Haidar Mohammad Karim, Yamashita Fumiyoshi, Hashida Mitsuru
Erzincan Binali Yıldırım University Faculty of Pharmacy, Department of Pharmaceutical Technology, Erzincan, Turkey.
Kyoto University Graduate School of Pharmaceutical Science, Department of Drug Delivery Research, Kyoto, Japan.
Turk J Pharm Sci. 2021 Dec 31;18(6):752-760. doi: 10.4274/tjps.galenos.2021.56492.
The objective of the present study is to establish a robust preparation method that could steadily produce minocycline hydrochloride (MCH) microspheres regardless of used polymer types.
Taguchi's Robust Experimental Design methodology was employed to optimize the process parameters for MCH-loaded poly(D,L-lactide-co-glycolide) (PLGA) microspheres. In the experimental design, seven controllable factors, i.e., preparation method, pH of the aqueous phase, volume of the aqueous phase, volume of dichloromethane, rotation speed, temperature, and amount of polyvinyl alcohol, were considered for the optimization of process parameters. PLGA types with different lactide/glycolide ratios were considered the uncontrollable (noise) factor. Based on the L18 orthogonal array, 18 experimental runs were conducted for each type of PLGA. The encapsulation efficiency (EE) and release rate were evaluated for all the prepared formulations.
Regardless of the PLGA type with different lactic/glycolic acid ratios, microspheres prepared via the solid-in-oil-in-water (S/O/W) method, showed a much higher EE and faster drug release than the microspheres prepared via the co-solvent method. Preparation methods, pH of the aqueous phase, and volume of the aqueous phase were the most influencing parameters on the EE. The confirmation experiment results indicated that the signal-to-noise ratio increased by 5.76 db from that of an initial condition. The release of minocycline was fastest with the PLGA (50:50) microspheres, followed by PLGA (75:25) and PLGA (85:15).
Although the interaction between the selected factors in the evaluation was ignored, the orthogonal array design of the experiment based on Taguchi's robust experimental design methodology was sufficient to optimize the process parameters for the PLGA microspheres of MCH. The S/O/W was the main factor affecting the EE. Microspheres prepared via the S/O/W method exhibited a higher EE and faster drug release than the microspheres prepared via co-solvent method. The pH and volume of the aqueous phase were also effective parameters on the EE. A robust experimental design has been successfully applied to the optimization of the process parameters for microsphere preparation.
本研究的目的是建立一种稳健的制备方法，无论使用何种聚合物类型，都能稳定地生产盐酸米诺环素（MCH）微球。
采用田口稳健实验设计方法优化载MCH聚（D，L-丙交酯-共-乙交酯）（PLGA）微球的工艺参数。在实验设计中，考虑了七个可控因素，即制备方法、水相pH值、水相体积、二氯甲烷体积、转速、温度和聚乙烯醇用量，以优化工艺参数。不同丙交酯/乙交酯比例的PLGA类型被视为不可控（噪声）因素。基于L18正交表，对每种类型的PLGA进行了18次实验。对所有制备的制剂评估包封率（EE）和释放率。
无论丙交酯/乙交酯比例不同的PLGA类型如何，通过水包油包水（S/O/W）法制备的微球比通过共溶剂法制备的微球具有更高的EE和更快的药物释放。制备方法、水相pH值和水相体积是对EE影响最大的参数。验证实验结果表明，信噪比相比初始条件提高了5.76分贝。米诺环素在PLGA（50:50）微球中的释放最快，其次是PLGA（75:25）和PLGA（85:15）。
尽管评估中所选因素之间的相互作用被忽略，但基于田口稳健实验设计方法的正交实验设计足以优化MCH的PLGA微球的工艺参数。S/O/W是影响EE的主要因素。通过S/O/W法制备的微球比通过共溶剂法制备的微球具有更高的EE和更快的药物释放。水相的pH值和体积也是影响EE的有效参数。稳健实验设计已成功应用于微球制备工艺参数的优化。
