Rodríguez M, Vila-Jato J L, Torres D
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, 15706-Santiago de Compostela, Spain.
J Control Release. 1998 Oct 30;55(1):67-77. doi: 10.1016/s0168-3659(98)00029-7.
A multiparticulate dosage form consisting of a hydrophobic core coated with a pH-dependent polymer is proposed for colonic specific delivery of drugs. Different approaches for colon-specific drug delivery have been studied over the last decade, including prodrugs, polymeric coating using pH-sensitive or bacterial degradable polymers and matrices. In this work, we present a new multiparticulate system to deliver active molecules to the colonic region, which combines pH-dependent and controlled drug release properties. This system was constituted by drug loaded cellulose acetate butyrate (CAB) microspheres coated by an enteric polymer (Eudragit(R) S). Both, CAB cores and pH-sensitive microcapsules, were prepared by the emulsion-solvent evaporation technique in an oily phase. Ondansetron (OS) and budesonide (BDS), two interesting drugs with a potentially new application for the local treatment of intestinal disorders, were efficiently microencapsulated in CAB microspheres at different polymer concentrations (6 and 8%). These hydrophobic cores (about 60 and 110 micrometer in size, respectively) were then microencapsulated with Eudragit(R) S, resulting in multinucleated structures, except in the case of BDS-CAB microspheres prepared at 8% CAB concentration, in which more mononucleated microcapsules were obtained. The in vitro drug release studies of pH-sensitive microcapsules containing the hydrophobic cores showed that no drug was released below pH 7. After that, CAB microspheres efficiently controlled the release of BDS, the release behavior being affected by the different polymer concentration used in their preparation. However, OS-CAB microspheres did not maintain their controlled-release properties once the enteric polymer dissolved. The extraction of the drug by the Eudragit(R) solvent during the second microencapsulation process was in this case the cause for the failure of the controlling release mechanism.
一种由涂有pH依赖性聚合物的疏水核心组成的多颗粒剂型被提出用于药物的结肠特异性递送。在过去十年中，人们研究了多种结肠特异性药物递送方法，包括前体药物、使用pH敏感或细菌可降解聚合物及基质的聚合物包衣。在这项工作中，我们展示了一种新的多颗粒系统，可将活性分子递送至结肠区域，该系统兼具pH依赖性和可控药物释放特性。该系统由负载药物的醋酸丁酸纤维素（CAB）微球组成，其表面涂覆有肠溶聚合物（尤特奇（R）S）。CAB核心和pH敏感微胶囊均通过油相中的乳液 - 溶剂蒸发技术制备。昂丹司琼（OS）和布地奈德（BDS）是两种有趣的药物，在肠道疾病局部治疗方面具有潜在的新应用，它们在不同聚合物浓度（6%和8%）下被有效地微囊化在CAB微球中。这些疏水核心（尺寸分别约为60和110微米）随后用尤特奇（R）S进行微囊化，形成多核结构，但8% CAB浓度制备的BDS - CAB微球除外，该条件下获得了更多单核微胶囊。含疏水核心的pH敏感微胶囊的体外药物释放研究表明，在pH 7以下无药物释放。此后，CAB微球有效地控制了BDS的释放，其释放行为受制备过程中使用的不同聚合物浓度影响。然而，一旦肠溶聚合物溶解，OS - CAB微球就无法维持其控释特性。在这种情况下，第二次微囊化过程中药物被尤特奇（R）溶剂萃取是控释机制失效的原因。
