Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., 11562, Cairo, Egypt.
AAPS PharmSciTech. 2012 Sep;13(3):990-1004. doi: 10.1208/s12249-012-9823-2. Epub 2012 Jul 18.
Multiparticulate floating drug delivery systems have proven potential as controlled-release gastroretentive drug delivery systems that avoid the "all or none" gastric emptying nature of single-unit floating dosage forms. An objective of the presence investigation was to develop calcium silicate (CaSi)/calcium alginate (Ca-Alg)/hydroxypropyl methylcellulose (HPMC) mucoadhesive-floating beads that provide time- and site-specific drug release of alfuzosin hydrochloride (Alf). Beads were prepared by simultaneous internal and external gelation method utilizing 3(2) factorial design as an experimental design; with two main factors evaluated for their influence on the prepared beads; the concentration of CaSi as floating aid (X (1)) and the percentage of HPMC as viscosity enhancer and mucoadhesive polymer (X (2)), each of them was tested in three levels. Developed formulations were evaluated for yield, entrapment efficiency, particle size, surface topography, and buoyancy. Differential scanning calorimetry, Fourier transform infrared spectroscopy, in vitro drug release, as well as in vitro mucoadhesion using rat stomach mucosal membrane were also conducted. Percentage yield and entrapment efficiency ranged from 57.03% to 78.51% and from 49.78% to 83.26%, respectively. Statistical analysis using ANOVA proved that increasing the concentration of either CaSi or HPMC significantly increased the beads yield. Both CaSi and HPMC concentrations were found to significantly affect Alf release from the beads. Additionally, higher CaSi concentration significantly increased the beads diameter while HPMC concentration showed significant positive effect on the beads mucoadhesive properties. CaSi/Ca-Alg/HPMC beads represent simple floating-mucoadhesive gastroretentive system that could be useful in chronopharmacotherapy of benign prostatic hyperplasia.
多颗粒漂浮药物递送系统已被证明具有作为控制释放胃滞留药物递送系统的潜力，可避免单单位漂浮剂型的“全部或无”胃排空性质。存在研究的目的是开发硅酸钙（CaSi）/海藻酸钠（Ca-Alg）/羟丙基甲基纤维素（HPMC）粘膜粘附漂浮珠，以提供盐酸阿夫唑嗪（Alf）的时间和部位特异性药物释放。通过同时进行内部和外部凝胶化方法，利用 3（2）因子设计作为实验设计，用两种主要因素评估其对制备珠的影响；作为漂浮助剂的 CaSi 的浓度（X（1））和作为粘度增强剂和粘膜粘附聚合物的 HPMC 的百分比（X（2）），每个因素都在三个水平上进行测试。对开发的配方进行了产率、包封效率、粒径、表面形貌和漂浮性评估。还进行了差示扫描量热法、傅里叶变换红外光谱、体外药物释放以及使用大鼠胃粘膜膜的体外粘膜粘附研究。产率和包封效率范围分别为 57.03%至 78.51%和 49.78%至 83.26%。使用方差分析的统计分析证明，增加 CaSi 或 HPMC 的浓度都会显著增加珠的产率。CaSi 和 HPMC 的浓度都显著影响了 Alf 从珠中的释放。此外，较高的 CaSi 浓度显著增加了珠的直径，而 HPMC 浓度对珠的粘膜粘附性能有显著的正影响。CaSi/Ca-Alg/HPMC 珠代表了一种简单的漂浮-粘膜粘附胃滞留系统，可用于良性前列腺增生的时间药理学治疗。
