:24602054

  10. Epidural buprenorphine or morphine for the relief of head and neck cancer pain.

    PubMed Central

    Hashimoto, Y.; Utsumi, T.; Tanioka, H.; Rigor, B. M.

    1991-01-01

    We present three cases in which epidural buprenorphine or morphine was used for intractable cancer pain of the head and neck. Excellent pain relief and minimal side effects offered by epidural opioids were of significant benefit. The use of epidural opioids prior to the administration of high doses of oral morphine may be the treatment of choice for pain from malignancy of the head and neck, especially when there is tumor extension or distant metastasis. PMID:1811431

  11. [Opium (heroin * morphine)].

    PubMed

    Hiramatsu, Masayuki

    2010-08-01

    The number of people dependent on opiate drugs, including heroin, is still high, and these abused drugs are major social issues, both in the social science and medically. The mechanisms of physical dependence and withdrawal symptoms in laboratory animals are becoming clear; however, no useful method to detoxify abusers with opioid dependence in clinical situation has been established, and alternative therapy with methadone, used in Europe and America, cannot be used in Japan. Here, I will outline the global trend of opium abuse, including heroin and morphine, and summarize the problems of heroin abuse. PMID:20715484

  12. A (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer)-dispersed sustained-release tablet for imperialine to simultaneously prolong the drug release and improve the oral bioavailability.

    PubMed

    Lin, Qing; Fu, Yu; Li, Jia; Qu, Mengke; Deng, Li; Gong, Tao; Zhang, Zhirong

    2015-11-15

    Imperialine, extracted from Bulbus Fritillariae Cirrhosae, is an efficient antitussive and expectorant medicine. However, its short half-life and stomach degradation limited imperialine from further clinical use. The current study was conducted to develop a sustained-release tablet for imperialine both to prolong absorption time and to improve the oral bioavailability of the drug. The tablets were prepared by a direct compression method formulated on optimized solid dispersion (SD) for imperialine based on polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus(®)) with imperialine/Soluplus(®) ratio of 1:8 (w/w). In order to obtain the optimized formulation, factors that affected the drug release were investigated by in vitro dissolution studies in the media of pH1.2, 5.8, 7.0 and 7.4. Powder X-ray diffraction and scanning electron microscope confirmed that the imperialine in SD was amorphous instead of crystalline, and still stayed amorphous even after the direct compression. And besides, pharmacokinetic study in Beagle dogs was performed to inspect the in vivo sustained release. Plasma concentration-time curves and pharmacokinetic parameters were gained. As a result, the Cmax of imperialine was one-fold reduced and Tmax was two-fold prolonged, and the mean AUC0-24 was expressed as 89.581±21.243μgh/L, which showed that the oral bioavailability of imperialine was 2.46-fold improved. Moreover, the in vitro-in vivo correlation was recommended to carry out, demonstrating the percentages of drug release in vitro were well-correlated with the absorptive fraction in vivo with the correlation coefficients above 0.9900. By mathematically modeling and moment imaging of the drug release, Peppas equation was selected as the most fitted model for the sustained-release tablets with the diffusional coefficient in the range of 0.59-0.62, indicating the release of imperialine from the sustained-release tablets was an anomalous process involving

  13. Investigation of the bioequivalence of montelukast chewable tablets after a single oral administration using a validated LC-MS/MS method

    PubMed Central

    Zaid, Abdel Naser; Abualhasan, Murad N; Watson, David G; Mousa, Ayman; Ghazal, Nadia; Bustami, Rana

    2015-01-01

    Background Montelukast (MT) is a leukotriene D4 antagonist. It is an effective and safe medicine for the prophylaxis and treatment of chronic asthma. It is also used to prevent acute exercise-induced bronchoconstriction and as a symptomatic relief of seasonal allergic rhinitis and perennial allergic rhinitis. Objective The aim of this study was to evaluate the bioequivalence (BE) of two drug products: generic MT 5 mg chewable tablets versus the branded drug Singulair® pediatric 5 mg chewable tablets among Mediterranean volunteers. Methods An open-label, randomized two-period crossover BE design was conducted in 32 healthy male volunteers with a 9-day washout period between doses and under fasting conditions. The drug concentrations in plasma were quantified by using a newly developed and fully validated liquid chromatography tandem mass spectrometry method, and the pharmacokinetic parameters were calculated using a non-compartmental model. The ratio for generic/branded tablets using geometric least squares means was calculated for both the MT products. Results The relationship between concentration and peak area ratio was found to be linear within the range 6.098–365.855 ng/mL. The correlation coefficient (R2) was always greater than 0.99 during the course of the validation. Statistical comparison of the main pharmacokinetic parameters showed no significant difference between the generic and branded products. The point estimates (ratios of geometric means) were 101.2%, 101.6%, and 98.11% for area under the curve (AUC)0→last, AUC0→inf, and Cmax, respectively. The 90% confidence intervals were within the predefined limits of 80.00%–125.00% as specified by the US Food and Drug Administration and European Medicines Agency for BE studies. Conclusion Broncast® pediatric chewable tablets (5 mg/tablet) are bioequivalent to Singulair® pediatric chewable tablets (5 mg/tablet), with a similar safety profile. This suggests that these two formulations can be

  14. Role of various natural, synthetic and semi-synthetic polymers on drug release kinetics of losartan potassium oral controlled release tablets

    PubMed Central

    Jayasree, J.; Sivaneswari, S.; Hemalatha, G.; Preethi, N.; Mounika, B.; Murthy, S. Vasudeva

    2014-01-01

    Objective: The objective of the present work was to formulate and to characterize controlled release matrix tablets of losartan potassium in order to improve bioavailability and to minimize the frequency of administration and increase the patient compliance. Materials and Methods: Losartan potassium controlled release matrix tablets were prepared by direct compression technique by the use of different natural, synthetic and semisynthetic polymers such as gum copal, gum acacia, hydroxypropyl methyl cellulose K100 (HPMC K100), eudragit RL 100 and carboxy methyl ethyl cellulose (CMEC) individually and also in combination. Studies were carried out to study the influence of type of polymer on drug release rate. All the formulations were subjected to physiochemical characterization such as weight variation, hardness, thickness, friability, drug content, and swelling index. In vitro dissolution studies were carried out simulated gastric fluid (pH 1.2) for first 2 h and followed by simulated intestinal fluid (pH 6.8) up to 24 h, and obtained dissolution data were fitted to in vitro release kinetic equations in order to know the order of kinetics and mechanism of drug release. Results and Discussion: Results of physiochemical characterization of losartan potassium matrix tablets were within acceptable limits. Formulation containing HPMC K100 and CMEC achieved the desired drug release profile up to 24 h followed zero order kinetics, release pattern dominated by Korsmeyer — Peppas model and mechanism of drug release by nonfickian diffusion. The good correlation obtained from Hixson-Crowell model indicates that changes in surface area of the tablet also influences the drug release. Conclusion: Based on the results, losartan potassium controlled release matrix tablets prepared by employing HPMC K100 and CMEC can attain the desired drug release up to 24 h, which results in maintaining steady state concentration and improving bioavailability. PMID:25426439

  15. Serotonin syndrome probably triggered by a morphine-phenelzine interaction.

    PubMed

    Mateo-Carrasco, Hector; Muñoz-Aguilera, Eva María; García-Torrecillas, Juan Manuel; Abu Al-Robb, Hiba

    2015-06-01

    Serotonin syndrome is a potentially life-threatening condition caused by excessive central and peripheral stimulation of serotonin brainstem receptors, usually triggered by inadvertent interactions between agents with serotonergic activity. Evidence supporting an association between nonserotonergic opiates, such as oxycodone or morphine, and serotonin syndrome is very limited and even contradictory. In this case report, we describe a patient who developed serotonergic-adverse effects likely precipitated by an interaction between morphine and phenelzine. A 57-year-old woman presented to the emergency department with complaints of increasing visual hallucinations, restlessness, photophobia, dizziness, neck stiffness, occipital headache, confusion, sweating, tachycardia, and nausea over the previous week. On admission, her blood pressure was 185/65 mm Hg, and clonus was noted in the lower extremities. The patient was hospitalized 10 days earlier for cellulitis of the left breast secondary to a left mastectomy 5 months earlier, and a short course of oral morphine was prescribed for pain control. Her routine medications consisted of aspirin, atorvastatin, bisoprolol, clopidogrel, gabapentin, omeprazole, phenelzine, and ramipril. Supportive measures were initiated on admission. Phenelzine and morphine were discontinued immediately, leading to a progressive resolution of symptoms over the next 48 hours. Phenelzine was restarted on discharge without further complications. Use of the Drug Interaction Probability Scale indicated a probable relationship (score of 6) between the patient's development of serotonin syndrome and the combination of morphine and phenelzine. The mechanism underlying this interaction, however, remains unclear and warrants further investigation. Clinicians should carefully weigh the risk and benefits of initiating morphine in patients taking monoamine oxidase inhibitors or any other serotonin-enhancing drugs. PMID:25903219

  16. Sensitivity of quantitative sensory models to morphine analgesia in humans

    PubMed Central

    Olesen, Anne Estrup; Brock, Christina; Sverrisdóttir, Eva; Larsen, Isabelle Myriam; Drewes, Asbjørn Mohr

    2014-01-01

    Introduction Opioid analgesia can be explored with quantitative sensory testing, but most investigations have used models of phasic pain, and such brief stimuli may be limited in the ability to faithfully simulate natural and clinical painful experiences. Therefore, identification of appropriate experimental pain models is critical for our understanding of opioid effects with the potential to improve treatment. Objectives The aim was to explore and compare various pain models to morphine analgesia in healthy volunteers. Methods The study was a double-blind, randomized, two-way crossover study. Thirty-nine healthy participants were included and received morphine 30 mg (2 mg/mL) as oral solution or placebo. To cover both tonic and phasic stimulations, a comprehensive multi-modal, multi-tissue pain-testing program was performed. Results Tonic experimental pain models were sensitive to morphine analgesia compared to placebo: muscle pressure (F=4.87, P=0.03), bone pressure (F=3.98, P=0.05), rectal pressure (F=4.25, P=0.04), and the cold pressor test (F=25.3, P<0.001). Compared to placebo, morphine increased tolerance to muscle stimulation by 14.07%; bone stimulation by 9.72%; rectal mechanical stimulation by 20.40%, and reduced pain reported during the cold pressor test by 9.14%. In contrast, the more phasic experimental pain models were not sensitive to morphine analgesia: skin heat, rectal electrical stimulation, or rectal heat stimulation (all P>0.05). Conclusion Pain models with deep tonic stimulation including C fiber activation and and/or endogenous pain modulation were more sensitive to morphine analgesia. To avoid false negative results in future studies, we recommend inclusion of reproducible tonic pain models in deep tissues, mimicking clinical pain to a higher degree. PMID:25525384

  17. Analgesic effects of dextromethorphan and morphine in patients with chronic pain.

    PubMed

    Heiskanen, Tarja; Härtel, Brita; Dahl, Marja-Liisa; Seppälä, Timo; Kalso, Eija

    2002-04-01

    N-methyl-aspartate (NMDA) receptor antagonists have been shown to improve opioid analgesia in the animal model. The cough suppressant dextromethorphan is a clinically available NMDA-receptor antagonist. In this randomised, double-blind, placebo-controlled study 20 patients with chronic pain of several years duration were given 100 mg of oral dextromethorphan or matching placebo 4 h prior to an intravenous infusion of morphine 15 mg. Pain intensity and adverse effects were assessed at 0, 4, 5 and 7 h. Dextromethorphan had no effect on morphine analgesia: the mean (+/-SEM) visual analogue scores for pain relief (VAS, 0-100 mm) at the end of the morphine infusion were 38 (+/-6) for dextromethorphan+morphine and 38 (+/-7) for placebo+morphine. VAS scores for pain intensity were comparable both at rest and at movement at all time points. The most common adverse effects reported were dizziness, nausea and sedation. There were no significant differences in either the incidence or severity of adverse effects. In conclusion, oral dextromethorphan 100 mg had no effect on pain relief by intravenous morphine 15 mg in patients with chronic pain. PMID:11972998

  18. 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…

  19. Inhibition by morphine and morphine-like drugs of nicotine-induced emesis in cats.

    PubMed

    Beleslin, D B; Krstić, S K; Stefanović-Denić, K; Strbac, M; Mićić, D

    1981-05-01

    The effect of morphine, methadone and pethidine injected into the cerebral ventricle of the unanesthetized cat upon emesis produced by nicotine induced similarly was investigated. Morphine and morphine-like drugs depress or abolish the emetic effect of nicotine. The inhibitory effect of morphine, methadone and pethidine is observed after a transient emetic action of these drugs. The emetic and anti-emetic action of morphine, methadone and pethidine can perhaps be ascribed to an agonist/antagonist activity. Further, the possible site of inhibitory action of morphine and morphine-like drugs on the emesis produced by nicotine may be the area postrema of fourth ventricle. PMID:7248811

  20. 21 CFR 520.2150b - Stanozolol chewable tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Stanozolol chewable tablets. 520.2150b Section 520.2150b 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 § 520.2150b Stanozolol chewable tablets. (a) Specifications....

  1. 21 CFR 520.88f - Amoxicillin trihydrate tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Amoxicillin trihydrate tablets. 520.88f Section 520.88f 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 § 520.88f Amoxicillin trihydrate tablets. (a) Specifications....

  2. 21 CFR 520.90b - Ampicillin trihydrate tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ampicillin trihydrate tablets. 520.90b Section 520.90b 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 § 520.90b Ampicillin trihydrate tablets. (a) Specifications. Each...

  3. 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 (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2220d Sulfadimethoxine-ormetoprim tablets....

  4. 21 CFR 520.2220d - Sulfadimethoxine-ormetoprim tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Sulfadimethoxine-ormetoprim tablets. 520.2220d Section 520.2220d 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 § 520.2220d Sulfadimethoxine-ormetoprim tablets....

  5. 21 CFR 520.1157 - Iodinated casein tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Iodinated casein tablets. 520.1157 Section 520.1157 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 § 520.1157 Iodinated casein tablets. (a) Specifications. Each 1-gram...

  6. 21 CFR 520.420 - Chlorothiazide tablets and boluses.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Chlorothiazide tablets and boluses. 520.420 Section 520.420 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 § 520.420 Chlorothiazide tablets and boluses. (a)(1)...

  7. 21 CFR 520.2220d - Sulfadimethoxine-ormetoprim tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Sulfadimethoxine-ormetoprim tablets. 520.2220d Section 520.2220d 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 § 520.2220d Sulfadimethoxine-ormetoprim tablets....

  8. 21 CFR 520.2220d - Sulfadimethoxine-ormetoprim tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Sulfadimethoxine-ormetoprim tablets. 520.2220d Section 520.2220d 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 § 520.2220d Sulfadimethoxine-ormetoprim tablets....

  9. 21 CFR 520.2220d - Sulfadimethoxine-ormetoprim tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Sulfadimethoxine-ormetoprim tablets. 520.2220d Section 520.2220d 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 § 520.2220d Sulfadimethoxine-ormetoprim tablets....

  10. 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) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.784 Doxylamine succinate tablets. (a) Specifications. The drug...

  11. 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 (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.82a Aminopropazine fumarate tablets. (a) Specifications....

  12. 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 520.1193 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 § 520.1193 Ivermectin tablets and chewables. (a) Specifications....

  13. Bronchoscopic and histological changes over time following acute ferrous sulphate tablet aspiration.

    PubMed

    Maw, Matthew; Chiu, Robert; Lim, Albert Yick Hou

    2012-01-01

    An 84-year-old woman accidentally aspirated an iron tablet. She was successfully treated with early endobronchial removal of the iron tablet remnants, oral corticosteroids and antibiotics. We describe the bronchoscopic and histological changes over time following acute iron tablet aspiration and highlight the importance of early intervention to avoid complications. PMID:23257641

  14. Morphine, morphine-6-glucuronide and morphine-3-glucuronide pharmacokinetics in newborn infants receiving diamorphine infusions.

    PubMed

    Barrett, D A; Barker, D P; Rutter, N; Pawula, M; Shaw, P N

    1996-06-01

    1. The pharmacokinetics of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) were studied in 19 ventilated newborn infants (24-41 weeks gestation) who were given a loading dose of 50 micrograms kg-1 or 200 micrograms kg-1 of diamorphine followed by an intravenous infusion of 15 micrograms kg-1 h-1 of diamorphine. Plasma concentrations of morphine, M3G and M6G were measured during the accrual to steady-state and at steady state of the diamorphine infusion. 2. Following both the 50 micrograms kg-1 or 200 micrograms kg-1 loading doses the mean steady-state plasma concentration (+/- s.d.) of morphine, M3G and M6G were 86 +/- 52 ng ml-1, 703 +/- 400 ng ml-1 and 48 +/- 28 ng ml-1 respectively and morphine clearance was found to be 4.6 +/- 3.2 ml min-1 kg-1. 3. M3G formation clearance was estimated to be 2.5 +/- 1.8 ml min-1 kg-1, and the formation clearance of M6G was estimated to be 0.46 +/- 0.32 ml min-1 kg-1. 4. M3G metabolite clearance was 0.46 +/- 0.60 ml min-1 kg-1, the elimination half-life was 11.1 +/- 11.3 h and the volume of distribution was 0.55 +/- 1.13 l kg-1. M6G metabolite clearance was 0.71 +/- 0.36 ml min-1 kg-1, the elimination half-life was 18.2 +/- 13.6 h and the volume of distribution was 1.03 +/- 0.88 l kg-1. 5. No significant effect of the loading dose (50 micrograms kg-1 or 200 micrograms kg-1) on the plasma morphine or metabolite concentrations or their derived pharmacokinetic parameters was found. 6. We were unable to identify correlations between gestational age of the infants and any of the determined pharmacokinetic parameters. 7. M3G: morphine and M6G: morphine steady-state plasma concentration ratios were 11.0 +/- 10.8 and 0.8 +/- 0.8, respectively. 8. The metabolism of morphine in neonates, in terms of the respective contributions of each glucuronide pathway, was similar to that in adults. PMID:8799518

  15. 21 CFR 520.2123a - Spectinomycin tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    .... (a) Specifications. Each tablet contains spectinomycin dihydrochloride pentahydrate equivalent to 100... use in dogs—(1) Amount. Administer orally to provide 10 mg per pound (lb) of body weight twice...

  16. 21 CFR 520.2150a - Stanozolol tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 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...

  17. 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...

  18. Role of prolactin in the modulation of NK and LAK cell activity after short- or long-term morphine administration in neoplastic patients.

    PubMed

    Provinciali, M; Di Stefano, G; Stronati, S; Raffaeli, W; Pari, G; Fabris, N

    1996-10-01

    In a previous work we demonstrated that chronic in vivo antalgic therapy of cancer patients with morphine reduced the endogenous cytotoxic activity of natural killer (NK) cells, while increasing the development of lymphokine activated killer (LAK) cell cytotoxicity. In order to investigate the mechanisms by which morphine affects NK and LAK cell function further, we evaluated the modulation exerted by short- or long-term morphine administration on either NK/LAK cell cytotoxicities or plasma levels of prolactin (PRL) and other immunomodulating neurohormones. An intravenous morphine injection (10 mg) significantly increased the plasma levels of PRL, reduced the cytotoxic activity of NK cells, and increased the development of LAK cell activity 30 min after drug injection in neoplastic patients. The administration of bromocriptine before the injection of morphine prevented both PRL augmentation and the increase in LAK cell activation, although it did not prevent the inhibition of NK cytotoxicity. The chronic oral administration of morphine (90 +/- 30 mg/day for 1 month) also resulted in higher PRL levels; the NK and LAK cell activities were, respectively, lower than or higher than those found in neoplastic patients untreated with morphine. The plasma levels of thyrotropin (TSH), adrenocorticotropic hormone (ACTH) and cortisol were not significantly modified in either short- or long-term experiments. The absolute number and the percentages of lymphocyte populations, as well as the percentage of IL-2 receptors, were not modified after short-term morphine administration whereas little changes of T lymphocyte populations and NK cell number were observed after oral treatment with morphine. In vitro morphine did not affect the development of LAK cell activity. In conclusion, our findings indicate that morphine reduces NK cytotoxicity and increases the development of LAK cell cytotoxicity after short- and long-term administration. The effect of morphine on LAK cell activation

  19. Evaluation of menstrual cycle effects on morphine and pentazocine analgesia

    PubMed Central

    Ribeiro-Dasilva, MC; Shinal, RM; Glover, T; Williams, RS; Staud, R; Riley, JL; Fillingim, RB

    2011-01-01

    Studies have demonstrated menstrual cycle influences on basal pain perception, but direct evidence of menstrual cycle influences on analgesic responses has not been reported in humans. Our aim was to determine whether the magnitude of morphine and pentazocine analgesia varied across the menstrual cycle. Sixty-five healthy women, 35 taking oral contraceptives (OC) and 30 normally cycling (NOC), underwent experimental pain assessment both before and after intravenous administration morphine (0.08 mg/kg) or pentazocine (0.5 mg/kg) compared to saline placebo. Both active drug and placebo were administered once during the follicular phase and once during the luteal phase. Measures of heat, ischemic and pressure pain sensitivity were obtained before and after drug administration. Change scores in pain responses were computed to determine morphine and pentazocine analgesic responses, and medication side effects were recorded. The data were analyzed using mixed-model ANOVAs. NOC women showed slightly greater heat pain sensitivity in the follicular vs. luteal phase, while the reverse pattern emerged for OC women (p=0.046). Also, OC women showed lower pressure pain thresholds compared to NOC women (p < .05). Regarding analgesic responses, NOC women showed greater morphine analgesia for ischemic pain during the follicular vs. the luteal phase (p=0.004). Likewise, side effects for morphine were significantly higher in NOC women in the follicular phase than in the luteal phase (p=0.02). These findings suggest that sex hormones may influence opioid responses; however, the effects vary across medications and pain modalities and are likely to be modest in magnitude. PMID:21239109

  20. Minocycline suppresses morphine-induced respiratory depression, suppresses morphine-induced reward, and enhances systemic morphine-induced analgesia

    PubMed Central

    Hutchinson, Mark R.; Northcutt, Alexis L.; Chao, Lindsey W.; Kearney, Jeffrey J.; Zhang, Yingning; Berkelhammer, Debra L.; Loram, Lisa C.; Rozeske, Robert R.; Bland, Sondra T.; Maier, Steven F.; Gleeson, Todd T.; Watkins, Linda R.

    2008-01-01

    Recent data suggest that opioids can activate immune-like cells of the central nervous system (glia). This opioid-induced glial activation is associated with decreased analgesia, owing to the release of proinflammatory mediators. Here we examine in rats whether the putative microglial inhibitor, minocycline, may affect morphine-induced respiratory depression and/or morphine-induced reward (conditioned place preference). Systemic co-administration of minocycline significantly attenuated morphine-induced reductions in tidal volume, minute volume, inspiratory force and expiratory force, but did not affect morphine-induced reductions in respiratory rate. Minocycline attenuation of respiratory depression was also paralleled with significant attenuation by minocycline of morphine-induced reductions in blood oxygen saturation. Minocycline also attenuated morphine conditioned place preference. Minocycline did not simply reduce all actions of morphine, as morphine analgesia was significantly potentiated by minocycline co-administration. Lastly, morphine dose-dependently increased cyclooxygenase-1 gene expression in a rat microglial cell line, an effect that was dose-dependently blocked by minocycline. Together, these data support that morphine can directly activate microglia in a minocycline-suppressible manner and suggest a pivotal role for minocycline-sensitive processes in the mechanisms of morphine-induced respiration depression, reward, and pain modulation. PMID:18706994

  1. Tablet Splitting: A Risky Practice

    MedlinePlus

    ... and splitting tablets in an effort to save money. Regarding the practice of splitting tablets, the Food ... tablet. So a patient may try to save money by buying the 30 mg tablets and splitting ...

  2. [Sustained-release Opioids: Morphine, Oxycodone and Tapentadol].

    PubMed

    Takahashi, Yoshika; Iseki, Masako

    2015-11-01

    Opioid analgesics are widely used for managing moderate to severe pain. In cancer pain management sustained-release opioids are used for continuous pain as well as immediate-release opioids for breakthrough pain. Sustained-release drugs have the advantage of stabilizing the blood concentration, although it takes some time to exert their effects. In Japan, the currently available oral sustained-release opioids include six types of sustained-release morphine (three are once-a-day formulations, while the rest are twice-a-day), one type of oxycodone and tapentadol. In this article, we will discuss the pharmacokinetic properties of MS Contin, Morphes, Kadian, P guard and Pacif as sustained-release morphine, Oxycontin as sustained-release oxycodone and Tapenta as sustained-release tapentadol. PMID:26689063

  3. The on- and off-target effects of morphine in acute coronary syndrome: A narrative review.

    PubMed

    McCarthy, Cian P; Mullins, Kieran V; Sidhu, Sunjeet S; Schulman, Steven P; McEvoy, John W

    2016-06-01

    With potent analgesic properties, perceived hemodynamic benefits and limited alternatives, morphine is the analgesic mainstay for patients with nitrate resistant chest pain due to acute Myocardial Infarction (MI). However, observational data suggest that morphine administration during MI may have negative consequences. While vomiting, hypotension and respiratory depression are established side effects, recent reports have demonstrated attenuated and delayed oral anti-platelet agent absorption, as well as suboptimal reperfusion after MI, all of which may translate into adverse cardiovascular outcomes. These data have resulted in reduced support for morphine in recent European and U.S. clinical practice guidelines for MI; despite the absence of any prospective randomized outcomes trials addressing this question. As such, randomized trials are now necessary to confirm whether or not morphine, which is administered in up to 30% of MI cases, causes adverse clinical outcomes in these patients. However, given that placebo-controlled randomized trial designs evaluating morphine in MI are limited by an ethical requirement for appropriate analgesia, alternative investigational approaches may be necessary. In this article we review the updated evidence for morphine in MI and outline novel strategies that may facilitate future investigation of this clinical dilemma. PMID:27264228

  4. 21 CFR 520.1451 - Moxidectin tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 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 § 520.1451 Moxidectin tablets. (a... Dirofilaria immitis and the subsequent development of canine heartworm disease. (3) Limitations. Use...

  5. 21 CFR 520.1451 - Moxidectin tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 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 § 520.1451 Moxidectin tablets. (a... Dirofilaria immitis and the subsequent development of canine heartworm disease. (3) Limitations. Use...

  6. 21 CFR 520.1451 - Moxidectin tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 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 § 520.1451 Moxidectin tablets. (a... Dirofilaria immitis and the subsequent development of canine heartworm disease. (3) Limitations. Use...

  7. 21 CFR 520.1451 - Moxidectin tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 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 § 520.1451 Moxidectin tablets. (a... Dirofilaria immitis and the subsequent development of canine heartworm disease. (3) Limitations. Use...

  8. 76 FR 51037 - Determination That Halflytely and Bisacodyl Tablets Bowel Prep Kit (Containing Two Bisacodyl...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-17

    ... (polyethylene glycol (PEG) 3350, sodium chloride, sodium bicarbonate, and potassium chloride for oral solution... potassium chloride for oral solution and two bisacodyl delayed release tablets, 5 mg. FOR FURTHER... Bisacodyl Tablets Bowel Prep Kit (PEG- 3350, sodium chloride, sodium bicarbonate, and potassium chloride...

  9. A Single-Dose, Single-Period Pharmacokinetic Assessment of an Extended-Release Orally Disintegrating Tablet of Methylphenidate in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

    PubMed Central

    Childress, Ann; Newcorn, Jeffrey; Stark, Jeffrey G.; McMahen, Russ; Tengler, Mark

    2016-01-01

    Abstract Objective: To determine the pharmacokinetic (PK) profile of a proprietary formulation of methylphenidate (MPH) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in a phase 1 study. Methylphenidate extended-release orally disintegrating tablets (MPH XR-ODTs) combine two technologies in a single-tablet formulation—an extended-release profile that was designed for once-daily dosing in an ODT that does not require water or chewing for ingestion. Methods: This was a single-dose, open-label, single-period, single-treatment study, in which 32 children with ADHD who were receiving MPH in doses of 40 or 60 mg before beginning the study each received a 60-mg dose (2 × 30 mg) of MPH XR-ODT. The following plasma PK parameters of MPH were determined for participants grouped by age (6–7, 8–9, 10–12, and 13–17 years old): maximum concentration (Cmax), time to maximum concentration (Tmax), elimination half-life (T½), area under the curve from 0 hours to infinity (AUCinf), oral clearance (CL/F), and volume of distribution in the terminal phase (Vz/F). Safety and tolerability were also assessed. Results: A total of 32 participants received the study drug. For all participants, plasma concentration–time profiles of MPH exhibited a broad peak after administration of MPH XR-ODT through ∼8 hours, indicating extended release from the formulation, followed by an apparent first-order elimination phase. As age increased, MPH exposure decreased and mean estimates of CL/F increased; however, weight-normalized CL/F values were comparable across age groups. Similarly, mean estimates of Vz/F increased with age, but weight-normalization decreased differences across age groups, with the exception of the youngest age group, which had higher values. All adverse events (AEs) were mild. Conclusion: This XR-ODT formulation of MPH demonstrated weight-normalized clearance rates that were consistent across all age groups, a PK profile

  10. Can coadministration of oxycodone and morphine produce analgesic synergy in humans? An experimental cold pain study

    PubMed Central

    Grach, Michael; Massalha, Wattan; Pud, Dorit; Adler, Rivka; Eisenberg, Elon

    2004-01-01

    Aims The coadministration of subantinociceptive doses of oxycodone with morphine has recently been shown to result in a synergistic antinociceptive effect in rats. The present study was aimed to investigate the possibility that coadministration of morphine and oxycodone can produce a similar synergistic effect in humans exposed to an experimental model of cold pressor test (CPT). Methods The enriched enrolment design was used to exclude ‘stoic’ and ‘placebo responders’ in a single-blind fashion. ‘Nonstoic’, placebo ‘nonresponder’ female volunteers (n = 30) were randomly assigned to receive 0.5 mg kg−1 oral morphine sulphate, 0.5 mg kg−1 oral oxycodone hydrochloride, and the combination of 0.25 mg kg−1 morphine sulphate with 0.25 mg kg−1 oxycodone hydrochloride, 1 week apart from each other, in a double-blind crossover design. Latency to pain onset (threshold), pain intensity (VAS), and pain tolerance (time until removal of the hand from the water) were measured six times over a 3-h period, subsequent to the administration of each medication, and were used to assess their antinociceptive effect. Results The combination produced a significantly higher effect on latency to pain onset than that of morphine alone [difference in mean postbaseline value 2.2; 95% confidence interval (CI) 0.48, 3.9; P = 0.01] but the effect was nonsignificantly smaller that that of oxycodone alone. Similarly, the effect of the combination on pain tolerance was significantly larger than that of morphine alone (combination difference 8.4; 95% CI 2.5, 14.3; P = 0.007), whereas oxycodone alone caused a nonsignificantly larger effect than that of the combination treatment. Comparisons of pain magnitude failed to show any significant differences between the three treatments. Conclusions These results indicate that at the doses tested, morphine and oxycodone do not produce synergistic antinociceptive effects in healthy humans exposed to the CPT. PMID:15327582

  11. An investigation into the influence of experimental conditions on in vitro drug release from immediate-release tablets of levothyroxine sodium and its relation to oral bioavailability.

    PubMed

    Kocic, Ivana; Homsek, Irena; Dacevic, Mirjana; Parojcic, Jelena; Miljkovic, Branislava

    2011-09-01

    The aim of this study was to investigate the influence of experimental conditions on levothyroxine sodium release from two immediate-release tablet formulations which narrowly passed the standard requirements for bioequivalence studies. The in vivo study was conducted as randomised, single-dose, two-way cross-over pharmacokinetic study in 24 healthy subjects. The in vitro study was performed using various dissolution media, and obtained dissolution profiles were compared using the similarity factor value. Drug solubility in different media was also determined. The in vivo results showed narrowly passing bioequivalence. Considering that levothyroxine sodium is classified as Class III drug according to the Biopharmaceutics Classification System, drug bioavailability will be less sensitive to the variation in its dissolution characteristics and it can be assumed that the differences observed in vitro in some of investigated media probably do not have significant influence on the absorption process, as long as rapid and complete dissolution exists. The study results indicate that the current regulatory criteria for the value of similarity factor in comparative dissolution testing, as well as request for very rapid dissolution (more than 85% of drug dissolved in 15 min), are very restricted for immediate-release dosage forms containing highly soluble drug substance and need further investigation. The obtained results also add to the existing debate on the appropriateness of the current bioequivalence standards for levothyroxine sodium products. PMID:21748540

  12. Simultaneous quantification of chlorogenic acid and taurocholic acid in human plasma by LC-MS/MS and its application to a pharmacokinetic study after oral administration of Shuanghua Baihe tablets.

    PubMed

    Gu, Pan; Liu, Rui-Juan; Cheng, Min-Lu; Wu, Yao; Zheng, Lu; Liu, Yu-Jie; Ma, Peng-Cheng; Ding, Li

    2016-04-01

    An LC-MS/MS method was developed and validated for the simultaneous quantification of chlorogenic acid (CGA) and taurocholic acid (TCA) in human plasma using hydrochlorothiazide as the internal standard. The chromatographic separation was achieved on a Hedera ODS-2 column with a gradient elution using 10 mmol·L(-1) of ammonium acetate buffer solution containing 0.5% of formic acid - acetonitrile as mobile phase at a flow rate of 300 μL·min(-1). The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring in negative ESI mode. The method was fully validated over the concentration ranges of 0.1-10 ng·mL(-1) for CGA and 2-150 ng·mL(-1) for TCA. It was successfully applied to a pharmacokinetic study of CGA and TCA in healthy Chinese volunteers after oral administration of Shuanghua Baihe tablets (SBTs). In the single-dose study, the maximum plasma concentration (Cmax), time to reach Cmax (Tmax) and elimination half-life (t1/2) of CGA were (0.763 8 ± 0.542 0) ng·mL(-1), (1.0 ± 0.5) h, and (1.3 ± 0.6) h, respectively. In the multiple-dose study, the Cmax, Tmax and t1/2 of CGA were (0.663 7 ± 0.583 3) ng·mL(-1), (1.1 ± 0.5) h, and (1.4 ± 0.7) h, respectively. For TCA, no significant characteristic increasing plasma TCA concentration-time curve was found in the volunteers after oral administration of SBTs, indicating its complicated process in vivo as an endogenous ingredient. PMID:27114321

  13. Morphine, morphine-6-glucuronide and morphine-3-glucuronide pharmacokinetics in newborn infants receiving diamorphine infusions

    PubMed Central

    BARRETT, D. A.; BARKER, D. P.; RUTTER, N.; PAWULA, M.; SHAW, P. N.

