Department of Pharmaceutical Sciences and Pharmaceutics, Applied Science University, Amman, Jordan.
Drug Dev Ind Pharm. 2011 Jul;37(7):798-808. doi: 10.3109/03639045.2010.545068. Epub 2011 Jan 20.
The aim of this study was to evaluate matrix tablets containing different ratios of Carbopol(®) 971P (CP) to low-viscosity sodium alginate (SA) and assess their suitability for pH-independent controlled drug release.
Two processing methods (physical mixing, PM and spray-drying, SD) were applied before compaction and the release from corresponding matrices was compared. The release from CP-SA PM matrices was also investigated using three model drugs (paracetamol, salicylic acid, and verapamil HCl) and two dissolution media (0.1 N HCl or phosphate buffer, pH = 6.8), and the release rate, mechanism, and pH-dependence were characterized by fitting of Higuchi and Peppas models, and evaluation of similarity factor. Furthermore, swelling behavior of CP-SA matrix tablets was studied for evaluating its impact on drug release.
The processing method (SD or PM) markedly affected the drug release from CP-SA matrices. ANOVA tests showed significant effects of the CP:SA ratio and drug type on the release rate (expressed by the constant, K(H), from Higuchi model) and of the dissolution medium on the release mechanism (expressed by the exponent, n, from Peppas model). Similarity factor (f₂) indicated that the CP:SA ratios ≥ 25:75 and ≥ 50:50 were suitable for pH-independent release of paracetamol and salicylic acid, respectively, although for verapamil HCl, the matrix with low CP:SA ratio (0:100) showed remarkably reduced pH-dependence of release. Swelling parameters (water uptake and mass loss) were significantly changed with experimental variables (CP:SA ratio, medium, and time) and were in good correlation with drug release.
Matrix tablets based on CP and SA form a potentially useful versatile system for pH-independent controlled drug release.
本研究旨在评估含有不同比例 Carbopol(®) 971P (CP) 和低粘度海藻酸钠 (SA) 的基质片剂，并评估其在 pH 无关型控制药物释放中的适用性。
在压片前应用两种加工方法（物理混合，PM 和喷雾干燥，SD），并比较相应基质的释放情况。还使用三种模型药物（对乙酰氨基酚、水杨酸和盐酸维拉帕米）和两种溶解介质（0.1 N HCl 或磷酸盐缓冲液，pH = 6.8）研究 CP-SA PM 基质片的释放情况，并通过 Higuchi 和 Peppas 模型拟合以及相似因子评价来表征释放速率、机制和 pH 依赖性。此外，还研究了 CP-SA 基质片剂的溶胀行为，以评估其对药物释放的影响。
加工方法（SD 或 PM）显著影响 CP-SA 基质的药物释放。方差分析表明 CP:SA 比和药物类型对 Higuchi 模型中释放速率（常数 K(H)）有显著影响，而溶解介质对 Peppas 模型中释放机制（指数 n）有显著影响。相似因子（f₂）表明，CP:SA 比≥25:75 和≥50:50 分别适合于对乙酰氨基酚和水杨酸的 pH 无关释放，尽管对于盐酸维拉帕米，低 CP:SA 比（0:100）的基质显示出显著降低的释放 pH 依赖性。溶胀参数（吸水率和质量损失）随实验变量（CP:SA 比、介质和时间）显著变化，与药物释放有良好的相关性。
基于 CP 和 SA 的基质片剂形成了一种潜在有用的多功能系统，可用于 pH 无关型控制药物释放。
