Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Enhancement of solubility and dissolution rate of atorvastatin calcium by co-crystallization

Yudi Wicaksono^1,2 , Budipratiwi Wisudyaningsih¹, Tri A Siswoyo²

¹Faculty of Pharmacy; ²Center for Development of Advanced Science and Technology, University of Jember, Jember, Indonesia.

For correspondence:- Yudi Wicaksono Email: yudi.farmasi@unej.ac.id Tel:+6285859421020

Received: 16 November 2016 Accepted: 17 June 2017 Published: 31 July 2017

Citation: Wicaksono Y, Wisudyaningsih B, Siswoyo TA. Enhancement of solubility and dissolution rate of atorvastatin calcium by co-crystallization. Trop J Pharm Res 2017; 16(7):1497-1502 doi: 10.4314/tjpr.v16i7.6

© 2017 The authors.
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Abstract

Purpose: To investigate the formation of atorvastatin calcium (AC) co-crystal to improve its solubility and dissolution rate.

Method: Co-crystallization of AC in equimolar ratio with isonicotinamide (INA) was carried out by slow solvent evaporation method using methanol. The solid obtained was characterized by powder x-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and then further evaluated for solubility and dissolution.

Results: The PXRD pattern of ACINA showed new crystalline peaks at 2θ values of 8.2 and 18.3^o, indicating the presence of a new crystalline phase of ACINA co-crystal. The DSC thermogram of ACINA displayed a melting point at 201.7 ^oC which is higher than the melting points of AC (159.4 ^oC) and INA (158.0 ^oC). The FTIR spectra of AC in ACINA shifted the absorption peak from 3363 to 3280 cm^-1 and to 1216 to 1222 cm^-1. The absorption peak shift is presumably due to N-H and C-N groups of AC form the hydrogen bonding interaction with groups in INA molecule. The solubility of ACINA co-crystal in distilled water was 270.7 mg/L which is significantly higher (p < 0.05) than that of pure AC (140.9 mg/L). The dissolution rate of ACINA co-crystal was 2 - 3 times faster than that of pure AC.

Conclusion: AC and INA in equimolar ratio forms a co-crystal by slow solvent evaporation. ACINA co-crystal significantly increases in solubility with a dissolution rate 2 - 3 times faster than that of pure AC. The enhancement of aqueous solubility and dissolution rate of AC with co-crystallization may be a potential way to solving the bioavailability problem of AC.

Keywords: Atorvastatin calcium, Co-crystal, Isonicotinamide, Solubility, Dissolution rate