Kiortsis S, Kachrimanis K, Broussali Th, Malamataris S
Department of Pharmaceutical Technology, School of Pharmacy, University of Thessaloniki, Thessaloniki, Greece.
Eur J Pharm Biopharm. 2005 Jan;59(1):73-83. doi: 10.1016/j.ejpb.2004.05.004.
The effects of component nature, proportion and processing on the release rate and mechanism were investigated for tablets comprising drug, cellulosic polymer and hydrophobic components. Four drugs differing in solubility (diclofenac sodium, ibuprofen, naproxen and indomethacin), two cellulosic polymers (HPC and HPMC) and hydrophobic Emvelop were used in two levels of mass fraction and weight ratio of drug:carrier and of cellulosic-hydrophobic component. Compression was applied after granulation or physical mixing. Drug release was evaluated in pH 6.5 phosphate buffer BP and elucidation of the release mechanism was attempted by fitting kinetic models. Statistical significance of the effects of formulation variables on the release rate and mechanism expressed by the coefficient, k, and exponent, n, of the power law kinetic model, respectively, was evaluated by ANOVA. It was found that for the release mechanism most significant is the effect of drug solubility followed by cellulosic polymer type, mixing procedure and drug mass fraction. Significant interaction between drug solubility and type of cellulosic polymer indicated that alteration in the swelling of HPMC and HPC is caused by the drug solubility. Weight ratio of cellulosic-hydrophobic component does not affect the release mechanism, but only the release rate. Similarly, for the release rate most significant was found the effect of drug solubility, followed by cellulosic polymer type, weight ratio of cellulosic-hydrophobic component, mixing method and drug mass fraction. Also significant were the interactions of drug solubility with the type and proportion of the cellulosic polymer and the processing applied. Depending on the drug solubility and type of polymer present, wet granulation can increase or decrease the release rate.
研究了药物、纤维素聚合物和疏水性成分组成的片剂中，成分性质、比例和加工工艺对释放速率及机制的影响。选用了四种溶解度不同的药物（双氯芬酸钠、布洛芬、萘普生和吲哚美辛）、两种纤维素聚合物（羟丙基纤维素和羟丙甲纤维素）以及疏水性包材Emvelop，采用两种质量分数和两种药物与载体、纤维素与疏水性成分的重量比。制粒或物理混合后进行压片。在pH 6.5的磷酸盐缓冲液BP中评估药物释放，并通过拟合动力学模型试图阐明释放机制。通过方差分析评估配方变量对幂律动力学模型的系数k和指数n所表示的释放速率及机制的影响的统计学显著性。结果发现，对于释放机制，最显著的影响因素是药物溶解度，其次是纤维素聚合物类型、混合工艺和药物质量分数。药物溶解度与纤维素聚合物类型之间的显著相互作用表明，羟丙甲纤维素和羟丙基纤维素溶胀的改变是由药物溶解度引起的。纤维素与疏水性成分的重量比不影响释放机制，但仅影响释放速率。同样，对于释放速率，最显著的影响因素是药物溶解度，其次是纤维素聚合物类型、纤维素与疏水性成分的重量比、混合方法和药物质量分数。药物溶解度与纤维素聚合物的类型、比例以及所采用的加工工艺之间的相互作用也很显著。根据药物溶解度和存在的聚合物类型，湿法制粒可提高或降低释放速率。
