Barzegar-Jalali M, Hanaee J, Omidi Y, Ghanbarzadeh S, Ziaee S, Bairami-Atashgah R, Adibkia K
Biotechnology Research Center Tabriz University of Medical Science, Tabriz, Iran.
Drug Res (Stuttg). 2013 Feb;63(2):60-4. doi: 10.1055/s-0032-1331755. Epub 2013 Jan 21.
The aim of this study was to develop sustained release dosage forms of acetazolamide (ACZ) preparing its calcium alginate beads and matrix tablets. ACZ was incorporated into calcium alginate beads using microencapsulation method. Two methods were applied to prolong ACZ release rate. In the first method, the drug was incorporated into calcium alginate beads either alone or with various polymers in internal phase. The second method involved the preparation of matrix tablet from the beads benefiting direct compression method with or without various polymers in external phase. The release rate of these prepared formulations and an innovator's sustained-release capsule (Diamox®) were assessed. In-vitro dissolution studies revealed that the matrix tablets prepared by the second method containing NaCMC could sustain ACZ release properly and the drug released until 9 h. It was also found that several parameters such as concentration of sodium alginate, calcium chloride and ACZ; type and concentration of polymers; syringe needle size as well as distance between needle tip and surface of the calcium chloride could affect the properties of beads, matrix tablets and subsequently release profile. Preparation of polymer free beads, incorporation of polymers in internal phase of the beads and direct compression of the beads did not give sustained release property. Whereas, incorporation of NaCMC in the external phase of the beads in matrix tablets or in combination with alginate powder in directly compressed conventional tablets could produce dosage form with sustained release property similar to reference formulation.
本研究的目的是通过制备乙酰唑胺（ACZ）的海藻酸钙珠粒和基质片剂来开发其缓释剂型。采用微囊化方法将ACZ包封入海藻酸钙珠粒中。应用两种方法来延长ACZ的释放速率。第一种方法是将药物单独或与各种聚合物在内相中包封入海藻酸钙珠粒。第二种方法是由珠粒制备基质片剂，采用直接压片法，在外相中加入或不加入各种聚合物。评估了这些制备制剂和一种创新者的缓释胶囊（醋氮酰胺®）的释放速率。体外溶出研究表明，第二种方法制备的含羧甲基纤维素钠（NaCMC）的基质片剂能够适当地维持ACZ的释放，药物释放可持续9小时。还发现，海藻酸钠、氯化钙和ACZ的浓度；聚合物的类型和浓度；注射器针头尺寸以及针尖与氯化钙表面之间的距离等几个参数会影响珠粒、基质片剂的性质以及随后的释放曲线。制备无聚合物珠粒、在珠粒内相中加入聚合物以及对珠粒进行直接压片均未获得缓释性能。然而，在基质片剂的珠粒外相中加入NaCMC或在直接压片的常规片剂中与海藻酸盐粉末联合使用，可以制备出具有与参比制剂相似缓释性能的剂型。