    1996-01-01

    1The pharmacokinetics of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) were studied in 19 ventilated newborn infants(24–41 weeks gestation) who were given a loading dose of 50 μg kg−1 or 200 μg kg−1 of diamorphine followed by an intravenous infusion of 15 μg kg−1 h−1 of diamorphine. Plasma concentrations of morphine, M3G and M6G were measured during the accrual to steady-state and at steady state of the diamorphine infusion. 2Following both the 50 μg kg−1 or 200 μg kg−1 loading doses the mean steady-state plasma concentration (±s.d.) of morphine, M3G and M6G were 86±52 ng ml−1, 703±400 ng ml−1 and 48±28 ng ml−1 respectively and morphine clearance was found to be 4.6±3.2 ml min−1 kg−1. 3M3G formation clearance was estimated to be 2.5±1.8 ml min−1 kg−1, and the formation clearance of M6G was estimated to be 0.46±0.32 ml min−1 kg−1. 4M3G metabolite clearance was 0.46±0.60 ml min−1 kg−1, the elimination half-life was 11.1±11.3 h and the volume of distribution was 0.55±1.13 l kg−1. M6G metabolite clearance was 0.71±0.36 ml min−1 kg−1, the elimination half-life was 18.2±13.6 h and the volume of distribution was 1.03±0.88 l kg−1. 5No significant effect of the loading dose (50 μg kg−1 or 200 μg kg−1) on the plasma morphine or metabolite concentrations or their derived pharmacokinetic parameters was found. 6We were unable to identify correlations between gestational age of the infants and any of the determined pharmacokinetic parameters. 7M3G:morphine and M6G:morphine steady-state plasma concentration ratios were 11.0±10.8 and 0.8±0.8, respectively. 8The metabolism of morphine in neonates, in terms of the respective contributions of each glucuronide pathway, was similar to that in adults. PMID:8799518

  14. Simultaneous determination of four phenolic acids and seven alkaloids in rat plasma after oral administration of traditional Chinese medicinal preparation Jinqi Jiangtang Tablet by LC-ESI-MS/MS.

    PubMed

    Chang, Yan-xu; Ge, Ai-hua; Yu, Xie-an; Jiao, Xiu-cheng; Li, Jin; He, Jun; Tian, Ji; Liu, Wei; Azietaku, John Teye; Zhang, Bo-li; Gao, Xiu-mei

    2016-01-01

    A rapid, sensitive and selective high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of four phenolic acids (neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid and ferulic acid) and seven alkaloids (berberine, epiberberine, coptisine, magnoflorine, berberubine, palmatine and jatrorrhizine) in rat plasma. After mixing with the internal standards tetrahydropalmatine (IS1) and rosmarinic acid (IS2), plasma samples were pretreated by protein precipitation using acetonitrile. The HPLC analysis was performed on an Agilent Eclipse plus C18 (4.6 mm×100 mm, 1.8 μm) column with mobile phase consisting of 0.1% formic acid aqueous solution and acetonitrile at a flow rate of 0.3 mL min(-1). The detection was accomplished for the analytes and internal standards using positive electrospray ionization for the alkaloids and negative electrospray ionization for the phenolic acids in multiple-reaction monitoring mode. The method showed a good linearity over a wide concentration range (r(2)>0.99). The lower limit of quantification of seven alkaloids was lower than 2 ng mL(-1) and that of four phenolic acids was less than 20 ng mL(-1). The developed method was applied to the pharmacokinetic study of 11 components after oral administration of traditional Chinese medicinal preparation Jinqi Jiangtang Tablet in rats. PMID:26340557

  15. Simultaneous determination of ginsenoside Rb1, naringin, ginsenoside Rb2 and oridonin in rat plasma by LC-MS/MS and its application to a pharmacokinetic study after oral administration of Weifuchun tablet.

    PubMed

    Jin, Yiran; Tian, Tingting; Ma, Yinghua; Xu, Huijun; Du, Yingfeng

    2015-09-01

    A sensitive, specific and rapid liquid chromatography-mass spectrometry (LC-MS) method was developed and validated for analysis of ginsenoside Rb1, naringin, ginsenoside Rb2 and oridonin in rat plasma using sulfamethoxazole as an internal standard (IS). Separation was conducted out on an Agilent Eclipse XDB C18 column with liner gradient elution using acetonitrile (A) and 0.1% aqueous acetic acid (B). A tandem mass spectrometric detection was conducted using multiple reaction monitoring (MRM) via an electrospray ionization (ESI) source. A novel multi-determination-periods program was executed to achieve a higher sensitivity by setting three scanning periods. All analytes exhibited good linearity within the concentration range (r>0.9973). The lower limits of quantitation (LLOQ) of ginsenoside Rb1, naringin, ginsenoside Rb2 and oridonin were 2.64, 4.32, 2.32 and 1.56ng/mL, respectively. Intra-day and inter-day precisions of the investigated components exhibited an RSD within 8.3%, and the accuracy (RE) ranged from -8.6% to 6.0% at all quality control levels. The developed method was successfully applied to a pharmacokinetic study of ginsenoside Rb1, naringin, ginsenoside Rb2 and oridonin in rats after oral administration of a Weifuchun tablet. PMID:26222904

  16. A paper-based lateral flow assay for morphine.

    PubMed

    Teerinen, Tuija; Lappalainen, Timo; Erho, Tomi

    2014-09-01

    Morphine was used as a model analyte to examine the possibility of using cellulose, physically modified by papermaking and converting techniques, as a capillary matrix in a lateral flow type of diagnostic assay. This research was directed toward low-cost, disposable, and portable paper-based diagnostics, with the aim of addressing the analytical performance of paper as a substrate in the analysis for drugs of abuse. Antibody Fab fragments were used as sensing molecules, and gold nanoparticle detection was employed. Inkjet printing was used to pattern sensing biomolecules as detection zones on paper. To validate the usefulness of paper as a diagnostic platform, the principle of a direct sandwich assay, based on immunocomplex formation between morphine and the anti-morphine Fab fragment and detection of the formed immunocomplex by another Fab fragment, was implemented. Results were compared with that achieved by using nitrocellulose as a reference material. Possible interfering from the sample matrix on assay quality was investigated with spiked oral fluid samples. Under optimized conditions, a visually assessed limit of detection for the sandwich assay was 1 ng/mL, indicating that the paper-based test devices developed in this work can perform screening for drugs of abuse and can fulfill the requirement for a sensitive assay in diagnostically relevant ranges. PMID:25023970

  17. Accuracy of tablet splitting.

    PubMed

    McDevitt, J T; Gurst, A H; Chen, Y

    1998-01-01

    We attempted to determine the accuracy of manually splitting hydrochlorothiazide tablets. Ninety-four healthy volunteers each split ten 25-mg hydrochlorothiazide tablets, which were then weighed using an analytical balance. Demographics, grip and pinch strength, digit circumference, and tablet-splitting experience were documented. Subjects were also surveyed regarding their willingness to pay a premium for commercially available, lower-dose tablets. Of 1752 manually split tablet portions, 41.3% deviated from ideal weight by more than 10% and 12.4% deviated by more than 20%. Gender, age, education, and tablet-splitting experience were not predictive of variability. Most subjects (96.8%) stated a preference for commercially produced, lower-dose tablets, and 77.2% were willing to pay more for them. For drugs with steep dose-response curves or narrow therapeutic windows, the differences we recorded could be clinically relevant. PMID:9469693

  18. Urinary concentrations of morphine and codeine after consumption of poppy seeds.

    PubMed

    Thevis, Mario; Opfermann, Georg; Schänzer, Wilhelm

    2003-01-01

    A quantitative analysis of morphine and codeine in human urine was performed after oral intake of cakes containing commercially available poppy seeds in order to estimate the possibility of positive doping results. Therefore, eight products from different manufacturers (poppy seeds or baking mixtures) and origin were obtained and analyzed by gas chromatography-mass spectrometry for the presence of the alkaloids. One selected batch of poppy seeds was used as an ingredient in a typical cake and was the object of an excretion study with nine volunteers. After application, several urine specimens contained morphine with concentrations higher than 1 microg/mL, and peak values of approximately 10.0 microg/mL were detected. Because the International Olympic Committee set a cutoff limit for morphine at 1 microg/mL, high-performance athletes could possibly test positive in doping control after consumption of products containing poppy seeds. PMID:12587685

  19. Social influences on morphine sensitization in adolescent females.

    PubMed

    Hofford, Rebecca S; Roberts, Kris W; Wellman, Paul J; Eitan, Shoshana

    2010-08-01

    We recently observed that social interactions influence morphine responsiveness in adolescent males. Given sex-related differences in both social interactions and responses to morphine, the present study examines social influences on morphine sensitization in adolescent female mice. Four experimental groups were examined: (1) morphine-treated mice (twice daily, 10-40 mg/kg, s.c.) housed physically and visually separated from saline-treated mice ('morphine only'), (2) morphine-treated mice housed together with saline-treated mice ('morphine cage-mates (of saline)'), (3) saline-treated mice housed together with morphine-treated mice ('saline cage-mates (of morphine)'), and (4) saline-treated mice housed physically and visually separated from morphine-treated mice ('saline only'). Following the treatment period, mice were tested individually for their locomotor response to 20 mg/kg morphine (s.c.). There were no significant differences in morphine-induced hyper-locomotion between saline only and saline cage-mates (of morphine) female adolescent mice. Notably, morphine only mice exhibited significantly greater morphine sensitization as compared to morphine cage-mates (of saline). Thus, this study demonstrates social influences on morphine sensitization in adolescent females. Drug use during early adolescence is a key predictor of later drug abuse and dependence during adulthood. Thus, understanding the specific vulnerabilities to drug use in this age group may represent a first step in helping develop more effective treatment programs. PMID:20456874

  20. Absorption of morphine from a slow-release emulsion used to induce morphine dependence in rats.

    PubMed

    Salem, A; Hope, W

    1998-10-01

    This study was performed to measure absorption of morphine from the injection site following treatment of rats with slow-release emulsions formulated with morphine hydrochloride and morphine base. Samples of emulsion were collected from the injection site of halothane anesthetized animals at 24 and 48 h following emulsion treatment and concentrations of morphine remaining in the emulsion were analyzed using high-performance liquid chromatography (HPLC). In another group of morphine-treated rats, at times equivalent to collecting samples of emulsion, the intensity of naloxone-precipitated withdrawal behaviors was monitored. Both morphine base- and hydrochloride-containing emulsions induced a high degree of physical dependence in animals treated over 48 h. Release of morphine from emulsions containing morphine base was slower than that from the hydrochloride formulations. In the 24-h morphine base-treated animals, approximately 45% was absorbed from the injection site as opposed to 99% in the 24-h morphine hydrochloride-treated animals. These results suggest that morphine base containing emulsions provide a more sustained exposure to the opioid. PMID:10334632

  1. Preparation and pharmaceutical evaluation of acetaminophen nano-fiber tablets: Application of a solvent-based electrospinning method for tableting.

    PubMed

    Hamori, Mami; Nagano, Kana; Kakimoto, Sayaka; Naruhashi, Kazumasa; Kiriyama, Akiko; Nishimura, Asako; Shibata, Nobuhito

    2016-03-01

    In this study, we developed nano-fiber-based tablets with acetaminophen (AAP; LogPow=0.51) for controlled-release delivery systems and evaluated in vitro drug dissolution and in vivo pharmacokinetics in rats. Nano-fibers made from methacrylic acid copolymer S (MAC; EUDRAGIT(®) S100) and containing AAP were prepared using a solvent-based electrospinning (ES) method. In vitro dissolution rate profiles of AAP showed tableting pressure-dependent decreases and pH-dependent increases. The results of tablet tracking by X-ray irradiation showed tablets based on MAC nano-fibers did not disintegrate in the upper intestinal lumen and had the properties of a long-term-acting tablet. In addition, the in vitro release profiles of AAP from nano-fiber tablets prepared by dissolving MAC with AAP (NFT), nano-fiber tablets prepared by adsorbing AAP to drug-free MAC nano-fibers (NFTadso), and tablets prepared by adsorbing half the amount of AAP to MAC nano-fibers containing the remaining amount of AAP (NFThalf) showed independent controlled-release aspects of AAP compared with physical mixture tablets (PMT). In vivo pharmacokinetic studies in rats after intraduodenal administration of 14mg/rat AAP in NFT, NFTadso, and NFThalf demonstrated that all these tablets based on MAC nano-fibers showed sustained-release profiles compared with PMT, and showed ultra-sustained release properties for AAP. These new tablets based on MAC nano-fibers did not disintegrate in the intestine in the lower pH region, and the tablets could regulate the release of AAP in a pH-dependent manner. The ES method is a useful technique to prepare nano-fibers and showed promising results as an oral delivery system for sustained-release regulation. PMID:26898420

  2. Can personality traits and gender predict the response to morphine? An experimental cold pain study.

    PubMed

    Pud, Dorit; Yarnitsky, David; Sprecher, Elliot; Rogowski, Zeev; Adler, Rivka; Eisenberg, Elon

    2006-02-01

    The aim of the present study was to examine the possible role of personality traits, in accordance with Cloninger's theory, and gender, in the variability of responsiveness to opioids. Specifically, it was intended to test whether or not the three personality dimensions - harm avoidance (HA), reward dependence (RD) and novelty seeking (NS) - as suggested by Cloninger, can predict inter-personal differences in responsiveness to morphine after exposure to experimental cold pain. Thirty-four healthy volunteers (15 females, 19 males) were given the cold pressor test (CPT). Pain threshold, tolerance, and magnitude (VAS) were measured before and after (six measures, 30 min apart) the administration of either 0.5 mg/kg oral morphine sulphate (n=21) or 0.33 mg/kg oral active placebo (diphenhydramine) (n=13) in a randomized, double blind design. Assessment of the three personality traits, according to Cloninger's Tridimensional Personality Questionnaire, was performed before the CPT. A high HA score (but not RD, NS, or baseline values of the three pain parameters) predicted a significantly larger pain relief following the administration of morphine sulphate (but not of the placebo). Women exhibited a larger response in response to both treatments, as indicated by a significantly increased threshold and tolerance following morphine sulphate as well as significantly increased tolerance and decreased magnitude following placebo administration. The present study confirms the existence of individual differences in response to analgesic treatment. It suggests that high HA personality trait is associated with better responsiveness to morphine treatment, and that females respond better than men to both morphine and placebo. PMID:16310713

  3. Delay of Morphine Tolerance by Palmitoylethanolamide

    PubMed Central

    Di Cesare Mannelli, Lorenzo; Corti, Francesca; Micheli, Laura; Zanardelli, Matteo; Ghelardini, Carla

    2015-01-01

    In spite of the potency and efficacy of morphine, its clinical application for chronic persistent pain is limited by the development of tolerance to the antinociceptive effect. The cellular and molecular mechanisms underlying morphine tolerance are complex and still unclear. Recently, the activation of glial cells and the release of glia-derived proinflammatory mediators have been suggested to play a role in the phenomenon. N-Palmitoylethanolamine (PEA) is an endogenous compound with antinociceptive effects able to reduce the glial activation. On this basis, 30 mg kg−1 PEA was subcutaneously daily administered in morphine treated rats (10 mg kg−1 intraperitoneally, daily). PEA treatment significantly attenuated the development of tolerance doubling the number of days of morphine antinociceptive efficacy in comparison to the vehicle + morphine group. PEA prevented both microglia and astrocyte cell number increase induced by morphine in the dorsal horn; on the contrary, the morphine-dependent increase of spinal TNF-α levels was not modified by PEA. Nevertheless, the immunohistochemical analysis revealed significantly higher TNF-α immunoreactivity in astrocytes of PEA-protected rats suggesting a PEA-mediated decrease of cytokine release from astrocyte. PEA intervenes in the nervous alterations that lead to the lack of morphine antinociceptive effects; a possible application of this endogenous compound in opioid-based therapies is suggested. PMID:25874232

  4. Synthetic substances with morphine-like effect

    PubMed Central

    Braenden, Olav J.; Eddy, Nathan B.; Halbach, H.

    1955-01-01

    For morphine-, morphinan-, pethidine-, methadone-, and dithienyl-butenylamine groups of analgesic compounds a systematic survey is given of how analgesic activity is quantitatively affected by alteration of the chemical constitution. Features common to the structural formulae of substances with morphine-like analgesic effect are pointed out. ImagesFIG. 1FIG. 1(Contd.) PMID:13284565

  5. Novel approach of aceclofenac fast dissolving tablet.

    PubMed

    Dave, Vivek; Yadav, Sachdev; Sharma, Swapnil; Vishwakarma, Pushpendra; Ali, Nasir

    2015-01-01

    Fast disintegrating tablets (FDTs) have received ever increasing demand during the last decade, and the field has become a hastily growing area in the pharmaceutical industry. Upon introduction into the mouth, these tablets dissolve or disintegrate in the mouth in the absence of additional water for easy administration of active pharmaceutical ingredients. Aceclofenac, an NSAID, has been recommended orally for the treatment of bone and connective tissue disorder and thus the formulation of the same resulted in development of several FDT technologies. The present aim is to formulate a tablet which disintegrate and dissolve rapidly and give its rapid onset of action: analgesic, antipyretic and anti-inflammatory action. Besides, the conventional tablets also show poor patient compliance an attempt had been made to formulate for FDT of aceclofenac by using various super disintegrants like sodium starch glycolate, croscarmellose sodium and crosspovidone (polyplasdone XL) and PEG 6000 followed by novel technique. The tablets were evaluated for friability, hardness, weight variation, disintegration time, wetting time, in vitro dissolution studies and drug content studies. It was concluded that the batch which was prepared by using combination of crosspovidone and sodium starch glycolate as a super disintegrant shows excellent disintegration time, enhance dissolution rate, taste masking and hence lead to improve efficacy and bioavailability of drug. PMID:25553683

  6. Intrathecal morphine for post-thoracotomy pain.

    PubMed

    Gray, J R; Fromme, G A; Nauss, L A; Wang, J K; Ilstrup, D M

    1986-08-01

    We wished to investigate possible differences in the duration of postoperative analgesia and the incidence of respiratory depression after the intrathecal injection in the lumbar area of 10 micrograms/kg morphine in hypobaric and hyperbaric solution for relief of post-thoracotomy pain. Twenty-nine patients received morphine plus dextrose (hyperbaric) and 21 received morphine in preservative-free normal saline. The duration of analgesia was longer with the morphine in the normal saline group than in the hyperbaric group (P less than 0.04). One patient developed delayed respiratory depression. Our data support the use of morphine in normal saline mixtures for greater duration of analgesia after thoracic operations. PMID:3755305

  7. 21 CFR 862.3640 - Morphine test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Morphine test system. 862.3640 Section 862.3640....3640 Morphine test system. (a) Identification. A morphine test system is a device intended to measure morphine, an addictive narcotic pain-relieving drug, and its analogs in serum, urine, and gastric...

  8. 21 CFR 862.3640 - Morphine test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Morphine test system. 862.3640 Section 862.3640....3640 Morphine test system. (a) Identification. A morphine test system is a device intended to measure morphine, an addictive narcotic pain-relieving drug, and its analogs in serum, urine, and gastric...

  9. 21 CFR 862.3640 - Morphine test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Morphine test system. 862.3640 Section 862.3640....3640 Morphine test system. (a) Identification. A morphine test system is a device intended to measure morphine, an addictive narcotic pain-relieving drug, and its analogs in serum, urine, and gastric...

  10. The combination of mitragynine and morphine prevents the development of morphine tolerance in mice.

    PubMed

    Fakurazi, Sharida; Rahman, Shamima Abdul; Hidayat, Mohamad Taufik; Ithnin, Hairuszah; Moklas, Mohamad Aris Mohd; Arulselvan, Palanisamy

    2013-01-01

    Mitragynine (MG) is the major active alkaloid found in Mitragyna speciosa Korth. In the present study, we investigated the enhancement of analgesic action of MG when combined with morphine and the effect of the combination on the development of tolerance towards morphine. Mice were administered intraperitoneally with a dose of MG (15 and 25 mg/kg b.wt) combined with morphine (5 mg/kg b.wt) respectively for 9 days. The antinociceptive effect was evaluated by a hot plate test. The protein expression of cyclic adenosine monophosphate (cAMP) and cAMP response element binding (CREB) was analyzed by immunoblot. Toxicological parameters especially liver and kidney function tests were assessed after the combination treatment with MG and morphine. The concurrent administration of MG and morphine showed significant (p < 0.05) increase in latency time when compared to morphine alone group and the outstanding analgesic effects in the combination regimens were maintained until day 9. For the protein expression, there was a significant increment of cAMP and CREB levels (p < 0.05) in group treated with 5 mg/kg morphine but there was no significant change of these protein expressions when MG was combined with morphine. There was a significant changes in toxicological parameters of various treated groups. The combination treatment of MG and morphine effectively reduce the tolerance due to the chronic administration of morphine. PMID:23292329

  11. Formulation of novel nano-encapsulated Newcastle disease vaccine tablets for vaccination of village chickens.

    PubMed

    Wambura, Philemon N

    2011-01-01

    Formulation of nano-encapsulated vaccine tablet is a novel technique for the delivery of Newcastle disease (ND) vaccine to village chickens. Vaccine tablets were prepared using gelatin, trehalose and casein as thermostabilisers and binders, respectively, and each vaccine tablet contained a nominal oral dose of Newcastle disease virus (NDV) strain I-2 for a single chicken. These ND vaccine tablets maintained a titre of 10(8.5) EID(50)/0.1 mL for 90 days at ambient room temperatures (25-34°C). When these vaccine tablets were given to village chickens, a single oral administration of the vaccine produced protective antibody response (≥3.0 log(2)) against challenge with virulent NDV. The findings from the present study showed that, if the vaccine tablet formulation technique is optimised, it will allow the delivery of the ND vaccine without depending on cold chains to rural areas in tropical countries. PMID:20683657

  12. Morphine-theophylline interaction: antagonism or facilitation?

    PubMed Central

    Brailowsky, S.; Guerrero-Muñoz, F.; Luján, M.; Shkurovich, M.

    1981-01-01

    1 Morphine-theophylline interactions were investigated in both acute and narcotic-dependent preparations, in vitro and in vivo, using four different experimental models: LD50 doses of morphine and naloxone in the mouse; naloxone-induced contractions in the electrically-stimulated and opiate-dependent isolated ileum of the guinea-pig; naloxone-induced jumps in the mouse; an calcium uptake in synaptosomal preparations. 2 The LD50 of morphine was significantly increased by theophylline. 3 The lethal effect of theophylline was potentiated by pretreatment of the animals with naloxone. 4 Theophylline displayed protective effects in the inhibitory response to morphine and antagonism to the withdrawal response induced by naloxone in the electrically-stimulated isolated ileum of the guinea-pig. 5 The number of jumps induced by naloxone in morphine-dependent mice was significantly diminished by theophylline. 6 The inhibitory effect of morphine on the synaptosomal uptake of calcium was decreased by theophylline. 7 The effects of both morphine and theophylline on the cyclic nucleotides and the possible role of calcium in these actions are discussed. PMID:7272590

  13. Effect of morphine on synaptosomal Ca++ uptake.

    PubMed

    Guerrero-Munoz, F; Cerreta, K V; Guerrero, M L; Way, E L

    1979-04-01

    The effect of morphine on the uptake of 45Ca++ was studied in synaptosomes from mouse brain using two procedures, centrifugation and filtration. The addition of morphine (1.7 x 10(-7) or 3.4 x 10(-7) M) reduced 45CA++ uptake by either technique, although the basal 45Ca++ uptake by the filtration method was approximately 7-fold higher than that by the centrifugation procedure. Similar effects were obtained after acute morphine treatment with 10 mg/kg s.c. Previous naloxone in vitro treatment (1.9 x 10(-8) M) or in vivo administration (2 mg/kg s.c.) reversed the morphine inhibition of the 45Ca++ uptake. On the other hand, after the animal was rendered tolerant and dependent by morphine pellet implantation, an enhancement of the synaptosomal 45Ca++ uptake was observed. It is concluded that changes in Ca++ fluxes in synaptosomes observed after acute and chronic morphine treatment may be involved with morphine pharmacological action related with analgesia, tolerance and physical dependence. PMID:571016

  14. Photoaffinity labeling of opioid receptor with morphine-7,8-oxide (morphine epoxide)

    SciTech Connect

    Takayanagi, I.; Shibata, R.; Miyata, N.; Hirobe, M.

    1982-05-01

    The opioid receptor mediating inhibitory action of morphine in the electrically stimulated guinea pig ileum was irreversibly photoinactivated by morphine epoxide (3 X 10(-6) M). Morphine epoxide (up to 3 X 10(-5) M) did not influence the responses of rat vas deferens (epsilon-receptor) or rabbit vas deferens (kappa-receptor) to electrical stimulation. Effective concentrations of morphine epoxide were much lower in the guinea pig ileum (mu-receptor) than in the mouse vas deference (delta-receptor). The inhibitory action of (Met)-enkephalin on the twitch responses of the rat vas deferens and mouse vas deferens to electrical stimulation were not influenced after irradiation in the presence of morphine epoxide (3 X 10(-6) M). Therefore, morphine epoxide is probably a useful probe for photoaffinity labeling of the mu-receptor in vitro.

  15. Effect of environmental enrichment on physical and psychological dependence signs and voluntary morphine consumption in morphine-dependent and morphine-withdrawn rats.

    PubMed

    Hammami-Abrand Abadi, Arezoo; Miladi-Gorji, Hossein; Bigdeli, Imanollah

    2016-04-01

    This study was designed to examine the effect of environmental enrichment during morphine dependency and withdrawal on the severity of naloxone-precipitated withdrawal signs, anxiety, and depressive-like behaviors and voluntary morphine consumption in morphine-dependent rats. The rats were injected with bi-daily doses (10 mg/kg, 12 h intervals) of morphine for 14 days following rearing in a standard environment (SE) or enriched environment (EE) during the development of morphine dependence and withdrawal. Then, rats were tested for withdrawal signs after naloxone injection, anxiety (the elevated plus maze) and depression-related behavior (sucrose preference test), and voluntary consumption of morphine using a two-bottle choice paradigm, in morphine-dependent and morphine-withdrawn rats. The results showed that EE decreased naloxone-precipitated withdrawal signs, but not anxiety or sucrose preference during dependence on morphine. The EE-withdrawn rats showed an increase in the elevated plus maze open arm time and entries and higher levels of sucrose preference than SE rats. Voluntary consumption of morphine was lower in the EE-withdrawn rats than in the SE groups in the second period of drug intake. Thus, exposure to EE reduced the severity of morphine dependence and voluntary consumption of morphine, alongside reductions in anxiety and depression-related behavior in morphine-withdrawn rats. PMID:26397757

  16. Yokukansan inhibits morphine tolerance and physical dependence in mice: the role of α₂A-adrenoceptor.

    PubMed

    Nakagawa, T; Nagayasu, K; Nishitani, N; Shirakawa, H; Sekiguchi, K; Ikarashi, Y; Kase, Y; Kaneko, S

    2012-12-27

    Yokukansan (YKS) is a traditional Japanese medicine consisting of seven medicinal herbs that is used for the treatment of neurosis, insomnia, and the behavioral/psychological symptoms of dementia. This study examined the effects of YKS on morphine tolerance and physical dependence in mice. Daily oral administration of YKS (0.5 or 1.0 g/kg) for 3 weeks significantly attenuated morphine tolerance and naloxone-precipitated morphine withdrawal signs (jumps and body weight loss) without affecting the analgesic effect of morphine. The inhibitory effect of YKS on withdrawal jumps in morphine-dependent mice was blocked by a single pretreatment with an α(2)-adrenoceptor antagonist, yohimbine, but not by an α(1)-adrenoceptor antagonist, prazosin. A similar inhibitory effect on withdrawal jumps was observed by repeated administration of yohimbine. The membrane expression of α(2A)-adrenoceptors in the pons/medulla was decreased in morphine withdrawn animals; this reduction was prevented by repeated administration of YKS or yohimbine. Competitive radioligand and [(35)S]guanosine-5'-O-(3-thiotriphosphate) binding assays revealed that YKS and its constituent herbs, Glycyrrhiza (GR) and Uncaria hook (UH), had specific binding affinity for and antagonist activity against the α(2A)-adrenoceptor. Certain chemical constituents, including GR -derived glycyrrhizin and its metabolite, 18β-glycyrrhetinic acid, and UH-derived geissoschizine methyl ether (GME), shared such activities. Repeated administration of GR, UH, glycyrrhizin or GME significantly inhibited morphine withdrawal signs. These results suggest that YKS and its active constituents inhibit morphine tolerance and physical dependence, and that the latter is due at least in part to the prevention of the decreased membrane expression of the α(2A)-adrenoceptor in the brainstem by its prolonged blockade. PMID:23069764

  17. Evaluation of rapidly disintegrating tablets manufactured by phase transition of sugar alcohols.

    PubMed

    Kuno, Yoshio; Kojima, Masazumi; Ando, Shuichi; Nakagami, Hiroaki

    2005-06-20

    The aim of the present study was to assess the properties of rapidly disintegrating (RD) tablets manufactured by the phase transition method. RD tablets were produced by compressing powder containing erythritol (melting point: 122 degrees C) and xylitol (melting point: 93 approximately 95 degrees C), and then heating at about 93 degrees C for 15 min. The hardness and oral disintegration time of the heated tablets increased with an increase of the xylitol content. These results suggested that the heating process and xylitol content might influence the properties of RD tablets. Then we evaluated the physicochemical properties of the RD tablets, including the median pore size, crystallinity, hardness, and oral disintegration time of tablets made with and without heating. After heating, the median pore size of the tablets was increased and tablet hardness was also increased. The increase of tablet hardness with heating and storage did not depend on the crystal state of the lower melting point sugar alcohol. It is concluded that a combination of low and high melting point sugar alcohols, as well as a phase transition in the manufacturing process, are important for making RD tablets without any special apparatus. PMID:15955365

  18. 21 CFR 520.2260c - Sulfamethazine sustained-release tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Sulfamethazine sustained-release tablets. 520.2260c Section 520.2260c 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 § 520.2260c Sulfamethazine sustained-release tablets....

  19. 21 CFR 520.2260c - Sulfamethazine sustained-release tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Sulfamethazine sustained-release tablets. 520.2260c Section 520.2260c 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 § 520.2260c Sulfamethazine sustained-release tablets....

  20. 21 CFR 520.2260c - Sulfamethazine sustained-release tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Sulfamethazine sustained-release tablets. 520.2260c Section 520.2260c 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 § 520.2260c Sulfamethazine sustained-release tablets....

  1. 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.

  2. Is intramuscular morphine satisfying frontline medical personnels’ requirement for battlefield analgesia in Helmand Province, Afghanistan? A questionnaire study

    PubMed Central

    Gibson, Lorna M; Claydon, Michael A

    2015-01-01

    Background: All deployed British Army personnel carry intramuscular (IM) morphine auto-injectors to treat battlefield casualties. No other nation supplies parenteral opiate analgesia on individual issue. Studies highlight this agent’s inefficacy and safety issues, but are limited by a relative lack of inclusion of frontline personnel. We aimed to determine the opinions of frontline medical personnel on current battlefield analgesia. Methods: We surveyed 88 British Army frontline medical personnel (medical officers (n = 12), nurses (n = 7), combat medical technicians (CMTs) (n = 67), paramedics (n = 1) and health-care assistants (n = 1)) upon completion of a six-month deployment (September 2011 to April 2012) to Helmand Province, Afghanistan, using Likert scale questions on the efficacy of battlefield analgesia, complications of IM morphine, safety of morphine auto-injectors and its suitability for treating child casualties. Results: A total of 88/88 questionnaires were returned. Of these, 61/88 had treated casualties on the battlefield, 26/86 agreed that current battlefield analgesia is effective, 80/87 agreed that a more potent analgesic with a faster onset than IM morphine is desirable in the first hour following injury, 47/65 CMTs agreed that they can manage complications of current battlefield analgesia and 53/86 respondents correctly disagreed that current battlefield analgesia is suitable for child casualties. The potential for accidental self-injection was reported. Conclusions: A more potent, faster onset analgesic than IM morphine is desirable in the first hour following injury. Pre-deployment training should emphasise management of complications of opiate analgesics and treatment of child casualties. Oral transmucosal fentanyl citrate is now being issued to all frontline medical personnel. IM morphine will remain on individual issue to all deployed soldiers for environments where an oral agent is not suitable, for example, chemical, biological

  3. Morphine is an arteriolar vasodilator in man

    PubMed Central

    Afshari, Reza; Maxwell, Simon R J; Webb, David J; Bateman, D Nicholas

    2009-01-01

    AIM The mechanisms of action of morphine on the arterial system are not well understood. The aim was to report forearm vascular responses, and their mediation, to intra-arterial morphine in healthy subjects. METHODS Three separate protocols were performed: (i) dose ranging; (ii) acute tolerance; (iii) randomized crossover mechanistic study on forearm blood flow (FBF) responses to intrabrachial infusion of morphine using venous occlusion plethysmography. Morphine was infused either alone (study 1 and 2), or with an antagonist: naloxone, combined histamine-1 and histamine-2 receptor blockade or during a nitric oxide clamp. RESULTS Morphine caused an increase in FBF at doses of 30 µg min−1[3.25 (0.26) ml min−1 100 ml−1][mean (SEM)] doubling at 100 µg min−1 to 5.23 (0.53) ml min−1 100 ml−1. Acute tolerance was not seen to 50 µg min−1 morphine, with increased FBF [3.96 (0.35) ml min−1 100 ml−1] (P = 0.003), throughout the 30-min infusion period. Vasodilatation was abolished by pretreatment with antihistamines (P = 0.008) and the nitric oxide clamp (P < 0.001), but not affected by naloxone. The maximum FBF with pretreatment with combined H1/H2 blockade was 3.06 (0.48) and 2.90 (0.17) ml min−1 100 ml−1 after 30 min, whereas with morphine alone it reached 4.3 (0.89) ml min−1 100 ml−1. CONCLUSIONS Intra-arterial infusion of morphine into the forearm circulation causes vasodilatation through local histamine-modulated nitric oxide release. Opioid receptor mechanisms need further exploration. PMID:19371311

  4. Comparison of a drug versus money and drug versus drug self-administration choice procedure with oxycodone and morphine in opioid addicts.

    PubMed

    Comer, Sandra D; Metz, Verena E; Cooper, Ziva D; Kowalczyk, William J; Jones, Jermaine D; Sullivan, Maria A; Manubay, Jeanne M; Vosburg, Suzanne K; Smith, Mary E; Peyser, Deena; Saccone, Phillip A

    2013-09-01

    This double-blind, placebo-controlled study investigated the effects of oral morphine (0, 45, 135 mg/70 kg) and oral oxycodone (0, 15, 45 mg/70 kg) on buprenorphine-maintained opioid addicts. As a 3: 1 morphine : oxycodone oral dose ratio yielded equivalent subjective and physiological effects in nondependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures - that is, a drug versus money and a drug versus drug procedure - were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater than those of high-dose morphine. The study demonstrated that a 3: 1 oral dose ratio of morphine : oxycodone was not equipotent in buprenorphine-dependent individuals. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest. PMID:23839029

  5. Formulation and Evaluation of Omeprazole Tablets for Duodenal Ulcer

    PubMed Central

    Choudhury, A.; Das, S.; Bahadur, S.; Saha, S.; Roy, A.

