CONTROLLED RELEASE OF THEOPHYLLINE-CHITOSAN COMPOSITE PARTICLES PREPARED USING SUPERCRITICAL ASSISTED ATOMIZATION

Abstract This study investigated the formation of composite particles of chitosan (CS) and theophylline (TPH) via supercritical assisted atomization (SAA) using aqueous ethanol (50%, v/v) as the solvent and supercritical CO2 as the spraying medium. According to XRD, DSC, and FTIR analyses, the crystal form of the SAA-treated TPH from the as-received TPH was unchanged. The effect of different mass ratios of CS to TPH on the in vitro release of TPH showed that the dissolution of the highly water-soluble TPH was retarded when included in the composite particles and could be controlled by the mass ratio of the component in the SAA process. The in vitro dissolution data showed a good fit with the Peppas-Sahlin model, which was used to conclude that the drug release from the composite particles resulted from a combination of drug diffusion and relaxation of the polymer. As the mass ratio of CS to TPH increased, the mechanism relating to polymer relaxation became crucial in the TPH-CS composite particles.

摘要 本研究以体积分数50%的乙醇水溶液为溶剂、超临界二氧化碳为雾化介质，采用超临界辅助雾化法（supercritical assisted atomization, SAA）制备了壳聚糖（chitosan, CS）与茶碱（theophylline, TPH）的复合微粒。经X射线衍射（X-ray diffraction, XRD）、差示扫描量热法（Differential Scanning Calorimetry, DSC）及傅里叶变换红外光谱（Fourier Transform Infrared Spectroscopy, FTIR）分析表明，经SAA处理后的茶碱晶型与原料茶碱保持一致。考察了壳聚糖与茶碱的不同质量比对茶碱体外释放行为的影响，结果显示：高水溶性的茶碱被包埋于复合微粒后，其溶出速率得到延缓，且可通过SAA制备过程中的组分质量比调控溶出行为。体外溶出数据与佩帕斯-萨林模型（Peppas-Sahlin model）拟合度良好，据此推断复合微粒中的药物释放为药物扩散与聚合物松弛共同作用的结果。随着壳聚糖与茶碱质量比的提升，聚合物松弛机制在茶碱-壳聚糖复合微粒的药物释放过程中逐渐占据主导地位。