Gliclazide Injectable Depot Forms: Development of Model Compounds and Efficacy Assessment

INTRODUCTION. Despite a broad range of available hypoglycemic agents, the choice of dosage forms, particularly those with prolonged release, remains limited. This necessitates the development of injectable depot formulations for the prolonged and controlled release of an active pharmaceutical ingredient. A key milestone and one of the pivotal factors in developing a stable parenteral depot formulation is testing solubility of the active pharmaceutical ingredient and selecting a solvent / solvent mixture that ensures effective release of the compound. One of the most frequently prescribed hypoglycemic agents is gliclazide, currently only available in oral dosage forms. Therefore, the development of a prolonged-release form for parenteral administration is urgent, since it will optimize therapy for a wide range of patients. AIM. This study aimed to develop a prolonged-release depot system of gliclazide for parenteral administration. MATERIALS AND METHODS. Gliclazide solubility in biocompatible solvents was determined according to a pharmacopeial method (under standard conditions and when heated). In vitro biopharmaceutical studies were based on dialysis with a cellophane membrane. Gliclazide in dialysate samples was quantified using UV spectrophotometry (λ=230 nm). Antidiabetic effect of the test samples was determined in male Wistar rats with an alloxan-induced diabetes model. Blood glucose was measured using an Accu-Chek® Performa Nano glucometer for 24 h after a single administration of the test samples. RESULTS. Gliclazide solubility assessment indicated better solubility in dimethyl sulfoxide and 95% ethyl alcohol. However, gliclazide was practically insoluble in polyethylene glycol-400, propylene glycol-1,2, isopropyl myristate, glycerol, and slightly soluble in 70% ethyl alcohol. When heated, gliclazide solubility in propylene glycol-1,2 and polyethylene glycol-400 increased to slightly soluble. Gliclazide release from an aqueous suspension model over 2 h was 15.69±0.49%. Comparable antidiabetic effect was established for injection depot models using binary dispersion media based on combinations of water for injection, propylene glycol-1,2, and dimethyl sulfoxide. A more pronounced hypoglycemic effect was observed when using water for injection : propylene glycol-1,2 and dimethyl sulfoxide : propylene glycol-1,2 as a dispersion medium. CONCLUSIONS. Model compounds have been obtained for gliclazide prolonged-release injectable depot forms based on the binary media, with a subsequent biopharmaceutical assessment. The findings necessitate the use of organic solvents in the suspension that would improve gliclazide release from the aqueous suspension.