    2010-01-01

    Omeprazole pellets containing mucoadhesive tablets were developed by direct punch method. Three mucoadhesive polymers namely hydroxypropylemethylcellulose K4M, sodium carboxy methylcellulose, carbopol-934P and ethyl cellulose were used for preparation of tablets which intended for prolong action may be due to the attachment with intestinal mucosa for relief from active duodenal ulcer. Mucoadhesive tablets were coated with respective polymer and coated with Eudragit L100 to fabricate enteric coated tablets. The prepared tablets were evaluated for different physical parameters and dissolution study were performed in three dissolution mediums like 0.1N hydrochloric acid for 2h, pH 6.5 and pH 7.8 phosphate buffer solution for 12hr. Sodium carboxymethylcellulose showed above 95% release within 10 h where as carbopol-934P showed slow release about 88% to 92% over a period of 12 h. having excellent mucoadhesive strength but ethyl cellulose containing tablets showed less than 65% release. The release mechanism of all formulation was diffusion controlled confirmed from Higuchi’s plot. Thus, the present study concluded that, carbopol-934P containing mucoadhesive tablets of omeprazole pellets can be used for local action in the ulcer disease as well as for oral controlled release drug delivery. PMID:21218061

  6. Orodispersible films and tablets with prednisolone microparticles.

    PubMed

    Brniak, Witold; Maślak, Ewelina; Jachowicz, Renata

    2015-07-30

    Orodispersible tablets (ODTs) and orodispersible films (ODFs) are solid oral dosage forms disintegrating or dissolving rapidly when placed in the mouth. One of the main issues related to their preparation is an efficient taste masking of a bitter drug substance. Therefore, the aim of this study was to prepare and evaluate the microparticles intended to mask a bitter taste of the prednisolone and use them in further preparation of two orodispersible dosage forms. Microparticles based on the Eudragit E PO or E 100 as a taste-masking agent were prepared with spray-drying technique. Tablets containing microparticles, co-processed ODT excipient Pharmaburst, and lubricant were directly compressed with single-punch tablet press. Orodispersible films were prepared by casting polymeric solutions of hydroxypropyl methylcellulose containing uniformly dispersed microparticles. Physicochemical properties of microparticles were evaluated, as well as mechanical properties analysis, disintegration time measurements and dissolution tests were performed for prepared dosage forms. Both formulations showed good mechanical resistance while maintaining excellent disintegration properties. The dissolution studies showed good masking properties of microparticles with Eudragit E 100. The amount of prednisolone released during the first minute in phosphate buffer 6.8 was around 0.1%. After incorporation into the orodispersible forms, the amount of released prednisolone increased significantly. It was probably the effect of faster microparticles wetting in orodispersible forms and their partial destruction by compression force during tableting process. PMID:25889975

  7. Morphine

    MedlinePlus

    ... breathing problems or other serious, life-threatening side effects. Tell your doctor if you are taking or plan to take any of the following medications: cimetidine (Tagamet); other narcotic pain medications; medications for anxiety, seizures, depression, mental illness, or nausea; muscle relaxants; ...

  8. Fast disintegrating tablets: Opportunity in drug delivery system

    PubMed Central

    Parkash, Ved; Maan, Saurabh; Deepika; Yadav, Shiv Kumar; Hemlata; Jogpal, Vikas

    2011-01-01

    Fast disintegrating tablets (FDTs) have received ever-increasing demand during the last decade, and the field has become a rapidly growing area in the pharmaceutical industry. Oral drug delivery remains the preferred route for administration of various drugs. Recent developments in the technology have prompted scientists to develop FDTs with improved patient compliance and convenience. Upon introduction into the mouth, these tablets dissolve or disintegrate in the mouth in the absence of additional water for easy administration of active pharmaceutical ingredients. The popularity and usefulness of the formulation resulted in development of several FDT technologies. FDTs are solid unit dosage forms, which disintegrate or dissolve rapidly in the mouth without chewing and water. FDTs or orally disintegrating tablets provide an advantage particularly for pediatric and geriatric populations who have difficulty in swallowing conventional tablets and capsules. This review describes various formulations and technologies developed to achieve fast dissolution/dispersion of tablets in the oral cavity. In particular, this review describes in detail FDT technologies based on lyophilization, molding, sublimation, and compaction, as well as approaches to enhancing the FDT properties, such as spray drying and use of disintegrants. In addition, taste-masking technologies, experimental measurements of disintegration times, and dissolution are also discussed. PMID:22247889

  9. Morphine and codeine concentrations in human urine following controlled poppy seeds administration of known opiate content.

    PubMed

    Smith, Michael L; Nichols, Daniel C; Underwood, Paula; Fuller, Zachary; Moser, Matthew A; LoDico, Charles; Gorelick, David A; Newmeyer, Matthew N; Concheiro, Marta; Huestis, Marilyn A

    2014-08-01

    Opiates are an important component for drug testing due to their high abuse potential. Proper urine opiate interpretation includes ruling out poppy seed ingestion; however, detailed elimination studies after controlled poppy seed administration with known morphine and codeine doses are not available. Therefore, we investigated urine opiate pharmacokinetics after controlled oral administration of uncooked poppy seeds with known morphine and codeine content. Participants were administered two 45 g oral poppy seed doses 8 h apart, each containing 15.7 mg morphine and 3mg codeine. Urine was collected ad libitum up to 32 h after the first dose. Specimens were analyzed with the Roche Opiates II immunoassay at 2000 and 300 μg/L cutoffs, and the ThermoFisher CEDIA(®) heroin metabolite (6-acetylmorphine, 6-AM) and Lin-Zhi 6-AM immunoassays with 10 μg/L cutoffs to determine if poppy seed ingestion could produce positive results in these heroin marker assays. In addition, all specimens were quantified for morphine and codeine by GC/MS. Participants (N=22) provided 391 urine specimens over 32 h following dosing; 26.6% and 83.4% were positive for morphine at 2000 and 300 μg/L GC/MS cutoffs, respectively. For the 19 subjects who completed the study, morphine concentrations ranged from <300 to 7522 μg/L with a median peak concentration of 5239 μg/L. The median first morphine-positive urine sample at 2000 μg/L cutoff concentration occurred at 6.6 h (1.2-12.1), with the last positive from 2.6 to 18 h after the second dose. No specimens were positive for codeine at a cutoff concentration of 2000 μg/L, but 20.2% exceeded 300 μg/L, with peak concentrations of 658 μg/L (284-1540). The Roche Opiates II immunoassay had efficiencies greater than 96% for the 2000 and 300 μg/L cutoffs. The CEDIA 6-AM immunoassay had a specificity of 91%, while the Lin-Zhi assay had no false positive results. These data provide valuable information for interpreting urine opiate results. PMID

  10. Modulation of morphine antinociception in the mouse by endogenous nitric oxide.

    PubMed Central

    Brignola, G; Calignano, A; Di Rosa, M

    1994-01-01

    1. L-Arginine (100-1000 mg kg-1) administered orally (p.o.) or intraperitoneally (i.p.), but not intracerebroventricularly (i.c.v., 0.08 mg per mouse), reduced the antinociceptive effect of morphine (0.5-10 mg kg-1 s.c.) assessed in mice using three different tests: hot plate, tail-flick and acetic acid-induced writhing. D-Arginine (up to 1000 mg kg-1 p.o. or i.p.) was ineffective. 2. NG-Monomethyl-L-arginine (L-NMMA, 5-50 mg kg-1 i.p.) and NG-nitro-L-arginine methyl ester (L-NAME, 5- 30 mg kg-1 i.p.), but not NG-nitro-D-arginine methyl ester (D-NAME, 30 mg kg-1 i.p.), reversed in all assays the effect of L-arginine on morphine-induced antinociception. 3. Morphine (10 mg kg-1 s.c.), L-arginine (1000 mg kg-1 p.o.) or L-NAME (30 mg kg-1 i.p.), either alone or in combination, did not produce changes in locomotor activity or sensorimotor performance of animals. 4. These results suggest that the L-arginine-nitric oxide pathway plays a modulating role in the morphine-sensitive nociceptive processes. PMID:7889294

  11. Pleiotrophin modulates morphine withdrawal but has no effects on morphine-conditioned place preference.

    PubMed

    Gramage, Esther; Vicente-Rodríguez, Marta; Herradón, Gonzalo

    2015-09-14

    Pleiotrophin (PTN) is a neurotrophic factor with important functions in addiction and neurodegenerative disorders. Morphine administration induces an increase in the expression of PTN and Midkine (MK), the only other member of this family of cytokines, in brain areas related with the addictive effects of drug of abuse, like the Ventral Tegmental Area or the hippocampus. In spite of previous studies showing that PTN modulates amphetamine and ethanol rewarding effects, and that PTN is involved in morphine-induced analgesia, it was still unknown if the rewarding effects of morphine may be regulated by endogenous PTN. Thus, we aim to study the role of PTN in the reward and physical dependence induced by morphine. We used the Conditioned Place Preference (CPP) paradigm in PTN genetically deficient (PTN-/-) and wild type (WT) mice to assess the rewarding effects of morphine in absence of endogenous PTN. Second, to study if PTN may be involved in morphine physical dependence, naloxone-precipitated withdrawal syndrome was induced in PTN-/- and WT morphine dependent mice. Although the increase in the time spent in the morphine-paired compartment after conditioning tended to be more pronounced in PTN-/- mice, statistical significance was not achieved. The data suggest that PTN does not exert an important role in morphine reward. However, our results clearly indicate that PTN-/- mice develop a more severe withdrawal syndrome than WT mice, characterized as a significant increase in the time standing and in the total incidences of forepaw licking, forepaw tremors, wet dog shake and writhing. The data presented here suggest that PTN is a novel genetic factor that plays a role in morphine withdrawal syndrome. PMID:26222257

  12. Evaluation of disintegrating time of rapidly disintegrating tablets by a paddle method.

    PubMed

    Que, Li; Wu, Wei; Cheng, Xiaofeng; Hu, Tao

    2006-01-01

    A paddle method for measurement of the disintegrating time of orally disintegrating tablets with rizatriptan benzoate as a model drug was evaluated. The paddle method employed a dissolution test assembly with tablets immersed in disintegrating medium through a fastened sinker. Paddle stirring rate, opening of the sinker sieve, and tablet crushing strength influenced disintegrating time greatly. A logarithmic relationship was observed between disintegrating time and paddle revolution speed, while disintegrating time values and tablet crushing strength were fitted to a linear equation. The paddle method values with limited deviation were in good correlation with in vivo results. The paddle method was employed to optimize the disintegrating time of rizatriptan benzoate orally disintegrating tablets using a factorial design. The best-fit quadratic equation with a regression coefficient of 0.996 was highly predictive, which was indicative that the paddle method was precise and applicable in formulation optimization. PMID:16895840

  13. Effects of morphine on the disposition of ampicillin in mice.

    PubMed Central

    Garty, M; Hurwitz, A

    1985-01-01

    Morphine raised the levels of intravenously administered ampicillin in the plasma of mice. Despite higher ampicillin levels in plasma after administration of morphine, levels of this antibiotic in bile and urine were not elevated. After ligation of the common bile duct, ampicillin levels in plasma were elevated. Morphine caused a further rise in drug levels in plasma of duct-ligated mice. Ampicillin levels in plasma were higher in mice made anephric by prolonged ligation of their external urethras. In such animals, morphine also caused ampicillin levels in plasma to be even higher. These experiments suggest that morphine impairs both renal and hepatobiliary elimination of ampicillin. These effects of morphine were completely reversed by naloxone. In contrast to effects on intravenously administered ampicillin, morphine markedly reduced drug levels in plasma when ampicillin was given by gastric intubation. This resulted from delayed absorption because of retardation of gastric emptying by morphine. PMID:4073871

  14. A Bacoside containing Bacopa monnieri extract reduces both morphine hyperactivity plus the elevated striatal dopamine and serotonin turnover.

    PubMed

    Rauf, Khalid; Subhan, Fazal; Sewell, Robert D E

    2012-05-01

    Bacopa monnieri (BM) has been used in Ayurvedic medicine as a nootropic, anxiolytic, antiepileptic and antidepressant. An n-butanol extract of the plant (nBt-ext BM) was analysed and found to contain Bacoside A (Bacoside A3, Bacopaside II and Bacopasaponin C). The effects of the BM extract were then studied on morphine-induced hyperactivity as well as dopamine and serotonin turnover in the striatum since these parameters have a role in opioid sensitivity and dependence. Mice were pretreated with saline or nBt-ext BM (5, 10 and 15 mg/kg, orally), 60 min before morphine administration and locomotor activity was subsequently recorded. Immediately after testing, striatal tissues were analysed for dopamine (DA), serotonin (5HT) and their metabolites using HPLC coupled with electrochemical detection. The results indicated that nBt-ext BM significantly (p < 0.001) decreased locomotor activity in both the saline and morphine treated groups. Additionally, nBt-ext BM significantly lowered morphine-induced dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-H1AA) upsurges in the striatum but failed to affect DA, 5-HT and their metabolites in the saline treated group. These findings suggest that nBt-ext BM has an antidopaminergic/serotonergic effect and may have potential beneficial effects in the treatment of morphine dependence. PMID:22105846

  15. A Randomized Controlled Trial on the Effect of Tapentadol and Morphine on Conditioned Pain Modulation in Healthy Volunteers

    PubMed Central

    Martini, Chris; van Velzen, Monique; Drewes, Asbjørn; Aarts, Leon; Dahan, Albert; Niesters, Marieke

    2015-01-01

    Background Modulatory descending pathways, originating at supraspinal sites that converge at dorsal horn neurons, influence pain perception in humans. Defects in descending pain control are linked to chronic pain states and its restoration may be a valuable analgesic tool. Conditioned pain modulation (CPM) is a surrogate marker of descending inhibition that reduces the perception of pain from a primary test stimulus during application of a conditioning stimulus. Here the effects of the analgesics tapentadol, a combined mu-opioid receptor agonist and noradrenaline reuptake inhibitor, and morphine, a strong mu-opioid receptor agonist, were tested on CPM in a randomized, double-blind, placebo-controlled crossover trial in 12 healthy pain-free volunteers, to understand possible differences in mechanism of action between these opioids. Methods and Results On three occasions CPM responses were obtained 60-90 and 120-150 min following intake of tapentadol (100 mg immediate release tablet), morphine (40 mg immediate release tablet) or placebo. At both time points, CPM was detectable after treatment with placebo and tapentadol (peak pain ratings reduced by 20-30% after application of the conditioning stimulus) but not after morphine. Compared to placebo morphine displayed significantly less CPM: mean treatment difference 18.2% (95% CI 3.4 to 32.9%) at 60-90 min after drug intake and 19.5% (95% CI 5.7 to 33.2%) at 120-150 min after drug intake (p = 0.001). No difference in CPM between placebo and tapentadol was detected: mean treatment difference 1.5% (95% CI -11.6 to 14.6%) at 60-90 min after drug intake and 1.5% (95% CI -16.0 to 18.9%) at 120-150 min after drug intake (p = 0.60). Conclusions Our data show that in volunteers morphine affects CPM, while tapentadol was without effect despite identical experimental conditions. These data confirm that tapentadol’s main mechanism of action is distinct from that of morphine and likely related to the effect of adrenergic

  16. The bioavailability of morphine applied topically to cutaneous ulcers.

    PubMed

    Ribeiro, Maria D C; Joel, Simon P; Zeppetella, Giovambattista

    2004-05-01

    A number of studies have reported the analgesic effect of morphine when applied topically to painful skin ulcers. It has been suggested that morphine may exert a local action, as opioid receptors have been demonstrated on peripheral nerve terminals. In this study, we investigated the bioavailability of topically applied morphine to cutaneous ulcers. Six hospice inpatients with skin ulcers were given morphine sulfate 10 mg in Intrasite gel topically and morphine sulfate 10 mg subcutaneously over 4 hours, at least 48 hours apart, in randomized order. Morphine, morphine-6-glucuronide (M6G), and morphine-3-glucuronide (M3G) were determined in plasma using a specific HPLC method. In five patients morphine and its metabolites were undetectable when applied topically. In one patient (with the largest ulcer), morphine and M6G were detected. The calculated morphine and M6G bioavailability in this patient were 20% and 21%, respectively. M3G was also detected but was below the lower limit of quantitation. When applied topically to ulcers, morphine was not absorbed in the majority of patients, suggesting any analgesic effect would be mediated locally rather than systemically. However, in ulcers with a large surface area, systemic absorption may occur. PMID:15120772

  17. The effect of different durations of morphine exposure on mesencephalic dopaminergic neurons in morphine dependent rats.

    PubMed

    Shi, Weibo; Ma, Chunling; Qi, Qian; Liu, Lizhe; Bi, Haitao; Cong, Bin; Li, Yingmin

    2015-12-01

    Mesencephalic dopaminergic neurons are heavily involved in the development of drug dependence. Thyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis, plays an important role in the survival of dopaminergic neurons. Therefore, this study investigated TH changes in dopaminergic neurons of the ventral tegmental area (VTA) and substantia nigra (SN), as well as the morphine effects on dopaminergic neurons induced by different durations of morphine dependence. Models of morphine dependence were established in rats, and paraffin-embedded sections, immunohistochemistry and western blotting were used to observe the changes in the expression of TH protein. Fluoro-Jade B staining was used to detect degeneration and necrosis, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) detected the apoptosis of mesencephalic dopaminergic nerve cells. Immunohistochemistry and western blotting showed that the number of TH positive cells and the protein levels in the VTA and SN were significantly decreased in the rats with a long period of morphine dependency. With prolonged morphine exposure, the dopaminergic nerve cells in the VTA and SN showed degeneration and necrosis, while apoptotic cells were not observed. The number of VTA and SN dopaminergic nerve cells decreased with increasing periods of morphine dependence, which was most likely attributable to the degeneration and necrosis of nerve cells induced by morphine toxicity. PMID:26386147

  18. Tabletability Modulation Through Surface Engineering.

    PubMed

    Osei-Yeboah, Frederick; Sun, Changquan Calvin

    2015-08-01

    Poor powder tabletability is a common problem that challenges the successful development of high-quality tablet products. Using noncompressible microcrystalline cellulose beads, we demonstrate that surface coating is an effective strategy for modulating tabletability, almost at will, through judicious selection of coating material. This strategy has broad applicability as tabletability of such particles is dictated by the properties of the outermost layer coat regardless the nature of the core. PMID:26059496

  19. Relative abuse liability of prescription opioids compared to heroin in morphine-maintained heroin abusers

    PubMed Central

    Comer, Sandra D; Sullivan, Maria A; Whittington, Robert A; Vosburg, Suzanne K; Kowalczyk, William J

    2013-01-01

    Abuse of prescription opioid medications has increased dramatically in the U.S. during the past decade, as indicated by a variety of epidemiological sources. However, few studies have systematically examined the relative reinforcing effects of commonly abused opioid medications. The current double-blind, placebo-controlled inpatient study was designed to compare the effects of intravenously delivered fentanyl (0, 0.0625, 0.125, 0.187, and 0.250 mg/70 kg), oxycodone (0, 6.25, 12.5, 25, and 50 mg/70 kg), morphine (0, 6.25, 12.5, 25, and 50 mg/70 kg), buprenorphine (0, 0.125, 0.5, 2, and 8 mg/70 kg), and heroin (0, 3.125, 6.25, 12.5, and 25 mg/70 kg) in morphine-maintained heroin abusers (N=8 completers maintained on 120 mg per day oral morphine in divided doses [30 mg q.i.d.]). All of the participants received all of the drugs tested; drugs and doses were administered in non-systematic order. All of the drugs produced statistically significant, dose-related increases in positive subjective ratings, such as “I feel a good drug effect” and “I like the drug.” In general, the order of potency in producing these effects, from most to least potent, was: fentanyl > buprenorphine ≥ heroin > morphine = oxycodone. In contrast, buprenorphine was the only drug that produced statistically significant increases in ratings of “I feel a bad drug effect” and it was the only drug that was not self-administered above placebo levels at any dose tested. These data suggest that the abuse liability of buprenorphine in heroin-dependent individuals may be low, despite the fact that it produces increases in positive subjective ratings. The abuse liabilities of fentanyl, morphine, oxycodone, and heroin, however, appear to be similar under these experimental conditions. PMID:17581533

  20. The Use of D-Optimal Mixture Design in Optimizing Development of Okara Tablet Formulation as a Dietary Supplement

    PubMed Central

    Mohamad Zen, Nur Izzati; Abd Gani, Siti Salwa; Shamsudin, Rosnah; Fard Masoumi, Hamid Reza

    2015-01-01

    The usage of soy is increasing year by year. It increases the problem of financial crisis due to the limited sources of soybeans. Therefore, production of oral tablets containing the nutritious leftover of soymilk production, called okara, as the main ingredient was investigated. The okara tablets were produced using the direct compression method. The percentage of okara, guar gum, microcrystalline cellulose (Avicel PH-101), and maltodextrin influenced tablets' hardness and friability which are analyzed using a D-optimal mixture design. Composition of Avicel PH-101 had positive effects for both hardness and friability tests of the tablets. Maltodextrin and okara composition had a significant positive effect on tablets' hardness, but not on percentage of friability of tablets. However, guar gum had a negative effect on both physical tests. The optimum tablet formulation was obtained: 47.0% of okara, 2.0% of guar gum, 35.0% of Avicel PH-101, and 14.0% of maltodextrin. PMID:26171418

  1. In vivo bioavailability studies of sumatriptan succinate buccal tablets

    PubMed Central

    Shivanand, K; Raju, SA; Nizamuddin, S; Jayakar, B

    2011-01-01

    Back ground and the purpose of study Sumatriptan succinate is a Serotonin 5- HT1 receptor agonist, used in treatment of migraine. It is absorbed rapidly but incompletely when given orally and undergoes first-pass metabolism, resulting in a low absolute bioavailability of about 15%. The aim of this work was to design mucoadhesive bilayered buccal tablets of sumatriptan succinate to improve its bioavailability. Methods Mucoadhesive polymers carbopol 934 (Carbopol), HPMC K4M, HPMC K15M along with ethyl cellulose as an impermeable backing layer were used for the preparation of mucoadhesive bilayered tablets. In vivo bioavailability studies was also conducted in rabbits for optimized formulation using oral solution of sumatriptan succinate as standard. Results Bilayered buccal tablets (BBT) containing the mixture of Carbopol and HPMC K4M in the ratio 1:1 (T1) had the maximum percentage of in vitro drug release within 6 hrs. The optimized formulation (T1) followed non-Fickian release mechanism. The percentage relative bioavailability of sumatriptan succinate from selected bilayered buccal tablets (T1) was found to be 140.78%. Conclusions Bilayered buccal tablets of sumatriptan succinate was successfully prepared with improved bioavailability. PMID:22615661

  2. Synthetic substances with morphine-like effect

    PubMed Central

    Eddy, Nathan B.; Halbach, H.; Braenden, Olav J.

    1957-01-01

    A review of effects in man of morphine-like drugs which have been brought under international narcotics control is presented in the form of individual monographs. These are based on controlled observations with quantitative data and significant reports of results obtained in medical practice. In a summarizing section, the drugs are compared with respect to effectiveness, side-effects and addiction liability. Morphine-like drugs of natural and synthetic origin now cover a wide range of potency (analgesic, antitussive), not necessarily paralleled by incidence of side-effects or addiction liability. PMID:13511135

  3. Morphine Promotes Tumor Angiogenesis and Increases Breast Cancer Progression

    PubMed Central

    Bimonte, Sabrina; Barbieri, Antonio; Palma, Giuseppe; Luciano, Antonio; Cuomo, Arturo; Arra, Claudio; Izzo, Francesco

    2015-01-01

    Morphine is considered a highly potent analgesic agent used to relieve suffering of patients with cancer. Several in vitro and in vivo studies showed that morphine also modulates angiogenesis and regulates tumour cell growth. Unfortunately, the results obtained by these studies are still contradictory. In order to better dissect the role of morphine in cancer cell growth and angiogenesis we performed in vitro studies on ER-negative human breast carcinoma cells, MDA.MB231 and in vivo studies on heterotopic mouse model of human triple negative breast cancer, TNBC. We demonstrated that morphine in vitro enhanced the proliferation and inhibited the apoptosis of MDA.MB231 cells. In vivo studies performed on xenograft mouse model of TNBC revealed that tumours of mice treated with morphine were larger than those observed in other groups. Moreover, morphine was able to enhance the neoangiogenesis. Our data showed that morphine at clinical relevant doses promotes angiogenesis and increases breast cancer progression. PMID:26064880

  4. The role of morphine glucuronides in cancer pain.

    PubMed

    Mercadante, S

    1999-03-01

    Morphine metabolites are involved in various ways in determining the complex effects of morphine, both favourable and adverse, and may complicate the clinical use of morphine in the treatment of cancer pain. The production and effects of the principal morphine metabolites, morphine-3-glucuronide and morphine-6-glucuronide, in both normal and pathological states have been reviewed in the current literature. Therapeutic implications are also reviewed on the basis of experimental and clinical reports. The presence of these metabolites should be recognized in the chronic treatment of cancer pain with morphine, especially in the presence of renal impairment, and should be considered to have an important influence on opioid responsiveness, defined as a balance between the achievement of an optimal analgesia and the occurrence of adverse effects. PMID:10474692

  5. Effect of morphine and morphine-like drugs on carbachol-induced fighting in cats.

    PubMed

    Krstić, S K; Stefanović-Denić, K; Beleslin, D B

    1982-08-01

    In the present experiments, morphine, methadone or pethidine was injected into the cerebral ventricle of the unanesthetized cat after fighting was induced with carbachol injected previously. The fighting evoked by carbachol was sensitive to the depressant action of morphine or pethidine but not to the depressant effect of methadone. The most likely explanation of the depressant effects of the former compounds is that they act on the postsynaptic receptors of central cholinergic neurons. PMID:6890210

  6. Ellagic acid enhances morphine analgesia and attenuates the development of morphine tolerance and dependence in mice.

    PubMed

    Mansouri, Mohammad Taghi; Naghizadeh, Bahareh; Ghorbanzadeh, Behnam

    2014-10-15

    According to our previous study, ellagic acid has both dose-related central and peripheral antinociceptive effect through the opioidergic and l-arginine-NO-cGMP-ATP sensitive K(+) channel pathways. In the present study, the systemic antinociceptive effects of ellagic acid in animal models of pain, and functional interactions between ellagic acid and morphine in terms of analgesia, tolerance and dependence were investigated. Ellagic acid (1-30mg/kg; i.p.) showed significant and dose-dependent antinociceptive effects in the acetic acid-induced writhing test. Intraperitoneal ellagic acid acutely interacted with morphine analgesia in a synergistic manner in this assay. Ellagic acid (1-10mg/kg; i.p.) also exerted analgesic activity in the hot-plate test. Pre-treatment with naloxone (1mg/kg; i.p.) significantly reversed ellagic acid, morphine as well as ellagic acid-morphine combination-induced antinociceptin in these two tests. More importantly, when co-administered with morphine, ellagic acid (1-10mg/kg) effectively blocked the development of tolerance to morphine analgesia in the hot-plate test. Likewise, ellagic acid dose-dependently prevented naloxone-precipitated withdrawal signs including jumping and weight loss. Ellagic acid treatment (1-30mg/kg; i.p.) had no significant effect on the locomotion activity of animals using open-field task. Therefore, these results showed that ellagic acid has notable systemic antinociceptive activity for both tonic and phasic pain models. Altogether, ellagic acid might be used in pain relief alone or in combination with opioid drugs because of enhancing morphine analgesia and preventing morphine-induced tolerance to analgesia and dependence. PMID:25179576

  7. Morphine effects on gentamicin disposition and toxicity in mice.

    PubMed

    Hurwitz, A; Garty, M; Ben-Zvi, Z

    1988-05-01

    Morphine has been shown to reduce renal and hepatic clearance of several xenobiotics in rodents. After iv administration of gentamicin, 10 to 30 mg/kg, its plasma levels were elevated in mice given morphine, 20 mg/kg sc. Plasma clearance of gentamicin was nearly halved by morphine, due primarily to lowering of the elimination constant of gentamicin from 0.03 to 0.02 min-1 (p less than 0.01). Morphine also significantly reduced urine levels of gentamicin and urine volume. In mice given naloxone, 2 mg/kg sc, morphine did not significantly raise plasma levels of gentamicin nor reduce its elimination into urine. Mice were made tolerant by morphine administration for 9 days at ascending doses to 100 mg/kg twice daily. An acute challenge with morphine, 20 mg/kg, was less effective in raising plasma levels of gentamicin or lowering its urinary elimination in tolerant mice than after chronic saline treatment. Partial tolerance to acutely administered morphine and reversal of morphine effects by naloxone suggest opioid receptor-mediated reduction of glomerular filtration by morphine in mice. Despite marked elevation of plasma gentamicin levels in morphine-treated mice, narcotic administration did not significantly increase the acute toxicity of a single dose of gentamicin. LD50 of acutely administered iv gentamicin was 51.6 mg/kg after saline and 45.3 mg/kg after treatment with morphine, 20 mg/kg sc. However, this dose of morphine enhanced the lethality of intravenously infused gentamicin. Morphine administration significantly reduced the dose of infused gentamicin needed to achieve the critical lethal plasma level. PMID:3368920

  8. CES 2011: Tablet Crazy

    ERIC Educational Resources Information Center

    Rapp, David

    2011-01-01

    Ereaders are so last year. Tablets were the watchword at this year's annual Consumer Electronics Show (CES) in Las Vegas, January 6-9. This year, the show set new records, with some 2700 companies from around the world exhibiting at the multiple exhibition halls and 30,000 attendees gawking at the products. What did they see? There were still some…

  9. Intrathecal combination of ziconotide and morphine for refractory cancer pain: a rapidly acting and effective choice.

    PubMed

    Alicino, Ilaria; Giglio, Mariateresa; Manca, Fabio; Bruno, Francesco; Puntillo, Filomena

    2012-01-01

    Ziconotide is a nonopioid intrathecal analgesic drug used to manage moderate to severe chronic pain. The aim of this work is to assess the safety and efficacy of intrathecal (IT) combination of ziconotide and morphine in malignant pain refractory to high doses of oral opioids. Patients with malignant pain refractory to high oral opioids doses with a mean visual analogue scale of pain intensity (VASPI) score of ≥ 70 mm were enrolled. An IT combination therapy was administered: Ziconotide was started at a dose of 2.4 μg/day, followed by increases of 1.2 μg/day at intervals of at least 7 days, and an initial IT daily dose of morphine was calculated based on its oral daily dose. Percentage change in VASPI scores from baseline was calculated at 2 days, at 7 days, and weekly until the first 28 days. The mean percentage change of VASPI score from baseline was used for efficacy assessment. Safety was monitored based on adverse events and routine laboratory values. Twenty patients were enrolled, with a mean daily VASPI score at rest of 90±7. All had a disseminated cancer with bone metastases involving the spine. The percentage changes in VASPI mean scores from baseline to 2 days, 7 days, and 28 days were 39±13% (95% confidence interval [CI]=13.61-64.49, P<.001), 51±12% (95% CI=27.56-74.56, P<.001), and 62±13% (95% CI=36.03-87.89%, P<.001), respectively. Four patients experienced mild adverse events related to the study drugs. In conclusion, an IT combination of low doses of ziconotide and morphine allows safe and rapid control of oral opioid-refractory malignant pain. PMID:22082570

  10. 75 FR 13292 - Determination That HalfLytely and Bisacodyl Tablets Bowel Prep Kit (Containing 4 Bisacodyl...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-19

    ... (polyethylene glycol (PEG) 3350, sodium chloride, sodium bicarbonate, and potassium chloride for oral solution... potassium chloride for oral solution and 4 bisacodyl delayed release tablets, 5 mg. FOR FURTHER INFORMATION... PREP KIT (PEG-3350, sodium chloride, sodium bicarbonate, and potassium chloride for oral solution and...

  11. Time Dependent Antinociceptive Effects of Morphine and Tramadol in the Hot Plate Test: Using Different Methods of Drug Administration in Female Rats

    PubMed Central

    Gholami, Morteza; Saboory, Ehsan; Mehraban, Sogol; Niakani, Afsaneh; Banihabib, Nafiseh; Azad, Mohamad-Reza; Fereidoni, Javid

    2015-01-01

    Morphine and tramadol which have analgesic effects can be administered acutely or chronically. This study tried to investigate the effect of these drugs at various times by using different methods of administration (intraperitoneal, oral, acute and chronic). Sixty adult female rats were divided into six groups. They received saline, morphine or tramadol (20 to 125 mg/Kg) daily for 15 days. A hot plate test was performed for the rats at the 1st, 8th and 15th days. After drug withdrawal, the hot plate test was repeated at the 17th, 19th, and 22nd days. There was a significant correlation between the day, drug, group, and their interaction (P<0.001). At 1st day (d1), both morphine, and tramadol caused an increase in the hot plate time comparing to the saline groups (P<0.001), while there was no correlation between drug administration methods of morphine and/or tramadol. At the 8th day (d8), morphine and tramadol led to the most powerful analgesic effect comparing to the other experimental days (P<0.001). At the 15th day (d15), their effects diminished comparing to the d8. After drug withdrawal, analgesic effect of morphine, and tramadol disappeared. It can be concluded that the analgesic effect of morphine and tramadol increases with the repeated use of them. Thereafter, it may gradually decrease and reach to a level compatible to d1. The present data also indicated that although the analgesic effect of morphine and tramadol is dose-and-time dependent, but chronic exposure to them may not lead to altered nociceptive responses later in life. PMID:25561936

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

    PubMed

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

    2015-07-01

    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. PMID:25869450

  13. Optical properties of aqueous morphine solutions

    NASA Astrophysics Data System (ADS)

    Kuznetsov, Pavel E.; Gracheva, Anna A.; Zlobin, Vladimir A.; Nazarov, Georgy V.; Kuznetsova, Nina B.; Rogacheva, Svetlana M.

    2003-10-01

    We have studied morphine action on mobility and structure of water by means of fluorescent investigations and light scattering analysis. Wave-like concentration dependences have been plotted in the both cases. Theoretical description of the discovered effect has been made based on the formalism of N.N.Bogolubov.

  14. Nebulized morphine in the palliation of dyspnoea.

    PubMed

    Zeppetella, G

    1997-07-01

    Seventeen terminally ill cancer patients with primary or secondary intrathoracic malignancy complaining of breathlessness were treated with nebulized morphine in doses of 20 mg 4-hourly for 48 h. The effect on dyspnoea was evaluated using the Dyspnoea Assessment Questionnaire. Most patients felt less dyspnoeic after 24 h; the effect was maintained, but not improved upon, after 48 h. PMID:9373577

  15. Stability and Analgesic Efficacy of Di-acetyl Morphine (Diamorphine) Compared with Morphine in Implanted Intrathecal Pumps In Vivo.

