Formulation of solid self-nanoemulsifying drug delivery systems using N-methyl pyrrolidone as cosolvent

Abstract

Atorvastatin calcium (ATRC) is a poor water soluble drug used for treatment of hypercholesterolemia. This research is aimed to improve solubility and dissolution rate of ATRC by formulating into solid self-nanoemulsifying drug delivery system (S-SNEDDS) using N-methyl pyrrolidone (NMP) as cosolvent. Solubility of ATRC was determined in various vehicles. Ternary phase diagrams were constructed to identify stable nanoemulsion region. SNEDDS formulations were evaluated for robustness to dilution, thermodynamic stability study, % transmittance, self-emulsification time, globule size and transmission electron microscopy. The optimized liquid SNEDDS showed robust to all dilutions exhibiting no signs of phase separation or precipitation for 24 h. Liquid SNEDDS was transformed into S-SNEDDS using different adsorbents. Differential scanning calorimetry and scanning electron microscopy studies unravel the transformation of native crystalline state to amorphous state/solubilized state. In vitro dissolution study of S-SNEDDS was found to be significantly higher in comparison to that from plain drug, irrespective of pH (p < 0.001). Furthermore, ex vivo permeation studies showed a 4.45-fold improvement in apparent permeability coefficient (P_app) from S-SNEDDS compared to plain drug. In conclusion, S-SNEDDS prepared using NMP as cosolvent provides an effective approach for improved oral delivery of ATRC.

• Atorvastatin calcium
• bioavailability
• emulsion
• oral drug delivery
• permeability
• SNEDDS
• solubility
• surfactant

Acknowledgements

The author Anuj G. Agrawal would like to thank Mr. S. K. Singh (Director) and Mr. Sanjay Kumar (VPFO) for providing the necessary facilities.

Declarations of interest

We have no personal relationships with other people or organizations that could inappropriately influence the presented work or any affiliation with any organization with a financial interest, direct or indirect, in the subject matter or materials discussed in the manuscript. The author Anuj G. Agrawal is responsible for the content and writing of this article.