Preparation, Characterization and <i>in Vivo</i> Evaluation of Antihyperglycemic Activity of Microwave Generated Repaglinide Solid Dispersion

Abstract

The influence of microwave technology on the in vitro dissolution rate and in vivo antihyperglycemic activity of a poorly water soluble drug, repaglinide (RG) was studied. Solid dispersions were prepared by conventional fusion method and microwave method using poloxamer 188. The dispersions were characterized by solubility study, dissolution study, Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) and scanning electron microscopy (SEM). Microwave generated solid dispersions exhibited remarkable improvement in solubility and dissolution rate compared to that of pure RG. Results of DSC, XRD and SEM study showed conversion of crystalline form of RG to amorphous form. In vivo studies revealed that the microwave generated solid dispersion showed significant improvements in antihyperglycemic activity as compared to RG alone, thus confirming the advantage of improved pharmacological activity of RG by microwave method. In conclusion, microwave method could be considered as simple, efficient and solvent free promising alternative method to prepare solid dispersion of poorly water soluble drug RG with significant enhancement in solubility, dissolution rate and antihyperglycemic activity.Key words microwave; repaglinide; solubility; dissolution rate; antihyperglycemic Therapeutic success of a drug depends upon the bioavailability and ultimately upon the solubility of drug molecules. Solubility is one of the significant parameter to achieve desired concentration of drug in systemic circulation to achieve pharmacological response. Currently only 8% of new drug candidates have both high solubility and permeability.1) Poorly soluble drugs have number of limitations such as need of higher dosage, rise in administration frequency and the consequential occurrence of side effects. The rate-limiting step in the absorption process for poorly water-soluble drugs is dissolution rate of such drugs in the gastrointestinal fluids rather than the rapidity of their diffusion across the gut wall; it is however, important to improve the oral bioavailability of poorly water soluble drugs by improving their dissolution rate and solubility.Solubility and dissolution rate of poorly soluble drugs can be enhanced using various techniques such as micronization, complexation, solubilization in surfactant system, drug derivatization etc. Among the methods to improve solubility and dissolution rate of poorly water soluble drugs, solid dispersion is one of the most popular.2-5) Mechanisms for the improved solubility and dissolution properties of poorly soluble drugs from solid dispersions include reduction of the particle size of the drug, transformation of the crystalline drug to the amorphous state, formation of solid solutions, formation of complexes, reduction of aggregation and agglomeration, improved wetting of the drug and solubilization of the drug by the carrier at the diffusion layer.6-8) It is highly acceptable, that often more than one of these mechanisms determine the r...

Formulation and Evaluation of Supramolecular Food-Grade Piperine HP β CD and TPGS Complex: Dissolution, Physicochemical Characterization, Molecular Docking, In Vitro Antioxidant Activity, and Antimicrobial Assessment

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Therapeutic Applications of Solid Dispersions for Drugs and New Molecules: In Vitro and In Vivo Activities

“…Repaglinide, a hypoglycemic drug indicated for the treatment of patients with type 2 diabetes mellitus, was used by Zawar and Bari [ 74 ] to develop dispersions with Poloxamer 188 in the 1:3 ( w / w ) drug:polymer proportion by the conventional fusion or microwave method. In vivo experiments conducted on Wistar rats showed that the SD prepared by the microwave method reduced the serum glucose level determined by the glucose-oxidase method to 88 ± 0.73 mg/dL within 2 h, while the pure drug and the control led to glucose levels of 94 ± 2.63 and 120 ± 2.1 mg/dL, respectively.…”

Design of modified xanthan mini-matrices for monitoring oral discharge of highly soluble Soluplus ® –glibenclamide dispersion

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