Department of Pharmaceutics, Rajiv Academy for Pharmacy, Mathura, India.
AAPS PharmSciTech. 2011 Jun;12(2):673-82. doi: 10.1208/s12249-011-9626-x. Epub 2011 May 19.
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.
本研究旨在开发一种具有高度水溶性和较差生物利用度的药物普伐他汀钠的粘膜粘附型多颗粒持续药物递送系统，该药物在胃 pH 下不稳定。采用 Eudragit S100 和乙基纤维素作为粘膜粘附性聚合物来制备粘膜粘附型微球。尝试采用 w/o/o 双乳液溶剂扩散法的终步修饰来提高产品的纯度，这会影响持续释放制剂的剂量计算，从而影响生物利用度。所形成的微球是离散的、自由流动的，并表现出良好的粘膜粘附性能。DSC 和 DRS 表明药物在微球中的稳定性以及药物-聚合物相互作用的不存在。药物与聚合物的比例和表面活性剂浓度对平均粒径、药物释放和包封效率有显著影响。药物：Eudragit S100 比例为 1:3（F6）的微球表现出最大的包封效率为 72.7%和体外粘膜粘附时间为 4.15 h。在山羊肠黏膜上的体外渗透研究表明，通量（1,243μg/cm(2)/h）比纯药物的通量高 169 倍。通过将优化的微球制成肠溶包衣胶囊来克服胃不稳定问题，该胶囊可在胃区外提供高度水溶性药物的持续释放达 12 h。释放机制被确定为优化配方 F6 的菲克扩散（n = 0.4137）。总之，成功开发了一种药物递送系统，该系统可延迟和持续释放长达 12 h，可能有助于克服与普伐他汀钠相关的生物利用度差的问题。
