Preparation and characterization of fast dissolving flurbiprofen and esomeprazole solid dispersion using spray drying technique

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• 作者：Roshan Pradhan^a ; Tuan Hiep Tran^a ; Sung Yub Kim^a ; Kyu Bong Woo^a ; Yong Joo Choi^a ; Han-Gon Choi^b ; Chul Soon Yong^a ; ^{csyong@yu.ac.kr" class="auth_mail" title="E-mail the corresponding author} ; Jong Oh Kim^a ; ^{jongohkim@yu.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Flurbiprofen ; Esomeprazole ; Solubility ; Solid dispersion ; Spray-drying ; Dissolution
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：11 April 2016
• 年：2016
• 卷：502
• 期：1-2
• 页码：38-46
• 全文大小：1444 K

文摘

We aimed to develop an immediate-release flurbiprofen (FLU) and esomeprazole (ESO) combination formulation with enhanced gastric aqueous solubility and dissolution rate. Aqueous solubility can be enhanced by formulating solid dispersions (SDs) with a polyvinylpyrrolidone (PVP)-K30 hydrophilic carrier, using spray-drying technique. Aqueous and gastric pH dissolution can be achieved by macro-environmental pH modulation using sodium bicarbonate (NaHCO₃) and magnesium hydroxide (Mg(OH)₂) as the alkaline buffer. FLU/ESO-loaded SDs (FLU/ESO-SDs) significantly improved aqueous solubility of both drugs, compared to each drug powder. Dissolution studies in gastric pH and water were compared with the microenvironmental pH modulated formulations. The optimized FLU/ESO-SD powder formulation consisted of FLU/ESO/PVP-K30/sodium carbonate (Na₂CO₃) in a weight ratio 1:0.22:1.5:0.3, filled in the inner capsule. The outer capsule consisted of NaHCO₃ and Mg(OH)₂, which created the macro-environmental pH modulation. Increased aqueous and gastric pH dissolution of FLU and ESO from the SD was attributed to the alkaline buffer effects and most importantly, to drug transformation from crystalline to amorphous SD powder, clearly revealed by scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffraction studies. Thus, the combined FLU and ESO SD powder can be effectively delivered as an immediate-release formulation using the macro-environmental pH modulation concept.