Fixed-Dose Combination Formulation and Development of Tamsulosin Hydrochloride and Dutasteride

• Main Authors: CHOU,MING-CHERNG, 周明誠
• Other Authors: LIN,HONG-LIANG
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/91900838247392203179

碩士 === 元培醫事科技大學 === 生物科技暨製藥技術系碩士班 === 104 === Abstract The objective of the study was to determine the optimum composition for controlled-release core pellets of tamsulosin hydrochloride (TSH) and immediate-release outer layer of Dutasteride (DTS) for orally multi-particulate pellets. An optimized formulation was prepared by extrusion/spheronization method. The TSH core pellets were consisted of microcrystalline cellulose (MCC) and eudragit L30D-55 etc. The delay release system was developed by coating the prepared pellets with aqueous dispersion of eudragit L30D-55. The high performance liquid chromatography analytical method for TSH pellets has been developed and validated. The proposed method was validated with respect to specificity,precision, accuracy, intermediate precision, linearity and range, and robustness. The linearity correlation co-efficient of TSH is 0.99984, the linear range of TSH is 0.02 ~ 0.52μg/ml. Recovery of TSH in formulation was found to be in a range of 97.0~103.0% and this confirms the non-interferences of the excipients in the formulation. The pellets were evaluated for in vitro drug release to assess in a commercial product, Duodart® Capsules. The similarity factor f2 value of the EC2 pellets (TSH) and commercial product (Duodart® ) was 62.37 (>50). An another drug layer – Dutasteride (DTS), prepared with polyvinyl pyrrolidone K-30, tween 80, capryol 90, was coated onto the EC2 pellets. The dissolution study of DTS depicted that, the presence of the drug with surfactants enhanced its dissolution rate, the similarity factor f2 value of the D1 pellets (DTS) and commercial product (Duodart® ) was 54.46. In conclusion, this development of formulation and process in multi-particulate pellets provided a controlled-release of TSH and immediate-release of DTS dosage form comparable to Duodart® Capsules. Keywords: tamsulosin hydrochloride, dutasteride, extrusion/ spheronization method, eudragit L30D-55, duodart, validation, capryol 90