Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No. 103 Wenhua Road, Shenyang 110016, China.
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No. 103 Wenhua Road, Shenyang 110016, China.
Int J Pharm. 2012 Apr 15;426(1-2):21-28. doi: 10.1016/j.ijpharm.2011.12.053. Epub 2012 Jan 14.
The objective of this study was to prepare different venlafaxine hydrochloride sustained-release products and to elucidate the influence of composition of the coating film on the in vitro drug release profiles and in vivo pharmacokinetics. Pellets were prepared by a standardized process of extrusion/spheronization. A selected fraction size (0.8-1.0 mm diameter) of pellets of each formulation was coated with Eudragit NE30D or ethylcellulose (10 cps). Many efforts have been made to tailor drug release rate by choosing different coating materials, different percent of pore forming components and coating weight variation to achieve a desired sustained-release effect. The dissolution studies were performed and data were analyzed in terms of cumulative release as a function of time. The influence on the release of venlafaxine from sustained-release capsules was observed in dissolution media of different pH and gradient pH. Scanning electron microscope (SEM) micrographs revealed morphological changes of the pellet coating surface which were related to in vitro drug release profiles. The relative bioavailability for Formulation 1 and Formulation 2 was evaluated in six healthy beagle dogs after oral administration in a fast state using sustained-release capsules (Effexor XR) as a reference. The results suggested that Formulation 1 and Formulation 2 both had better bioavailability compared with Effexor XR. It could be found that there existed quite difference in the in vivo release and oral absorption performances, despite the similar in vitro drug release behavior for the two formulations. It might be attributable to complex in vivo environment and then variation in the release behavior. Thus differences in the film micro-structure and surface roughness caused by aqueous dispersion and organic solvent coating techniques strongly influence the in vivo release and oral absorption performances.
本研究的目的是制备不同的盐酸文拉法辛缓释产品，并阐明包衣膜组成对体外药物释放曲线和体内药代动力学的影响。采用挤出/滚圆的标准工艺制备微丸。对每个配方的微丸进行选择的粒径（直径 0.8-1.0 毫米）的分级，用 Eudragit NE30D 或乙基纤维素（10cps）进行包衣。通过选择不同的包衣材料、不同比例的成孔剂和包衣重量变化来调整药物释放速率，以达到所需的缓释效果，从而进行了许多努力。在不同 pH 值和梯度 pH 值的溶出介质中观察了缓释胶囊中文拉法辛的释放对缓释胶囊中文拉法辛释放的影响。扫描电子显微镜（SEM）照片显示了与体外药物释放曲线相关的丸芯包衣表面的形态变化。在快速状态下，以缓释胶囊（Effexor XR）为参比制剂，在 6 只健康比格犬中进行口服给药后，对配方 1 和配方 2 的相对生物利用度进行了评价。结果表明，配方 1 和配方 2 的生物利用度均优于 Effexor XR。可以发现，尽管两种制剂的体外药物释放行为相似，但体内释放和口服吸收性能存在明显差异。这可能归因于复杂的体内环境，然后释放行为发生变化。因此，水相分散和有机溶剂包衣技术引起的薄膜微观结构和表面粗糙度的差异强烈影响体内释放和口服吸收性能。
