Amit Kumar Aggarwal1, Samarpreet Singh. 1. Department of Pharmaceutical Chemistry, G.H.G. Khalsa College of Pharmacy, Gurusar Sadhar, Ludhiana, Punjab, India. amitaggarwal78@yahoo.co.in
Abstract
OBJECTIVE: Diacerein (DCN) is a new anti-inflammatory analgesic and antipyretic drug developed specially for the treatment of osteoarthritis. DCN is a poorly water-soluble drug with relatively low bioavailability. Therefore, the purpose of this study was to enhance the solubility and dissolution of DCN by complexation with polyethylene glycol 6000 (PEG). METHODS: Solid dispersions (SDs) of DCN were prepared in weight ratios of 60:40, 40:60, 20:80, and 5:95 by the melting method using PEG as carrier. These SDs were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared (FTIR) spectroscopy to ascertain whether there were any physicochemical interactions between drug and carrier that could affect dissolution. Solubility and dissolution studies were conducted with pure DCN, physical mixtures (PMs) and SDs. RESULTS AND DISCUSSION: Solubility studies indicated that PEG significantly increased the solubility of DCN in water. The Gibbs free energy (ΔG(tr)°) values were negative, indicating the spontaneous nature of DCN solubilization. Phase solubility studies indicated complex with a possible stoichiometry of 1:1. CONCLUSION: FTIR, DSC and PXRD studies indicate that there is no chemical interaction between DCN and PEG in solid state. In contrast to slow dissolution rate of pure DCN, the dispersion of drug in PEG considerably enhanced the dissolution rate. Even PMs of DCN prepared with PEG also showed better dissolution profiles compared with that of DCN, indicating the solubilization effect of PEG. Therefore, it is concluded that the preparation of SDs of DCN with PEG provides a promising way to increase its solubility and dissolution rate.
OBJECTIVE: Diacerein (DCN) is a new anti-inflammatory analgesic and antipyretic drug developed specially for the treatment of osteoarthritis. DCN is a poorly water-soluble drug with relatively low bioavailability. Therefore, the purpose of this study was to enhance the solubility and dissolution of DCN by complexation with polyethylene glycol 6000 (PEG). METHODS: Solid dispersions (SDs) of DCN were prepared in weight ratios of 60:40, 40:60, 20:80, and 5:95 by the melting method using PEG as carrier. These SDs were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared (FTIR) spectroscopy to ascertain whether there were any physicochemical interactions between drug and carrier that could affect dissolution. Solubility and dissolution studies were conducted with pure DCN, physical mixtures (PMs) and SDs. RESULTS AND DISCUSSION: Solubility studies indicated that PEG significantly increased the solubility of DCN in water. The Gibbs free energy (ΔG(tr)°) values were negative, indicating the spontaneous nature of DCN solubilization. Phase solubility studies indicated complex with a possible stoichiometry of 1:1. CONCLUSION: FTIR, DSC and PXRD studies indicate that there is no chemical interaction between DCN and PEG in solid state. In contrast to slow dissolution rate of pure DCN, the dispersion of drug in PEG considerably enhanced the dissolution rate. Even PMs of DCN prepared with PEG also showed better dissolution profiles compared with that of DCN, indicating the solubilization effect of PEG. Therefore, it is concluded that the preparation of SDs of DCN with PEG provides a promising way to increase its solubility and dissolution rate.