    PubMed

    Raphael, Jon H; Palfrey, Stephen M; Rayen, Arasu; Southall, Jane L; Labib, Maurad H

    2004-07-01

    The objective of this study was to investigate di-acetyl morphine as an alternative opioid analgesic for use in implanted intrathecal drug delivery systems because of its greater solubility through evaluation of its stability in vivo and analgesic efficacy in the period between pump refills. Contents of intrathecal drug delivery system reservoirs (SynchroMed, Medtronic, Inc., Minneapolis, MN) that had been filled with di-acetyl morphine dissolved in saline (21), bupivacaine (9), or in both bupivacaine and clonidine (19) were sampled in vivo between 1 and 125 days after refill. The samples were assayed for di-acetyl morphine and its breakdown products by micellar electrokinetic capillary chromatography. Prospective daily numerical pain scores between pump refills, using 11-point Likert scales, on 24 patients with implanted SynchroMed pumps (12 delivering di-acetyl morphine in saline, 12 were delivering morphine in saline) were collected. Results showed that di-acetyl morphine immediately started to decay to mono-acetyl morphine in implanted Synchromed pumps with half-life of 50 days. Mono-acetyl morphine decayed to morphine with a maxima estimated at 125 days. There was no clinically significant change in average weekly pain scores for up to ten weeks in either group (range, 2.5 to 2.8 for diamorphine and 2.7 to 3.1 for morphine) (2-way repeated ANOVA, F(9,220) = 0.98, n.s.). We conclude that di-acetyl morphine and its breakdown products, 6 mono-acetyl morphine and morphine, provide similar analgesia to morphine alone when administered by intrathecal pump for a period of at least ten weeks and may be a useful alternative when a more soluble agent is favored. PMID:22151270

  16. Comparison of a drug versus money and drug versus drug self-administration choice procedure with oxycodone and morphine in opioid addicts

    PubMed Central

    Comer, Sandra D; Metz, Verena E; Cooper, Ziva D; Kowalczyk, William J; Jones, Jermaine D; Sullivan, Maria A; Manubay, Jeanne M; Vosburg, Suzanne K; Smith, Mary E; Peyser, Deena; Saccone, Phillip A

    2014-01-01

    This double-blind, placebo-controlled study investigated effects of oral morphine (0, 45, 135 mg/70kg) and oral oxycodone (0, 15, 45 mg/70kg) in buprenorphine-maintained opioid addicts. Since a 3:1 morphine:oxycodone dose ratio had yielded equivalent subjective and physiological effects in non-dependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures, i.e. a drug vs. money and a drug vs. drug procedure, were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater compared to high-dose morphine. The study demonstrated that a 3:1 dose ratio of morphine:oxycodone was not equipotent in buprenorphine-dependent subjects. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest. PMID:23839029

  17. Sex differences in locomotor effects of morphine in the rat

    PubMed Central

    Craft, Rebecca M.; Clark, James L.; Hart, Stephen P.; Pinckney, Megan K.

    2007-01-01

    Sex differences in reinforcing, analgesic and other effects of opioids have been demonstrated; however, the extent to which sex differences in motoric effects of opioids contribute to apparent sex differences in their primary effects is not known. The goal of this study was to compare the effects of the prototypic mu opioid agonist morphine on locomotor activity in male vs. female rats. Saline or morphine (1-10 mg/kg) was administered s.c. to adult Sprague-Dawley rats, which were placed into a photobeam apparatus for 3-5 hr to measure activity. Modulation of morphine's effects by gonadal hormones and by handling (either during the test session or for 4 days before the test session) were examined. Morphine initially suppressed and later increased locomotor activity in both sexes relative to their saline-injected controls, but males were more sensitive than females to the initial locomotor suppressant effect of morphine. Intermittent, brief handling during the 3-hr test session blunted morphine-induced locomotor activation in both sexes. Females in proestrus were the most sensitive to morphine's locomotor-stimulant effect, with females in estrus showing the least response to morphine. Gonadectomized (GDX) males with or without testosterone were equally sensitive to morphine's effects, whereas GDX females treated with estradiol showed a blunted response to morphine's effects, similar to intact females in estrus. Brief handling on each of 4 consecutive days pre-test attenuated morphine's locomotor suppressant effect in males but had no effect in females, thereby eliminating the sex difference. These data suggest that sex differences in morphine's effects on locomotor activity can be attributed to gonadal hormones in females, and to differential stress-induced modulation of morphine's effects in males vs. females. PMID:17217999

  18. Pediatric drugs--a review of commercially available oral formulations.

    PubMed

    Strickley, Robert G; Iwata, Quynh; Wu, Sylvia; Dahl, Terrence C

    2008-05-01

    Pediatric oral formulations can be quite scientifically challenging to develop and the prerequisites for both a measurable dosage form to administer based upon bodyweight, and also taste-masking are two of the challenges unique for pediatric oral formulations. The physicochemical and organoleptic properties of the active drug substance such as solubility, chemical stability, and taste along with the intended dose can determine which formulations are feasible to develop. Oral pediatric formulations are available in 17 different varieties and can be either a ready-to-use formulation such as a solution, syrup, suspension, tablet, scored tablet, chewable tablet, orally disintegrating tablet, or thin strip, or can also be a formulation that requires manipulation such as a powder for constitution to a suspension, tablet for constitution to a suspension, powder for constitution to a solution, drops for reconstitution to a suspension, concentrated solution for dilution, effervescent tablet, bulk oral granules, bulk oral powder, or solid in a capsule to mix with food or drink. Recently there has been an increase in pediatric formulation development inspired by increased regulatory incentives. The intent of this review is to educate the reader on the various types of formulations administered orally to pediatrics, the rationale in deciding which type of formulation to develop, the excipients used, development challenges, the in-use handling of oral pediatric formulations, and the regulatory incentives. PMID:17823956

  19. Bioavailability of lithium from lithium citrate syrup versus conventional lithium carbonate tablets.

    PubMed

    Guelen, P J; Janssen, T J; De Witte, T C; Vree, T B; Benson, K

    1992-10-01

    The bioavailability of lithium citrate syrup was compared with that of regular lithium carbonate tablets in 18 healthy male human volunteers. Blood samples were collected up to 48 h after dosing. Lithium serum concentrations were determined by means of AAS. The absorption rate following oral administration of the syrup was greater (tmax 0.8 h) than following administration of regular tablets (tmax 1.4 h). Maximum lithium serum concentrations, however, were only about 10 per cent higher after syrup dosing and serum concentrations resulting from syrup and tablets were almost superimposable from 2 h after dosing. The terminal half-life of lithium was found to be 22 h after syrup as well as after tablet dosing. No side-effects were observed during the study. The bioavailability of lithium from syrup relative to tablets was found to be bioequivalent with respect to the maximum lithium serum concentration and the extent of drug absorption (AUC). PMID:1489941

  20. Role of kappa and delta opioid receptors in mediating morphine-induced antinociception in morphine tolerant infant rats

    PubMed Central

    Stoller, Dawn C.; Sim-Selley, Laura J.; Smith, Forrest L.

    2011-01-01

    We have previously noted that the antinociceptive efficacy of morphine was significantly decreased in rat pups chronically infused with morphine from implanted osmotic minipumps. In this study, morphine was fully efficacious (i.e., 100% maximum possible effect, %MPE) in the 52 ºC tail-immersion test after a 72-h infusion from implanted saline-filled osmotic minipumps. However, administration of up to 1000 mg/kg s.c. morphine failed to elicit greater than a 27% MPE in rats infused with morphine at 2 mg/kg/h. Morphine was more efficacious when the water bath temperature was decreased to 49 ºC. Experiments were conducted to determine the mechanisms whereby chronic morphine administration leads to a decrease in antinociceptive efficacy. The kappa-opioid antagonist nor-binalorphimine completely blocked the antinociceptive effects of morphine in morphine-infused rat pups. The kappa agonist U50,488 elicited antinociception however, the requirement to use higher doses in morphine- than saline-infused rats indicates that kappa cross-tolerance was present. Thus, in tolerant rats the antinociceptive effects of high doses of morphine appear to be mediated through kappa-opioid receptors. The delta-opioid antagonist naltrindole was inactive in both treatment groups. DAMGO-stimulated [35S]GTPγS and [3H]naloxone binding reveal that the anatomical distribution of the mu-opioid receptor was consistent with that of the adult rat brain. In adult rats, the mu-opioid receptor is desensitized during morphine tolerance. However, desensitization was not evident in P17 rats based on the lack of significant decreases in [35S]GTPγS binding. Furthermore, [3H]naloxone binding indicated a lack of mu receptor downregulation in morphine-tolerant rat pups. PMID:17300766

  1. Morphine Enhances Hepatitis C Virus (HCV) Replicon Expression

    PubMed Central

    Li, Yuan; Zhang, Ting; Douglas, Steven D.; Lai, Jian-Ping; Xiao, Wei-Dong; Pleasure, David E.; Ho, Wen-Zhe

    2003-01-01

    Little information is available regarding whether substance abuse enhances hepatitis C virus (HCV) replication and promotes HCV disease progression. We investigated whether morphine alters HCV mRNA expression in HCV replicon-containing liver cells. Morphine significantly increased HCV mRNA expression, an effect which could be abolished by either of the opioid receptor antagonists, naltrexone or β-funaltrexamine. Investigation of the mechanism responsible for this enhancement of HCV replicon expression demonstrated that morphine activated NF-κB promoter and that caffeic acid phenethyl ester, a specific inhibitor of the activation of NF-κB, blocked morphine-activated HCV RNA expression. In addition, morphine compromised the anti-HCV effect of interferon alpha (IFN-α). Our in vitro data indicate that morphine may play an important role as a positive regulator of HCV replication in human hepatic cells and may compromise IFN-α therapy. PMID:12937158

  2. Aloe vera Aqueous Extract Effect on Morphine Withdrawal Syndrome in Morphine-Dependent Female Rats

    PubMed Central

    Shahraki, Mohammad Reza; Mirshekari, Hamideh; Sabri, Azame

    2014-01-01

    Background: Aloe vera is a medicinal herb used as an anti-inflammatory and sedative agent. Objectives: The current study aimed to evaluate the effect of Aloe vera aqueous extract on morphine withdrawal symptoms in morphine-dependent female rats. Patients and Methods: The current research was performed on 40 female Wista-Albino rats which were made dependent on morphine using Houshyar protocol and were randomly divided into five groups (A, B, C, D, and E). Group A did not receive any agent in the period of handling but other groups (B, C, D and E) received 5, 10, 20 and 40 mg/kg of Aloe vera aqueous extract by gavage, three times daily for a week, respectively. Withdrawal symptoms, stool form, agitation, disparity, floppy eyelids, and body mass variations were checked for 10 days. The obtained data were analyzed using SPSS v.11 software, and Friedman, Kruskal-Wallis, and Mann-Whitney statistical tests. Statistical difference was considered significant (P < 0.05). Results: The results of the present study showed that agitation, disparity, and floppy eyelids in group E were significantly higher than those of others groups; however, these symptoms in group C were significantly lower than those of the other groups. Conclusions: The results of the present study revealed that the Aloe vera aqueous extract had various effects on morphine withdrawal syndrome in morphine-dependent female rats . PMID:25593890

  3. Metabolism and pharmacokinetics of morphine in neonates: A review

    PubMed Central

    Pacifici, Gian Maria

    2016-01-01

    Morphine is an agonist of the µ and k receptors, whose activation results in analgesia. Morphine-like agonists act through the µ opioid receptors to cause pain relief, sedation, euphoria and respiratory depression. Morphine is glucuronidated and sulfated at positions 3 and 6; the plasma concentration ratios correlate positively with birth weight, which probably reflects increased liver weight with increasing birth weight. Moreover, morphine clearance correlates positively with gestational age and birth weight. Steady-state morphine plasma concentrations are achieved after 24-48 hours of infusion, but the glucuronide metabolite plasma concentrations do not reach steady state before 60 hours. The morphine-3-glucuronide metabolite has lower clearance, a shorter half-life and a smaller distribution volume compared with the morphine-6 metabolite, which is the most active morphine-like agonist. Ordinary doses cause constipation, urinary retention and respiratory depression. Neonatal pain relief may require a blood level of approximately 120 ng/ml, whereas lower levels (20-40 ng/ml) seem adequate for children. A bibliographic search was performed using the PubMed database and the keywords “morphine metabolism neonate” and “morphine pharmacokinetics neonate”. The initial and final cutoff points were January 1990 and September 2015, respectively. The results indicate that morphine is extensively glucuronidated and sulfated at positions 3 and 6, and that the glucuronidation rate is lower in younger neonates compared with older infants. Although much is known about morphine in neonates, further research will be required to ensure that recommended therapeutic doses for analgesia in neonates are evidence based.

  4. Blockade of tolerance to morphine analgesia by cocaine.

    PubMed

    Misra, A L; Pontani, R B; Vadlamani, N L

    1989-07-01

    Tolerance to morphine analgesia was induced in male Sprague-Dawley rats by s.c. implantation of a morphine base pellet (75 mg) on the first and second day and determining the magnitude of tolerance 72 h after the first implant by s.c. injection of a test dose of morphine (5 mg/kg). Implantation of a cocaine hydrochloride pellet (25 mg), concurrently with morphine pellets or of a cocaine hydrochloride (50 mg) pellet after the development of tolerance, blocked both the development and expression of morphine analgesic tolerance. In morphine-pelleted animals pretreatment for 3 days with desipramine or zimelidine or phenoxybenzamine but not haloperidol produced no significant morphine tolerance. Pretreatment with a combination of desipramine and zimelidine, however, was as effective as cocaine in blocking morphine tolerance. Alpha-Methyl-p-tyrosine methyl ester counteracted the effect of cocaine in blocking morphine tolerance and potentiated the tolerance development. Blockade of morphine tolerance by cocaine was reinforced and facilitated by pretreatment with fenfluramine or p-chlorophenylalanine ethyl ester and to a lesser extent by clonidine and haloperidol. Acute administration of fenfluramine or zimelidine or a combination of desipramine and zimelidine or alpha-methyl-p-tyrosine methyl ester or p-chlorophenylalanine ethyl ester did not significantly affect morphine analgesia. The study suggests an important role of the concomitant depletion of both central noradrenaline and serotonin in the blockade of morphine tolerance by cocaine and stresses the importance of the counter-balancing functional relationship between these two neurotransmitters in the central nervous system. PMID:2780065

  5. Valproate attenuates the development of morphine antinociceptive tolerance.

    PubMed

    Dobashi, Tamae; Tanabe, Serabi; Jin, Hisayo; Nishino, Takashi; Aoe, Tomohiko

    2010-11-19

    Morphine is a potent opioid analgesic. Repeated administration of morphine induces tolerance, thus reducing the effectiveness of analgesic treatment. Although some adjuvant analgesics can increase morphine analgesia, the precise molecular mechanism behind their effects remains unclear. Opioids bind to the mu opioid receptor (MOR). Morphine tolerance may be derived from alterations in the intracellular signal transduction after MOR activation. Chronic morphine treatment activates glycogen synthase kinase 3β (GSK3β), whose inhibition diminishes morphine tolerance. Valproate is widely prescribed as an anticonvulsant and a mood stabilizer for bipolar disorders because it increases the amount of γ-aminobutyric acid (GABA) in the central nervous system. Although the activation of GABAergic neurons may be responsible for the chief pharmacologic effect of valproate, recent studies have shown that valproate also suppresses GSK3β activity. We examined the effect of valproate on the development of morphine antinociceptive tolerance in a mouse model of thermal injury. Mice were treated with morphine alone or with morphine and valproate twice daily for 5 days. The resulting antinociceptive effects were assessed using a hot plate test. While mice treated with morphine developed tolerance, co-administration of valproate attenuated the development of tolerance and impaired the activation of GSK3β in mice brains. Valproate alone did not show analgesic effects; nevertheless, it functioned as an adjuvant analgesic to prevent the development of morphine tolerance. These results suggest that the modulation of GSK3β activity by valproate may be useful and may play a role in the prevention of morphine tolerance. PMID:20816918

  6. Solid self-microemulsifying dispersible tablets of celastrol: formulation development, charaterization and bioavailability evaluation.

    PubMed

    Qi, Xiaole; Qin, Jiayi; Ma, Ning; Chou, Xiaohua; Wu, Zhenghong

    2014-09-10

    The aims of this study were to choose a suitable adsorbent of self-microemulsion and to develop a fine solid self-microemulsifying dispersible tablets for promoting the dissolution and oral bioavailability of celastrol. Solubility test, self-emulsifying grading test, droplet size analysis and ternary phase diagrams test were performed to screen and optimize the composition of liquid celastrol self-microemulsifying drug delivery system (SMEDDS). Then microcrystalline cellulose KG 802 was added as a suitable adsorbent into the optimized liquid celastrol-SMEDDS formulation to prepare the dispersible tablets by wet granulation compression method. The optimized formulation of celastrol-SMEDDS dispersible tablets was finally determinated by the feasibility of the preparing process and redispersibility. The in vitro study showed that the dispersible tablets could disperse in the dispersion medium within 3 min with the average particle size of 25.32 ± 3.26 nm. In vivo pharmacokinetic experiments of rats, the relative bioavailability of celastrol SMEDDS and SMEDDS dispersible tablets compared to the 0.4% CMC-Na suspension was 569 ± 7.07% and 558 ± 6.77%, respectively, while there were no significant difference between the SMEDDS and SMEDDS dispersible tablets. The results suggest the potential use of SMEDDS dispersible tablets for the oral delivery of poorly water-soluble terpenes drugs, such as celastrol. PMID:24929011

  7. Controlled release tablet formulation containing natural Δ(9)-tetrahydrocannabinol.

    PubMed

    Punyamurthula, Nagendra S; Hingorani, Tushar; Adelli, Goutham; Gul, Waseem; ElSohly, Mahmoud A; Repka, Michael A; Majumdar, Soumyajit

    2016-07-01

    Cannabinoids are increasingly being used in the treatment of chemotherapy-induced nausea and vomiting (CINV) because of their action on the cannabinoid receptors, CB1 and CB2. The currently marketed capsule formulations (sesame oil based and crystalline powder) are required to be administered frequently to maintain therapeutic levels, which leads to non-compliance. In the present study, oral controlled release tablet formulations of Δ(9)-tetrahydrocannabinol (THC) were prepared using the lipids Precirol® and Compritol®. Release profiles using THC-lipid matrices and/or with the lipids in the external phase (blend) were evaluated. The effect of directly compressible diluents lactose mixture (Ludipress®), dicalcium phosphate anhydrous (Emcompress®) and microcrystalline cellulose (Avicel® 102) on tablet characteristics and in vitro drug release was also investigated. Further, in vitro THC release in the presence of a lipase inhibitor, Pluronic® F68, was also studied. A 24 h zero-order THC release profile was obtained with a combination of Precirol® and Compritol® in the compression blend. Addition of Pluronic® F68 did not alter THC release in vitro. These optimized tablets were chemically and physically stable for 3 months, the last time point tested, at 25 °C/60% RH. The overall results demonstrate the feasibility of preparing oral THC tablets for once a day administration which can improve CINV management. PMID:26585693

  8. Controlled release camptothecin tablets based on pluronic and poly(acrylic acid) copolymer. Effect of fabrication technique on drug stability, tablet structure, and release mode.

    PubMed

    Bromberg, Lev; Hatton, T Alan; Barreiro-Iglesias, Rafael; Alvarez-Lorenzo, Carmen; Concheiro, Angel

    2007-06-01

    Poly(ethylene oxide)-b-poly(propylene oxide)-b-(polyethylene oxide)-g-poly(acrylic acid), a graft-comb copolymer of Pluronic 127 and poly(acrylic acid) (Pluronic-PAA), was explored as an excipient for tablet dosage form of camptothecin (CPT). The tablets were prepared by either direct compression of the drug-polymer physical blend, suspension in ethanol followed by evaporation, or compression after kneading and characterized with respect to their physical structures, drug stability, and release behavior. Porosity and water uptake rate were strongly dependent on the fabrication procedure, ranking in the order: direct compression of physical blend > compression after suspension/evaporation in ethanol > compression after kneading. Tablets prepared by compression of physical blends swelled in water with a rapid surface gel layer formation that impeded swelling and disintegration of the tablets core. These tablets were able to sustain the CPT release for a period of time longer than those observed with the tablets made by either suspension/evaporation or kneading, which disintegrated within a few minutes. Despite the tablet disintegration, the CPT release was impeded for at least 6 hr, which was attributed to the ability of the Pluronic-PAA copolymers to form micellar aggregates at the hydrated surface of the particles. Physical mixing did not alter the fraction of CPT being in the pharmaceutically active lactone form, whilst the preparation of the tablets by the other two methods caused a significant reduction in the lactone form content. Tablets prepared from the physical blends demonstrated CPT release rates increasing with the pH due to the PAA ionization leading to the increase in the rate and extent of the tablet swelling. The results obtained demonstrate the potential of the Pluronic-PAA copolymers for the oral administration of chemotherapeutic agents. PMID:17613025

  9. The effect of morphine consumption on plasma corticosteron concentration and placenta development in pregnant rats

    PubMed Central

    Kazemi, Masoomeh; Sahraei, Hedayat; Azarnia, Mahnaz; Dehghani, Leila; Bahadoran, Hossein; Tekieh, Elaheh

    2011-01-01

    Background: Previous studies have shown that morphine consumption during pregnancy may delay embryo development or cause abnormal nervous system function. Objective: The present study focused on the effect of maternal morphine consumption on development of placenta and blood corticosteron concentration in addictive pregnant mothers. Materials and Methods: 24 female rats, 170-200g weight, were used. The experimental groups after pregnancy received an oral dose of 0.05 mg/ml of morphine by tap water while the control group received only tap water. On 10th and 14th day of pregnancy, rats were anesthetized and placenta removed surgically, 1ml blood was collected from each pregnant mother from retro-orbital sinus, the concentration of blood corticosteron was determined by corticosteron Elisa kit after centrifugation. The fixed tissue was processed, sectioned and stained with hematoxylin and eosin. Placenta was studied microscopically according to the thickness of layers, area of blood cisterns, and the number of cells. Results: Comparing the plasma corticosteron concentration of the treatment and the control groups, not only a severe increase in the treatment group was detected, but also the thickness of maternal and embryonic portions of the placenta at day 10th and 14th of gestation was different significantly (p≤0.05). Furthermore, an increase in number of cells in maternal and embryonic portion of placenta and a decrease in blood cistern area were demonstrated in both the experimental and the control groups. Conclusion: The effects of morphine, including an increase in blood concentration of corticosteron, in dependent pregnant mothers were seen. Development of placenta in the experimental group was delayed. PMID:25587250

  10. Effect of morphine on PC12 cells with molecular radar

    NASA Astrophysics Data System (ADS)

    Shi, Chen; Yu, Xiaoli; Lu, Jiuyi; Zhang, Chunyang; Jin, Lei; Ma, Hui; Zhang, Dacheng; Chen, Die Yan

    2000-10-01

    Molecular Radar (MR) is a new method to detect biological processes in living cells at the level of molecular, it is also the newest means to get intracellular information. In this paper we study the effect of morphine on PC12 cells using MR. The results show that the effect of morphine on PC12 cells is time- and concentration-dependent. Morphine treating for short time induces the increase and fluctuation of intracellular (CA2+), while morphine treating for long time induces chromatin condensation, loss of mitochondria membrane potential apoptosis.

  11. Antinatriuretic effect of acute morphine administration in conscious rats.

    PubMed

    Walker, L A; Murphy, J C

    1984-05-01

    The renal response to the acute administration of morphine was examined in conscious, chronically catheterized, nonhydrated rats. After control clearance periods, morphine sulfate was injected i.v. at 4 mg/kg followed by an infusion of 2 mg/kg X hr. Morphine caused an increase in urine flow which was variable in magnitude and duration. The initial diuresis was not maintained despite continued morphine administration and replacement of lost fluid. Compared to vehicle treatment morphine also induced marked sodium and chloride retention which was sustained throughout the 2-hr infusion period. There were no changes in blood pressure or heart during the clearance periods, although an initial transient hypotension and bradycardia were observed with morphine injection. There were no changes in glomerular filtration rate which could account for the antinatriuresis. Naloxone pretreatment blocked all of the observed renal responses. The results indicate that morphine exerts its effects on electrolyte excretion by enhancing renal tubular sodium or chloride reabsorption rather than changes in systemic hemodynamics or glomerular filtration rate. In a separate series of experiments, urine osmolality, osmolar clearance and free water clearance were estimated. All rats receiving morphine transiently excreted a hypotonic urine (minimum 183 +/- 23 mOsmol/kg of H2O) with a reduction in osmolar clearance and a sharp increase in free water clearance. These findings are consistent with a temporary inhibition of vasopressin release by morphine. PMID:6716265

  12. Synergy between the antinociceptive effects of morphine and NSAIDs.

    PubMed

    Miranda, H F; Silva, E; Pinardi, G

    2004-05-01

    The intraperitoneal administration of morphine, diclofenac, ketoprofen, meloxicam, metamizol, paracetamol and piroxicam induced dose-dependent antinociception in mice tested with the acetic acid writhing test. The isobolographic analysis of the simultaneous intraperitoneal administration of fractions of the ED50's of morphine with each nonsteroidal anti-inflammatory drug (NSAID) demonstrated the existence of a supra-additive interaction (synergy). The selective antagonist of micro -opioid receptors naltrexone partially reversed the supra-additive interactions to additive interactions; however, the combinations of morphine/metamizol and morphine/paracetamol were completely antagonized, resulting in subadditive interactions. The selective antagonist of delta-opioid receptors naltrindole failed to significantly attenuate the combinations of morphine with ketoprofen, meloxicam and piroxicam, but decreased the activity of the combinations of morphine with diclofenac, metamizol and paracetamol, transforming the interactions from supra-additive to additive. Nor-binaltorphimine was used to evaluate the involvement of kappa-opioid receptors. Nor-binaltorphimine did not modify the supra-additive interaction of morphine and NSAIDs and the additive interaction of the co-administration of morphine and metamizol. The synergy between morphine and NSAIDs could be related to different pathways of pain transmission, probably related to the different intracellular signal transduction mechanisms of action of opioid and non-opioid agents. PMID:15213733

  13. Parkinson's disease, L-DOPA, and endogenous morphine: a revisit.

    PubMed

    Stefano, George B; Mantione, Kirk J; Králíčková, Milena; Ptacek, Radek; Kuzelova, Hana; Esch, Tobias; Kream, Richard M

    2012-08-01

    Clinical observations stemming from widespread employment of restorative L-3,4-dihydroxyphenylalanine (L-DOPA) therapy for management of dyskinesia in Parkinson's Disease (PD) patients implicate a regulatory role for endogenous morphine in central nervous system dopamine neurotransmission. Reciprocally, it appears that restorative L-DOPA administration has provided us with a compelling in vivo pharmacological model for targeting peripheral sites involved in endogenous morphine expression in human subjects. The biological activities underlying endogenous morphine expression and its interaction with its major precursor dopamine strongly suggest that endogenous morphine systems are reciprocally dysregulated in PD. These critical issues are examined from historical and current perspectives within our short review. PMID:22847214

  14. Novel levocetirizine HCl tablets with enhanced palatability: synergistic effect of combining taste modifiers and effervescence technique

    PubMed Central

    Labib, Gihan S

    2015-01-01

    Objectives Levocetirizine HCl, a second-generation piperazine derivative and H1-selective antihistaminic agent, possesses few side effects. The first objective of the study was to compare and evaluate the taste-masking effect of different ratios of 2-hydroxypropyl-β-cyclodextrin and mannitol on levocetirizine HCl using an inclusion complex and solid dispersion, respectively. The second objective was to study the possibility of preparing and evaluating effervescent tablets from the best-chosen taste-masked blends for the purpose of their use either as orodispersible tablets or as water-soluble effervescent tablets, according to patients’ will. Materials and methods Prepared taste-masked blends were prepared and subjected to palatability, Fourier-transform infrared spectroscopy, and differential scanning calorimetry studies. Tablets containing different percentages of effervescent mixtures were prepared by direct compression on the selected taste-modified blends. Evaluation tests were conducted, including flowability and compressibility on the precompressed blends and hardness, friability, wetting time, effervescent time, in vitro, in vivo disintegration time, and in vitro dissolution study on the compressed tablets. Formulated tablets were evaluated and compared to marketed orodispersible tablets for mouth feel and palatability. Results All prepared tablets showed convenient physical and palatability properties compared to the selected brand. The in vitro drug-release study revealed fast release of levocetirizine HCl within 5 minutes from all prepared tablets. Conclusion Levocetirizine HCl effervescent tablets are likely to increase patient compliance with drug administration. Moreover, the use of these effervescent tablets in an orodispersible dosage form can improve oral drug bioavailability and act as an attractive pediatric dosage form. PMID:26379426

  15. Evaluation of binders in the preparation of medicinal carbon tablets by wet granule compression.

    PubMed

    Ito, Akihiko; Onishi, Hiraku; Yamamoto, Kenta; Machida, Yoshiharu

    2006-04-01

    Medicinal carbon (MC) tablets were prepared to obtain an oral dosage form that can be easily taken. The MC tablets were made by the wet granule compression method, in which hydroxypropyl cellulose (HPC), carboxymethyl cellulose sodium (CMC-Na) and maltitol (MT) were applied as binders. Brilliant Blue FCF (BB) was used as a model drug. The binders were evaluated in terms of formability of the granules and tablets, their strength, disintegration of the tablets, and their effect on the adsorption potential of MC. HPC and CMC-Na gave the strong granules at a fairly low concentration, but more MT was needed to obtain the strong granules. The tablets could be formed only when using MT at 120% (w/w) of the MC amount. The tablet displayed good hardness and rapid disintegration. The adsorption potential was not affected by CMC-Na, and slightly prevented by MT. However, the adsorption ability of MC was lowered more with the increase in HPC. The granules and tablets exhibited similar adsorption potentials, which were a little lower than that of MC suspended in MT aqueous solution. Similar adsorption characteristics were also observed in a real drug, acetaminophen. It is suggested that the MC tablets prepared by the wet granule compression using MT as a binder should be useful as a compact dosage form of MC. PMID:16596024

  16. Evaluation of enteric-coated tablets as a whole cell inactivated vaccine candidate against Vibrio cholerae.

    PubMed

    Fernández, Sonsire; Año, Gemma; Castaño, Jorge; Pino, Yadira; Uribarri, Evangelina; Riverón, Luis A; Cedré, Bárbara; Valmaseda, Tania; Falero, Gustavo; Pérez, José L; Infante, Juan F; García, Luis G; Solís, Rosa L; Sierra, Gustavo; Talavera, Arturo

    2013-01-01

    A vaccine candidate against cholera was developed in the form of oral tablets to avoid difficulties during application exhibited by current whole cell inactivated cholera vaccines. In this study, enteric-coated tablets were used to improve the protection of the active compound from gastric acidity. Tablets containing heat-killed whole cells of Vibrio cholerae strain C7258 as the active pharmaceutical compound was enteric-coated with the polymer Kollicoat(®) MAE-100P, which protected them efficiently from acidity when a disintegration test was carried out. Enzyme-linked immunosorbent assay (ELISA) anti-lipopolysaccharide (LPS) inhibition test and Western blot assay revealed the presence of V. cholerae antigens as LPS, mannose-sensitive haemagglutinin (MSHA) and outer membrane protein U (Omp U) in enteric-coated tablets. Immunogenicity studies (ELISA and vibriocidal test) carried out by intraduodenal administration in rabbits showed that the coating process of tablets did not affect the immunogenicity of V. cholerae-inactivated cells. In addition, no differences were observed in the immune response elicited by enteric-coated or uncoated tablets, particularly because the animal model and immunization route used did not allow discriminating between acid resistances of both tablets formulations in vivo. Clinical studies with volunteers will be required to elucidate this aspect, but the results suggest the possibility of using enteric-coated tablets as a final pharmaceutical product for a cholera vaccine. PMID:23492079

  17. Pharmaceutical and pharmacokinetic characterization of a novel sublingual buprenorphine/naloxone tablet formulation in healthy volunteers

    PubMed Central

    Fischer, Andreas; Hjelmström, Peter

    2015-01-01

    Abstract Context Bitter taste, as well as dissolve time, presents a significant challenge for the acceptability of formulations for oral transmucosal drug delivery. Objective To characterize a novel sublingual tablet formulation of buprenorphine/naloxone with regards to pharmacokinetics, dissolve time and formulation acceptability. Methods Dry mixing techniques were employed to produce a small and fast dissolving buprenorphine/naloxone sublingual tablet formulation, OX219 (Zubsolv®), using sucralose and menthol as sweetener and flavor to mask the bitter taste of the active ingredients. Two cross-over studies were performed in healthy volunteers to evaluate pharmacokinetics, dissolve time and acceptability of OX219 5.7/1.4 mg tablets compared to the commercially available buprenorphine/naloxone formulations Suboxone® tablets and films (8/2 mg). Results Buprenorphine exposure was equivalent in OX219 and Suboxone tablets. Sublingual dissolve times were significantly shorter for OX219 than for Suboxone tablets and were similar to Suboxone films. The OX219 formulation received significantly higher subjective ratings for taste and overall acceptability than both Suboxone formulations. OX219 was preferred over Suboxone tablet and film formulations by 77.4% and 88.9% of subjects, respectively. Conclusions A sublingual tablet formulation with an improved acceptability has been successfully developed. PMID:24099551

  18. Comparative rewarding properties of morphine and butorphanol.

    PubMed

    Mamoon, A M; Barnes, A M; Ho, I K; Hoskins, B

    1995-01-01

    Because butorphanol (Stadol), a synthetic morphinan compound, has been demonstrated in our laboratories to produce physical dependence and withdrawal symptoms in rats, we have hypothesized that butorphanol has rewarding properties indicative of abuse potential. To test this hypothesis, the effects of equimolar doses of butorphanol tartrate (0.5-5.0 micrograms) and morphine sulfate (0.8-8.0 micrograms) were assessed in inbred Lewis male rats using the conditioned place preference (CPP) paradigm. Unilateral microinjections (1 microl/inj) of saline or opioids were made into the ventral tegmental area (VTA). Microinjections of saline to controls were associated with both sides of modified Skinner boxes, whereas opioid injections were associated only with the white chambers (less preferred side to the naive animals). Opioids were administered alternating with saline in the drug-treated animals on alternating days. During eight conditioning sessions the rats learned to associate light and dark sides of the Skinner boxes with microinjections of opioids or saline, respectively. Although all doses of morphine induced significant preference over saline, only the higher doses of butorphanol (2.0-5.0 micrograms) produced significant conditioned place preference for the sides of the chambers associated with the drugs. These results suggest that, like morphine which is widely abused, butorphanol also has rewarding properties, and, therefore, further investigations regarding its abuse potential are necessary. PMID:8665275

  19. New insights into segregation during tabletting.

    PubMed

    Lakio, S; Siiriä, S; Räikkönen, H; Airaksinen, S; Närvänen, T; Antikainen, O; Yliruusi, J

