Optimization of therapy by chronopharmacology requires knowledge of rhythmic manifestations of disease activity and chronopharmacokinetic data of the drugs prescribed. Rhythmic functioning of the cardiovascular system in healthy and diseased subjects is manifested as circadian rhythms in blood pressure, cardiac output, heart rate, etc. The disposition of several cardiovascular drugs in man has been reported to be time-dependent. This study reports the effect of time of administration on the disposition of pentoxifylline. Twelve healthy volunteers were treated with 400 mg pentoxifylline orally at 0100, 0700, 1300 and 1900 h in a randomized crossover Latin-square design with a wash-out period of one week. Serum samples were analysed for unchanged pentoxifylline by HPLC. Pharmacokinetic parameters were calculated using a model-independent method. The mean values of various pharmacokinetic parameters after drug treatment at these times were, respectively: maximum plasma concentration (Cmax) 485+/-174, 646+/-175, 735+/-271 and 781+/-217 ng mL(-1); time to reach the maximum plasma concentration (Tmax) 1.90+/-0.39, 1.66+/-0.4, 1.31+/-0.41 and 1.32+/-0.44 h, mean residence time (MRT) 3.8+/-0.8, 2.9+/-0.5, 2.9+/-0.4 and 2.7+/-0.3 h, elimination half-life (t1/2) 1.93+/-0.86, 1.23+/-0.3, 1.39+/-0.3 and 1.23+/-0.18 h and volume of distribution at steady state (VdSS/f) 11991+/-4862, 8823+/-3484, 8275+/-2357 and 7063+/-1950 mL kg(-1). The mean Cmax value was significantly (P < 0.05) lower after drug administration at 0100 h than after other time-points whereas mean Tmax, MRT, VdSS/f and t1/2 values were significantly (P < 0.05) higher. These variations might be because of time-dependent changes in absorption and biliary excretion of pentoxifylline and should be borne in mind when designing sustained action dosage forms for the drug.
Glycyrrhetinic acid (GA) is an anti-inflammatory drug with potential for development. However, the poor solubility of GA in water leads to extremely low bioavailability, which limits its clinical applications. Solid dispersions have become some of the most effective strategies for improving the solubility of poorly soluble drugs. Soluplus®, a non-cytotoxic amphiphilic solubilizer, significantly improves the solubility of BCS II drugs and improves the bioavailability of insoluble drugs. l-arginine (L-Arg) can be used as a small molecular weight excipient to assist in improving the solubility of insoluble drugs. In this study, we developed a new formulation for oral administration by reacting GA and L-Arg to form salts by co-solvent evaporation and then adding the polymer-solvent Soluplus® with an amphiphilic chemical structure to prepare a solid dispersion GA-SD. The chemical and physical properties of GA-SD were characterized by DLS, TEM, XRD, FT-IR and TG. The anti-inflammatory activity of GA-SD was verified by LPS stimulation of RAW 267.5 cells simulating a cellular inflammation model, TPA-induced ear edema model in mice, and ethanol-induced gastric ulcer model. The results showed that the amide bond and salt formation of GA-SD greatly improved GA solubility. GA-SD effectively improved the anti-inflammatory effect of free GA in vivo and in vitro, and GA-SD had no significant effect on liver and kidney function, no significant tissue toxicity, and good biosafety. In conclusion, GA-SD with L-Arg and Soluplus® is an effective method to improve the solubility and bioavailability of GA. As a safe and effective solid dispersion, it is a promising anti-inflammatory oral formulation and provides some references for other oral drug candidates with low bioavailability.
Sumatriptan succinate is a 5-HT1B/1D receptor agonist which has well established efficacy in treating migraine. The main objective of the study was to formulate Oral Fast Disintegrating Films (ODF) and Oral Fast Disintegrating Tablets (ODT) to achieve a better dissolution rate and further improving the bioavailability of the drug. ODFs were prepared by solvent casting method using film forming polymers like HPMC – E15,5cps,50cps in different ratios & prepared batches of films were evaluated for the drug content, film thickness, disintegration time and in vitro dissolution studies. Among the prepared formulation F7 containing HPMC – 50cps (drug: polymer ratios = 1:1) was found to be best formulations which releases 98.2±1.1of the drug within 17±0.02 sec. ODTs prepared by direct compression method using in different concentrations of super-disintegrants. The prepared formulation T12 (combination of disintegrants) containing CP + CCS (6%) was considered to be the best formulation, which releases up to 100±0.38% of the drug in 23±0.75 sec, respectively. Based on these results, it is suggested that ODFs have faster disintegration time and drug release than ODTs.
Aim & Background: Ornidazole an antimicrobial drug used to treat certain types of vaginal, urinary tract, and interstitial infections. The objective of this study is to formulate and evaluate the dental inserts by using drug candidate to sustained release of drug to improve patient compliance, reduce dosing frequency, better therapeutic efficacy and fewer side effects, reduce the risk of dose dumping as well as also to avoid the first-pass metabolism. Materials & Method: The dental inserts were prepared using various polymers and in combination with the different ratios of polymers. The evaluation parameters like thickness, drug content, content uniformity, moisture reuptake, weight variation, swelling studies, and erosion studies of the optimized inserts were studied. The in-vivo studies were conducted for determining the reduction of pocket depth in human volunteers. Results: The system containing ethylcellulose and hydroxyl methyl propyl cellulose K100M (4:1) formulation F6 was optimized because drug release was sustained up to 120 hrs with respect to other formulations. Optimized formulation follows first-order kinetics and Peppas release kinetics via fickian diffusion. There was no swelling, itching, irritation and the reduction of pocket depth was absorbed in in-vivo studies. Conclusion: The study concluded that dental inserts can extend the release of Ornidazole for many hours also enhanced bioavailability, further it also helps in avoiding the first-pass effect. The observations of in vivo studies were, there was no itching, irritation, swelling, and reduction in pocket depth was observed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.