Glibenclamide–malonic acid cocrystal with an enhanced solubility and bioavailability

Abstract

Objective

The objective of the work is to enhance the solubility, dissolution, and pharmacokinetic properties of glibenclamide (GLB) via cocrystallization technique.

Significance

Glibenclamide is an oral hypoglycemic agent used for treating non-insulin-dependent (type II) diabetes mellitus. It exhibits poor aqueous solubility and oral bioavailability, thereby compromising its therapeutic effect. Therefore, utilizing cocrystal approach for enhancing the solubility will modulate the physicochemical properties of GLB without altering its molecular structure.

Methods

Cocrystal was prepared by solution crystallization method using coformer malonic acid. The cocrystal was characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared (FT-IR) studies. The prepared cocrystal was subjected to solubility, in vitro dissolution, and pharmacokinetic studies.

Results

The DSC endotherms, PXRD patterns, and the FT-IR spectra of the cocrystal established the formation of a cocrystal. The formation of eutectic mixture was refuted upon comparing the DSC endotherm and PXRD pattern of the cocrystal with that of the physical mixture. GLB showed a twofold enhancement in solubility and a significant improvement in the rate of dissolution (p < 0.05, independent t-test) after cocrystallization. The pharmacokinetic parameters on male Sprague Drawly rats showed 1.45 enhancement in AUC_0–24 and 1.36-fold enhancement in the C_max of GLB as compared to the pure drug.

Conclusion

These findings demonstrate that cocrystallization technique was able to tailor the solubility and dissolution profile of GLB leading to an enhanced pharmacokinetic property.

Keywords:

• Cocrystal
• glibenclamide
• malonic acid
• powder X-diffraction
• solubility
• bioavailability

Acknowledgements

The authors are thankful to Amity Institute of Pharmacy, Amity University Uttar Pradesh, Lucknow Campus for providing the necessary facilities to carry out the research, Central Instrumentation Facilities, BIT Mesra (India) for FT-IR studies and DSC studies and Sophisticated Test and Instrumentation Centre, Cochin University (India) for PXRD analysis.

Disclosure statement

The authors declare that they have no conflicts of interest.

The animal experimental protocol was approved by the Institutional Animal Ethical Committee of CSIR-C.D.R.I., Lucknow (IAEC/2017/287/Renew-0/Dated 31/10/2017). The animals were handled as per the guidelines of the Committee for Control and Supervision on Experimental Animals (CPCSEA), New Delhi, India.