Das Sanjoy Kumar, Khanam Jasmina, Nanda Arunabha
Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India.
Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India.
Mater Sci Eng C Mater Biol Appl. 2016 Dec 1;69:598-608. doi: 10.1016/j.msec.2016.07.010. Epub 2016 Jul 5.
In the present investigation, simplex lattice mixture design was applied for formulation development and optimization of a controlled release dosage form of ketoprofen microspheres consisting polymers like ethylcellulose and Eudragit(®)RL 100; when those were formed by oil-in-oil emulsion solvent evaporation method. The investigation was carried out to observe the effects of polymer amount, stirring speed and emulsifier concentration (% w/w) on percentage yield, average particle size, drug entrapment efficiency and in vitro drug release in 8h from the microspheres. Analysis of variance (ANOVA) was used to estimate the significance of the models. Based on the desirability function approach numerical optimization was carried out. Optimized formulation (KTF-O) showed close match between actual and predicted responses with desirability factor 0.811. No adverse reaction between drug and polymers were observed on the basis of Fourier transform infrared (FTIR) spectroscopy and Differential scanning calorimetric (DSC) analysis. Scanning electron microscopy (SEM) was carried out to show discreteness of microspheres (149.2±1.25μm) and their surface conditions during pre and post dissolution operations. The drug release pattern from KTF-O was best explained by Korsmeyer-Peppas and Higuchi models. The batch of optimized microspheres were found with maximum entrapment (90%), minimum loss (10%) and prolonged drug release for 8h (91.25%) which may be considered as favourable criteria of controlled release dosage form.
在本研究中，采用单纯形格子混合设计进行剂型开发，并优化由乙基纤维素和尤特奇（®）RL 100等聚合物组成的酮洛芬微球控释剂型；这些微球通过油包油乳液溶剂蒸发法制备。本研究旨在观察聚合物用量、搅拌速度和乳化剂浓度（% w/w）对微球的产率、平均粒径、药物包封率以及8小时体外药物释放的影响。采用方差分析（ANOVA）评估模型的显著性。基于合意函数法进行数值优化。优化后的制剂（KTF - O）的实际响应与预测响应之间匹配良好，合意因子为0.811。基于傅里叶变换红外光谱（FTIR）和差示扫描量热法（DSC）分析，未观察到药物与聚合物之间的不良反应。通过扫描电子显微镜（SEM）观察微球（149.2±1.25μm）在溶解前后的离散性及其表面状况。KTF - O的药物释放模式最好用Korsmeyer - Peppas模型和Higuchi模型来解释。发现优化后的微球批次具有最大包封率（约90%）、最小损失率（约10%）以及8小时的延长药物释放（91.25%），这些可被视为控释剂型的有利标准。
