Physicochemical Properties of Solid Dispersions of Gliclazide in Polyvinylpyrrolidone K90

Abstract

INTRODUCTIONGliclazide is a second generation hypoglycemic sulfonyl-urea which is useful in the treatment of type 2 diabetesmellitus (1). Following oral administration, however, glicla-zide exhibits slow rate of absorption and interindividualvariation in bioavailability. Statedproblemsofgliclazidemightbe due to its poor water solubility and slow dissolution rate (2–4). But gliclazide exhibits good tolerability, low incidence ofhypoglycemiceffect, low rate ofsecondary failure,and low rateof progression of diabetic retinopathy (2,5). Hence, gliclazideappearstobeadrugofchoiceinlong-termsulfonylureatherapyfor treatment of type 2 diabetes mellitus. Few attempts havebeen made for improvement of solubility and bioavailability ofgliclazide including complexation with cyclodextrin (6,7)orcyclodextrin–hydroxypropylmethylcellulose (8) and using PEG400 (9) as per present literature. The authors investigated thephysicochemical characteristics and dissolution behaviors ofgliclazide in physical mixtures as well as solid dispersions withpolyethylene glycol 6000 in a previous study (10).The main objective of this work was to investigate thephysicochemical characteristics of gliclazide in physical mix-tures (PMs) and solid dispersions (SDs) prepared by usingpolyvinylpyrrolidone K90 (PVP K90). The possible interac-tions between gliclazide and PVP K90 in both solid and liquidstates were investigated. Interaction in solid state was investi-gated by Fourier-transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD) analysis, and differential scanningcalorimetry (DSC). Interaction in solution was studied byphase solubility analysis and dissolution experiments.MATERIALS AND METHODSMaterialsA gift sample of gliclazide was received from AristoPharmaceuticals Ltd. (Mumbai, India). PVP K90 was re-ceived from BASF (Germany). Double-distilled water wasused throughout the study and all the other chemicals usedwere of analytical grade.Preparation of SDsThe SDs of gliclazide with PVP K90 containing threedifferent weight ratios (1:1, 1:2, 1:5; gliclazide/PVP K90) anddenoted as SD 1/1, SD 1/2, and SD 1/5, respectively, wereprepared by solvent evaporation method. In the solventevaporation method, to a solution of gliclazide in chloroform,an appropriate amount of PVP K90 in solution was added.The solvent was evaporated under reduced pressure at 40°Cby using a rotary evaporator and the resulting residue wasdried under vacuum for 3 h. The mixture was storedovernight in a desiccator. The hardened mixture was pow-dered in a mortar, sieved through a 100-mesh screen, andstored in a screw-cap vial at room temperature until furtheruse (11,12).The PMs having the same weight ratio as SDs wereprepared by thoroughly mixing the required amount ofgliclazide and PVP K90 for 10 min in a mortar. The resultingmixtures were sieved through a 100-mesh sieve and denotedas PM 1/1, PM 1/2, and PM 1/5, respectively. The mixtureswere stored in a screw-cap vial at room temperature untiluse.Phase Solubility of GliclazideSolubility determinations were performed in triplicateaccording to the method of Higuchi and Connors (13). Inbrief, an excess amount of gliclazide was taken into a screw-capped glass vial to which 20 ml of aqueous solutioncontaining various concentrations of PVP K90 was added.Then, the samples were shaken at 37±0.5°C for 72 h in awater bath (Remi Pvt Ltd, Mumbai). After 72 h, sampleswere filtered through a 0.45-μm membrane filter. The filtratewas suitably diluted and analyzed spectrophotometrically at thewavelength of 227 nm using a UV–VIS spectrophotometer(Shimadzu 1700, Pharm Spec, Japan).329