    2010-09-15

    The aim of this study was to evaluate how different granule size distributions affect the tablet compression process. The emphasis was on developing new analytic methods for compression data for entire batch. In all, 18 batches of granules containing theophylline and lactose were tabletted, using an instrumented eccentric tabletting machine. During tablet compression, upper and lower punch forces were recorded. Mathematical methods were developed for analysing the compression data during tabletting. The results suggested two types of undulation in the tabletting data: (1) short-time scale variation or tablet-to-tablet changes in force data and (2) long-time scale undulation describing the changes occurring throughout the tabletting process, such as segregation. These undulation phenomena were analysed, using various mathematical methods. In addition the results suggest that smaller particles have better tabletting properties, to a certain limit. However particle size alone cannot explain the tabletability of granules. PMID:20600718

  20. Respiratory depression following morphine and morphine-6-glucuronide in normal subjects.

    PubMed Central

    Thompson, P I; Joel, S P; John, L; Wedzicha, J A; Maclean, M; Slevin, M L

    1995-01-01

    1. Morphine 6-glucuronide (M6G) is a metabolite of morphine with analgesic activity. A double-blind, randomised comparison of the effects of morphine and M6G on respiratory function was carried out in 10 normal subjects after i.v. morphine (10 mg 70 kg-1) or M6G (1, 3.3 and 5 mg 70 kg-1). Analgesic potency was also assessed using an ischaemic pain test and other toxic effects were monitored. 2. Following morphine there was a significant increase in arterial PCO2, as measured by blood gases 45 min post dose (0.54 +/- 0.24 (s.d.) kPa, P < 0.001), and in transcutaneous PCO2 from 15 min post dose until the end of the study period (4 h), whereas blood gas and transcutaneous PCO2 were unchanged after M6G at 1.0, 3.3 and 5.0 mg 70 kg-1. This increased PCO2 following morphine was associated with an increase in expired CO2 concentration (FECO2) (0.20 +/- 0.14% expired air at 15 min post dose, P = 0.002), compared with small but significant reductions in FECO2 following morphine 6-glucuronide (-0.15 +/- 0.17% at 1 mg 70 kg-1 P = 0.030, -0.14 +/- 0.15% at 3.3 mg 70 kg-1 P = 0.017, -0.18 +/- 0.11% at 5 mg 70 kg-1 P = 0.024). Maximum transcutaneous PCO2 was significantly increased after morphine (0.63 +/- 0.28 kPa P = 0.009), but was not changed after M6G at 1 mg (0.10 +/- 0.34 kPa P = 0.11) 3.3 mg (0.06 +/- 0.37 kPa P = 0.34) or 5 mg (0.26 +/- 0.07 kPa P = 0.10).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8562297

  1. 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…

  2. 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…

  3. Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction: the randomized, double-blind, placebo-controlled IMPRESSION trial

    PubMed Central

    Kubica, Jacek; Adamski, Piotr; Ostrowska, Małgorzata; Sikora, Joanna; Kubica, Julia Maria; Sroka, Wiktor Dariusz; Stankowska, Katarzyna; Buszko, Katarzyna; Navarese, Eliano Pio; Jilma, Bernd; Siller-Matula, Jolanta Maria; Marszałł, Michał Piotr; Rość, Danuta; Koziński, Marek

    2016-01-01

    Aims The currently available data indicate a drug–drug interaction between morphine and oral P2Y12 receptor inhibitors, when administered together. The aim of this trial was to assess the influence of infused morphine on pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite (AR-C124910XX) in patients with acute myocardial infarction. Methods and results In a single-centre, randomized, double-blind trial, patients were assigned in a 1:1 ratio to receive intravenously either morphine (5 mg) or placebo, followed by a 180 mg loading dose of ticagrelor. Pharmacokinetics was determined with liquid chromatography tandem mass spectrometry and ticagrelor antiplatelet effects were measured with up to three different platelet function tests: vasodilator-stimulated phosphoprotein phosphorylation assay, multiple electrode aggregometry and VerifyNow. The pharmacokinetic and pharmacodynamic assessment was performed in 70 patients (35 in each study group). Morphine lowered the total exposure to ticagrelor and its active metabolite by 36% (AUC(0–12): 6307 vs. 9791 ng h/mL; P = 0.003), and 37% (AUC(0–12): 1503 vs. 2388 ng h/mL; P = 0.008), respectively, with a concomitant delay in maximal plasma concentration of ticagrelor (4 vs. 2 h; P = 0.004). Multiple regression analysis showed that lower AUC(0–12) values for ticagrelor were independently associated with the administration of morphine (P = 0.004) and the presence of ST-segment elevation myocardial infarction (P = 0.014). All three methods of platelet reactivity assessment showed a stronger antiplatelet effect in the placebo group and a greater prevalence of high platelet reactivity in patients receiving morphine. Conclusions Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction. ClinicalTrials.gov Identifier: NCT02217878. PMID:26491112

  4. Methadone Reverses Analgesic Tolerance Induced by Morphine Pretreatment

    PubMed Central

    Posa, Luca; Accarie, Alison; Marie, Nicolas

    2016-01-01

    Background: Opiates such as morphine are the most powerful analgesics, but their protracted use is restrained by the development of tolerance to analgesic effects. Recent works suggest that tolerance to morphine might be due to its inability to promote mu opioid receptor endocytosis, and the co-injection of morphine with a mu opioid receptor internalizing agonist like [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin reduces tolerance to morphine. So far, no studies have been conducted to evaluate the ability of methadone to reduce morphine tolerance in morphine-pretreated animals, a treatment sequence that could be encountered in opiate rotation protocol. We investigated the ability of methadone (a mu opioid receptor internalizing agonist used in therapy) to reverse morphine tolerance and the associated cellular mechanisms in the periaqueductal gray matter, a region involved in pain control. Methods: We measured analgesic response following a challenge dose of morphine in the hot plate test and investigated regulation of mu opioid receptor (coupling and endocytosis) and some cellular mechanisms involved in tolerance such as adenylate cyclase superactivation and changes in N-methyl-d-aspartate receptor subunits expression and phosphorylation state. Results: A chronic treatment with morphine promoted tolerance to its analgesic effects and was associated with a lack of mu opioid receptor endocytosis, adenylate cyclase overshoot, NR2A and NR2B downregulation, and phosphorylation of NR1. We reported that a methadone treatment in morphine-treated mice reversed morphine tolerance to analgesia by promoting mu opioid receptor endocytosis and blocking cellular mechanisms of tolerance. Conclusions: Our data might lead to rational strategies to tackle opiate tolerance in the frame of opiate rotation. PMID:26390873

  5. Biotransformation and pharmacokinetics of ethylmorphine after a single oral dose.

    PubMed Central

    Aasmundstad, T A; Xu, B Q; Johansson, I; Ripel, A; Bjørneboe, A; Christophersen, A S; Bodd, E; Mørland, J

    1995-01-01

    1. The pharmacokinetics of ethylmorphine after administration of a single dose of the cough mixture Cosylan were investigated in 10 healthy subjects. 2. The median urinary recovery of ethylmorphine and measured metabolites was 77% over 48 h. The median tmax of unchanged ethylmorphine was 45 min, and the terminal elimination t1/2 was 2 h. Ethylmorphine-6-glucuronide was found to be the major metabolite. 3. Two subjects had significantly lower urinary recovery (0.48 h) of morphine and morphine-glucuronides than the remainder. Furthermore, these two had urinary metabolic ratios (MRO) and partial metabolic clearances (CLmO) for O-deethylation of ethylmorphine tentatively classifying them phenotypically as poor metabolisers of the debrisoquine/sparteine type. 4. Genotyping for cytochrome P450 (CYP) 2D6 alleles revealed five homozygote (wt/wt) and five heterozygote subjects. Two subjects phenotypically classified as poor metabolisers were genotypically CYP2D6A/wt and CYP2D6D/wt, respectively. 5. Serum and urine samples taken more than 8 and 24 h after administration of ethyl-morphine respectively, contained morphine and morphine-glucuronides, but no ethylmorphine, ethylmorphine-6-glucuronide or (serum only) norethylmorphine. Norethylmorphine could be detected after hydrolysis of urine samples in all subjects. The urinary recovery of the active metabolites morphine and morphine-6-glucuronide after administration of ethylmorphine varied by a factor of 9 between individuals. 6. The wide variation in recovery of morphine and morphine-glucuronides after oral administration of ethylmorphine could not be explained simply by a difference in CYP2D6 genotype. Constitutional variation in other enzymatic pathways involved in ethylmorphine metabolism is probably crucial. Ratios of morphine to parent drug cannot be used to distinguish the source of morphine after administration of ethylmorphine. Norethylmorphine should be included in urine assays for opiates in forensic toxicology

  6. A Traditional Chinese Medicine Xiao-Ai-Tong Suppresses Pain through Modulation of Cytokines and Prevents Adverse Reactions of Morphine Treatment in Bone Cancer Pain Patients

    PubMed Central

    Cong, Yan; Sun, Kefu; He, Xueming; Li, Jinxuan; Dong, Yanbin; Zheng, Bin; Tan, Xiao; Song, Xue-Jun

    2015-01-01

    Treating cancer pain continues to possess a major challenge. Here, we report that a traditional Chinese medicine Xiao-Ai-Tong (XAT) can effectively suppress pain and adverse reactions following morphine treatment in patients with bone cancer pain. Visual Analogue Scale (VAS) and Quality of Life Questionnaire (EORTC QLQ-C30) were used for patient's self-evaluation of pain intensity and evaluating changes of adverse reactions including constipation, nausea, fatigue, and anorexia, respectively, before and after treatment prescriptions. The clinical trials showed that repetitive oral administration of XAT (200 mL, bid, for 7 consecutive days) alone greatly reduced cancer pain. Repetitive treatment with a combination of XAT and morphine (20 mg and 30 mg, resp.) produced significant synergistic analgesic effects. Meanwhile, XAT greatly reduced the adverse reactions associated with cancer and/or morphine treatment. In addition, XAT treatment significantly reduced the proinflammatory cytokines interleukin-1β and tumor necrosis factor-α and increased the endogenous anti-inflammatory cytokine interleukin-10 in blood. These findings demonstrate that XAT can effectively reduce bone cancer pain probably mediated by the cytokine mechanisms, facilitate analgesic effect of morphine, and prevent or reduce the associated adverse reactions, supporting a use of XAT, alone or with morphine, in treating bone cancer pain in clinic. PMID:26617438

  7. Zomepirac sodium -- a new oral analgesic.

    PubMed

    1981-01-01

    Zomepirac sodium is a new oral analgesic that is more effective than aspirin, with no apparent tolerance or potential for addiction. It causes gastrointestinal bleeding similar to that caused by large doses of aspirin. For occasional moderate pain not responsive to aspirin, zomepirac may prove to be preferable to oral narcotics such as codeine, oxycodone, propoxyphene, pentazocine and meperidine. For chronic use, the safety and continued effectiveness of the new drug remain to be determined; it probably cannot replace oral narcotics in narcotic-dependent patients. For severe pain, as in myocardial infarction, renal colic and after some operations, zomepirac is no substitute for parenteral morphine. PMID:7005639

  8. CB1 antagonism: interference with affective properties of acute naloxone-precipitated morphine withdrawal in rats

    PubMed Central

    Wills, Kiri L.; Vemuri, Kiran; Kalmar, Alana; Lee, Alan; Limebeer, Cheryl L.; Makriyannis, Alexandros

    2014-01-01

    Rationale Modulation of the endocannabinoid system has been found to interfere with opiate withdrawal. The potential of activation and blockade of the endocannabinoid system to prevent the aversive-affective state of naloxone-precipitated morphine withdrawal (MWD) was investigated in a one-trial conditioned place aversion (CPA) paradigm. Objective CPA provides a sensitive measure of the motivational effects of acute MWD. The potential of the fatty acid amide hydrolase (FAAH) inhibitors, URB597 and PF-3845, the CB1 antagonist/inverse agonist, AM251, and the neutral CB1 antagonists, AM4113 and AM6527 (oral), to interfere with establishment of a MWD-induced CPA was investigated. As well, the potential of AM251 and AM4113 to interfere with reinstatement of a previously established MWD-induced CPA was investigated. Materials and methods Using a one-trial place conditioning paradigm, rats were administered naloxone (1 mg/kg, subcutaneous (sc)) 24 h after receiving a high dose of morphine (20 mg/kg, sc) and were placed on the conditioning floor. To determine the effect of each pretreatment drug on the establishment of the MWD-induced CPA, URB597 (0.3 mg/kg, intraperitoneally (ip)), PF-3845 (10 mg/kg, ip), AM251 (1 or 2.5 mg/kg, ip), AM4113 (1 or 2.5 mg/kg, ip), and AM6527 (5 mg/kg, oral) were administered prior to conditioning. Results AM251 (2.5, but not 1 mg/k), AM4113, and AM6527, but not URB597 or PF-3845, interfered with the establishment of the MWD-induced CPA. AM251 and AM4113 did not prevent reinstatement of the CPA. Conclusions Neutral antagonism of the CB1 receptor reduces the aversive affective properties of morphine withdrawal. PMID:24770676

  9. Increased probability of GABA release during withdrawal from morphine.

    PubMed

    Bonci, A; Williams, J T

    1997-01-15

    Opioid receptors located on interneurons in the ventral tegmental area (VTA) inhibit GABA(A)-mediated synaptic transmission to dopamine projection neurons. The resulting disinhibition of dopamine cells in the VTA is thought to play a pivotal role in drug abuse; however, little is known about how this GABAA synapse is affected after chronic morphine treatment. The regulation of GABA release during acute withdrawal from morphine was studied in slices from animals treated for 6-7 d with morphine. Slices containing the VTA were prepared and maintained in morphine-free solutions, and GABAA IPSCs were recorded from dopamine cells. The amplitude of evoked IPSCs and the frequency of spontaneous miniature IPSCs measured in slices from morphine-treated guinea pigs were greater than placebo-treated controls. In addition, activation of adenylyl cyclase, with forskolin, and cAMP-dependent protein kinase, with Sp-cAMPS, caused a larger increase in IPSCs in slices from morphine-treated animals. Conversely, the kinase inhibitors staurosporine and Rp-CPT-cAMPS decreased GABA IPSCs to a greater extent after drug treatment. The results indicate that the probability of GABA release was increased during withdrawal from chronic morphine treatment and that this effect resulted from an upregulation of the cAMP-dependent cascade. Increased transmitter release from opioid-sensitive synapses during acute withdrawal may be one adaptive mechanism that results from prolonged morphine treatment. PMID:8987801

  10. Tests for addiction (chronic intoxication) of morphine type

    PubMed Central

    Halbach, H.; Eddy, Nathan B.

    1963-01-01

    A survey is presented of laboratory and clinical methods for the determination of addiction liability of substances with morphine-like effects. Since physical dependence is the outstanding pharmacological criterion of addiction of morphine type, the procedures for its qualitative and quantitative assessment are described in detail. PMID:13952049

  11. Cholera toxin effects on body temperature changes induced by morphine.

    PubMed

    Basilico, L; Parenti, M; Fumagalli, A; Parolaro, D; Giagnoni, G

    1997-03-01

    The present study evaluates the influence of cholera toxin and its B-subunit on thermic responses to morphine in the rats. The holotoxin (1 microg/rat) and the B-subunit (5 microg) were administered ICV and three days later rats were challenged ICV with morphine and tested for changes of body temperature. Cholera toxin, but not its B-subunit, modified the time course of the hyperthermic response induced by a low dose of morphine (2.5 microg), converted the hypothermia due to a higher dose of morphine (18 microg) to a consistent hyperthermia and only partially reduced the greater hypothermia induced by 36 microg of morphine. Cholera toxin-induced modifications of thermic responses to morphine were paralleled with a decreased Gs(alpha) immunoreactivity and a reduced ability for the toxin to catalyse the "in vitro" ADP-ribosylation of Gs(alpha) in hypothalamic membranes. In contrast, at the same time when morphine-induced effects on body temperature were assessed, no changes in pertussis toxin-mediated ADP-ribosylation of Gi(alpha)/Go(alpha), or basal adenylate cyclase activity, or binding of mu-opioid receptor selective ligand [3H]-DAMGO were observed in hypothalamic areas from rats treated with cholera toxin. These findings suggest that adaptative events secondary to prolonged activation of Gs(alpha) play a role in the modifications of thermic responses to morphine induced by CTX. PMID:9077589

  12. Analgesic efficacy of morphine applied topically to painful ulcers.

    PubMed

    Zeppetella, Giovambattista; Paul, James; Ribeiro, Maria D C

    2003-06-01

    The analgesic effects of morphine applied topically to painful ulcers was assessed in a randomized, double-blind, placebo-controlled, crossover pilot study of five patients with painful sacral sores. Patients were treated for two days with either 10 mg morphine sulfate or placebo (water for injection) applied topically to the ulcer. After a two-day wash-out period, patients were crossed over for a further two days of the alternative treatment. Patients were asked to rate analgesia using a visual analogue scale (VAS) and to document any local or systemic adverse effects. All patients reported lower VAS scores with morphine compared to placebo and no local or systemic adverse events attributable to morphine were noted by either patients or nursing staff. This pilot study suggests that morphine applied topically is an effective method of producing local analgesia, well tolerated by patients, and not associated with systemic adverse effects. PMID:12782436

  13. Primary sensory neurones and naloxone-precipitated morphine withdrawal.

    PubMed Central

    Donnerer, J.

    1989-01-01

    1. The C-fibre-evoked depressor reflex following i.a. injection of capsaicin and the wiping movements following chemical irritation of the cornea by capsaicin were both found to be augmented in the naloxone-precipitated morphine withdrawal phase. 2. The in vitro capsaicin-evoked release of substance P from central terminals of C-fibre afferents in the spinal cord was decreased in morphine-treated rats. Following naloxone, the release in the morphine-treated group was as large as in the control group. 3. The C-fibre mediated plasma extravasation in the rat paw after naloxone was found to be the same in morphine-treated and control rats. 4. It is concluded that C-fibre-evoked reflex reactions are augmented during morphine withdrawal, but that the mechanisms responsible are either located postsynaptically to the primary sensory neurone or further centrally. PMID:2472843

  14. Enhancement of tolerance development to morphine in rats prenatally exposed to morphine, methadone, and buprenorphine

    PubMed Central

    2010-01-01

    Background Abuse of addictive substances is a serious problem that has a significant impact on areas such as health, the economy, and public safety. Heroin use among young women of reproductive age has drawn much attention around the world. However, there is a lack of information on effects of prenatal exposure to opioids on their offspring. In this study, an animal model was established to study effects of prenatal exposure to opioids on offspring. Methods Female pregnant Sprague-Dawley rats were sub-grouped to receive (1) vehicle, (2) 2-4 mg/kg morphine (1 mg/kg increment per week), (3) 7 mg/kg methadone, and (4) 3 mg/kg buprenorphine, subcutaneously, once or twice a day from E3 to E20. The experiments were conducted on animals 8-12 weeks old and with body weight between 250 and 350 g. Results Results showed that prenatal exposure to buprenorphine caused higher mortality than other tested substance groups. Although we observed a significantly lower increase in body weight in all of the opioid-administered dams, the birth weight of the offspring was not altered in all treated groups. Moreover, no obvious behavioral abnormality or body-weight difference was noted during the growing period (8-12 weeks) in all offspring. When the male offspring received morphine injection twice a day for 4 days, the prenatally opioid-exposed rats more quickly developed a tolerance to morphine (as shown by the tail-flick tests), most notably the prenatally buprenorphine-exposed offspring. However, the tolerance development to methadone or buprenorphine was not different in offspring exposed prenatally to methadone or buprenorphine, respectively, when compared with that of the vehicle controlled group. Similar results were also obtained in the female animals. Conclusions Animals prenatally exposed to morphine, methadone, or buprenorphine developed tolerance to morphine faster than their controlled mates. In our animal model, prenatal exposure to buprenorphine also resulted in higher

  15. Morphine Liposomal--SkyePharma: C 0401, D 0401, morphine--DepoFoam, SKY 0401.

    PubMed

    2003-01-01

    The SkyePharma PLC subsidiary SkyePharma Inc. (formerly DepoTech) is developing a sustained-release formulation of morphine sulphate [DepoMorphine, C 0401, D 0401, SKY 0401] using its DepoFoam proprietary drug delivery technology. It is intended for epidural administration in the treatment of acute postoperative pain. DepoFoam consists of microscopic spherical particles with internal aqueous chambers separated by lipid membranes containing the encapsulated drug. DepoFoam particles are synthetic replicas of natural lipids that are biodegradable and biocompatible. DepoFoam can be administered subcutaneously, intramuscularly and intrathecally. In December 2002, SkyePharma and Endo Pharmaceuticals signed a development and commercialisation agreement providing Endo Pharmaceuticals with exclusive marketing and distribution rights in the US and Canada for Depomorphine and another product, Propofol IDD-D trade mark, with options for other development products. Under the terms of the agreement, SkyePharma will receive an upfront payment and may receive further milestone payments. Skye-Pharma will also receive a share of each product's sales revenue. SkyePharma is responsible for clinical development towards the US FDA approval and for product manufacture and associated costs. Following the approval, SkyePharma will as act as a supplier, while Endo will market each product in the US and Canada. SkyePharma has received 30 million US dollars from Paul Capital Partners, a US private equity group, to develop DepoMorphine. This capital will enable SkyePharma to fund phase III clinical trials without raising extra funds. Paul Capital will have rights to 15% of any revenues from DepoMorphine until 2014, and also receive some royalties on three other SkyePharma products. However, if DepoMorphine fails in clinical trials or is declined for registration, Paul Capital will not be compensated for the investment. SkyePharma expect to conclude a European license by the end of 2003, and

  16. Dopamine-dependent responses to morphine depend on glucocorticoid receptors

    PubMed Central

    Marinelli, Michela; Aouizerate, Bruno; Barrot, Michel; Le Moal, Michel; Piazza, Pier Vincenzo

    1998-01-01

    Previous work has shown that glucocorticoid hormones facilitate the behavioral and dopaminergic effects of morphine. In this study we examined the possible role in these effects of the two central corticosteroid receptor types: mineralocorticoid receptor (MR), and glucocorticoid receptor (GR). To accomplish this, specific antagonists of these receptors were infused intracerebroventricularly and 2 hr later we measured: (i) locomotor activity induced by a systemic injection of morphine (2 mg/kg); (ii) locomotor activity induced by an infusion of morphine (1 μg per side) into the ventral tegmental area, which is a dopamine-dependent behavioral response to morphine; (iii) morphine-induced dopamine release in the nucleus accumbens, a dopaminergic projection site mediating the locomotor and reinforcing effects of drugs of abuse. Blockade of MRs by spironolactone had no significant effects on locomotion induced by systemic morphine. In contrast, blockade of GRs by either RU38486 or RU39305, which is devoid of antiprogesterone effects, reduced the locomotor response to morphine, and this effect was dose dependent. GR antagonists also reduced the locomotor response to intraventral tegmental area morphine as well as the basal and morphine-induced increase in accumbens dopamine, as measured by microdialysis in freely moving rats. In contrast, spironolactone did not modify dopamine release. In conclusion, glucocorticoids, via GRs, facilitate the dopamine-dependent behavioral effects of morphine, probably by facilitating dopamine release. The possibility of decreasing the behavioral and dopaminergic effects of opioids by an acute administration of GR antagonists may open new therapeutic strategies for treatment of drug addiction. PMID:9636221

  17. Postmortem redistribution of the heroin metabolites morphine and morphine-3-glucuronide in rabbits over 24 h.

    PubMed

    Maskell, Peter D; Albeishy, Mohammed; De Paoli, Giorgia; Wilson, Nathan E; Seetohul, L Nitin

    2016-03-01

    The interpretation of postmortem drug levels is complicated by changes in drug blood levels in the postmortem period, a phenomena known as postmortem drug redistribution. We investigated the postmortem redistribution of the heroin metabolites morphine and morphine-3-glucuronide in a rabbit model. Heroin (1 mg/kg) was injected into anesthetised rabbit; after 1 h, an auricular vein blood sample was taken and the rabbit was euthanised. Following death rabbits were placed in a supine position at room temperature and divided into three groups namely (1) immediate autopsy, (2) autopsy after 30 minutes and (3) autopsy 24 h after death. Various samples which included femoral blood, cardiac blood, lung, liver, kidney, vitreous humour, subcutaneous and abdominal fat, liver, bone marrow and skeletal muscle were taken. The samples were analysed with a validated LC-MS/MS method. It was observed that within minutes there was a significant increase in free morphine postmortem femoral blood concentration compared to the antemortem sample (0.01 ± 0.01 to 0.05 ± 0.02 mg/L).Various other changes in free morphine and metabolite concentrations were observed during the course of the experiment in various tissues. Principal component analysis was used to investigate possible correlations between free morphine in the various samples. Some correlations were observed but gave poor predictions (>20 % error) when back calculating. The results suggest that rabbits are a good model for further studies of postmortem redistribution but that further study and understanding of the phenomena is required before accurate predictions of the blood concentration at the time of death are possible. PMID:25863436

  18. Postoperative morphine requirements, nausea and vomiting following anaesthesia for tonsillectomy. Comparison of intravenous morphine and non-opioid analgesic techniques.

    PubMed

    Mather, S J; Peutrell, J M

    1995-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be as effective as opioid analgesia following tonsillectomy in children. Opioids are still frequently used but tonsillectomy is associated with a high incidence of vomiting. This study has attempted to assess postoperative analgesic consumption and nausea and vomiting after general anaesthesia for tonsillectomy using either paracetamol premedication, paracetamol plus a NSAID or intravenous morphine to provide postoperative analgesia. Some children required a rescue dose of morphine in the recovery room, including some who had received intravenous morphine at induction. Least supplementary morphine was required by those who had received paracetamol plus ketorolac. Postoperative nausea and vomiting was significantly less in the two groups which were not given intraoperative morphine. The number of vomiting incidents was also much less. We conclude that the preoperative administration of paracetamol alone provides satisfactory analgesia in many children but that supplementary analgesia is still required for some. PMID:7489439

  19. Analgesic effect of intramuscular and oral nalbuphine in postoperative pain.

    PubMed

    Beaver, W T; Feise, G A; Robb, D

    1981-02-01

    In a double-blind study using patients' subjective reports as indices of analgesia, the relative analgesic potency of intramuscular and oral nalbuphine was determined in 104 postoperative patients. Effects of single doses of 3 and 9 mg of intramuscular nalbuphine were compared with those of 15- and 45-mg oral doses of nalbuphine by means of a parallel study design (26 patients per treatment group). When both intensity and duration of analgesia are considered (i.e., total analgesic effect), oral nalbuphine is 1/4 to 1/5 as potent as intramuscular nalbuphine. In terms of peak effect, however, oral nalbuphine is only 1/10 as potent. The oral/parenteral potency ratio for total effect is close to those obtained by Houde et al. in studies of morphine (1/6), metopon (1/5), hydromorphone (1/5), and oxymorphone (1/6) and suggests that oral nalbuphine undergoes substantial biotransformation on first pass through gut mucosa and liver. Since intramuscular nalbuphine is approximately equipotent to morphine, it should be feasible to equal the analgesia induced by the usual intramuscular doses of morphine with reasonable oral doses of nalbuphine. Although nalbuphine is a mixed agonist/antagonist analgesic, no psychotomimetic reactions were observed. PMID:7006884

  20. Relative bioavailability of oral dosage forms of tenoxicam.

    PubMed

    Guentert, T W; Stebler, T; Banken, L; Defoin, R; Schmitt, M

    1994-09-01

    The bioavailability of tenoxicam (Ro 12-0068, Tilcotil, CAS 59804-37-4) from an effervescent tablet and an instant milk drink formulation relative to the commercial 20 mg tablet was investigated in a randomized cross-over study. Twelve healthy male volunteers (age 18-35 years; weight 63-95 kg) received on three different occasions a single oral tablet, an effervescent tablet or an instant milk drink (dissolved in water) with each dose containing 20 mg of tenoxicam. The wash-out period between two consecutive treatments was at least 5 weeks. Plasma concentrations after dosing were determined with a specific HPLC method. With the effervescent tablet and the milk drink, maximum concentrations were obtained at the same time (0.5-3.0 h) as with the reference tablet (0.5-4.0 h). Plasma peak concentrations appeared highest after the commercial tablet (mean +/- SD: Cmax 2.8 +/- 0.55 mg/l), but the difference to the effervescent tablet (2.7 +/- 0.41 mg/l) and the milk formulation (2.5 +/- 0.41 mg/l) was negligible. Similar mean elimination half-lives of 73, 77, and 77 h were obtained with the effervescent tablet, the milk drink, and the commercial tablet, respectively. Average bioavailability relative to the tablet was for the effervescent tablet and for the milk drink 96% with a coefficient of variation of 8%. The 90%-confidence intervals of the mean differences between the test and standard preparations in log-transformed AUC0-infinity and Cmax were within 20% around the respective mean parameter value calculated for the standard preparation allowing to conclude bioequivalence of the three oral formulations. PMID:7986242

  1. Potentiation of morphine analgesia by caffeine.

    PubMed Central

    Misra, A. L.; Pontani, R. B.; Vadlamani, N. L.

    1985-01-01

    Significant potentiation of morphine (5 mg kg-1 s.c. or 1 mg kg-1 i.v.) analgesia (tail-withdrawal reflex at 55 degrees C) was observed in caffeine-treated (100 mg kg-1 i.p.) rats as compared to the control group and lower doses of caffeine (2mg kg-1 i.p.) did not show this effect. Potentiated analgesia was reversed by naloxone. Pharmacokinetic or dispositional factors appear to be involved in part in this potentiation. PMID:4005485

  2. Potentiation of morphine analgesia by caffeine.

    PubMed

    Misra, A L; Pontani, R B; Vadlamani, N L

    1985-04-01

    Significant potentiation of morphine (5 mg kg-1 s.c. or 1 mg kg-1 i.v.) analgesia (tail-withdrawal reflex at 55 degrees C) was observed in caffeine-treated (100 mg kg-1 i.p.) rats as compared to the control group and lower doses of caffeine (2mg kg-1 i.p.) did not show this effect. Potentiated analgesia was reversed by naloxone. Pharmacokinetic or dispositional factors appear to be involved in part in this potentiation. PMID:4005485

  3. Formulation Development and Characterization of Meclizine Hydrochloride Sublimated Fast Dissolving Tablets.

    PubMed

    Vemula, Sateesh Kumar; Vangala, Mohan

    2014-01-01

    The intention of present research is to formulate and develop the meclizine hydrochloride fast dissolving tablets using sublimation method to enhance the dissolution rate. In this study an attempt was made to fasten the drug release from the oral tablets by incorporating the superdisintegrants and camphor as sublimating agent. The prepared fast dissolving tablets were subjected to precompression properties and characterized for hardness, weight variation, friability, wetting time, water absorption ratio, and disintegration time. From in vitro release studies, the formulation F9 exhibited fast release profile of about 98.61% in 30 min, and disintegration time 47 sec when compared with other formulations. The percent drug release in 30 min (Q 30) and initial dissolution rate for formulation F9 was 98.61 ± 0.25%, 3.29%/min. These were very much higher compared to marketed tablets (65.43 ± 0.57%, 2.18%/min). The dissolution efficiency was found to be 63.37 and it is increased by 1.4-fold with F9 FDT tablets compared to marketed tablets. Differential scanning calorimetry and Fourier transform infrared spectroscopy studies revealed that there was no possibility of interactions. Thus the development of meclizine hydrochloride fast dissolving tablets by sublimation method is a suitable approach to improve the dissolution rate. PMID:27355021

  4. Preparation and pharmacokinetics study on gastro-floating sustained-release tablets of troxipide.

    PubMed

    Gao, Yunyun; Gao, Yang; Yin, Fei; Wang, Mi; Wang, Zhenhong; Ye, Tiantian; Yang, Yonggang; Pan, W S; Yang, Xinggang

    2015-01-01

    The purpose of this research aimed at preparing gastro-floating sustained-release tablets of troxipide and a further study on in vitro release and in vivo bioavailability. Under the circumstances of direct powder compression, the floating tablets were successfully prepared with HPMC as main matrix material, Carbopol as assistant matrix material, octadecanol as floating agent and sodium bicarbonate as foaming agent to float by gas-forming. The floating time and accumulative release amount as evaluation indexes were utilized to perform pre-experiment screening and single-factor test, respectively, while central composite design response surface method was applied for formulation optimization, followed by in vivo pharmacokinetic study in beagles after oral administration for floating tablets and commercial tablets used as the control. The results indicated that the floating sustained-release tablets held a better capability for floating and drug release and more satisfactory pharmacokinetic parameters, such as a lower Cmax, a prolonged Tmax, but an equivalent bioavailability calculated by AUC0-24 compared to commercial tablets. So a conclusion was finally drawn that the floating sustained-release tablets possessing a good release property could be suitable for demands of design. PMID:25190152

  5. Formulation Development and Characterization of Meclizine Hydrochloride Sublimated Fast Dissolving Tablets

    PubMed Central

    Vangala, Mohan

    2014-01-01

    The intention of present research is to formulate and develop the meclizine hydrochloride fast dissolving tablets using sublimation method to enhance the dissolution rate. In this study an attempt was made to fasten the drug release from the oral tablets by incorporating the superdisintegrants and camphor as sublimating agent. The prepared fast dissolving tablets were subjected to precompression properties and characterized for hardness, weight variation, friability, wetting time, water absorption ratio, and disintegration time. From in vitro release studies, the formulation F9 exhibited fast release profile of about 98.61% in 30 min, and disintegration time 47 sec when compared with other formulations. The percent drug release in 30 min (Q30) and initial dissolution rate for formulation F9 was 98.61 ± 0.25%, 3.29%/min. These were very much higher compared to marketed tablets (65.43 ± 0.57%, 2.18%/min). The dissolution efficiency was found to be 63.37 and it is increased by 1.4-fold with F9 FDT tablets compared to marketed tablets. Differential scanning calorimetry and Fourier transform infrared spectroscopy studies revealed that there was no possibility of interactions. Thus the development of meclizine hydrochloride fast dissolving tablets by sublimation method is a suitable approach to improve the dissolution rate. PMID:27355021

  6. Pharmacokinetics of rizatriptan tablets during and between migraine attacks.

    PubMed

    Cutler, N R; Jhee, S S; Majumdar, A K; McLaughlin, D; Brucker, M J; Carides, A D; Kramer, M S; Matzura-Wolfe, D; Reines, S A; Goldberg, M R

    1999-04-01

    Gastric stasis during migraine attacks results in delayed absorption of several orally administered antimigraine agents. This study, as part of a larger trial, was conducted to examine the pharmacokinetics of rizatriptan tablets during and between migraine attacks. Participating patients met IHS criteria for migraine with or without aura, and suffered between one and eight migraines per month for the previous 6 months. In part 1 of the study, 21 patients were randomized to receive a single 5-mg tablet of rizatriptan or placebo in the migraine-free state. In part 2, the same patients were treated during migraine with rizatriptan 5-mg tablets (n=18) or placebo (n=3). Blood samples were obtained before dosing and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after dosing. The plasma concentration profile (ie, AUC((0-infinity)), C(max), T(max)) of rizatriptan 5-mg tablets administered during and between migraine attacks were comparable. The median T(max) for rizatriptan between and during attacks was 1 hour, indicating rapid absorption even during a migraine attack. Rizatriptan 5 mg was well tolerated and 67% of the patients experienced headache relief 2 hours postdose. PMID:15613223

