Farhana S Ayesha, Shantakumar S M, Narasu Laxmi
Department of Pharmaceutics, V.L. College of Pharmacy, Raichur, Karnataka, India 584103.
Curr Drug Deliv. 2009 Jul;6(3):238-48. doi: 10.2174/156720109788680840.
The objective of the present study was to develop sustained release formulation of Diltiazem hydrochloride (DH) using biodegradable polymers. For this purpose microcapsules embedded Diltiazem hydrochloride were prepared using chitosan alone and also by incorporating some co polymers like methyl cellulose (MC), sodium carboxy methyl cellulose (SCMC) and poly vinyl pyrollidone (PVP) by employing complex emulsion method of microencapsulation. Glutaraldehyde saturated toluene solution is used as cross linking agent. Microcapsules were prepared in various core: coat ratios to know the effect of polymer and co polymers on drug release. Overall eight formulations were prepared and evaluated for flow behaviour, sieve analysis, drug entrapment efficiency, in vitro dissolution studies, stability studies, including scanning electron microscopy. The resulting microcapsules were discrete, large, spherical and also free flowing. The drug content in all the batches of microcapsules was found to be uniform. The release was depended on core: coat ratio and nature of the polymers. FTIR analysis revealed chemical integrity between diltiazem hydrochloride (DH), chitosan and between the copolymers. Among the three copolymers used methyl cellulose retarded the drug release more than the other two, hence the same formulation was subjected for in vivo studies. The drug release from the microcapsules was found to be following non fickian diffusion. Mechanism of drug release was diffusion controlled first order kinetics. Drug diffusion co efficient and correlation co efficient were also assessed using various mathematical models. In vivo result analysis of pharmacokinetic parameters revealed that t max of reference and test formulations were the same. From the study it was concluded that, sustained release Diltiazem hydro chloride microcapsules could be achieved with success using chitosan alone and also in combination with other biodegradable polymers.
本研究的目的是使用可生物降解聚合物开发盐酸地尔硫䓬（DH）的缓释制剂。为此，采用微囊化的复乳法，单独使用壳聚糖以及加入一些共聚物如甲基纤维素（MC）、羧甲基纤维素钠（SCMC）和聚乙烯吡咯烷酮（PVP）制备了包埋盐酸地尔硫䓬的微囊。用戊二醛饱和甲苯溶液作为交联剂。制备了不同核芯：包衣比例的微囊，以了解聚合物和共聚物对药物释放的影响。总共制备了八种制剂，并对其流动性、筛分分析、药物包封率、体外溶出度研究、稳定性研究（包括扫描电子显微镜）进行了评估。所得微囊离散、大、呈球形且流动性良好。发现所有批次微囊中的药物含量均一。药物释放取决于核芯：包衣比例和聚合物的性质。傅里叶变换红外光谱（FTIR）分析揭示了盐酸地尔硫䓬（DH）、壳聚糖以及共聚物之间的化学完整性。在所使用的三种共聚物中，甲基纤维素比其他两种更能延缓药物释放，因此对相同制剂进行了体内研究。发现微囊中药物的释放遵循非菲克扩散。药物释放机制为扩散控制的一级动力学。还使用各种数学模型评估了药物扩散系数和相关系数。药代动力学参数的体内结果分析表明，参比制剂和受试制剂的t max相同。从该研究得出结论，单独使用壳聚糖以及与其他可生物降解聚合物联合使用，均可成功制备盐酸地尔硫䓬缓释微囊。
