Nokhodchi Ali, Hassan-Zadeh Davoud, Monajjem-Zadeh Farnaz, Taghi-Zadeh Nita
Medway School of Pharmacy, The University of Kent and Greenwich, Central Av., Chatham Maritime ME4 4TB Kent, UK.
Acta Pharm. 2008 Jun;58(2):151-62. doi: 10.2478/v10007-008-0004-5.
Various methods are available to formulate water soluble drugs into sustained release dosage forms by retarding the dissolution rate. One of the methods used to control drug release and thereby prolong therapeutic activity is to use hydrophilic and lipophilic polymers. In this study, the effects of various polymers such as hydroxypropyl methylcellulose (HPMC), ethylcellulose (EC) and sodium carboxymethylcellulose (CMC) and surfactants (sodium lauryl sulphate, cetyltrimethylammonium bromide and Arlacel 60) on the release rate of captopril were investigated. The results showed that an increase in the amount of HPMC K15M resulted in reduction of the release rate of captopril from these matrices. When HPMC was partly replaced by NaCMC (the ratio of HPMC/NaCMC was 5:1), the release rate of the drug significantly decreased. However, there was no significant difference in release rate of captopril from matrices produced with ratios of 5:1 and 2:1 of HPMC/NaCMC. The presence of lactose in matrices containing HPMC and NaCMC increased the release rate of captopril. It was interesting to note that although partial replacement of HPMC by EC reduced the release rate of the drug (ratio of HPMC/EC 2:1), the release rate was increased when the ratio of HPMC/EC was reduced to 1:1. The effects of various surfactants on the release rate of captopril from HPMC/EC (1:1) matrices were also investigated. The results showed that the surfactants did not significantly change the release rate of the drug. Release data were examined kinetically and the ideal kinetic models were estimated for the drug release. The kinetic analysis of drug release data from various formulations showed that incorporation of surfactants in HPMC/EC matrices did not produce a zero-order release pattern.
有多种方法可通过延缓溶解速率将水溶性药物制成缓释剂型。用于控制药物释放从而延长治疗活性的方法之一是使用亲水性和疏水性聚合物。在本研究中，研究了各种聚合物，如羟丙基甲基纤维素（HPMC）、乙基纤维素（EC）和羧甲基纤维素钠（CMC）以及表面活性剂（十二烷基硫酸钠、十六烷基三甲基溴化铵和司盘60）对卡托普利释放速率的影响。结果表明，HPMC K15M用量的增加导致卡托普利从这些基质中的释放速率降低。当HPMC被NaCMC部分替代（HPMC/NaCMC比例为5:1）时，药物的释放速率显著降低。然而，HPMC/NaCMC比例为5:1和2:1的基质中卡托普利的释放速率没有显著差异。含有HPMC和NaCMC的基质中乳糖的存在增加了卡托普利的释放速率。有趣的是，虽然用EC部分替代HPMC降低了药物的释放速率（HPMC/EC比例为2:1），但当HPMC/EC比例降至1:1时，释放速率增加。还研究了各种表面活性剂对卡托普利从HPMC/EC（1:1）基质中释放速率的影响。结果表明，表面活性剂没有显著改变药物的释放速率。对释放数据进行动力学检查，并估算药物释放的理想动力学模型。对各种制剂的药物释放数据进行的动力学分析表明，在HPMC/EC基质中加入表面活性剂不会产生零级释放模式。