  7. FDA-Approved Natural Polymers for Fast Dissolving Tablets.

    PubMed

    Alam, Md Tausif; Parvez, Nayyar; Sharma, Pramod Kumar

    2014-01-01

    Oral route is the most preferred route for administration of different drugs because it is regarded as safest, most convenient, and economical route. Fast disintegrating tablets are very popular nowadays as they get dissolved or facilely disintegrated in mouth within few seconds of administration without the need of water. The disadvantages of conventional dosage form, especially dysphagia (arduousness in swallowing), in pediatric and geriatric patients have been overcome by fast dissolving tablets. Natural materials have advantages over synthetic ones since they are chemically inert, non-toxic, less expensive, biodegradable and widely available. Natural polymers like locust bean gum, banana powder, mango peel pectin, Mangifera indica gum, and Hibiscus rosa-sinenses mucilage ameliorate the properties of tablet and utilized as binder, diluent, and superdisintegrants increase the solubility of poorly water soluble drug, decrease the disintegration time, and provide nutritional supplement. Natural polymers are obtained from the natural origin and they are cost efficacious, nontoxic, biodegradable, eco-friendly, devoid of any side effect, renewable, and provide nutritional supplement. It is proved from the studies that natural polymers are more safe and efficacious than the synthetic polymers. The aim of the present article is to study the FDA-approved natural polymers utilized in fast dissolving tablets. PMID:26556207

  8. FDA-Approved Natural Polymers for Fast Dissolving Tablets

    PubMed Central

    Alam, Md Tausif; Parvez, Nayyar; Sharma, Pramod Kumar

    2014-01-01

    Oral route is the most preferred route for administration of different drugs because it is regarded as safest, most convenient, and economical route. Fast disintegrating tablets are very popular nowadays as they get dissolved or facilely disintegrated in mouth within few seconds of administration without the need of water. The disadvantages of conventional dosage form, especially dysphagia (arduousness in swallowing), in pediatric and geriatric patients have been overcome by fast dissolving tablets. Natural materials have advantages over synthetic ones since they are chemically inert, non-toxic, less expensive, biodegradable and widely available. Natural polymers like locust bean gum, banana powder, mango peel pectin, Mangifera indica gum, and Hibiscus rosa-sinenses mucilage ameliorate the properties of tablet and utilized as binder, diluent, and superdisintegrants increase the solubility of poorly water soluble drug, decrease the disintegration time, and provide nutritional supplement. Natural polymers are obtained from the natural origin and they are cost efficacious, nontoxic, biodegradable, eco-friendly, devoid of any side effect, renewable, and provide nutritional supplement. It is proved from the studies that natural polymers are more safe and efficacious than the synthetic polymers. The aim of the present article is to study the FDA-approved natural polymers utilized in fast dissolving tablets. PMID:26556207

  9. Risedronate-loaded Eudragit S100 microparticles formulated into tablets.

    PubMed

    Velasquez, Aline A; Mattiazzi, Juliane; Ferreira, Luana M; Pohlmann, Lauren; Silva, Cristiane B; Rolim, Clarice M B; Cruz, Letícia

    2014-05-01

    Risedronate, an anti-osteoporotic drug, is associated with low patient compliance due to the upper gastrointestinal side-effects and stringent dosing regimes. This study aimed to prepare and characterize risedronate-loaded Eudragit® S100 microparticles and develop a final dosage form by the compression of microparticles using direct tableting excipients. Microparticles were prepared by spray-drying and presented yield of 54%, encapsulation efficiency higher than 90%, mean diameter of 3.3 µm, moisture content around 8% and exhibited spherical shape and poor flowability. At pH 1.2, 23% of risedronate was released from microparticles in 120 min, while at pH 6.8 the drug took 90 min to reach 99.5%. Microparticles were compressed into tablets using microcrystalline cellulose, magnesium stearate, colloidal silicon dioxide and 2 polyvinylpyrrolidone concentrations (5% and 15%). Tablets presented low variations in weight, thickness and drug content. Besides, the formulations showed sufficient hardness, low friability and disintegrated in less than 15 min. In acid medium, no more than 16% of the drug was released in 120 min, while in intestinal medium the formulations prolonged the risedronate release for 240 min. Finally, the developed tableted microparticles can be considered a promising dosage form for oral risedronate administration. PMID:23506303

  10. Tablet formulation of levothyroxine is absorbed less well than powdered levothyroxine.

    PubMed

    Yamamoto, Toshihide

    2003-12-01

    The comparative bioavailability of oral doses of levothyroxine (LT(4)) formulation taken as tablets, after being crushed, or chewed before swallowing has not been well studied. Three patients with hypothyroidism who showed persistent elevation of serum thyrotropin (TSH) despite taking 200, 150, and 125 microg of LT(4) tablets per day are presented. They did not show signs and symptoms of gastrointestinal illness that could interfere with the absorption of LT(4) nor history of such a condition. They did not concurrently take medications known to affect the absorption of LT(4) from the gut. Their serum TSH levels normalized when the tablets were taken after being pulverized. The difference appeared attributable to the slow dissolution of the tablets in the gut of these patients. PMID:14751040

  11. Fast relief from migraine attacks using fast-disintegrating sublingual zolmitriptan tablets.

    PubMed

    Mahmoud, Azza A; Salah, Salwa

    2012-06-01

    Zolmitriptan is a potent molecule for treatment of migraine. Its current oral therapies present drawbacks such as slow onset of action, low bioavailability and large inter-subject variability. Fast disintegrating sublingual zolmitriptan tablet (FDST) using freeze-drying technique has been developed to enhance tablet disintegration and dissolution with the intention of speeding drug absorption and onset of effect, hence mitigating the effects on the gastrointestinal dysmotility that typically accompanies the migraine attack. The FDSTs were prepared using different concentrations of gelatin as binder and mannitol or L-alanine as matrix supporting/disintegration enhancing agents. The effect of formulation variables on the physicochemical and solid-state properties, as well as the dissolution behaviour of the tablets, was studied. The formulated FDSTs disintegrated within 30 s and showed significantly faster dissolution rate of zolmitriptan compared to the zolmitriptan oral tablet. Tablet containing 2% gelatin and mannitol showed acceptable weight variation, drug content and friability values. Furthermore, it had a low in-vitro and in-vivo disintegration time (11 s) and it reached 100% of drug release within 30 s. This sublingual formulation gave faster and higher zolmitriptan plasma concentration in rabbits compared to the oral zolmetriptan market product. Zolmitriptan FDST may therefore constitute an advance in the management of acute migraine attacks. PMID:22023340

  12. Micturition in naive and morphine-dependent rats.

    PubMed Central

    Carpenter, F. G.

    1986-01-01

    Voiding responses were recorded in conscious water-loaded rats. Morphine sulphate (5 mg kg-1) elevated the volume threshold for micturition (MV); the group mean MV of 16 rats after morphine was 40% larger than control. Micturition was nevertheless complete since no urine remained in the bladder afterwards. The implantation of 2 or 4 morphine-base pellets (150 or 300 mg morphine) elevated for 12 days the MV in water-loaded rats. On the 3rd to the 10th day following implantation the group mean was approximately twice that of untreated controls. After micturition was over no residual urine was found in the bladder. Within 3 days the rats became tolerant to the antinociceptive action of the morphine-base pellets but little apparent tolerance developed to their action on micturition. On the 1st day after the pellets were removed, the mean MV was reduced. When withdrawal was precipitated by the administration of naloxone the MV was often too small to measure. This component of a withdrawal syndrome could be elicited in the rats throughout the 12 days of morphine pellet implantation. The administration of 20 mg kg-1 morphine sulphate to anaesthetized rats did not decrease the contractions of the urinary bladder to repetitive stimulation of its motor nerves at 1 and 20 Hz. PMID:3708205

  13. Morphine versus Hydromorphone: Does Choice of Opioid Influence Outcomes?

    PubMed Central

    Gulur, Padma; Koury, Katharine; Arnstein, Paul; Lee, Hang; McCarthy, Patricia; Coley, Christopher; Mort, Elizabeth

    2015-01-01

    Morphine has traditionally been considered the first line agent for analgesia in hospitals; however, in the last few years there has been a shift towards the use of hydromorphone as a first line agent. We conducted a hospital population based observational study to evaluate the increasing use of hydromorphone over morphine in both medical and surgical populations. Additionally, we assessed the effect of this trend on three key outcomes, including adverse events, length of stay, and readmission rates. We evaluated data from the University Health Systems Consortium. Data from 38 hospitals from October 2010 to September 2013 was analyzed for patients treated with either hydromorphone or morphine. The use of morphine steadily decreased while use of hydromorphone increased in both medical and surgical groups. Rescue drugs were used more frequently in patients treated with hydromorphone in comparison to patients treated with morphine (p < 0.01). Patients receiving morphine tended to stay in the hospital for almost one day longer than patients receiving hydromorphone. However, 30-day all cause readmission rates were significantly higher in patients treated with hydromorphone (p < 0.01). Our study highlights that the choice of hydromorphone versus morphine may influence outcomes. There are implications related to resource utilization and these outcomes. PMID:26609431

  14. Morphine tolerance offers protection from radiogenic performance deficits

    SciTech Connect

    Mickley, G.A.; Stevens, K.E.; Burrows, J.M.; White, G.A.; Gibbs, G.L.

    1983-02-01

    When rats are exposed to a sufficiently large dose of ionizing radiation they exhibit lethargy, hypokinesia, and deficits in performance. These and other behavioral changes parallel those often observed in this species after a large dose of morphine. Since the release of endogenous opiates has been implicated in some stress reactions, we sought to determine if they might play a part in radiogenic behavioral deficits. Rats were trained to criterion on a signaled avoidance task. Some subjects were then implanted with a pellet containing 75 mg of morphine. Other animals received placebo implants. Over a number of days, morphine tolerance was evaluated by measurement of body temperature changes. Prior to 2500 rad /sup 60/Co exposure or sham irradiation, morphine (or placebo) pellets were removed. Twenty-four hours later rats were retested to assess their performance on the avoidance task. Morphine-tolerant subjects performed significantly better than the irradiated placebo-implanted group and no differently than morphine-tolerant/sham-irradiated animals. Morphine tolerance seems to provide a degree of behavioral radiation resistance. These data are consistent with the hypothesis that endogenous opiate hyperexcretion may play some part in the behavioral deficits often observed after irradiation.

  15. Endogenous Cholinergic Neurotransmission Contributes to Behavioral Sensitization to Morphine

    PubMed Central

    Bajic, Dusica; Soiza-Reilly, Mariano; Spalding, Allegra L.; Berde, Charles B.; Commons, Kathryn G.

    2015-01-01

    Neuroplasticity in the mesolimbic dopaminergic system is critical for behavioral adaptations associated with opioid reward and addiction. These processes may be influenced by cholinergic transmission arising from the laterodorsal tegmental nucleus (LDTg), a main source of acetylcholine to mesolimbic dopaminergic neurons. To examine this possibility we asked if chronic systemic morphine administration affects expression of genes in ventral and ventrolateral periaqueductal gray at the level of the LDTg using rtPCR. Specifically, we examined gene expression changes in the area of interest using Neurotransmitters and Receptors PCR array between chronic morphine and saline control groups. Analysis suggested that chronic morphine administration led to changes in expression of genes associated, in part, with cholinergic neurotransmission. Furthermore, using a quantitative immunofluorescent technique, we found that chronic morphine treatment produced a significant increase in immunolabeling of the cholinergic marker (vesicular acetylcholine transporter) in neurons of the LDTg. Finally, systemic administration of the nonselective and noncompetitive neuronal nicotinic antagonist mecamylamine (0.5 or 2 mg/kg) dose-dependently blocked the expression, and to a lesser extent the development, of locomotor sensitization. The same treatment had no effect on acute morphine antinociception, antinociceptive tolerance or dependence to chronic morphine. Taken together, the results suggest that endogenous nicotinic cholinergic neurotransmission selectively contributes to behavioral sensitization to morphine and this process may, in part, involve cholinergic neurons within the LDTg. PMID:25647082

  16. Gene expression following acute morphine administration.

    PubMed

    Loguinov, A V; Anderson, L M; Crosby, G J; Yukhananov, R Y

    2001-08-28

    The long-term response to neurotropic drugs depends on drug-induced neuroplasticity and underlying changes in gene expression. However, alterations in neuronal gene expression can be observed even following single injection. To investigate the extent of these changes, gene expression in the medial striatum and lumbar part of the spinal cord was monitored by cDNA microarray following single injection of morphine. Using robust and resistant linear regression (MM-estimator) with simultaneous prediction confidence intervals, we detected differentially expressed genes. By combining the results with cluster analysis, we have found that a single morphine injection alters expression of two major groups of genes, for proteins involved in mitochondrial respiration and for cytoskeleton-related proteins. RNAs for these proteins were mostly downregulated both in the medial striatum and in lumbar part of the spinal cord. These transitory changes were prevented by coadministration of the opioid antagonist naloxone. Data indicate that microarray analysis by itself is useful in describing the effect of well-known substances on the nervous system and provides sufficient information to propose a potentially novel pathway mediating its activity. PMID:11526201

  17. Tolerance to hyperthermia produced by morphine in rat.

    PubMed

    Mucha, R F; Kalant, H; Kim, C

    1987-01-01

    The present study addressed the prevailing notion that the rat develops tolerance only to the hypothermic effect of morphine and not to its hyperthermic effect. Rectal temperatures were measured at different intervals after various test doses of morphine in rats that had been rendered tolerant to morphine antinociception, by daily intraperitoneal injections of 0, 20, or 200 mg/kg morphine, and dependent, as seen by naloxone-produced loss of body weight. The well-known tolerance to the hypothermic effect was confirmed by changes in the dose-response curves for latency to peak hyperthermic response. In the falling arm of the test dose time/effect curve, consistent, clear decreases in morphine hyperthermia were seen. These decreases were proportional to the chronic treatment dose, and occurred in a normal test environment, where acute hypothermic effects were produced by morphine at short test intervals, and in a warm test environment, where no hypothermia was seen. Similar effects were noted when the data were analyzed in terms of area under the time/effect curve for hyperthermia. In the morphine-treated animals, decreased hyperthermia was seen despite serum morphine levels at the time of testing being up to twice as high as those in control rats. It was concluded that substantial tolerance develops to hyperthermia produced by opiates in rats. The previous difficulty in seeing this effect is discussed in regard to the probability that, in naive rats, the effect of morphine shortly after administration of a test dose reflects a summation of two opposing, acute thermic effects. The findings challenge the view that tolerance develops only to the depressant, and not to the excitatory, effects of opiates. PMID:3114798

  18. Effects of morphine and naloxone on feline colonic transit

    SciTech Connect

    Krevsky, B.; Libster, B.; Maurer, A.H.; Chase, B.J.; Fisher, R.S.

    1989-01-01

    The effects of endogenous and exogenous opioid substances on feline colonic transit were evaluated using colonic transit scintigraphy. Naloxone accelerated emptying of the cecum and ascending colon, and filling of the transverse colon. Endogenous opioid peptides thus appear to play a significant role in the regulation of colonic transit. At a moderate dose of morphine cecum and ascending colon transit was accelerated, while at a larger dose morphine had no effect. Since naloxone, a relatively nonspecific opioid antagonist, and morphine, a principally mu opioid receptor agonist, both accelerate proximal colonic transit, a decelerating role for at least one of the other opioid receptors is inferred.

  19. Cholescintigraphy in acute cholecystitis: use of intravenous morphine

    SciTech Connect

    Choy, D.; Shi, E.C.; McLean, R.G.; Hoschl, R.; Murray, I.P.C.; Ham, J.M.

    1984-04-01

    Conventional cholescintigraphy (60 patients) and a modified protocol (59 patients) were compared in 74 females and 45 males with acute cholecystitis. In the modified protocol, intravenous morphine was administered whenever the gallbladder was not seen 40 minutes after injection of Tc-99m-pyroxylidene-glutamate. Accuracy was 98% with morphine, compared with 88% for the conventional protocol; specificity improved from 83% to 100% with no loss of sensitivity. Low doses of morphine are well tolerated and can result in a highly accurate diagnosis of acute cholecystitis without the need for delayed imaging.

  20. Recent Advances in the Synthesis of Morphine and Related Alkaloids

    NASA Astrophysics Data System (ADS)

    Chida, Noritaka

    Morphine, an alkaloid isolated from the opium poppy, has been widely used as an analgesic, and has been a fascinating synthetic target of organic chemists. After the first total synthesis reported in 1952, a number of synthetic studies toward morphine have been reported, and findings obtained in such studies have greatly contributed to the progress of synthetic organic chemistry as well as medicinal chemistry. This review provides an overview of recent studies toward the total synthesis of morphine and related alkaloids. Work reported in the literature since 2004 will be reviewed.

  1. Specific serum binding of morphine, levorphanol and heroin

    PubMed Central

    Herndon, B. L.; Baeder, D. H.; Ringle, D. A.

    1976-01-01

    Effects of repeated subcutaneous pellet implantation of a series of narcotic drugs on the serum binding of [14C]morphine was studied in rabbits. Three of the compounds, morphine, heroin and levorphanol, elicited production of a morphine-binding globulin in the implanted rabbits. This serum response did not occur with several other compounds tested, including the potent analgesic methadone, and the narcotic antagonist naloxone. The time course of production of this globulin response, as well as the specificity of the binding for the drug that induced the response are both characteristic of an immunological reaction.

  2. Stress antagonizes morphine-induced analgesia in rats

    NASA Technical Reports Server (NTRS)

    Vernikos, J.; Shannon, L.; Heybach, J. P.

    1981-01-01

    Exposure to restraint stress resulted in antagonism of the analgesic effect of administered morphine in adult male rats. This antagonism of morphine-induced analgesia by restraint stress was not affected by adrenalectomy one day prior to testing, suggesting that stress-induced secretion of corticosteroids is not critical to this antagonism. In addition, parenteral administration of exogenous adrenocorticotropin (ACTH) mimicked the effect of stress in antagonizing morphine's analgesic efficacy. The hypothesis that ACTH is an endogenous opiate antagonist involved in modulating pain sensitivity is supported.

  3. The role of fluoride tablets in the prophylaxis of dental caries. A literature review

    PubMed Central

    Tomasin, Lisa; Pusinanti, Luca; Zerman, Nicoletta

    2015-01-01

    Summary Aim Doing a meta-analysis to answer the question: “Does fluoride tablets prevent dental caries among children and adolescents?” Materials and methods A review of the literature is performed using the following databases: PubMed, Embase, CINAHL, Cochrane Library, Embase, NHS Evidence Oral Health, PsycINFO, Web of Knowledge, Metalib. The keywords used are dental fluoride, fluoride tablets. The studies analyzed was limited to English language with free abstract. For the studies selection was taken into consideration the criteria proposed by the Cochrane Oral Health Group. Results Few studies with good quality were identified in general. Only 3 out of 779 studies were acceptable. Conclusions Evident disagreements among the results show that there’s a limited effectiveness on fluoride tablets. PMID:26161245

  4. The effects of morphine and morphine conditioned context on 50 kHz ultrasonic vocalisation in rats.

    PubMed

    Hamed, Adam; Taracha, Ewa; Szyndler, Janusz; Krząścik, Paweł; Lehner, Małgorzata; Maciejak, Piotr; Skórzewska, Anna; Płaźnik, Adam

    2012-04-15

    The 50 kHz ultrasonic vocalisations (USVs) that are emitted by rats are dependent on activity of dopaminergic neurons projecting from the ventral tegmental area to the limbic and cortical structures. According to many experimental data, emission of the 50 kHz USV reflects a positive emotional state. The appetitive calls are also emitted in response to the administration of drugs of abuse, e.g., cocaine or amphetamine (AMPH), or in a reply to a positively conditioned context. However, there is no strong evidence in the literature that morphine can also modulate 50 kHz USVs. The aim of this paper is to study the effects of morphine and morphine-conditioned context on 50 kHz USVs, using spontaneously or drug-modulated 50 kHz USVs. Our results showed that acute administration of morphine to rats after withdrawal period inhibited the emission of 50 kHz USVs. The stimulating effect of morphine-conditioned context on 50 kHz USVs appeared on the post-withdrawal challenge day immediately before drug injection, 14 days after the last episode of morphine-induced context conditioning. The context-induced 50 kHz USVs can be used as a sensitive test for drug dependency. The current study also shows that 50 kHz USVs can be useful tool for studying the mechanisms of long lasting central effects of morphine. PMID:22326697

  5. Intra-administration associations and withdrawal symptoms: morphine-elicited morphine withdrawal.

    PubMed

    McDonald, Robert V; Siegel, Shepard

    2004-02-01

    On the basis of a conditioning analysis, some drug "withdrawal symptoms" are conditional responses elicited by stimuli paired with the drug effect. Prior demonstrations of conditional elicitation of withdrawal symptoms evaluated the role of environmental cues; however, pharmacological cues also typically signal a drug effect. Within each administration, early drug onset cues (DOCs) may become associated with the later, larger drug effect (intra-administration associations). This experiment evaluated the contribution of intra-administration associations to withdrawal symptoms. The results indicated that (a). 5 mg/kg morphine elicited behavioral and thermic withdrawal symptoms in rats previously injected on a number of occasions with 50 mg/kg morphine and that (b). DOC-elicited withdrawal symptoms are not a sensitized response to the opiate but rather an associative phenomenon. PMID:14769091

  6. Mechanical property characterization of bilayered tablets using nondestructive air-coupled acoustics.

    PubMed

    Akseli, Ilgaz; Dey, Dipankar; Cetinkaya, Cetin

    2010-03-01

    A noncontact/nondestructive air-coupled acoustic technique to be potentially used in mechanical property determination of bilayer tablets is presented. In the reported experiments, a bilayer tablet is vibrated via an acoustic field of an air-coupled transducer in a frequency range sufficiently high to excite several vibrational modes (harmonics) of the tablet. The tablet vibrational transient responses at a number of measurement points on the tablet are acquired by a laser vibrometer in a noncontact manner. An iterative computational procedure based on the finite element method is utilized to extract the Young's modulus, the Poisson's ratio, and the mass density values of each layer material of a bilayer tablet from a subset of the measured resonance frequencies. For verification purposes, a contact ultrasonic technique based on the time-of-flight data of the longitudinal (pressure) and transverse (shear) acoustic waves in each layer of a bilayer tablet is also utilized. The extracted mechanical properties from the air-coupled acoustic data agree well with those determined from the contact ultrasonic measurements. The mechanical properties of solid oral dosage forms have been shown to impact its mechanical integrity, disintegration profile and the release rate of the drug in the digestive tract, thus potentially affecting its therapeutic response. The presented nondestructive technique provides greater insight into the mechanical properties of the bilayer tablets and has the potential to identify quality and performance problems related to the mechanical properties of the bilayer tablets early on the production process and, consequently, reduce associated cost and material waste. PMID:20063078

  7. Increased brain uptake of morphine in the presence of the antihistamine tripelennamine.

    PubMed

    Vadlamani, N L; Pontani, R B; Misra, A L

    1984-01-01

    Disposition of [6 3H (N)]morphine in plasma, brain and liver of rats was studied 15 min after intravenous injection of either a 2 mg kg-1 dose of morphine or a combination of the same dose of morphine with a 6 mg kg-1 dose of tripelennamine. The concentrations of morphine in brain and the brain to plasma morphine ratios in animals receiving the combination of drugs concurrently were significantly higher than those in the control morphine group. No significant differences were seen in the morphine or morphine metabolite concentrations in plasma and liver or liver to plasma morphine concentration ratios in the 2 groups. Data suggest that pharmacokinetic factors play a role in the potentiation of opiate effects by antihistamine on concurrent i.v. administration of the two drugs. PMID:6141270

  8. PolyMorphine: an innovative biodegradable polymer drug for extended pain relief

    PubMed Central

    Rosario-Meléndez, Roselin; Harris, Carolyn L.; Delgado-Rivera, Roberto; Yu, Lei; Uhrich, Kathryn E.

    2012-01-01

    Morphine, a potent narcotic analgesic used for the treatment of acute and chronic pain, was chemically incorporated into a poly(anhydride-ester) backbone. The polymer termed “PolyMorphine”, was designed to degrade hydrolytically releasing morphine in a controlled manner to ultimately provide analgesia for an extended time period. PolyMorphine was synthesized via melt-condensation polymerization and its structure was characterized using proton and carbon nuclear magnetic resonance spectroscopies, and infrared spectroscopy. The weight-average molecular weight and the thermal properties were determined. The hydrolytic degradation pathway of the polymer was determined by in vitro studies, showing that free morphine is released. In vitro cytocompatibility studies demonstrated that PolyMorphine is non-cytotoxic towards fibroblasts. In vivo studies using mice showed that PolyMorphine provides analgesia for 3 days, 20 times the analgesic window of free morphine. The animals retained full responsiveness to morphine after being subjected to an acute morphine challenge. PMID:22877734

  9. 21 CFR 520.2345h - Tetracycline hydrochloride, sodium novobiocin, and prednisolone tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Tetracycline hydrochloride, sodium novobiocin, and prednisolone tablets. 520.2345h Section 520.2345h 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 § 520.2345h...

  10. 21 CFR 520.2345g - Tetracycline hydrochloride and sodium novobiocin tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Tetracycline hydrochloride and sodium novobiocin tablets. 520.2345g Section 520.2345g 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 § 520.2345g Tetracycline...

  11. 21 CFR 520.2345h - Tetracycline hydrochloride, sodium novobiocin, and prednisolone tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Tetracycline hydrochloride, sodium novobiocin, and prednisolone tablets. 520.2345h Section 520.2345h 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 § 520.2345h...

  12. 21 CFR 520.2345g - Tetracycline hydrochloride and sodium novobiocin tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Tetracycline hydrochloride and sodium novobiocin tablets. 520.2345g Section 520.2345g 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 § 520.2345g Tetracycline...

  13. Effect of postoperative extradural morphine on lower urinary tract function.

    PubMed

    Husted, S; Djurhuus, J C; Husegaard, H C; Jepsen, J; Mortensen, J

    1985-02-01

    The effect of postoperative extradurally administered morphine on lower urinary tract function was studied in female patients undergoing uterine surgery. Urodynamic measurements were made on the day before and on the day after the operation, using a DISA 2-channel carbon dioxide (CO2) cystomictrograph. In ten patients without postoperative urinary retention no changes in cystometry were found during morphine administration, while two patients who developed acute urinary retention had a marked increase in bladder capacity and of detrusor pressure. In contrast, the urethral pressure profile was unchanged in both groups of patients. Intravenously administered naloxone tended to normalize the bladder capacity in the patients with urinary retention. These findings seem to indicate a marked effect in some patients of extradurally administered morphine and the acute urinary retention, following morphine administration, may be treated with naloxone. PMID:3976331

  14. Stability of morphine sulphate and diamorphine hydrochloride in intrasite gel.

    PubMed

    Zeppetella, Giovambattista; Joel, Simon P; Ribeiro, Maria D C

    2005-03-01

    Several studies have reported that opioids applied topically to painful ulcers produce an analgesic effect. It is unknown whether these opioids (usually mixed with hydrogels) are stable and, if so, for how long. We investigated the stability of morphine sulphate and diamorphine hydrochloride, each mixed with intrasite gel at a concentration of 1.25 mg/mL. Samples were prepared in the laboratory and then stored in plastic containers in the dark, at room temperature, in conditions of normal day/night at room temperature, and at 4 degrees C. Aliquots were collected from each container over a 28-day period and analysed using HPLC. No known degradation products were measured in the morphine-intrasite gel mixture stored for up to 28 days, irrespective of the temperature and whether or not samples were exposed to light, suggesting that morphine remains stable. Diamorphine, breaks down to morphine and no other degradation products are measurable. PMID:15810752

  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....

  16. Attenuation of morphine tolerance and dependence by thymoquinone in mice

    PubMed Central

    Hosseinzadeh, Hossein; Parvardeh, Siavash; Masoudi, Alireza; Moghimi, Mahsa; Mahboobifard, Fatemeh

    2016-01-01

    Objective: Dependence and tolerance are major restricting factors in the clinical use of opioid analgesics. In the present study, the effects of thymoquinone, the major constituent of Nigella sativa seeds, on morphine dependence and tolerance were investigated in mice. Materials and Methods: Male adult NMRI mice were made tolerant and dependent by repeated injections of morphine (50, 50, and 75 mg/kg, i.p. on 9 a.m., 1 p.m., and 5 p.m., respectively) during a 3-day administration schedule. The hot-plate test was used to assess tolerance to the analgesic effects of morphine. Naloxone (2 mg/kg, i.p.) was injected to precipitate withdrawal syndrome in order to assess the morphine dependence. To evaluate the effects of thymoquinone on tolerance and dependence to morphine, different single or repeated doses of thymoquinone were administered in mice. Rotarod was used to assess the motor coordination. Results: Administration of single or repeated doses of thymoquinone (20 and 40 mg/kg, i.p.) significantly decreased the number of jumps in morphine dependent animals. Repeated administration of thymoquinone (20 and 40 mg/kg, for 3 days) and also single injection of thymoquinone (40 mg/kg, on the fourth day) attenuated tolerance to the analgesic effect of morphine. None of the thymoquinone doses (10, 20, and 40 mg/kg) produced any antinociceptive effects on their own. Motor coordination of animals was impaired by the high dose of thymoquinone (40 mg/kg). Conclusion: Based on these results, it can be concluded that thymoquinone prevents the development of tolerance and dependence to morphine. PMID:27247922

  17. Dipeptides delay the onset of morphine withdrawal in the mouse.

    PubMed

    Kovács, G L; Szontágh, L; Baláspiri, L; Telegdy, G

    1984-01-01

    The effect of dipeptides was studied on naloxone-precipitated morphine withdrawal in the mouse. In accordance with previous data, s.c. treatment with Z-prolyl-D-leucine delayed the onset of withdrawal jumpings . Replacement of L-proline by L-glutamate or L-pyroglutamate resulted in dipeptides which were more potent in morphine withdrawal than was Z-prolyl-D-leucine. PMID:6540034

  18. Temporal effects of topical morphine application on cutaneous wound healing

    PubMed Central

    Rook, Jerri M.; Hasan, Wohaib; McCarson, Kenneth E.

    2008-01-01

    Background Studies have shown that topical administration of exogenous opioid drugs impairs wound healing by inhibiting the peripheral release of neuropeptides, thereby inhibiting neurogenic inflammation. This delay is immediate and peaks during the first days of wound closure. This study examined the effects of topical morphine treatment in a cutaneous wound healing model in the rat. Methods Full-thickness 4mm diameter wounds were placed on the periscapular region of rats that subsequently received twice-daily topical applications of IntraSite Gel (Smith+Nephew, Hull, United Kingdom) alone or gel infused with 5 mM morphine sulfate on days 0–3 or 4–10 post-wounding or throughout the time course. Wound tissue was taken on days 1, 3, 5, 8, and 18 post-wounding and immunostained for myofibroblast and macrophage markers or stained with hematoxylin and eosin. Results Delays in wound closure observed during morphine application on days 0–3 post-wounding mimicked those seen in wounds treated with morphine throughout the entire healing process. However, no significant delays in closure were seen in wounds treated with morphine beginning on day 4 post-wounding. Treatment of wounds with morphine significantly reduced the number of myofibroblasts and macrophages in the closing wound. Additionally, morphine application resulted in decreases in skin thickness and an increase in residual scar tissue in healed skin. Conclusions These findings demonstrate the time-dependent and persistent nature of the detrimental effects of topical morphine on cutaneous wound healing. The data identify specific limitations that could be ameliorated to optimize topical opioid administration as an analgesic therapeutic strategy in the treatment of painful cutaneous wounds. PMID:18580183

  19. Persistent Pain Model Reveals Sex Difference in Morphine Potency

    PubMed Central

    Wang, Xiaoya; Traub, Richard J.; Murphy, Anne Z.

    2010-01-01

    Central or systemic administration of agonists directed at the mu or delta opiate receptors generally produce a greater degree of analgesia in males than in females. To date, the majority of studies examining sex based differences in opioid analgesia have employed acute noxious stimuli (i.e. tail-flick and hot plate test); thus, the potential dimorphic response of centrally acting opiates in the alleviation of persistent inflammatory pain is not well established. In the present study, right hindpaw withdrawal latency (PWL) to radiant thermal stimuli was measured in intact male and cycling female Sprague-Dawley rats before and after unilateral hindpaw injection of the inflammatory agent complete Freund’s adjuvant (CFA). Control animals received intraplantar injection of saline. Twenty four hours after CFA or saline injection, animals received either saline or morphine bisulfate (0.5 – 15 mg/kg; s.c.). Separate groups of control or inflamed animals were tested on their responsiveness to morphine at 7, 14 and 21 days post-CFA or saline. No sex differences were noted for baseline PWLs, and females displayed slightly less thermal hyperalgesia at 24 hrs post-CFA. At all morphine doses administered, both the antihyperalgesic effects of morphine in the inflamed animals, and the antinociceptive effects of morphine in control animals, were significantly greater in males in comparison to females. Similarly, in males, the antihyperalgesic effects of morphine increased significantly at 7–21 days post-CFA; no significant shift in morphine potency was noted for females. These studies demonstrate sex-based differences in the effects of morphine on thermal hyperalgesia in a model of persistent inflammatory pain. PMID:16497818

  20. Epidural morphine for outpatients with severe anginal pain.

    PubMed Central

    Clemensen, S E; Thayssen, P; Hole, P

    1987-01-01

    Seven patients who had chronic coronary artery disease and had undergone coronary artery bypass surgery still suffered from anginal attacks several times daily despite optimal medical treatment. An epidural system of analgesia was implanted subcutaneously and treatment with epidural morphine started. The morphine was administered by the patients themselves or members of their family. During a median observation time of four months (range three to 11) all patients were free of pain while receiving this treatment. Images p476-a PMID:2435345

  1. 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 Central

    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

    Background 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. Methods 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. Results 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. Conclusion The PD, PK, and tolerability profiles of gemigliptin and metformin XR in FDC and separate tablets were found to be comparable

  2. Tablets of pre-liposomes govern in situ formation of liposomes: concept and potential of the novel drug delivery system.

