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基于卡拉胶和羟丙甲纤维素的 L-多巴胃滞留给药系统。

Gastroretentive drug delivery systems with L-dopa based on carrageenans and hydroxypropylmethylcellulose.

机构信息

Department of Pharmaceutical Technology and Biopharmaceutics, Pharmaceutical Faculty, Jagiellonian University, ul Medyczna 9, 30-688 Kraków, Poland.

出版信息

Int J Pharm. 2011 Feb 14;404(1-2):169-75. doi: 10.1016/j.ijpharm.2010.11.032. Epub 2010 Nov 21.

Abstract

A comprehensive study was conducted to investigate the effects of carrageenans, and hydroxypropylmethylcellulose (HPMC) on the properties of hydrodynamically balanced systems (HBS) containing L-dopa as a model drug. The novel integrated approach included measurements of: solvent uptake, erosion, apparent density and changes in the internal structure of dosage forms during dissolution test by means of a USP4 compatible MRI. Differences in water ingress into the matrices with pure carrageenans (ι, κ, λ) or low viscous HPMC, were detected by non-invasive magnetic resonance imaging. Matrices based on carrageenans subjected to rapid hydration and erosion, were not able to maintain satisfactory floating properties for a sufficiently long period of time. The application of carrageenans in mixtures with HMC promoted water uptake by HBS formulations. The effect produced by varying the polymer blend's composition on release of the L-dopa was also studied. Dissolution data was fitted to Korsmeyer-Peppas equation. For matrices containing mixtures of carrageenan and HPMC, the linear increase in the releasing rate constant, K, with the carrageenan content in the matrix was observed.

摘要

一项综合研究调查了卡拉胶和羟丙甲纤维素(HPMC)对含有左旋多巴作为模型药物的流体动力学平衡系统(HBS)性质的影响。新的综合方法包括:通过 USP4 兼容的 MRI 测量:溶剂摄取、侵蚀、表观密度和溶出试验过程中剂型内部结构的变化。通过非侵入性磁共振成像检测到纯卡拉胶(ι、κ、λ)或低粘性 HPMC 基质中水分进入的差异。基于卡拉胶的基质经历快速水合和侵蚀,无法在足够长的时间内保持令人满意的漂浮性能。在 HMC 混合物中应用卡拉胶促进了 HBS 配方的水分摄取。还研究了聚合物共混物组成变化对 L-多巴释放的影响。释放数据拟合到 Korsmeyer-Peppas 方程。对于含有卡拉胶和 HPMC 混合物的基质,观察到释放速率常数 K 随基质中卡拉胶含量的线性增加。

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