Sateesha Sb, Rajamma Aj, Narode Mk, Vyas Bd
Department of Pharmaceutics, Nargund College of Pharmacy, Bangalore 560 085, India.
J Young Pharm. 2010 Jul;2(3):229-33. doi: 10.4103/0975-1483.66793.
The matrix tablets of diltiazem hydrochloride were prepared by direct compression using hydroxypropyl methyl cellulose (HPMC) and various amounts (2.5%, 5.0%, 10% and 20%) of citric acid, malic acid and succinic acid. The characterization of physical mixture of drug and organic acids was performed by Infra-red spectroscopy. An organic acid was incorporated to set up a system bringing about gradual release of this drug. The influence of organic acids on the release rate were described by the Peppas equation: M (t) /M(∞) = Kt (n) and Higuchi's equation: Q (t) = K(1)t(1/2). The addition of organic acids and the pH value of medium could notably influence the dissolution behavior and mechanism of drug-release from matrices. Increasing amounts of organic acid produced an increase in drug release rate, which showed a good linear relationship between contents of organic acid and drug accumulate release (%) in phosphate buffer, pH 7.4. The drug release increased significantly (P < 0.05) with use of succinic acid in tablet formulation. Increasing amounts of succinic acid above 10% produced decreasing values of n and increasing values of k, in a linear relationship, which indicated there was a burst release of drug from the matrix. Optimized formulations are found to be stable upon 3-month study.
采用羟丙基甲基纤维素（HPMC）以及不同用量（2.5%、5.0%、10%和20%）的柠檬酸、苹果酸和琥珀酸，通过直接压片法制备盐酸地尔硫䓬骨架片。采用红外光谱法对药物与有机酸的物理混合物进行表征。加入有机酸以建立一个能使该药物逐步释放的体系。用Peppas方程：M(t)/M(∞)=Kt(n)和Higuchi方程：Q(t)=K(1)t(1/2)描述有机酸对释放速率的影响。有机酸的加入和介质的pH值可显著影响药物从骨架片中的溶出行为和释放机制。有机酸用量增加会使药物释放速率提高，在pH 7.4的磷酸盐缓冲液中，有机酸含量与药物累积释放率（%）之间呈现良好的线性关系。在片剂配方中使用琥珀酸时，药物释放显著增加（P<0.05）。当琥珀酸用量超过10%时，n值降低，k值呈线性增加，这表明药物从骨架片中出现突释。经3个月研究发现优化后的制剂具有稳定性。
