Gavini Elisabetta, Sanna Vanna, Juliano Claudia, Bonferoni Maria Cristina, Giunchedi Paolo
Dipartimento di Scienze del Farmaco, Università di Sassari, via Muroni 23/a, 07100 Sassari, Italy.
AAPS PharmSciTech. 2002;3(3):E20. doi: 10.1208/pt030320.
The aim of the study was the development of mucoadhesive vaginal tablets designed for the local controlled release of acriflavine, an antimicrobial drug used as a model. The tablets were prepared using drug-loaded chitosan microspheres and additional excipients (methylcellulose, sodium alginate, sodium carboxymethylcellulose, or Carbopol 974). The microspheres were prepared by a spray-drying method, using the drug to polymer weight ratios 1:1 and 1:2 and were characterized in terms of morphology, encapsulation efficiency, and in vitro release behavior, as MIC (Minimum Inhibitory Concentration), MBC (Minimum Bacterial Concentration), and killing time (KT). The tablets were prepared by direct compression, characterized by in vitro drug release and in vitro mucoadhesive tests. The microparticles have sizes of 4 to 12 microm; the mean encapsulation yields are about 90%. Acriflavine, encapsulated into the polymer, maintains its antibacterial activity; killing time of the encapsulated drug is similar to that of the free drug. In vitro release profiles of tablets show differences depending on the excipient used. In particular Carbopol 974, which is highly cross-linked, is able to determine a drug-controlled release from the matrix tablets for more than 8 hours. The in vitro adhesion tests, carried out on the same formulation, show a good adhesive behavior. The formulation containing microspheres with drug to polymer weight ratios of 1:1 and Carbopol 974 is characterized by the best release behavior and shows good mucoadhesive properties. These preliminary data indicate that this formulation can be proposed as a mucoadhesive vaginal delivery system for the controlled release of acriflavine.
本研究的目的是开发用于局部控释吖啶黄的粘膜粘附阴道片，吖啶黄是一种用作模型的抗菌药物。片剂采用载药壳聚糖微球和其他辅料（甲基纤维素、海藻酸钠、羧甲基纤维素钠或卡波姆974）制备。微球通过喷雾干燥法制备，使用药物与聚合物的重量比为1:1和1:2，并根据形态、包封效率和体外释放行为进行表征，如最低抑菌浓度（MIC）、最低杀菌浓度（MBC）和杀菌时间（KT）。片剂通过直接压片法制备，通过体外药物释放和体外粘膜粘附试验进行表征。微粒尺寸为4至12微米；平均包封率约为90%。包裹在聚合物中的吖啶黄保持其抗菌活性；包裹药物的杀菌时间与游离药物相似。片剂的体外释放曲线因所用辅料而异。特别是高度交联的卡波姆974能够使基质片剂中的药物控释超过8小时。对相同配方进行的体外粘附试验显示出良好的粘附行为。含有药物与聚合物重量比为1:1的微球和卡波姆974的配方具有最佳的释放行为，并显示出良好的粘膜粘附性能。这些初步数据表明，该配方可作为一种用于吖啶黄控释的粘膜粘附阴道给药系统。
