Design and In Vitro Performance Evaluation of Purified Microparticles of Pravastatin Sodium for Intestinal Delivery

Abstract

Abstract. The purpose of research was to develop a mucoadhesive multiparticulate sustained drug delivery system of pravastatin sodium, a highly water-soluble and poorly bioavailable drug, unstable at gastric pH. Mucoadhesive microparticles were formulated using eudragit S100 and ethyl cellulose as mucoadhesive polymers. End-step modification of w/o/o double emulsion solvent diffusion method was attempted to improve the purity of the product, that can affect the dose calculations of sustained release formulations and hence bioavailability. Microparticles formed were discrete, free flowing, and exhibited good mucoadhesive properties. DSC and DRS showed stable character of drug in microparticles and absence of drug polymer interaction. The drug to polymer ratio and surfactant concentration had significant effect on mean particle size, drug release, and entrapment efficiency. Microparticles made with drug: eudragit S100 ratio of 1:3 (F6) exhibited maximum entrapment efficiency of 72.7% and ex vivo mucoadhesion time of 4.15 h. In vitro permeation studies on goat intestinal mucosa demonstrated a flux rate (1,243 μg/cm 2 /h) that was 169 times higher than the flux of pure drug. The gastric instability problem was overcome by formulating the optimized microparticles as enteric-coated capsules that provided a sustained delivery of the highly water-soluble drug for 12 h beyond the gastric region. The release mechanism was identified as fickian diffusion (n=0.4137) for the optimized formulation F6. Conclusively, a drug delivery system was successfully developed that showed delayed and sustained release up to 12 h and could be potentially useful to overcome poor bioavailability problems associated with pravastatin sodium.

Bioadhesive vaginal tablets containing spray dried microspheres loaded with clotrimazole for treatment of vaginal Candidiasis

“…However, the melting endotherm of M4 was not as sharp as that of pure CTZ, which may be a result of the presence of polymers and the change in heat capacity of the polymer as it undergoes transition from the glassy to liquid state during microsphere formation (20).…”

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“…This melting endotherm was also observed for formulation (TBHMs V) at 197.58 °C, indicating the absence of drug and polymer changes. However, the melting endotherm of formulation (TBHMs V) was not as sharp as that of pure TBH, which may be a result of the presence of polymers and the change in heat capacity of the polymer as it undergoes transition from the glassy to liquid state during microsphere formation 62 .…”

Formulation development and statistical optimization of ibuprofen-loaded polymethacrylate microspheres using response surface methodology

“…M t /M α is the fraction of the drug release at time t and n is the release exponent. When n is 0.45 it means Fickian diffusion, > 0.45 < 0.89 for non-Fickian diffusion, 0.89 for case II release, and >0.89 for super case II type release (Garg and Pathak, 2011).…”