preparation and characterization of amino acids-based trimethoprim salts的制备和表征氨基酸acids-based甲氧苄氨嘧啶盐.pdfVIP

Pharmaceutics 2012, 4, 179-196; doi:10.3390/pharmaceutics4010179 OPEN ACCESS pharmaceutics ISSN 1999-4923 /journal/pharmaceutics Article Preparation and Characterization of Amino Acids-Based Trimethoprim Salts Amr ElShaer, Peter Hanson, Tony Worthington, Peter Lambert and Afzal R. Mohammed * Aston Pharmacy School, Aston University, Aston Triangle, Birmingham B4 7ET, UK * Author to whom correspondence should be addressed; E-Mail: a.u.r.mohammed@aston.ac.uk; Tel.: +44-121-2044183. Received: 11 January 2012; in revised form: 8 February 2012 / Accepted: 8 February 2012 / Published: 16 February 2012 Abstract: Trimethoprim (TMP) is a dihydrofolate reductase (DHFR) inhibitor which prevents the conversion of dihydrofolic acid into tetrahydrofolic acid, resulting in the depletion of the latter and leading to bacterial death. Oral bioavailability of TMP is hindered by both its low solubility and low permeability. This study aims to prepare novel salts of TMP using anionic amino acids; aspartic and glutamic acid as counter ions in order to improve solubility and dissolution. TMP salts were prepared by lyophilisation and 1 characterized using FT-IR spectroscopy, proton nuclear magnetic resonance ( HNMR), Differential Scanning Calorimetry (DSC) and Thermogravimetric analysis (TGA). Both the amino acids formed salts with TMP in a 1:1 molar r