Optimizing Nateglinide Liquisolid Compacts: Achieving Formulation Excellence Through the Quality by Design Approach

Abstract

Purpose

The present study aimed to improve the dissolution properties of nateglinide, an anionic drug with poor water solubility and a high log P value, which results in decreased solubility in acidic pH environments. Additionally, the research sought to evaluate the effectiveness of the liquisolid compact technique as a simple, scalable, and cost-efficient approach for enhancing the nateglinide dissolution rate.

Methods

Employing the central composite design (CCD), formulations were prepared with microcrystalline cellulose (carrier), colloidal silicon dioxide (coating materials), and polyethylene glycol 400 utilized as a non-volatile vehicle. Utilizing Response Surface Methodology (RSM), the formulation was optimized with drug concentration and excipient ratios as independent variables, while evaluations focused on the angle of repose, Carr’s index, and percentage cumulative drug release as dependent responses.

Results

The findings demonstrated that liquisolid compacts exhibited superior dissolution profiles (99.13%) and favourable flow properties and compressible properties (angle of repose of 20.53⁰ and Carr’s compressibility index of 12.37% compared to directly compressible tablets. Further analyses through FTIR, DSC, and XRD studies indicated that enhanced dissolution of the drug could exist in an amorphous form or molecular dispersion state.

Conclusion

In conclusion, this work successfully established that the liquisolid compact presents a novel method for enhancing the dissolution rate of nateglinide in acidic pH conditions.