‘Exploring the preparation of griseofulvin CAMS with amino acids of different hydrophobicity as co-formers using a modified hot-melt extrusion process’
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引用次数: 0
Abstract
Co-amorphous systems (CAMS) of griseofulvin (GRI) with the amino acids (AA): L-lysine (LYS), L-valine (VAL) and L-methionine (MET) of increasing hydrophobicity were prepared using a solvent assisted hot-melt extrusion (HME). Co-formability was evaluated by thermodynamic miscibility prediction, thermal analysis (DSC), powder crystallography (pXRD) and vibrational spectroscopy (ATR-FTIR). Decomposition temperature range was defined by thermogravimetry (TGA) and DSC. Solubilities of crystalline and amorphous drug were determined by the UV-extinction method. The physical stability of GRI/AA CAMS was evaluated by accelerated tests and for ratios 1:1 and 1:2 was excellent. Non-sink dissolution tests of equimolar CAMS of the more hydrophobic MET and VAL revealed long lasting supersaturation, above the solubility of amorphous drug, whereas ratios 2:1 and 1:2 gave lower supersaturation due to partial recrystallization during dissolution, despite the good physical stability. CAMS of the hydrophilic LYS were physically stable but showed poor dissolution, possibly due to self-association of LYS in water. Addition of wetting agent in the dissolution medium improved dissolution without altering the profile. Since previous attempts to formulate GRI/AA CAMS with purely mechanical methods found only moderate success, the feed pretreatment HME method employed in this work makes an excellent alternative for drug/AA CAMS where mechanical or solvent evaporation methods fail.
期刊介绍:
The International Journal of Pharmaceutics is the third most cited journal in the "Pharmacy & Pharmacology" category out of 366 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.