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Purpose: To improve the solubility and bioavailability of atorvastatin calcium (ATC), a poorly watersoluble 3-hydroxy 3-methyl glutaryl CoA (HMG-CoA) reductase inhibitor, by a solid dispersion technique using polyethylene glycol 6000 (PEG 6000) or polyvinylpyrrolidone k30 (PVP K30).
Methods: The solid dispersions were characterised by differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD) and Fourier transformed infrared (FT-IR) spectroscopy. The dissolution characteristics of the formulations were determined in vitro, while the bioavailability of the solid dispersion and suspension was evaluated in rats.
Results: DSC, PXRD and FT-IR data confirmed the formation of solid dispersion. The dissolution results showed that almost 95 % of ATC in ATC- PVP K30 solid dispersion dissolved in 5 min. The amount of ATC in ATC-PVP K30 SD, ATC-PEG 6000 SD and pure ATC that dissolved in 60 min was 103, 85 and 93 %, respectively. In addition, in vivo bioavailability studies in rats showed that area under concentration-time curve (AUC) and peak concentration (Cmax) of ATC-PVP K30 solid dispersion was 3.5-fold and 4.9-fold higher than that of the drug in suspension. Time to attain peak concentration (Tmax) of ATC-PVP K30 solid dispersion was 0.25 ± 0.00 h, which is shorter than 0.83 ± 0.26 h for suspension.
Conclusion: The results obtained indicates that solid dispersions of ATC made with polyethylene glycol 6000 and polyvinylpyrrolidone K30 are an effective new approach to designing formulations of poorly soluble ATC for greatly enhanced solubility and bioavailability.
Keywords: Solid dispersion, Atorvastatin, Polyethylene glycol, Polyvinypyrrolidone K30, Bioavailability, Dissolution