    PubMed

    Vanić, Željka; Planinšek, Odon; Škalko-Basnet, Nataša; Tho, Ingunn

    2014-10-01

    The purpose of this study was to develop a novel drug delivery system for challenging drugs with potential for scale-up manufacturing and controlled release of incorporated drug. Pre-liposomes powder containing metronidazole, lecithin and mannitol, prepared by spray-drying, was mixed with different tableting excipients (microcrystalline cellulose, lactose monohydrate, mannitol, dibasic calcium phosphate, pregelatinized starch, pectin or chitosan) and compressed into tablets. The delivery system was characterized with respect to (i) dry powder characteristics, (ii) mechanical tablet properties and drug release, and (iii) liposomal characteristics. The pre-liposomes powder was free-flowing, and tablets of similarly high qualities as tablets made of physical mixtures were prepared with all excipients. Liposomes were formed in situ upon tablet disintegration, dissolution or erosion depending on the type of tablet excipient used. The liposomal characteristics and drug release were found to depend on the tablet excipient. The new delivery system offers a unique synergy between the ability of liposomes to encapsulate and protect drugs and increased stability provided by compressed formulations. It can be adjusted for drug administration via various routes, e.g. oral, buccal and vaginal. PMID:24929211

  3. Prediction of dissolution profiles by non-destructive near infrared spectroscopy in tablets subjected to different levels of strain.

    PubMed

    Hernandez, Eduardo; Pawar, Pallavi; Keyvan, Golshid; Wang, Yifan; Velez, Natasha; Callegari, Gerardo; Cuitino, Alberto; Michniak-Kohn, Bozena; Muzzio, Fernando J; Romañach, Rodolfo J

    2016-01-01

    This study describes how the strain on formulation components affects dissolution and how near infrared spectroscopy can be used to predict dissolution. Strain (exposure to shear stress) applied during powder mixing affects the interaction between formulation components. Particles experience shear strain when they move relative to each other in a process affecting the properties of the final product. This stress affects the dissolution of oral solid dosages forms. However, dissolution testing destroys the entire tablet, making it impossible to further evaluate tablet properties when an out of specification result is obtained. Thus, a nondestructive technique such as near infrared spectroscopy is desirable to predict dissolution. The aim of this study was to predict dissolution on tablets with different levels of strain (shear) using near infrared spectroscopy in combination with multivariate data analysis. Shear was induced using a modified Couette cell on the powder mixture and tablets from these mixtures were produced using a tablet press emulator. Tablets produced with different strain levels were measured using near infrared spectroscopy. Spectra were obtained in diffuse reflectance mode and pretreated with baseline correction to maintain the physical and chemical information of the tablets. Dissolution profiles were obtained using USP Apparatus 2 as a reference method. Principal component analysis was used to study the sources of variation in the spectra obtained. Partial least squares 2 was used to predict dissolution on tablets with different levels of strain. PMID:26604167

  4. Morphine withdrawal, treatments 1900-30.

    PubMed

    Malcolm, M T

    1999-03-01

    The treatments used between 1900 and 1930 for morphine withdrawal are discussed. The accounts are mainly taken from contemporary textbooks which contain fascinating descriptions of their authors' preferred methods and criticisms of regimes given by other therapists. Delirium, produced by atropine or similar substances, is advocated to cover withdrawal symptoms. The present paper draws parallels with current issues, e.g. withdrawal of opiate under cover of general anaesthesia, follow-up studies and cost-benefit analyses. The particular problems of addicted doctors in 1900-1930 are addressed as are the comparisons then made with non-medically qualified addicts. It is important we keep in mind past mistakes and over-valued ideas so as to reduce any similarly misplaced optimism in our current treatment options. PMID:11623818

  5. Characterization of omega-3 tablets.

    PubMed

    Vestland, Tina Lien; Jacobsen, Øyvind; Sande, Sverre Arne; Myrset, Astrid Hilde; Klaveness, Jo

    2016-04-15

    Omega-3 nutraceuticals are extensively used as health supplements worldwide. Various administration forms for delivery of omega-3 are available. However, the niche omega-3 tablets have so far remained unexplored. In this work tablets containing 25-40% (w/w) omega-3 oil as triglycerides or ethyl esters were prepared utilizing a direct compaction grade powder with β-cyclodextrin as encapsulating agent. It was found that powders with up to 35% (w/w) triglyceride oil and 30% (w/w) ethyl ester oil, respectively, can be directly compressed into tablets of excellent quality. Physical properties of omega-3 containing powders and tablets are described. The powder X-ray diffractograms of the powders and crushed tablets show evidence of the formation of new crystalline phases not present in β-cyclodextrin. In addition, (1)H NMR data suggest that the ethyl esters form inclusion complexes with β-cyclodextrin. Compaction of other, commercially available, omega-3 powders was performed as a comparison and deemed unsuccessful. PMID:26616980

  6. 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.

  7. Physical compatibility of binary and ternary mixtures of morphine and methadone with other drugs for parenteral administration in palliative care.

    PubMed

    Destro, Massimo; Ottolini, Luca; Vicentini, Lorenza; Boschetti, Silvia

    2012-10-01

    The parenteral administration of combinations of drugs is often necessary in palliative medicine, particularly in the terminal stage of life, when patients are no longer able to take medication orally. The use of infusers to administer continuous subcutaneous infusions is a well-established practice in the palliative care setting and enables several drugs to be given simultaneously, avoiding the need for repeated administrations and the effects of peaks and troughs in the doses of medication. The method is also appreciated by patients and caregivers in the home care setting because the devices and infusion sites are easy to manage. Despite their frequent use, however, the mixtures of drugs adopted in clinical practice are sometimes not supported by reliable data concerning their chemical and physical compatibility. The present study investigates the chemical compatibility of binary mixtures (morphine with ketorolac) and the physical compatibility of binary (morphine or methadone with ketorolac) or ternary mixtures (morphine with ketorolac and/or haloperidol, and/or dexamethasone, and/or metoclopramide, and/or hyoscine butylbromide) with a view to reducing the aleatory nature of the empirical use of such combinations, thereby increasing their safety and clinical appropriateness. PMID:22252547

  8. Effect of chronic morphine administration on circulating dendritic cells in SIV-infected rhesus macaques.

    PubMed

    Cornwell, William D; Wagner, Wendeline; Lewis, Mark G; Fan, Xiaoxuan; Rappaport, Jay; Rogers, Thomas J

    2016-06-15

    We studied the effect of chronic morphine administration on the circulating dendritic cell population dynamics associated with SIV infection using rhesus macaques. Animals were either first infected with SIV and then given chronic morphine, or visa versa. SIV infection increased the numbers of myeloid DCs (mDCs), but morphine treatment attenuated this mDC expansion. In contrast, morphine increased the numbers of plasmacytoid DCs (pDCs) in SIV-infected animals. Finally, chronic morphine administration (no SIV) transiently increased the numbers of circulating pDCs. These results show that chronic morphine induces a significant alteration in the available circulating levels of critical antigen-presenting cells. PMID:27235346

  9. Protective effect of crocin on liver toxicity induced by morphine

    PubMed Central

    Salahshoor, Mohammad Reza; khashiadeh, Mojtaba; Roshankhah, Shiva; Kakabaraei, Seyran; Jalili, Cyrus

    2016-01-01

    Crocin, a bioactive molecule of saffron can be purely isolated from the saffron extract. It has different pharmacological effects such as antioxidant and anticancer activities. Morphine is an opioid analgesic drug. It is mainly metabolized in liver and causes devastating effects. It can increase the generation of free radicals. This study was designed to evaluate the protective role of crocin against morphine-induced toxicity in the mouse liver. In this study, various doses of crocin (12.5, 25 and 50 mg/kg) and crocin plus morphine were administered interaperitoneally once daily to 48 male mice for 20 consecutive days. These mice were randomly assigned to 8 groups of 6 each. The liver weight and histology, aspartate amino transferase, alanine aminotransferase, alkaline phosphatase (ALP) and serum nitric oxide levels were studied. The results indicated that morphine administration significantly decreased liver weight and increased the mean diameter of hepatocyte, central hepatic vein diameters, liver enzyme levels, and blood serum nitric oxide level compared to saline group (P<0.05). However, crocin administration significantly boosted liver weight and decreased the mean diameter of hepatocyte, central hepatic vein, liver enzymes and nitric oxide levels in all groups compared to the group received morphine alone (P<0.05). It seems that crocin administration could protect the liver damage induced by morphine. The antioxidant effect of crocin may be a major reason for its positive impact on liver parameters. PMID:27168751

  10. Regional cerebral glucose utilization during morphine withdrawal in the rat.

    PubMed Central

    Wooten, G F; DiStefano, P; Collins, R C

    1982-01-01

    Regional cerebral glucose utilization was studied by 2-deoxy[14C]glucose autoradiography in morphine-dependent rats and during naloxone-induced morphine withdrawal. In morphine-dependent rats, glucose utilization was increased compared with naive controls uniformly (23-54%) in hippocampus, dentate gyrus, and subiculum and reduced in frontal cortex, striatum, anterior ventral thalamus, and medial habenular nucleus. On precipitation of morphine withdrawal by subcutaneous administration of naloxone at 0.5 mg/kg to morphine-dependent rats, glucose utilization was increased in the central nucleus of amygdala (51%), lateral mammillary nucleus (40%), lateral habenular nucleus (39%), medial mammillary nucleus (35%), and medial septal nucleus (35%) (all, P less than 0.01). Significant increases also occurred in several other limbic structures including interpeduncular nucleus, anterior medial and ventral thalamic nuclei, and lateral septal nucleus. Knowledge of the functional cerebral anatomy of the morphine-withdrawal syndrome should facilitate studies directed toward understanding the molecular mechanisms of opiate withdrawal. Images PMID:6954484

  11. Mitragynine Attenuates Withdrawal Syndrome in Morphine-Withdrawn Zebrafish

    PubMed Central

    Khor, Beng-Siang; Amar Jamil, Mohd Fadzly; Adenan, Mohamad Ilham; Chong Shu-Chien, Alexander

    2011-01-01

    A major obstacle in treating drug addiction is the severity of opiate withdrawal syndrome, which can lead to unwanted relapse. Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawal phase. Adult zebrafish were subjected to two weeks chronic morphine exposure at 1.5 mg/L, followed by withdrawal for 24 hours prior to tests. Using the novel tank diving tests, we first showed that morphine-withdrawn zebrafish display anxiety-related swimming behaviors such as decreased exploratory behavior and increased erratic movement. Morphine withdrawal also elevated whole-body cortisol levels, which confirms the phenotypic stress-like behaviors. Exposing morphine-withdrawn fish to mitragynine however attenuates majority of the stress-related swimming behaviors and concomitantly lower whole-body cortisol level. Using real-time PCR gene expression analysis, we also showed that mitragynine reduces the mRNA expression of corticotropin releasing factor receptors and prodynorphin in zebrafish brain during morphine withdrawal phase, revealing for the first time a possible link between mitragynine's ability to attenuate anxiety during opiate withdrawal with the stress-related corticotropin pathway. PMID:22205946

  12. Protective effect of crocin on liver toxicity induced by morphine.

    PubMed

    Salahshoor, Mohammad Reza; Khashiadeh, Mojtaba; Roshankhah, Shiva; Kakabaraei, Seyran; Jalili, Cyrus

    2016-01-01

    Crocin, a bioactive molecule of saffron can be purely isolated from the saffron extract. It has different pharmacological effects such as antioxidant and anticancer activities. Morphine is an opioid analgesic drug. It is mainly metabolized in liver and causes devastating effects. It can increase the generation of free radicals. This study was designed to evaluate the protective role of crocin against morphine-induced toxicity in the mouse liver. In this study, various doses of crocin (12.5, 25 and 50 mg/kg) and crocin plus morphine were administered interaperitoneally once daily to 48 male mice for 20 consecutive days. These mice were randomly assigned to 8 groups of 6 each. The liver weight and histology, aspartate amino transferase, alanine aminotransferase, alkaline phosphatase (ALP) and serum nitric oxide levels were studied. The results indicated that morphine administration significantly decreased liver weight and increased the mean diameter of hepatocyte, central hepatic vein diameters, liver enzyme levels, and blood serum nitric oxide level compared to saline group (P<0.05). However, crocin administration significantly boosted liver weight and decreased the mean diameter of hepatocyte, central hepatic vein, liver enzymes and nitric oxide levels in all groups compared to the group received morphine alone (P<0.05). It seems that crocin administration could protect the liver damage induced by morphine. The antioxidant effect of crocin may be a major reason for its positive impact on liver parameters. PMID:27168751

  13. Mitragynine attenuates withdrawal syndrome in morphine-withdrawn zebrafish.

    PubMed

    Khor, Beng-Siang; Jamil, Mohd Fadzly Amar; Adenan, Mohamad Ilham; Shu-Chien, Alexander Chong

    2011-01-01

    A major obstacle in treating drug addiction is the severity of opiate withdrawal syndrome, which can lead to unwanted relapse. Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawal phase. Adult zebrafish were subjected to two weeks chronic morphine exposure at 1.5 mg/L, followed by withdrawal for 24 hours prior to tests. Using the novel tank diving tests, we first showed that morphine-withdrawn zebrafish display anxiety-related swimming behaviors such as decreased exploratory behavior and increased erratic movement. Morphine withdrawal also elevated whole-body cortisol levels, which confirms the phenotypic stress-like behaviors. Exposing morphine-withdrawn fish to mitragynine however attenuates majority of the stress-related swimming behaviors and concomitantly lower whole-body cortisol level. Using real-time PCR gene expression analysis, we also showed that mitragynine reduces the mRNA expression of corticotropin releasing factor receptors and prodynorphin in zebrafish brain during morphine withdrawal phase, revealing for the first time a possible link between mitragynine's ability to attenuate anxiety during opiate withdrawal with the stress-related corticotropin pathway. PMID:22205946

  14. Impacts of morphine addiction on spermatogenesis in rats

    PubMed Central

    Takzare, Nasrin; Samizadeh, Esmaeil; Shoar, Saeed; Majidi Zolbin, Masoumeh; Naderan, Mohammad; Lashkari, Ali; Bakhtiarian, Azam

    2016-01-01

    Background: There are numerous investigations on wide range of issues that disrupt regulatory spermatogenesis, individuals who are exposed to drug abuse faced infertility and immature spermatogenesis. Objective: The aim of this study was to evaluate the addiction effects of morphine and its derivatives on rats spermatogenesis. Materials and Methods: 40 male Wistar rats were randomly divided into 5 equal groups, which were exposed either with intravenous morphine, naloxone, naloxone and morphine, sham (with normal saline injection) and a control group without infusion. Spermatogenesis was assessed after three months via histological sections with hematoxylin and eosin staining, using a light microscope based on measurement of spermatogonia, spermatocyte, spermatid, and spermatozoa. Results: Those rats that received opioids had changes in spermatogenesis function. The population of spermatogenesis cycle cells at spermatogonia, spermatocyte, spermatid, and spermatozoa stages was significantly decreased in those rats that received opioid in comparison to the control group (p<0.05). Histological studies revealed that changes in different groups of opioid application might affect sperm formation. Sperm count in morphine group was (0±0) and in naloxone group, naloxone+morphine, sham and control were 235±3.77, 220±3.81, 247.12±6.10 and 250±6.54, respectively (p<0.001). Conclusion: Morphine could affect all spermatogenesis stages. PMID:27326414

  15. Endogenous morphine: up-to-date review 2011.

    PubMed

    Stefano, G B; Ptáček, R; Kuželová, H; Kream, R M

    2012-01-01

    Positive evolutionary pressure has apparently preserved the ability to synthesize chemically authentic morphine, albeit in homeopathic concentrations, throughout animal phyla. Despite the establishment of a progressively rigorous and mechanistically focused historical literature extending from the mid 1970s to the mid 1980s that supported the expression of chemically authentic morphine by animal cellular and organ systems, prejudicial scepticism and early dismissal by scientists and clinicians most often obscured widespread acceptance of the biological importance and medical implications of endogenous morphine. The current critical paper presents and evaluates key recent coordinated studies in endogenous morphine research, highlighting those that have advanced our understanding of the functional roles of cognate alkaloid-selective μ(3) and μ(4) opiate receptors. We propose that the expression of endogenous morphine by animal and human cells is designed to mediate homeopathic regulation of metabolic activity via activation of cognate μ(3) and μ(4) receptors that serve as transductive conduits for shortcircuit Ca(++) fluxes. The implications of endogenous morphine coupling to nitric oxide regulation of mitochondrial function, with special reference to the cardiovascular system, are now formulated after many years of neglect. PMID:22578954

  16. SWIM (sickle with ibuprofen and morphine) randomised controlled trial fails to recruit: lessons learnt

    PubMed Central

    Cho, Gavin; Anie, Kofi A; Buckton, Jacky; Kiilu, Patricia; Layton, Mark; Alexander, Lydia; Hemmaway, Claire; Sutton, Dorothy; Amos, Claire; Doré, Caroline J; Kahan, Brennan; Meredith, Sarah

    2016-01-01

    Objectives Sickle With Ibuprofen and Morphine (SWIM) trial was designed to assess whether co-administration of ibuprofen (a non-steroidal anti-inflammatory drug) resulted in a reduction of opioid consumption delivered by patient-controlled analgesia (PCA) for acute pain in sickle cell disease. Design A randomised, placebo-controlled, double-blind trial. Setting UK multicentre trial in acute hospital setting. Participants Adults with sickle cell disease of any gender and phenotype aged 16 years and over. Interventions Oral ibuprofen at a dose of 800 mg three times daily or placebo in addition to opioids (morphine or diamorphine) administered via PCA pump for up to 4 days. Main outcome measures The primary outcome measure was opioid consumption over 4 days following randomisation. Results The SWIM trial closed early because it failed to randomise to its target of 316 patients within a reasonable time. Conclusions The key issues identified include the unanticipated length of time between informed consent and randomisation, difficulties in randomisation of patients in busy emergency departments, availability of trained staff at weekends and out of hours, fewer centres than expected using PCA routinely for sickle cell pain treatment, lack of research staff and support for participation, and the trial design. There are implications for future UK trials in sickle cell disease. Trial registration number ISRCTN97241637, NCT00880373; Pre-results. PMID:27288381

  17. 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…

  18. 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…

  19. 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…

  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. Bioavailability of valsartan oral dosage forms.

    PubMed

    Sunkara, Gangadhar; Bende, Girish; Mendonza, Anisha E; Solar-Yohay, Susan; Biswal, Shibadas; Neelakantham, Srikanth; Wagner, Robert; Flarakos, Jimmy; Zhang, Yiming; Jarugula, Venkateswar

    2014-03-01

    The oral bioavailability of valsartan from extemporaneous suspension and solution formulations were evaluated relative to tablet formulation in two separate open-label, randomized crossover studies in healthy adults. In both studies, the plasma concentrations of valsartan after oral administration were analyzed using validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods, and the corresponding pharmacokinetic parameters were estimated using noncompartmental analysis. The peak plasma concentration (Cmax ) and area under the concentration time-curves (AUC(0-∞) ) of valsartan from the extemporaneous suspension were higher by 1.93- and 1.56-fold, respectively, relative to the tablet formulation (P < .001). The Cmax and AUC(0-∞) of valsartan from the oral solution were higher by 2.21- and 1.74-fold, respectively, relative to the tablet formulation (P < .001). These results indicate that both rate and extent of absorption of valsartan are higher in the two liquid dosage forms (extemporaneous suspension and solution formulations) relative to the solid oral dosage form (tablet formulation). PMID:27128457

  2. Ultrasonic determination of Young's moduli of the coat and core materials of a drug tablet.

    PubMed

    Akseli, Ilgaz; Becker, Douglas C; Cetinkaya, Cetin

    2009-03-31

    Many modern tablet presses have system controls that monitor the force exerted to compress the solid oral dosage forms; however this data provides only limited information about the mechanical state of the tablet due to various process and materials uncertainties. A contact pulse/echo ultrasonic scheme is presented for the determination of the local Young's moduli of the coat and the core materials of enteric-coated and monolayer coated tablets. The Young's modulus of a material compacted into solid dosage can be related to its mechanical hardness and, consequently, its dissolution rate. In the current approach, short ultrasonic pulses are generated by the active element of a delay line transducer and are launched into the tablet. The waveforms reflected from the tablet coat-core interface are captured by the same transducer and are processed for determining the reflection and transmission coefficients of the interface from partially overlapping echoes. The Young's moduli of the coat and the core materials are then extracted from these coefficients. The results are compared to those obtained by an air-coupled acoustic excitation study, and good agreement is found. The described measurement technique provides greater insight into the local physical properties of the solid oral dosage form and, as a result, has the potential to provide better hardness-related performance predictability of compacts. PMID:19059326

  3. Combined morphine-bupivacaine caudals for reconstructive penile surgery in children: systemic absorption of morphine and postoperative analgesia.

    PubMed

    Wolf, A R; Hughes, D; Hobbs, A J; Prys-Roberts, C

    1991-02-01

    We wished to determine if the addition of a small dose of morphine (0.05 mg.kg-1) to a caudal solution of 0.25% bupivacaine could extend the duration of analgesia after major reconstructive penile surgery and also to measure the systemic absorption of morphine after caudal injection. Thirty children undergoing reconstructive penile surgery received a caudal injection of 0.25% bupivacaine 0.75 ml.kg-1 with or without morphine 0.05 mg.kg-1. All patients awoke pain-free, but eight of the fifteen patients receiving bupivacaine alone required supplementary injections of opioid postoperatively, whereas none of the patients receiving the bupivacaine-morphine mixture required additional opioids. The incidence of side-effects was similar for the two groups. Morphine was absorbed rapidly after caudal injection to reach a peak plasma level of 21.2 (+/- 4.8) ng.ml-1 at ten minutes and then fell to 10.1 (+/- 3.8) ng.ml-1 at one hour and 4.1 (+/- 2.6) ng.ml-1 at three hours. These levels are low compared with plasma levels associated with systemic analgesia. We conclude that the extended duration of analgesia from morphine 0.05 mg/kg given caudally is due at least in part to specific spinal analgesia. PMID:2012289

  4. Trans-stilbene oxide administration increased hepatic glucuronidation of morphine but decreased biliary excretion of morphine glucuronide in rats

    SciTech Connect

    Fuhrman-Lane, C.; Fujimoto, J.M.

    1982-09-01

    The effect of the inducing agent trans-stilbene oxide (TSO) on the metabolism and biliary excretion of (/sup 14/C)morphine was studied in the isolated in situ perfused rat liver. After administration of morphine by intraportal injection or by the segmented retrograde intrabiliary injection technique, the TSO-treated group showed a marked decrease in the biliary recovery of morphine as its glucuronide conjugate (morphine-3-glucuronide (MG)). However, recovery of MG in the venous outflow of the single pass perfusate was greatly increased. These findings suggested that TSO treatment enhanced the formation of MG from morphine and changed the primary route of hepatic elimination of MG. TSO treatment also decreased the excretion of morphine (as MG) in the bile of anesthetized renal-ligated rats. This decreased biliary function required several days to develop and appeared closely associated with the inductive effect of TSO. After i.v. administration of (/sup 14/C)MG itself, biliary recovery was also markedly decreased in TSO-treated rats. It is postulated that the effect of the TSO treatment led to either a decrease in canalicular transport of MG into bile or an increase in the efficiency of transfer of MG to the blood at the sinusoidal side of the hepatocyte. Regardless of the mechanism, the results indicate the need to study compartmentalization of drug transport and metabolism functions.

  5. 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. PMID:24300215

  6. Development and Characterization of Novel Floating-Mucoadhesive Tablets Bearing Venlafaxine Hydrochloride

    PubMed Central

    Misra, Raghvendra

    2016-01-01

    The present investigation is concerned about the development of floating bioadhesive drug delivery system of venlafaxine hydrochloride which after oral administration exhibits a unique combination of floating and bioadhesion to prolong gastric residence time and increase drug bioavailability within the stomach. The floating bioadhesive tablets were prepared by the wet granulation method using different ratios of hydroxypropyl methyl cellulose (HPMC K4MCR) and Carbopol 934PNF as polymers. Sodium bicarbonate (NaHCO3) and citric acid were used as gas (CO2) generating agents. Tablets were characterized for floating properties, in vitro drug release, detachment force, and swelling index. The concentration of hydroxypropyl methyl cellulose and Carbopol 934PNF significantly affects the in vitro drug release, floating properties, detachment force, and swelling properties of the tablets. The optimized formulation showed the floating lag time 72 ± 2.49 seconds and duration of floating 24.50 ± 0.74 hr. The in vitro release studies and floating behavior were studied in simulated gastric fluid (SGF) at pH 1.2. Different drug release kinetics models were also applied. The in vitro drug release from tablets was sufficiently sustained (more than 18 hr) and the Fickian transports of the drug from the tablets were confirmed. The radiological evidence suggests that the tablets remained buoyant and altered position in the stomach of albino rabbit and mean gastric residence time was prolonged (more than > 6 hr). PMID:27274884

  7. Formulation and bioavailability of controlled release salbutamol sulphate tablets using natural additives.

    PubMed

    Nouh, A T; Abd El-Gawad, A H; Guda, T K

    2010-04-01

    Salbutamol sulphate granules and physical mixtures were prepared using mastic with various natural additives. The prepared granules and physical mixtures were examined using IR and DSC. The obtained results indicate that there is no interaction between salbutamol sulphate and the formulation ingredients used. The physical properties and release behavior of the formulated tablets prepared from granules and physical mixtures were evaluated and showed good physical properties. The rate of drug release from tablets prepared from granules was found to be lower than that prepared from physical mixtures at fixed mastic concentration and the same additive. The rate of drug release decreased with increased mastic concentration in formulated tablets. Pectin and sodium alginate allowed the best controlled release rate of the drug. On the basis of the results obtained from the controlled release studies, selected sulbutamol formulations were subjected to an in vivo comparison with commercial sulbutamol tablets. The pharmacokinetic parameters AUC(0-24), C(max), and T(max) of sulbutamol from the selected formulation were determined after administration of a single oral dose of 8 mg and compared statistically using an ANOVA test. There was no significant difference in the AUC(0-24). On the other hand, there was a significant difference in the C(max) and T(max) between the commercial and the formulated tablets. These results demonstrate that the formulated tablets extended the time of the drug effect. PMID:22491165

  8. Formulation and evaluation of sustained release bioadhesive tablets of ofloxacin using 32 factorial design

    PubMed Central

    Gangurde, Hemant H; Chordiya, Mayur A; Tamizharasi, S; Senthilkumaran, K; Sivakumar, T

    2011-01-01

    Background: Oral sustained release gastroretentive dosage forms offer many advantages for drugs having absorption from upper gastrointestinal tract and improve the bioavailability of medications that are characterized by narrow absorption window. The aim of current study was to design sustained release bioadhesive gastroretentive dosage form of ofloxacin. Materials and Methods: A 32 full factorial design was employed to systematically study the drug release profile and bioadhesive strength. Carbopol 934P and HPMC K100M were selected as the independent variables. Compatibility between drug and polymer was tested by fourier transform infrared (FTIR) and X-ray diffraction (XRD) techniques. Tablets were prepared by direct compression and were evaluated for tablet characteristics, swelling study, adhesion strength, percent drug released, radiographic imaging study and stability study. The optimized formulation was then compared with marketed formulation (Oflin OD®). Results: Tablets prepared showed good tablet characteristics, optimum swelling property, and good adhesion strength with high detachment force. Most of the formulations including the optimized formulation followed Higuchi kinetics and the drug release mechanism was found to be anomalous. Radiographic image proved that tablet remains intact in its structural integrity and shape in stomach up to 24 h. The short-term accelerated stability testing was carried out for the optimized formulation, and results revealed that drug content, in-vitro dissolution and all other parameters were within acceptable limits. Conclusion: Thus, the prepared bioadhesive gastroretentive ofloxacin tablet may prove to be a potential candidate which increases the bioavailability of ofloxacin for any intragastric condition. PMID:23071937

  9. Development and Characterization of Novel Floating-Mucoadhesive Tablets Bearing Venlafaxine Hydrochloride.

    PubMed

    Misra, Raghvendra; Bhardwaj, Peeyush

    2016-01-01

    The present investigation is concerned about the development of floating bioadhesive drug delivery system of venlafaxine hydrochloride which after oral administration exhibits a unique combination of floating and bioadhesion to prolong gastric residence time and increase drug bioavailability within the stomach. The floating bioadhesive tablets were prepared by the wet granulation method using different ratios of hydroxypropyl methyl cellulose (HPMC K4MCR) and Carbopol 934PNF as polymers. Sodium bicarbonate (NaHCO3) and citric acid were used as gas (CO2) generating agents. Tablets were characterized for floating properties, in vitro drug release, detachment force, and swelling index. The concentration of hydroxypropyl methyl cellulose and Carbopol 934PNF significantly affects the in vitro drug release, floating properties, detachment force, and swelling properties of the tablets. The optimized formulation showed the floating lag time 72 ± 2.49 seconds and duration of floating 24.50 ± 0.74 hr. The in vitro release studies and floating behavior were studied in simulated gastric fluid (SGF) at pH 1.2. Different drug release kinetics models were also applied. The in vitro drug release from tablets was sufficiently sustained (more than 18 hr) and the Fickian transports of the drug from the tablets were confirmed. The radiological evidence suggests that the tablets remained buoyant and altered position in the stomach of albino rabbit and mean gastric residence time was prolonged (more than > 6 hr). PMID:27274884

  10. Evaluation of the effects of tableting speed on the relationships between compaction pressure, tablet tensile strength, and tablet solid fraction.

    PubMed

    Tye, Ching Kim; Sun, Changquan Calvin; Amidon, Gregory E

    2005-03-01

    It is well known that compression speed can have significant effects on the compaction properties of pharmaceutical powders. This is a challenge during scale up and technology transfer when tableting speeds are significantly increased. This study examined the effects of tableting speed on the compressibility (solid fraction vs. compaction pressure), tabletability (tensile strength vs. compaction pressure), and compactibility (tensile strength vs. solid fraction) of four common direct compression excipients and a placebo formulation. The tabletability and compressibility of some of these materials were observed to be speed dependent whereas the compactibility of all materials tested was essentially independent of tableting speed. It is therefore proposed that the compactibility profile (tensile strength vs. solid fraction) is a predictor that is independent of tableting speed and can be used to predict tablet strength during formulation development and scale up. PMID:15696587

  11. Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections.

    PubMed

    Wiederhold, Nathan P

    2016-01-01

    Posaconazole is a broad-spectrum triazole antifungal agent with potent activity against various pathogenic fungi, including yeast and moulds. Clinical studies have demonstrated that this agent is efficacious as prophylaxis against invasive fungal infections in patients at high risk, and may also be useful as salvage therapy against invasive aspergillosis and mucormycosis. However, the bioavailability of posaconazole following administration by oral suspension, which was the only formulation clinically available for many years, is highly variable and negatively influenced by several factors. Because of this, many patients had subtherapeutic or undetectable posaconazole levels when the oral suspension was used. To overcome this limitation, a delayed-release tablet was developed and is now available for clinical use. Hot-melt extrusion technology is used to combine a pH-sensitive polymer with posaconazole to produce a formulation that releases the drug in the elevated pH of the intestine where absorption occurs rather than in the low-pH environment of the stomach. This results in enhanced bioavailability and increased posaconazole exposure. Studies in healthy volunteers have demonstrated significantly higher and more consistent exposures with the tablet formulation compared to the oral suspension. In addition, pharmacokinetic parameters following administration of the tablets were not significantly affected by medications that raise gastric pH or increase gastric motility, and the tablets could also be administered without regard to food. Similar results have also been found in patients at high risk for invasive fungal infections who have received posaconazole tablets. The tablet formulation also appears to be well tolerated to date, although data regarding clinical efficacy are needed. PMID:26730212

  12. Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections

    PubMed Central

    Wiederhold, Nathan P

    2016-01-01

    Posaconazole is a broad-spectrum triazole antifungal agent with potent activity against various pathogenic fungi, including yeast and moulds. Clinical studies have demonstrated that this agent is efficacious as prophylaxis against invasive fungal infections in patients at high risk, and may also be useful as salvage therapy against invasive aspergillosis and mucormycosis. However, the bioavailability of posaconazole following administration by oral suspension, which was the only formulation clinically available for many years, is highly variable and negatively influenced by several factors. Because of this, many patients had subtherapeutic or undetectable posaconazole levels when the oral suspension was used. To overcome this limitation, a delayed-release tablet was developed and is now available for clinical use. Hot-melt extrusion technology is used to combine a pH-sensitive polymer with posaconazole to produce a formulation that releases the drug in the elevated pH of the intestine where absorption occurs rather than in the low-pH environment of the stomach. This results in enhanced bioavailability and increased posaconazole exposure. Studies in healthy volunteers have demonstrated significantly higher and more consistent exposures with the tablet formulation compared to the oral suspension. In addition, pharmacokinetic parameters following administration of the tablets were not significantly affected by medications that raise gastric pH or increase gastric motility, and the tablets could also be administered without regard to food. Similar results have also been found in patients at high risk for invasive fungal infections who have received posaconazole tablets. The tablet formulation also appears to be well tolerated to date, although data regarding clinical efficacy are needed. PMID:26730212

  13. Comparative Efficacy of an Imidacloprid/Flumethrin Collar (Seresto®) and an Oral Fluralaner Chewable Tablet (Bravecto®) against Tick (Dermacentor variabilis and Amblyomma americanum) Infestations on Dogs: a Randomised Controlled Trial.

