methylcellulose and vinpocetine

In the present work, to maintain a suitable blood level of vinpocetine (VP) for a long period of time, VP-cyclodextrin-tartaric acid multicomponent complexes were prepared and formulated in hydroxypropylmethylcellulose matrix tablets. In vitro and in vivo performances of these formulations were investigated over a VP immediate release dosage form. Solubility studies were performed to evaluate the drug pH solubilization profile and to assess the effect of multicomponent complexation on VP solubility. The drug release process was investigated using United States Pharmacopeia apparatus 3 and a comparative oral pharmacokinetic study was subsequently undertaken in rabbits. Solubility studies denoted the pH-solubility dependence of VP and solubility improvement attained by complexation. Dissolution results showed controlled and almost complete release behavior of VP over a 12-h period from complex hydroxypropylmethylcellulose-based formulations. A clear difference between the pharmacokinetic patterns of VP immediate release and VP complex-based formulations was revealed. The area under the plasma concentration-time curve after oral administration of complex-based formulations was 2.1-2.9 times higher than that for VP immediate release formulation. Furthermore, significant differences found for mean residence time, elimination half-life, and elimination rate constant values corroborated prolonged release of VP from complex-based formulations. These results suggest that the oral bioavailability of VP was significantly improved by both multicomponent complexation and controlled release delivery strategies.

Topics: Administration, Oral; Animals; Area Under Curve; beta-Cyclodextrins; Biological Availability; Chromatography, High Pressure Liquid; Delayed-Action Preparations; Drug Compounding; Half-Life; Hydrogen-Ion Concentration; Metabolic Clearance Rate; Methylcellulose; Molecular Weight; Rabbits; Reproducibility of Results; Solubility; Tablets; Tartrates; Therapeutic Equivalency; Vinca Alkaloids; Water

The objective of this study was to investigate the effect of multicomponent complexation (MCC) of vinpocetine (VP), a poorly soluble base-type drug, with beta-cyclodextrin (betaCD), sulfobutylether beta-cyclodextrin (SBEbetaCD), tartaric acid (TA), polyvinylpyrrolidone (PVP) and hydroxypropylmethylcellulose (HPMC), on the design of controlled release hydrophilic HPMC tablets and to evaluate their in vitro release profiles by a pH gradient method. Multicomponent complexation led to enhanced dissolution properties of VP both in simulated gastric and intestinal fluids, and became possible the development of HPMC tablet formulations with more independent pH dissolution profiles. Drug release process was investigated experimentally using USP apparatus 3 and by means of model-independent parameters. Responses studied included similarity of dissolution profiles, time for 60% of the drug to dissolve (T(60%)), percent of VP released after 7 h (PD(7 h)) and the dissolution efficiency parameter at 12 h (DE(12 h)). Influence of multicomponent complexation was proved to increase the release of VP from HPMC tablets and superior PD(7 h) and DE(12 h) values were obtained in formulations containing VP-CD-TA complexes. Results supported the use of HPMC matrices to provide a useful tool in retarding the release of VP and that dissolution characteristics of the drug may be modulated by multicomponent complexation in these delivery systems, suggesting an improvement on VP bioavailability.

Topics: beta-Cyclodextrins; Body Fluids; Drug Compounding; Gastric Mucosa; Humans; Hydrogen-Ion Concentration; Hypromellose Derivatives; Intestinal Mucosa; Kinetics; Methylcellulose; Models, Biological; Solubility; Tablets, Enteric-Coated; Tartrates; Vinca Alkaloids

Vinpocetine is a pH-dependent experimental drug with a short half-life. The sustained-release matrix tablets of vinpocetine were prepared by direct compression using hydroxypropyl methylcellulose (HPMC) and different amounts of citric acid to set up a system bringing about gradual release of this drug. In order to investigate the influence of citric acid and the pH value of medium on the drug release from HPMC matrix tablets, an in vitro release test was carried out in either phosphate buffer pH 6.8 [0.5% sodium dodecyl sulfate (SDS)] for 12 hr or in 0.1 N HCl (0.5% SDS) (0-2 hr) and phosphate buffer pH 6.8 (0.5% SDS) (2-12 hr). Dissolution curves were described by the Peppas equation: M(t)/M(inf)=ktn, and the influence of citric acid on the dissolution mechanism was estimated according to the regression parameter-n and k values. The addition of citric acid and the pH value of medium could notably influence the dissolution behavior and mechanism of drug-release from matrices. Increasing the amounts of citric acid produced an increase in drug release rate, which showed a good linear relationship between contents of citric acid and drug accumulate release (%) in phosphate buffer pH 6.8 (0.5% SDS) (r>0.99). Moreover, a higher drug release rate could be found in 0.1 N HCl (0.5% SDS) than that in phosphate buffer pH 6.8 (0.5% SDS) during the first two hours when the content of citric acid added to matrices was lower than 45 mg/tab., but no significant difference could be found when the content of citric acid was above that value. Increasing amounts of citric acid produced decreasing values of n and increasing values of k, in a linear relationship, which indicated there was a trend favoring the mechanism of diffusion with the addition of increasing quantities of citric acid.

Topics: Buffers; Citric Acid; Delayed-Action Preparations; Excipients; Hydrogen-Ion Concentration; Hypromellose Derivatives; Methylcellulose; Phosphates; Solubility; Tablets; Time Factors; Vinca Alkaloids