Dürig Thomas, Fassihi Reza
School of Pharmacy, Temple University, 3307 N. Broad Street, Philadelphia, PA 19140, USA.
J Control Release. 2002 Apr 23;80(1-3):45-56. doi: 10.1016/s0168-3659(01)00546-6.
The effect of ionic and non-ionic excipients and additives as modulators of swelling and erosion kinetics and verapamil HCl release from guar-based matrix tablets was investigated. Tablet dissolution, erosion and water uptake studies were carried out using a modified USP 23 Apparatus 2 method. The kinetics of gel strength and texture development were studied by textural analysis. Near linear drug release over 24 h was obtained from formulations containing water soluble, ionizable sodium chloride and glycine. The contribution of Fickian release to overall drug release was lowest for these formulations and was correlated with greater gel strength and lower water uptake in the early time period. For soluble sugars (lactose and sucrose) the Fickian contribution to overall drug release was large and associated with pronounced curvilinear profiles. Water uptake was greatest for these additives (450% in 6 h). The lowest water uptake and negligible matrix erosion was observed for microcrystalline cellulose. Release from this formulation was predominantly Fickian. It was found that the physico-chemical nature of added excipients significantly influences the release kinetics from guar-based formulations. Ionic, water soluble materials (sodium chloride, glycine) reduce initial hydration of the matrix and thus have the ability to limit the initial rapid diffusion of drug and to sustain near linear release over 24 h.
研究了离子型和非离子型辅料及添加剂作为瓜尔胶基骨架片溶胀和侵蚀动力学以及盐酸维拉帕米释放调节剂的作用。采用改良的美国药典23装置2法进行片剂溶出、侵蚀和吸水研究。通过质地分析研究凝胶强度和质地发展的动力学。含有水溶性、可离子化的氯化钠和甘氨酸的制剂在24小时内药物释放接近线性。这些制剂中菲克扩散释放对总药物释放的贡献最低，且与早期更高的凝胶强度和更低的吸水量相关。对于可溶性糖（乳糖和蔗糖），菲克扩散对总药物释放的贡献很大，且与明显的曲线轮廓相关。这些添加剂的吸水量最大（6小时内为450%）。微晶纤维素的吸水量最低，基质侵蚀可忽略不计。该制剂的释放主要是菲克扩散。研究发现，添加辅料的物理化学性质显著影响瓜尔胶基制剂的释放动力学。离子型水溶性材料（氯化钠、甘氨酸）减少了基质的初始水合作用，因此有能力限制药物的初始快速扩散，并在24小时内维持接近线性的释放。
