In situ miniemulsions of glimepiride using D-optimal mixture design-in silico, in vitro and in vivo studies

Purpose

Glimepiride, a BCS class II oral hypoglycaemic drug shows dissolution rate limited absorption. Oral in situ miniemulsions can improve Glimepiride solubility by enhancing dissolution rate for faster absorption, subsequently rapid onset of action and reducing variations in oral bioavailability for effective control of blood glucose levels.

Methods

Capryol 90, Tween 20, PEG 400 and stearyl amine were used to develop in situ miniemulsions of Glimepiride using D-Optimal mixture design. In silico molecular modelling studies were performed to understand role of stearyl amine in modifying Glimepiride solubility. In situ miniemulsions were characterized for globule size, zeta potential, polydispersity index, drug content, pH and accelerated aging. Further, the optimized in situ miniemulsions were converted into granules by adsorbing on Syloid XDP 3150.

Results

Molecular dynamics simulation confirmed that stearyl amine enhanced Glimepiride solubility in Capryol 90. DSC thermograms revealed amorphous state of Glimepiride while in vitro release studies indicated >90 % Glimepiride release from in situ miniemulsions and granules as compared to suspensions at the end of 10 min. Ex vivo studies performed on non-everted gut sacs from Wistar rats displayed greater ex vivo intestinal permeability of Glimepiride from the developed granules than suspensions. In vivo studies in male Wistar rats revealed that developed Glimepiride granules showed statistically significant (p < 0.001) decrease in blood glucose levels as compared to conventional marketed tablets of Glimepiride.

Conclusions

The present research work holds potential in delivering in situ miniemulsions of Glimepiride for effective treatment of diabetes and proposes novelty for enhancing oral bioavailability.