Formulation and evaluation of co-prodrug of flurbiprofen and methocarbamol
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- 作者：Neela Bhatia ; neela.bhatia20@gmail.com" class="auth_mail" title="E-mail the corresponding author ; Kiran Katkar ; Snehal Ashtekar
- 关键词：NSAIDs ; Flurbiprofen ; Skeletal muscle relaxant ; Methocarbamol ; Ester prodrug ; RP-HPLC ; Ulcerogenicity
- 刊名：Asian Journal of Pharmaceutical Sciences
- 出版年：2016
- 出版时间：June 2016
- 年：2016
- 卷：11
- 期：3
- 页码：449-458
- 全文大小：1443 K
文摘
The current work envisages synthesis of an ester prodrug of flurbiprofen whereby its carboxylic group was condensed with a skeletal muscle relaxant methocarbamol, with the aim of synergistic activity of two drugs, avoid flurbiprofen mediated gastro-intestinal damage and minimize the ulceration tendency of flurbiprofen. The synthesized prodrug was characterized and confirmed by physicochemical and spectroscopic studies. Solubility and partition coefficient studies indicated an increased lipophilicity and thus better suitability for oral administration than the parent drugs and the protein binding studies revealed a low protein binding capacity of the mutual prodrug. Subsequently, in-vitro hydrolysis was studied in different pH, simulated gastric fluid, simulated intestinal fluid and plasma and quantitative evaluation was performed by high performance liquid chromatography. It was found that the prodrug remained unhydrolyzed in the stomach after absorption however, underwent rapid cleavage by the esterases in blood to give the parent drug. Furthermore, the mutual ester prodrug was evaluated for its anti-inflammatory, analgesic, skeletal muscle relaxation, ulcerogenic and total acid content activity and was found to possess comparable activity with that of the parent drugs. Microscopic structures of the stomach tissues revealed significant reduction in gastric ulcer formation of mice gastric mucosa as compared to parent carboxylic acid drug.