Preparation and in vitro & in vivo evaluation of cephalexin matrix tablets

The purpose of the study is to develop cephalexin controlled-release matrix tablets by using lower proportions of release retardant polymer and to establish their in vitro & in vivo correlation. Tablets were compressed by incorporating polymers in a matrix form along with drug which prolong the drug release. Twelve formulations were prepared by mixing ethyl cellulose (EC) and hydroxypropyl methylcellulose (HPMC) (three different viscosity grades) in various proportions. F-1 to F-4 formulations were prepared by incorporating drug, HPMC K4M and ethyl cellulose in 100 : 5 : 5, 100 : 10 : 5, 100 : 15 : 5 and 100 : 20 : 5; similarly, F-5 to F-8 were prepared with HPMC K15M; and F-9 to F-12 were prepared with HPMC K100M using a wet granulation process maintained same proportions, along with drug and EC. Tablets were evaluated for their pre-compression and post-compression characteristics and they were found to be in limits. From the dissolution testing, F-4 showed 100.34% medicament release in 12 h. In vivo studies were conducted on rabbit and pharmacokinetic parameters of the optimized formulation were evaluated using HPLC method. It was found that matrix tablets showed increased t1/2 and decreased Kel. The design signified that the drug release rate from tablets was influenced by the small proportion (around 7% of a tablet weight) of polymer mixture and it controlled 100% medicament release upto 12 h effectively with the low grade viscosity of HPMC combination, with good in vitro & in vivo correlation.

本研究旨在以低比例的缓释阻滞聚合物（release retardant polymer）制备头孢氨苄（cephalexin）控释骨架片（controlled-release matrix tablets），并建立其体内外相关性（in vitro & in vivo correlation）。通过将药物与聚合物以骨架形式共混以延长药物释放，进而制备该片剂。本研究采用湿法制粒工艺，以不同比例混合乙基纤维素（ethyl cellulose, EC）与三种不同黏度等级的羟丙基甲基纤维素（hydroxypropyl methylcellulose, HPMC），共制备12种处方。F-1至F-4处方按照药物、HPMC K4M与乙基纤维素的质量比分别为100:5:5、100:10:5、100:15:5及100:20:5进行制备；同理，F-5至F-8处方采用HPMC K15M制备，F-9至F-12处方则采用HPMC K100M，且均保持上述投料比例，与药物、乙基纤维素共同制粒。对所得片剂分别开展压前与压后质量特性考察，结果显示各项指标均符合规定限度。溶出度测试结果表明，F-4处方在12小时内的药物累积释放率达100.34%。以家兔为实验对象开展体内研究，采用高效液相色谱法（HPLC）对优化处方的药代动力学参数进行测定。研究发现，该骨架片的药物半衰期（t1/2）显著延长，消除速率常数（Kel）明显降低。本研究设计证实，仅需占片重约7%的少量聚合物混合物即可有效调控药物释放速率；采用低黏度等级的羟丙基甲基纤维素复配体系，可在12小时内实现100%的药物平稳释放，且具备良好的体内外相关性。