AMELIORATED SOLUBILITY AND DISSOLUTION RATE OF GLIMEPIRIDE BY CYCLODEXTRIN TERNARY COMPLEXES EMPLOYING AMINOACIDSAbstract
The purpose of the current investigation was to ameliorate the aqueous solubility and dissolution rate of an anti diabetic drug Glimepiride by cyclodextrin ternary complexes employing aminoacids. Initially, Glimepiride (GMP) binary complexes with β-Cyclodextrin (βCD) and Hydroxy propyl β-Cyclodextrin (HPβCD) were formulated by physical mixing, kneading, solvent evaporation and spray drying techniques which was followed by ternary complex preparation of selected GMP-Cyclodextrin binary complex employing various aminoacids by kneading method. The kneading method was used in preparing ternary complexes of GMP, because it was proved to be the best method comparatively in yielding promising binary complexes of glimepiride in the initial stage of this study. GMP formed 1:1 M stoichiometric binary and ternary inclusion complexes as demonstrated by the AL-type of phase solubility curve. An increment in the stability constant value (Kc) of GMP- βCD/HPβCD complex in the presence of aminoacids conceded higher complexation competency. FTIR and DSC studies evidenced the perfect inclusion complex formation. Ternary complexes ameliorated drug dissolution compared with GMP and GMP-βCD. The ternary complex containg 1:3:2 molar ratio of GMP:HPβCD:L-ARGININE exhibited 98.85% drug dissolution in 2 hours, which was significantly high in relation to ternary complexes containg other aminoacids and it was found to follow imperatively first order release mechanism in relation to Hixson-Crowell’s cube root law. On aging studied complexes showed no significant change in physical appearance, drug content and drug dissolution attributes, which clearly shows high in-vitro stability of the complexes.
Md. Jafar *, A. Malpani and Md. Imran Khan
Department of Pharmaceutics, College of Clinical Pharmacy, University of Dammam, Dammam, Saudi Arabia.
02 December, 2016
22 January, 2017
17 February, 2017
01 June, 2017