IMPROVED BIOAVAILABILITY OF ATORVASTATIN AND FENOFIBRATE THROUGH TERNARY SOLID DISPERSIONS: A POLYMER-SUPPORTED METHOD FOR THE ULTIMATE SOLUBILITY ENHANCEMENT

RAMESH BALASAHEB NAWALE; SANJEEV KUMAR SAHU; MANISH VYAS

doi:10.22159/ijap.2025v17i6.54838

Authors

RAMESH BALASAHEB NAWALE Lovely Professional University, Phagwara, Punjab-144411, India
SANJEEV KUMAR SAHU Lovely Professional University, Phagwara, Punjab-144411, India https://orcid.org/0000-0002-5472-1976
MANISH VYAS Lovely Professional University, Phagwara, Punjab-144411, India. Research and Development Cell, Parul University,Vadodara-391760,Gujarat, India

DOI:

https://doi.org/10.22159/ijap.2025v17i6.54838

Keywords:

Atorvastatin, Polyvinyl pyrrolidone, Fenofibrate, Binary solid dispersion, Ternary solid dispersion, Soluplus, Kolliphor® P 407, Kollidon, Pharmacokinetics

Abstract

Objective: This study aimed to improve the solubility and dissolution rate of a fixed-dose combination of atorvastatin (ATR) and fenofibrate (FEN) characterized by poor solubility via solid dispersion techniques.

Methods: Soluplus and Kollidon were used for formulating binary solid dispersion (BSD), and PVP and Kollidon were used for ternary solid dispersion (TSD) employing the solvent evaporation technique. Saturation solubility studies and in vitro drug release were done to quantify improvements in solubility and drug dissolution. Further characterization of solid dispersions was carried out by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR).

Results: Among binary systems, the SF8 formulation (drug-to-Soluplus® ratio of 1:4) showed an edge in solubilization enhancement, dissolution rate, and other physicochemical properties. The ternary composition KDF11 exhibited the best performance in terms of solubility and dissolution rate. In vivo, pharmacokinetic studies reaffirmed that drug bioavailability was greatly improved. SF8 BSD increased solubility by 17-fold. ATR solid dispersion produced 2.87 times more C_max and 2.56 times more AUC₀–₂₄ₕ while FEN nanoformulation produced 3.56 times more C_max and 3.44 times more AUC₀–₂₄ₕ after their pure drug counterparts. C_max increased 2.87-fold for ATR. These increases can be understood to be attributed to the conversion of the crystalline structure into an amorphous state, thereby enhancing solubility and facilitating a more favorable concentration gradient across gastrointestinal and systemic barriers.

Conclusion: The study demonstrated that in the ternary system, solid dispersion formulations were very much better than binary dispersions in improving the solubility and dissolution of poorly soluble drug combinations. TSD offers a viable strategy for enhancing FDC bioavailability with potential application in the effective management of hyperlipidemia.

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