Solubility-permeability interplay of hydrotropic solubilization of piroxicam

Abstract

Objectives

In this research paper, an investigation has been made to assess the simultaneous effect of a solubility enhancement approach, i.e., hydrotropy on the solubility and apparent permeability of piroxicam. The solubility of piroxicam (PRX) a BCS (biopharmaceutics classification system) class II drug has been increased using a mixed hydrotropy approach. This study is based on identifying the pattern of solubility-permeability interplay and confirming whether every solubility gain results in a concomitant decrease in permeability or permeability remains unaffected.

Method

Solid dispersions of PRX were formulated using two hydrotropes, viz., sodium benzoate (SB) and piperazine (PP) by solvent evaporation method. A comprehensive 3²factorial design was employed to study the effect of hydrotropes on the solubility and permeability of PRX. Subsequently, PRX tablets containing these solid dispersions were formulated and evaluated.

Key findings

SB and PP displayed a significant increase in the solubility of PRX ranging from 0.99 to 2.21 mg/mL for F1–F9 batches attributed to the synergistic effect of hydrotropes. However, there is a reduction in PRX permeability with increasing hydrotrope levels. The decline in permeability was notably less pronounced compared to the simultaneous rise in aqueous solubility of PRX.

Conclusion

An evident tradeoff between permeability and solubility emerged through the mixed hydrotropic solubilization for PRX. As PRX has generally higher intrinsic permeability, it has been assumed that this permeability loss will not affect the overall absorption of PRX. However, it may affect the absorption of drugs with limited permeability. Therefore, solubility permeability interplay should be investigated during solubility enhancement.

Graphical Abstract

Keywords:

• Mixed hydrotropes
• optimization
• sodium benzoate
• piperazine
• solubility
• permeability

Author contributions

The aquisition, analysis or interpretation of data and original draft of manuscript was prepared by Dr. Nidhi Nainwal. Mr. Surojit Banerjee helped in writing and substantive revision. Dr. Vikas Anand Saharan provided research supervision, project administration, review and editing of the manuscript. Dr. Ranjit Singh and Dr. Sunil Jawla provided the research supervision and research support.

Data availability

The authors confirm that the data supporting the findings of this study are available within the article.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.