Giao Thong Ngo, Ha Bui Thi Ngoc, Thuong Bui Thi, Thanh Hai Nguyen, Tran Thi Hai Yen
Faculty of Pharmaceutics and Pharmaceutical technology, Hanoi University of Pharmacy, Hanoi, Vietnam.
VNU University of Medicine and Pharmacy, Hanoi, Vietnam.
Drug Dev Ind Pharm. 2024 Dec;50(12):981-994. doi: 10.1080/03639045.2024.2433621. Epub 2024 Dec 1.
Poly(lactic--glycolic acid) microsphere containing leuprolide acetate - an extended-release drug delivery system whose characteristics (i.e. loading capacity, particle size and initial burst phase) depend on processing parameters.
Microspheres were prepared by water/oil/water double-emulsion solvent evaporation method; drug content in microspheres was determined by high-performance liquid chromatography (HPLC); peptide concentration in the release medium was measured by fluorescence spectrometer; particle size and particle size distribution were measured by laser diffraction method; interaction between poly(lactic--glycolic acid) (PLGA) and leuprolide acetate (LA) was determined by differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR).
DSC curves and assay results proved LA adsorption ability of PLGA film. FTIR spectra proved ionic interactions between positive charged LA molecules and negative charged PLGA chains in phosphate buffer pH 7.4. Ten processing parameters including LA concentration (mg/mL), PLGA concentration (mg/mL), W1/O ratio (v/v), the first homogenization time (min), the first homogenization speed (rpm), O/W2 ratio (v/v), PVA concentration of W2 phase (mg/ml), the second homogenization time (s), the volume of diluted solution (ml) and nitrogen aeration time (min) have impacts on loading capacity, particle size and initial burst phase of microspheres. The release exponent (n) of Korsmeyer-Peppas model was 0.3571 (lower than 0.43), indicating that Fickian diffusion manipulated release kinetics of initial burst phase.
Processing parameter modification contributes to small microspheres with high loading capacity and controlled initial burst phase.
含醋酸亮丙瑞林的聚乳酸-乙醇酸共聚物微球——一种缓释药物递送系统，其特性（即载药量、粒径和初始突释阶段）取决于加工参数。
采用水/油/水双乳液溶剂蒸发法制备微球；通过高效液相色谱法（HPLC）测定微球中的药物含量；用荧光光谱仪测量释放介质中的肽浓度；采用激光衍射法测量粒径和粒径分布；通过差示扫描量热法（DSC）和傅里叶变换红外光谱法（FTIR）确定聚乳酸-乙醇酸共聚物（PLGA）与醋酸亮丙瑞林（LA）之间的相互作用。
DSC曲线和测定结果证明了PLGA膜对LA的吸附能力。FTIR光谱证明了在pH 7.4的磷酸盐缓冲液中带正电荷的LA分子与带负电荷的PLGA链之间存在离子相互作用。包括LA浓度（mg/mL）、PLGA浓度（mg/mL）、W1/O比（v/v）、第一次均质时间（min）、第一次均质速度（rpm）、O/W2比（v/v）、W2相的PVA浓度（mg/ml）、第二次均质时间（s）、稀释溶液体积（ml）和氮气曝气时间（min）在内的10个加工参数对微球的载药量、粒径和初始突释阶段有影响。Korsmeyer-Peppas模型的释放指数（n）为0.3571（低于0.43），表明初始突释阶段的释放动力学受菲克扩散控制。
加工参数的调整有助于制备出载药量高、初始突释阶段可控的小微球。