    PubMed

    Ohmes, Cameon M; Hostetler, Joe; Davis, Wendell L; Settje, Terry; McMinn, Amy; Everett, William R

    2015-08-01

    This controlled laboratory study demonstrated the residual speed of efficacy of an imidacloprid/flumethrin collar (Seresto(®), Bayer) for the control of ticks (Dermacentor variabilis, Amblyomma americanum) at 6 and 12 hours post-infestation on dogs when compared to oral fluralaner (Bravecto(®), Merck). Dogs were randomised by pre-treatment tick counts: Group 1) imidacloprid 10 % (w/w)/flumethrin 4.5 % (w/w) collar, 2) fluralaner (dosage 25.1 - 49.4 mg/kg), and 3) non-treated controls. Ticks (50/species/dog) were infested on days 3, 14, 21, 28, 42, and 56 followed by 50 D. variabilis on days 70 and 84. Live and dead attached ticks were counted 6 and 12 hours later. Efficacy against both species at 6 and 12 hours for Group 1 was 94 - 100 %. Efficacy for Group 2 against both species at 6 hours was 4 - 69 %; efficacy at 12 hours was 8 - 100 %. Live (attached and non-attached) tick counts at 6 hours in Group 1 were significantly lower (p ≤ 0.05) than counts in Group 2 and 3 on all days. At 12 hours, live counts were significantly lower (p ≤ 0.05) in Group 1 than Group 2 for D. variabilis from days 56 - 84 and for A. americanum from days 28 - 56. There were significantly fewer (p ≤ 0.05) total ticks (total live and dead attached) on dogs in Group 1 compared to Group 2 and 3 at all time points. This study demonstrated that an imidacloprid/flumethrin collar was highly efficacious (94 - 100 %) at repelling and killing ticks on dogs at 6 and 12 hours post-infestation and was more efficacious than fluralaner as early as 6 hours post-infestation on all challenge days. PMID:26152411

  14. Evaluation of some compression aids in tableting of roller compacted swellable core drug layer.

    PubMed

    Golchert, D; Bines, E; Carmody, A

    2013-09-10

    Swellable core technology (SCT) represents a broadly applicable oral osmotic drug delivery platform for the controlled release of drugs. SCT tablets control drug delivery by using osmosis to regulate the influx of water into the tablet's core. The tablet consists of two layers; drug layer and sweller layer, with a semi-permeable membrane coating and delivery port located in the drug layer side of the tablet. The key component of SCT formulations is polyethylene oxide (PEO), which is typically wet granulated with organic solvents to prevent rapid gel hydration observed during contact with aqueous environments. However, the use of organic solvents has their own environmental and cost considerations which make this form of processing undesirable. To overcome this issue, dry granulation can be employed. However, PEO is a very plastic material and problems may be encountered during the tableting process, when work hardening occurs upon double compression. The addition of compression aids to the drug layer will help to increase the roll force when generating ribbons - reducing fines and segregation potential - while also reducing work hardening effects which impact tablet friability. The five compression aids used in this study were microcrystalline cellulose (MCC), xylitol, di-calcium phosphate (anhydrous), lactose monohydrate and starch. The work undertaken here studies the compression properties of the drug layer blends with different levels of the five compression aids as part of the formulation. Roller compaction properties are also varied to provide granules with differing solid fractions. The results of this study indicate that addition of microcrystalline cellulose in the formulation in levels between 10% and 30% significantly improve the tablet hardness at lower tablet compression forces. Further work is required to investigate the impact on dissolution. PMID:23796839

  15. Purification and characterization of guinea pig liver morphine 6-dehydrogenase.

    PubMed

    Yamano, S; Kageura, E; Ishida, T; Toki, S

    1985-05-10

    Morphine 6-dehydrogenase, which catalyzes the dehydrogenation of morphine to morphinone, has been purified about 440-fold from the soluble fraction of guinea pig liver with a yield of 38%. The purified enzyme was a homogeneous protein on polyacrylamide gel disc electrophoresis and isoelectric focusing. The molecular weight and isoelectric point of the enzyme were 29,000 and 7.6, respectively. The enzyme utilizes both NAD and NADP as a cofactor, and the Km values were 0.12 mM for NAD and 0.42 mM for NADP. The Vmax values for morphine were 588 milliunits/mg of protein (with NAD) and 1600 milliunits/mg of protein (with NADP). The Km values for morphine were 0.12 mM (with NAD) and 0.49 mM (with NADP). The enzyme also exhibited activity for morphine-related compounds: nalorphine, normorphine, codeine, and ethylmorphine; however, 7,8-saturated congeners such as dihydromorphine and dihydrocodeine were poor substrates. The enzyme was inactivated by removal of 2-mercaptoethanol from the enzyme solution. The inactivated enzyme was rapidly recovered by the addition of 2-mercaptoethanol. Phenylarsine oxide and CdCl2 (dithiol modifiers) inhibited competitively toward cofactor binding and noncompetitively toward morphine binding. These results suggest that the enzyme possesses the essential thiol groups, probably vicinal dithiol, at or near the cofactor-binding site. Using the partially purified enzyme, 8-(2-hydroxyethylthio)dihydromorphinone was isolated as the product and identified by UV, mass, and NMR spectra. It was confirmed that morphinone proposed as the dehydrogenation product was nonenzymatically and covalently bound to 2-mercaptoethanol. Accordingly, the isolated morphinone-2-mercaptoethanol conjugate must be formed by two steps: enzymatic production of morphinone from morphine and then nonenzymatic binding of 2-mercaptoethanol to morphinone. PMID:2580834

  16. Novel gastroretentive sustained-release tablet of tacrolimus based on self-microemulsifying mixture: in vitro evaluation and in vivo bioavailability test

    PubMed Central

    Wang, Yan-ping; Gan, Yong; Zhang, Xin-xin

    2011-01-01

    Aim: To develop a novel gastroretentive drug delivery system based on a self-microemulsifying (SME) lipid mixture for improving the oral absorption of the immunosuppressant tacrolimus. Methods: Liquid SME mixture, composed of Cremophor RH40 and monocaprylin glycerate, was blended with polyethylene oxide, chitosan, polyvinylpyrrolidone and mannitol, and then transformed into tablets via granulation, with ethanol as the wetting agent. The tablets were characterized in respect of swelling, bioadhesive and SME properties. In vitro dissolution was conducted using an HCl buffer at pH 1.2. Oral bioavailability of the tablets was examined in fasted beagle dogs. Results: The tablet could expand to 13.5 mm in diameter and 15 mm in thickness during the initial 20 min of contact with the HCl buffer at pH 1.2. The bioadhesive strength was as high as 0.98±0.06 N/cm2. The SME gastroretentive sustained-release tablets preserved the SME capability of the liquid SME formations under transmission electron microscope. The drug-release curve was fit to the zero-order release model, which was helpful in reducing fluctuations in blood concentration. Compared with the commercially available capsules of tacrolimus, the relative bioavailability of the SME gastroretentive sustained-release tablets was 553.4%±353.8%. Conclusion: SME gastroretentive sustained-release tablets can enhance the oral bioavailability of tacrolimus with poor solubility and a narrow absorption window. PMID:21927013

  17. Water-sorption properties of tablet disintegrants.

    PubMed

    Khan, K A; Rhodes, C T

    1975-03-01

    The water-sorption properties of four tablet disintegrants, starch, sodium carboxymethylcellulose, sodium starch glycolate, and a cation-exchange resin, were examined in the form of powders and in compressed tablets prepared from calcium phosphate dibasic dihydrate. Dissolution properties of the tablets compare well to the water-sorption properties. The effect of storage in the presence of water vapor upon tablets containing the various disintegrants was evaluated in terms of tablet hardness and disintegration time. Differences in the effects produced in the various tablet formulations can be related to the differing mechanisms whereby the disintegrants effect tablet rupture. Photomicrographic data support the conclusions drawn from the water-sorption, disintegration, and dissolution studies. Sodium starch glycolate and the cation-exchange resin merit careful consideration by formulators using calcium phosphate dibasic dihydrate or similar direct compression matrixes. PMID:1151632

  18. Availability of cefixime 400 mg tablets--United States, April 2008.

    PubMed

    2008-04-25

    The only current CDC-recommended options for treating Neisseria gonorrhoeae infections are from a single class of antibiotics, the cephalosporins. Within this class, ceftriaxone, available only as an injection, is the recommended treatment for all types of gonorrhea infections (i.e., urogenital, rectal, and pharyngeal). The only oral agent recommended currently by CDC for treatment of uncomplicated urogenital or rectal gonorrhea is a single dose of cefixime 400 mg. Availability of cefixime had been limited since July 2002, when Wyeth Pharmaceuticals (Collegeville, Pennsylvania) discontinued manufacturing cefixime tablets in the United States. Beginning in April 2008, cefixime (Suprax) 400 mg tablets are again available in the United States. PMID:18437119

  19. The Effect of Acute and Chronic Morphine on Some Blood Biochemical Parameters in an Inflammatory Condition in Gonadectomized Male Rats

    PubMed Central

    Chahkandi, Mohadeseh; Askari, Nayerreh; Asadikaram, Gholamreza

    2015-01-01

    Background Opiates affect blood factors as well as pain and inflammation in a gender-dependent manner. The aim of the present study was to evaluate the effects of morphine on serum glucose, cholesterol, triglycerides, and urea in gonadectomized and inflammation conditions. Methods Animals were divided as follows: control group, carrageenan and chronic morphine recipients, acute morphine recipients, chronic morphine recipients, carrageenan recipients, acute morphine and carrageenan recipients, gonadectomized group, gonadectomized recipients of carrageenan, gonadectomized recipients of morphine, gonadectomized recipients of chronic morphine, gonadectomized recipients of carrageenan and chronic morphine, gonadectomized recipients of acute morphine and carrageenan. Findings Our results have shown that acute and chronic morphine elevates blood glucose level in the acute and chronic morphine group. Cholesterol level has shown to be increasing in the morphine and carrageenan recipient group compared with a group which merely received morphine. Triglyceride has shown to be decreasing in acute and chronic morphine recipient group compared with control group. A significant increase in serum urea was observed in acute and chronic morphine recipients compared with the carrageenan recipient group. Conclusion Morphine alters the serum glucose, cholesterol, triglyceride, and urea in the normal and inflammatory conditions differently, hence, this finding should be considered in the patients who use morphine as a relief of pain, especially in an inflammatory condition. PMID:26885349

  20. Learning, Tablet, Culture-Coherence?

    ERIC Educational Resources Information Center

    Norqvist, Lars

    2016-01-01

    This paper presents understandings of learning in schools where Internet-enabled Information and Communication Technologies (ICTs) are taken for granted. The context is a full-scale 1:1 tablet project in Danish municipality schools where this study bring forward expressions of learning from one class (12-13 year old children) in order to offer…

  1. An open-label, randomized bioavailability study with alternative methods of administration of crushed ticagrelor tablets in healthy volunteers

    PubMed Central

    Teng, Renli; Carlson, Glenn; Hsia, Judith

    2015-01-01

    Objective: To compare the bioavailability and safety profile of crushed ticagrelor tablets suspended in water and administered orally or via nasogastric tube, with that of whole tablets administered orally. Methods: In this single-center, open-label, randomized, three-treatment crossover study, 36 healthy volunteers were randomized to receive a single 90-mg dose of ticagrelor administered orally as a whole tablet or as crushed tablets suspended in water and given orally or via a nasogastric tube into the stomach, with a minimum 7-day wash-out between treatments. Plasma concentrations of ticagrelor and AR-C124910XX were assessed at 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-ticagrelor dose for pharmacokinetic analyses. Safety and tolerability was assessed throughout the study. Results: At 0.5 hours postdose, plasma concentrations of ticagrelor and AR-C124910XX were higher with crushed tablets administered orally (148.6 ng/mL and 13.0 ng/mL, respectively) or via nasogastric tube (264.6 ng/mL and 28.6 ng/mL, respectively) compared with whole-tablet administration (33.3 ng/mL and 5.2 ng/mL, respectively). A similar trend was observed at 1 hour postdose. Ticagrelor tmax was shorter following crushed vs. whole-tablet administration (1 vs. 2 hours, respectively). Geometric mean ratios between treatments for AUC and Cmax were contained within the bioequivalence limits of 80 – 125% for ticagrelor and AR-C124910XX. All treatments were generally well tolerated. Conclusions: Ticagrelor administered as a crushed tablet is bioequivalent to whole-tablet administration, independent of mode of administration (oral or via nasogastric tube), and resulted in increased plasma concentrations of ticagrelor and AR-C124910XX at early timepoints. PMID:25500486

  2. Adherence to a flexible extended regimen for oral hormonal contraception provided in blister packaging compared with an adherence-supporting digital tablet dispenser: historical comparison of data from two clinical studies

    PubMed Central

    Elliesen, Jörg; Trummer, Dietmar

    2016-01-01

    Background The Clyk™ digital pill dispenser helps ensure correct and consistent administration of a flexible extended regimen of the combined oral contraceptive, ethinylestradiol (EE) 20 μg/drospirenone 3 mg (EE/drospirenone ; YAZ® Flex Flex), guiding users through the intake cycle and 4-day pill break and providing visible and acoustic daily reminders when pill intake is due. A study showed that the audible alarm function of the dispenser could help reduce the number of missed pills, but it lacked an appropriate “non-dispenser” group for a meaningful assessment of the impact of the dispenser on adherence. This study indirectly assessed the overall effect of the digital dispenser on adherence by comparing data from a treatment with standard blister packaging. Materials and methods One-year adherence data were compared from two similarly designed, Phase III, open-label, randomized trials of EE/drospirenoneFlex. In study 1, women used diary cards to record adherence with EE/drospirenoneFlex dispensed in blister packs (n=640), and in study 2 the dispenser was used with the alarm activated (n=250) or deactivated (n=248) in addition to using diary cards. Results A mean (±SD) of 4.3 (±4.24) missed pills over 1 year were recorded in diary cards among women who dispensed their pills from the blister packages (study 1) compared with 1.0 (±2.4) recorded by the alarm-activated dispenser (study 2). In study 2, a mean of 1.9 (±4.2) missed pills were reported in the diaries over 1 year compared with 4.4 (±9.1) from automatic recording by the dispenser (both arms of study 2), indicating underreporting of missed pills in diary cards vs the digital dispenser. Adjusting for this rate of underreporting, an estimated mean of ten pills were missed over 1 year by women using EE/drospirenoneFlex in blister packs, or ten times more than with the digital dispenser with activated acoustic alarm. Conclusion The digital dispenser helps reduce the number of missed pills and

  3. Extended-release morphine sulfate in treatment of severe acute and chronic pain

    PubMed Central

    Balch, Robert J; Trescot, Andrea

    2010-01-01

    Morphine is the archetypal opioid analgesic. Because it is a short-acting opioid, its use has been limited to the management of acute pain. The development of extended-release formulations have resulted in the increased utilization of morphine in chronic pain conditions. This review documents the history of morphine use in pain treatment, and describes the metabolism, pharmacodynamics, formulations, and efficacy of the currently available extended-release morphine medications. PMID:21197323

  4. Bromocriptine tablet of self-microemulsifying system adsorbed onto porous carrier to stimulate lipoproteins secretion for brain cellular uptake.

    PubMed

    Thongrangsalit, Sirigul; Phaechamud, Thawatchai; Lipipun, Vimolmas; Ritthidej, Garnpimol C

    2015-07-01

    Both low solubility and high hepatic metabolism cause low oral bioavailability of bromocriptine mesylate (BM) leading to very low drug amount in brain. Self-microemulsion (SME) tablets were developed to improve solubility, stimulate lipoprotein synthesis to promote lymphatic transport, avoid hepatic metabolism and target drug to brain. SME liquid containing castor oil, Tween(®) 80 and Cremophor(®) EL was prepared and then adsorbed onto solid carries, Aerosil(®)200, Aeroperl(®)300 or NeusilinUS2(®), yielding SME powders. The optimal ratios of SME liquid to carriers determined from flowability and scanning electron photomicrographs before tableting were 1.5:1, 2:1 and 2.5:1 for Aerosil(®)200, Aeroperl(®)300 and NeusilinUS2(®), respectively. Only Aeroperl(®)300 SME tablet had comparable dissolution to BM commercial tablet. From in vitro study in Caco-2 cells, fluorescein loaded SME tablet showed higher uptake than fluorescein loaded in either oil or surfactant. Although significantly lower amount of drug was permeated from SME tablet than from commercial tablet, higher drug uptake was obviously observed (P<0.05). In addition, higher lipoprotein synthesis expressing as content of apolipoprotein B (apo-B) found in secreted chylomicron resulted in higher drug uptake in co-culture of brain endothelial cells (bEnd.3) and astrocytes (CTX TNA2) from drug loaded SME tablet when compared to commercial tablet (P<0.05) due to binding of apo-B to LDL receptors expressed on the surface of endothelial cells. Therefore, tablet of SME adsorbed onto porous carrier potentially delivered BM to brain via lymphatic transport by increasing the lipoprotein synthesis. PMID:25988280

  5. Stability of an extemporaneously compounded levothyroxine sodium oral liquid.

    PubMed

    Boulton, D W; Fawcett, J P; Woods, D J

    1996-05-15

    The stability of levothyroxine sodium in oral liquid dosage forms compounded from commercially available tablets was studied. Levothyroxine sodium oral liquids (25 micrograms/mL) were prepared from tablets and from powder with and without methylparaben preservative and transferred to amber, high-density polyethylene bottles. Five bottles of each tablet-based formulation were stored at 2-8 degrees C, 23-27 degrees C, and 38-42 degrees C, and five bottles of each powder-based formulation were stored at 38-42 degrees C. On days 3, 8, 14, 22, 31, 61, and 90, samples were taken from each bottle and analyzed for drug concentration by stability-indicating high-performance liquid chromatography. There was significant degradation of levothyroxine sodium in all the formulations. However, the tablet-based formulation without preservative stored at 4 degrees C retained at least 90% of its initial concentration for eight days after compounding. Degradation occurred faster in the tablet-based formulation with preservative. None of the formulations retained > or = 90% initial potency by day 14. An extemporaneous oral liquid formulation of levothyroxine sodium 25 micrograms/mL compounded from crushed tablets was stable for eight days when stored in amber bottles at 4 degrees C. PMID:8734676

  6. Reversal of morphine analgesic tolerance by ethanol in the mouse.

    PubMed

    Hull, L C; Gabra, B H; Bailey, C P; Henderson, G; Dewey, W L

    2013-06-01

    The chronic use of opioids in humans, accompanied by the development of tolerance, is a dangerous phenomenon in its own right. However, chronic opioid use is often made more dangerous by the coconsumption of other substances. It has been observed that the blood level of opioids in postmortem analyses of addicts, who consumed ethanol along with the opioid, was much less than that observed in individuals who died from opioids alone. This relationship between ethanol and opioids led us to investigate the hypothesis that ethanol alters tolerance to opioids. In the present study, we report that ethanol significantly and dose-dependently reduced the antinociceptive tolerance produced by morphine and the cross-tolerance between [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) and morphine in the mouse tail-flick test. The reversal of morphine tolerance was partially blocked by both the gamma receptor blocker bicuculline and by the γ-aminobutyric acid (GABA)(B) receptor blocker phaclofen and the administration of both inhibitors completely reversed the effects of ethanol on morphine tolerance. Diazepam, like ethanol, decreased morphine tolerance. However, this inhibition was reversed by the GABA(A) antagonist bicuculline but not by the GABA(B) antagonist phaclofen. These findings have important implications for individuals who abuse opioids and ethanol as well as suggest a mechanism to reduce the amount of opioid needed in chronic pain treatment. PMID:23528610

  7. Reversal of Morphine Analgesic Tolerance by Ethanol in the Mouse

    PubMed Central

    Hull, L. C.; Gabra, B. H.; Bailey, C. P.; Henderson, G.

    2013-01-01

    The chronic use of opioids in humans, accompanied by the development of tolerance, is a dangerous phenomenon in its own right. However, chronic opioid use is often made more dangerous by the coconsumption of other substances. It has been observed that the blood level of opioids in postmortem analyses of addicts, who consumed ethanol along with the opioid, was much less than that observed in individuals who died from opioids alone. This relationship between ethanol and opioids led us to investigate the hypothesis that ethanol alters tolerance to opioids. In the present study, we report that ethanol significantly and dose-dependently reduced the antinociceptive tolerance produced by morphine and the cross-tolerance between [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) and morphine in the mouse tail-flick test. The reversal of morphine tolerance was partially blocked by both the gamma receptor blocker bicuculline and by the γ-aminobutyric acid (GABA)B receptor blocker phaclofen and the administration of both inhibitors completely reversed the effects of ethanol on morphine tolerance. Diazepam, like ethanol, decreased morphine tolerance. However, this inhibition was reversed by the GABAA antagonist bicuculline but not by the GABAB antagonist phaclofen. These findings have important implications for individuals who abuse opioids and ethanol as well as suggest a mechanism to reduce the amount of opioid needed in chronic pain treatment. PMID:23528610

  8. Morphine treatment alters nucleotidase activities in rat blood serum

    PubMed Central

    Rozisky, Joanna Ripoll; Nonose, Yasmine; Laste, Gabriela; dos Santos, Vinicius Souza; de Macedo, Isabel Cristina; Battastini, Ana Maria Oliveira; Caumo, Wolnei; Torres, Iraci LS

    2012-01-01

    Morphine has been widely used in neonatal pain management. However, this treatment may produce adaptive changes in several physiologic systems. Our laboratory has demonstrated that morphine treatment in neonate rats alters nucleoside triphosphate diphosphohydrolase (NTPDase) activity and gene expression in central nervous system structures. Considering the relationship between the opioid and purinergic systems, our aim was to verify whether treatment with morphine from postnatal days 8 (P8) through 14 (P14) at a dose of 5 µg per day alters NTPDase and 5′-nucleotidase activities in rat serum over the short, medium, and long terms. After the in vivo assay, the morphine group showed increased hydrolysis of all nucleotides at P30, and a decrease in adenosine 5′-diphosphate hydrolysis at P60. Moreover, we found that nucleotidase activities change with age; adenosine 5′-triphosphate hydrolysis activity was lower at P16, and adenosine 5′-monophosphate hydrolysis activity was higher at P60. These changes are very important because these enzymes are the main regulators of blood nucleotide levels and, consequently, nucleotide signaling. Our findings showed that in vivo morphine treatment alters nucleotide hydrolysis in rat blood serum, suggesting that purine homeostasis can be influenced by opioid treatment during the neonatal period.

  9. Effect of morphine on sympathetic nerve activity in humans

    NASA Technical Reports Server (NTRS)

    Carter, Jason R.; Sauder, Charity L.; Ray, Chester A.

    2002-01-01

    There are conflicting reports for the role of endogenous opioids on sympathetic and cardiovascular responses to exercise in humans. A number of studies have utilized naloxone (an opioid-receptor antagonist) to investigate the effect of opioids during exercise. In the present study, we examined the effect of morphine (an opioid-receptor agonist) on sympathetic and cardiovascular responses at rest and during isometric handgrip (IHG). Eleven subjects performed 2 min of IHG (30% maximum) followed by 2 min of postexercise muscle ischemia (PEMI) before and after systemic infusion of morphine (0.075 mg/kg loading dose + 1 mg/h maintenance) or placebo (saline) in double-blinded experiments on separate days. Morphine increased resting muscle sympathetic nerve activity (MSNA; 17 +/- 2 to 22 +/- 2 bursts/min; P < 0.01) and increased mean arterial pressure (MAP; 87 +/- 2 to 91 +/- 2 mmHg; P < 0.02), but it decreased heart rate (HR; 61 +/- 4 to 59 +/- 3; P < 0.01). However, IHG elicited similar increases for MSNA, MAP, and HR between the control and morphine trial (drug x exercise interaction = not significant). Moreover, responses to PEMI were not different. Placebo had no effect on resting, IHG, and PEMI responses. We conclude that morphine modulates cardiovascular and sympathetic responses at rest but not during isometric exercise.

  10. Fangchinoline inhibited the antinociceptive effect of morphine in mice.

    PubMed

    Fang, L H; Zhang, Y H; Ku, B S

    2005-03-01

    Fangchinoline (FAN), a non-specific calcium antagonist, is a major alkaloidal component of the creeper Stephania tetrandra S. Moore (or fenfangji). It has been shown to possess antagonistic activity on morphine-induced antinociception in mice. This study was undertaken to assess the antagonistic mechanism. The results demonstrated that FAN (IP) attenuated morphine (SC)-induced antinociception in a dose-dependent manner with significant effect at doses of 30 and 60mg/kg body wt. (IP) in the tail-flick test but not the tail-pinch tests, carried out in mice. This antagonism was abolished by pretreatment with a serotonin precursor, 5-hydroxytryptophan (5-HTP, IP), but not by pretreatment with a noradrenaline precursor, L-dihydroxyphenylalanine (L-DOPA, IP) in the tail-flick test. On the other hand, the development of morphine-induced analgesic tolerance was not prevented by FAN. These results suggest that the serotonergic pathway may be involved in the antagonism of morphine-induced antinociception by FAN and, in agreement with other reports, also indicates the possible dissociation of the morphine analgesic effect from its tolerance-development mechanism. PMID:15830839

  11. [Analysis of the accessibility of short acting oral opioids in Hungary].

    PubMed

    Lovas, Kornélia; Hadnagy, László; Jobban, Eszter; Kullmann, Tamás

    2016-05-01

    Short acting oral formulas make part of optimal opioid analgesia. The use of short acting oral morphine has not widely spread in Hungary, and these drugs completely lacked from the market for three years. Since December 2015 short acting morphine-sulphate has again been commercialised. The causes of the market failure are analysed in this article. The aim of the retrospective analysis is to help the accessibility of the medicine to every patient in need. Prescription morphine use depends on the harmonised cooperation of a number of actors. Besides regulating and financing authorities and professional organisations, patients and the opinion forming media are also responsible for building up the right routine. PMID:27106724

  12. A randomized controlled trial on the benefits and respiratory adverse effects of morphine for refractory dyspnea in patients with COPD: Protocol of the MORDYC study.

    PubMed

    Verberkt, C A; van den Beuken-van Everdingen, M H J; Franssen, F M E; Dirksen, C D; Schols, J M G A; Wouters, E F M; Janssen, D J A

    2016-03-01

    Dyspnea is one of the most reported symptoms of patients with advanced Chronic Obstructive Pulmonary Disease (COPD) and is often undertreated. Morphine has proven to be an effective treatment for dyspnea and is recommended in clinical practice guidelines, but questions concerning benefits and respiratory adverse effects remain. This study primarily evaluates the impact of oral sustained release morphine (morphine SR) on health-related quality of life and respiratory adverse effects in patients with COPD. Secondary objectives include the impact on exercise capacity, the relationship between description and severity of dyspnea and the presence of a clinically relevant response to morphine, and cost-effectiveness. A single-center, randomized, double blind, placebo controlled intervention study will be performed in 124 patients with COPD who recently completed a comprehensive pulmonary rehabilitation program. Participants will receive 20-30 mg/24h morphine SR or placebo for four weeks. After the intervention, participants will be followed for twelve weeks. Outcomes include: the COPD Assessment Test, six minute walking test, Multidimensional Dyspnea Scale and a cost diary. Furthermore, lung function and arterial blood gasses will be measured. These measures will be assessed during a baseline and outcome assessment, two home visits, two phone calls, and three follow-up assessments. The intervention and control group will be compared using uni- and multivariate regression analysis and logistic regression analysis. Finally, an economic evaluation will be performed from a societal and healthcare perspective. The current manuscript describes the rationale and methods of this study and provides an outline of the possible strengths, weaknesses and clinical consequences. PMID:26825021

  13. Slow-release of famotidine from tablets consisting of chitosan/sulfobutyl ether β-cyclodextrin composites.

    PubMed

    Anraku, Makoto; Hiraga, Ayumu; Iohara, Daisuke; Pipkin, James D; Uekama, Kaneto; Hirayama, Fumitoshi

    2015-06-20

    An intermolecular complex formed from a 1:1 weight ratio of chitosan (CS, molecular weight 30 kDa) and sulfobutyl ether β-cyclodextrin (SBE-β-CyD, degree of substitution 7) was less soluble than either of the original components. The release of famotidine from tablets composed of a simple mixture of CS and SBE-β-CyD is slower in media at pH 1.2 than at 6.8. Macroscopic observation of tablets and a kinetic analysis of release profiles suggested that, at pH 1.2, the drug was slowly released from the less-soluble CS/SBE-β-CyD complex formed on the surface of the tablet immediately after exposure to water, accompanied by the dissolution of the interpolymer complex and, ultimately, the erosion and disintegration of the tablet. In the case of the medium at pH 6.8, the formation of a gel by CS was the cause of the slow release, especially for CS/SBE-β-CyD tablets which were significantly gelated and both the diameter and thickness of the tablet had expanded. The in vitro slow releasing characteristic of the CS/SBE-β-CyD tablet was reflected in the in vivo absorption of the drug after oral administration to rats. These results suggest that a simple mixing of CS and SBE-β-CyD is potentially useful for the controlled release of a drug. PMID:25882010

  14. Profiling of Ecstasy Tablets Seized in Iran

    PubMed Central

    Khajeamiri, Ali Reza; Kobarfard, Farzad; Ahmadkhaniha, Reza; Mostashari, Gelareh

    2011-01-01

    In this study 50 samples of ecstasy tablets seized in Iran during the period of 2007 through 2008 were examined and their physical characteristics (appearance, marking, scored/not scored, color, weight, diameter, thickness) were determined. In order to determine the chemical characteristics of these tablets, color tests (Marquis test, Simon’s test, Chen’s test and Gallic acid test), Thin Layer Chromatography (TLC), anion test, residual solvents, Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS) were carried out on the tablets. The range of tablets weight was 96–308 mg and the range of 3,4-methylenedioxymethamphetamine (MDMA) hydrochloride content in these tablets was 60–180 mg. No good correlation was found between the tablets weight and their MDMA contents. All of the tablets containing MDMA had this compound in hydrochloride form. Ketamine, phenmetrazine and ephedrine (or pseudoephedrine) were found in some of the tablets along with MDMA. No MDMA was found in 20% of the tablets. Some of these tablets contained compounds such as caffeine or tramadol as their active ingredient. PMID:24250345

  15. 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

  16. Terbutaline slow-release tablets in children with asthma. A comparison with t.i.d. beta 2-agonist therapy.

    PubMed

    Croner, S; Gustafsson, M; Kjellman, N I; Säwedal, L

    1986-07-01

    The effects of 5 mg slow-release terbutaline sulphate tablets (Bricanyl Depot) given twice daily were compared with those of ordinary oral beta 2-agonist treatment given three times daily. The study was open, randomized and cross-over and was carried out over 8 weeks in 18 children with bronchial asthma. Compared with ordinary medication, the slow-release tablets obtained higher morning expiratory peak flow values and an improvement in the asthma symptoms during the night and during exercise (P less than 0.05). No differences were found in side effects in spite of a higher total daily dose during the period with terbutaline slow-release tablets. The slow-release tablets were preferred by 15 of 18 children and their families when the effects, side effects and dosage were evaluated. PMID:2876658

  17. Early clinical development of artemether-lumefantrine dispersible tablet: palatability of three flavours and bioavailability in healthy subjects

    PubMed Central

    2010-01-01

    Background Efforts to ease administration and enhance acceptability of the oral anti-malarial artemether-lumefantrine (A-L) crushed tablet to infants and children triggered the development of a novel dispersible tablet of A-L. During early development of this new formulation, two studies were performed in healthy subjects, one to evaluate the palatability of three flavours of A-L, and a second one to compare the bioavailability of active principles between the dispersible tablet and the tablet (administered crushed and intact). Methods Study 1 was performed in 48 healthy schoolchildren in Tanzania. Within 1 day, all subjects tasted a strawberry-, orange- and cherry-flavoured oral A-L suspension for 10 seconds (without swallowing) in a randomized, single-blind, crossover fashion. The palatability of each formulation was rated using a visual analogue scale (VAS). Study 2 was an open, randomized crossover trial in 48 healthy adults given single doses of A-L (80 mg artemether + 480 mg lumefantrine) with food. The objectives were to compare the bioavailability of artemether, dihydroartemisinin (DHA) and lumefantrine between the dispersible tablet and the tablet administered crushed (primary objective) and intact (secondary objective). Results Study 1 showed no statistically significant difference in VAS scores between the three flavours but cherry had the highest score in several ratings (particularly for overall liking). Study 2 demonstrated that the dispersible and crushed tablets delivered bioequivalent artemether, DHA and lumefantrine systemic exposure (area under the curve [AUC]); mean ± SD AUC0-tlast were 208 ± 113 vs 195 ± 93 h.ng/ml for artemether, 206 ± 81 vs 199 ± 84 h.ng/ml for DHA and 262 ± 107 vs 291 ± 106 h.μg/ml for lumefantrine. Bioequivalence was also shown for peak plasma concentrations (Cmax) of DHA and lumefantrine. Compared with the intact tablet, the dispersible tablet resulted in bioequivalent lumefantrine exposure, but AUC and Cmax values

  18. Interaction of prenatal stress and morphine alters prolactin and seizure in rat pups.

    PubMed

    Saboory, Ehsan; Ebrahimi, Loghman; Roshan-Milani, Shiva; Hashemi, Paria

    2015-10-01

    Prenatal exposure to stress and morphine has complicated effects on epileptic seizure. In the present study, effect of prenatal forced-swim stress and morphine co-administration on pentylenetetrazol (PTZ) induced epileptic behaviors and prolactin blood level (PBL) was investigated in rat offspring. Pregnant Wistar rats were divided to four groups of control-saline, control-morphine, stressed-saline and stressed-morphine. In the stressed group, pregnant rats were placed in 25°C water on gestation days 17, 18 and 19 (GD17, GD18 and GD19) for 30 min. In the morphine/saline group, pregnant rats received morphine (10, 12 and 15 mg/kg, IP, on GD17, GD18 and GD19, respectively) or saline (1 ml, IP). In the morphine/saline-stressed group, the rats received morphine or saline and then exposed to stress. On postnatal days 6 and 15 (P6 and P15), blood samples were obtained and PBL was determined. At P15 and P25, the rest of the pups was injected with PTZ to induce seizure. Then, epileptic behaviors of each rat were observed individually. Latency of first convulsion decreased in control-morphine and stressed-saline groups while increased in stressed-morphine rats compared to control-saline group on P15 (P=0.04). Number of tonic-clonic seizures significantly increased in control-morphine and stressed-saline rats compared to control-saline group at P15 (P=0.02). PBL increased in stressed-saline, control-morphine and stress-morphine groups compared to control-saline rats. It can be concluded that prenatal exposure of rats to forced-swim stress and morphine changed their susceptibility to PTZ-induced seizure and PBL during infancy and prepubertal period. Co-administration of morphine attenuated effect of stress on epileptic behaviors. PMID:26056076

  19. Harpagophytum procumbens extract potentiates morphine antinociception in neuropathic rats.

    PubMed

    Parenti, Carmela; Aricò, Giuseppina; Pennisi, Marzio; Venditti, Alessandro; Scoto, Giovanna M

    2016-06-01

    The association of opioids and non-steroidal anti-inflammatory drugs, to enhance pain relief and reduce the development of side effects, has been demonstrated. Given many reports concerning the antinociceptive and anti-inflammatory effects of Harpagophytum procumbens extracts, the aim of our study was to investigate the advantage of a co-administration of a subanalgesic dose of morphine preceded by a low dose of H. procumbens to verify this therapeutically useful association in a neuropathic pain model. Time course, registered with the association of the natural extract, at a dose that does not induce an antinociceptive effect, followed by a subanalgesic dose of morphine showed a well-defined antiallodynic and antihyperalgesic effect, suggesting a synergism as a result of the two-drug association. H. procumbens cooperates synergistically with morphine in resolving hyperalgesia and allodynia, two typical symptoms of neuropathic pain. The results support the strategy of using an adjuvant drug to improve opioid analgesic efficacy. PMID:26189616

  20. Quaternary naltrexone reverses radiogenic and morphine-induced locomotor hyperactivity

    SciTech Connect

    Mickley, G.A.; Stevens, K.E.; Galbraith, J.A.; White, G.A.; Gibbs, G.L.

    1984-04-01

    The present study attempted to determine the relative role of the peripheral and central nervous system in the production of morphine-induced or radiation-induced locomotor hyperactivity of the mouse. Toward this end, we used a quaternary derivative of an opiate antagonist (naltrexone methobromide), which presumably does not cross the blood-brain barrier. Quaternary naltrexone was used to challenge the stereotypic locomotor response observed in these mice after either an i.p. injection of morphine or exposure to 1500 rads /sup 60/Co. The quaternary derivative of naltrexone reversed the locomotor hyperactivity normally observed in the C57BL/6J mouse after an injection of morphine. It also significantly attenuated radiation-induced locomotion. The data reported here support the hypothesis of endorphin involvement in radiation-induced and radiogenic behaviors. However, these conclusions are contingent upon further research which more fully evaluates naltrexone methobromide's capacity to cross the blood-brain barrier.