TY - JOUR
T1 - Preparation and characterization of co-amorphous Ritonavir-Indomethacin systems by solvent evaporation technique
T2 - Improved dissolution behavior and physical stability without evidence of intermolecular interactions
AU - Dengale, Swapnil J.
AU - Ranjan, Om Prakash
AU - Hussen, Syed Sajjad
AU - Krishna, B. S.M.
AU - Musmade, Prashant B.
AU - Gautham Shenoy, G.
AU - Bhat, Krishnamurthy
PY - 2014/10/1
Y1 - 2014/10/1
N2 - The aim of this study was to stabilize the amorphous form of Ritonavir (RTV) a BCS class-II drug with known amorphous stabilizing small molecule Indomethacin (IND) by co-amorphous technology. The co-amorphous samples were prepared by solvent evaporation technique in the molar ratios RTV:IND (2:1), RTV:IND (1:1), RTV:IND (1:2) and their amorphous nature was confirmed by XRPD, DSC and FT-IR. Physical stability studies were carried out at temp 25 °C and 40 °C for maximum up to 90 days under dry conditions. Solubility and dissolution testing were carried out to investigate the dissolution advantage of prepared co-amorphous systems. The amorphous mixtures of all tested molar ratios were found to become amorphous after solvent evaporation. The same was confirmed by detecting halo pattern in diffractograms of co-amorphous mixtures. The Tg values of all three systems were found to be more than 40 °C, the highest being 51.88 °C for RTV:IND (2:1) system. Theoretical Tg values were calculated by Gordon-Taylor equation. Insignificant deviation of theoretical Tg values from that of practical one, corroborated by FT-IR studies showed no evidence of intermolecular interactions between RTV and IND. Almost 3-folds increase in the solubility for both amorphous RTV and IND was found as compared to their respective crystalline counterparts. The study demonstrated significant increase in the dissolution rate as well as increase in the total amount of drug dissolved for amorphous RTV, however it failed to demonstrate any significant improvement in the dissolution behavior of IND.
AB - The aim of this study was to stabilize the amorphous form of Ritonavir (RTV) a BCS class-II drug with known amorphous stabilizing small molecule Indomethacin (IND) by co-amorphous technology. The co-amorphous samples were prepared by solvent evaporation technique in the molar ratios RTV:IND (2:1), RTV:IND (1:1), RTV:IND (1:2) and their amorphous nature was confirmed by XRPD, DSC and FT-IR. Physical stability studies were carried out at temp 25 °C and 40 °C for maximum up to 90 days under dry conditions. Solubility and dissolution testing were carried out to investigate the dissolution advantage of prepared co-amorphous systems. The amorphous mixtures of all tested molar ratios were found to become amorphous after solvent evaporation. The same was confirmed by detecting halo pattern in diffractograms of co-amorphous mixtures. The Tg values of all three systems were found to be more than 40 °C, the highest being 51.88 °C for RTV:IND (2:1) system. Theoretical Tg values were calculated by Gordon-Taylor equation. Insignificant deviation of theoretical Tg values from that of practical one, corroborated by FT-IR studies showed no evidence of intermolecular interactions between RTV and IND. Almost 3-folds increase in the solubility for both amorphous RTV and IND was found as compared to their respective crystalline counterparts. The study demonstrated significant increase in the dissolution rate as well as increase in the total amount of drug dissolved for amorphous RTV, however it failed to demonstrate any significant improvement in the dissolution behavior of IND.
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U2 - 10.1016/j.ejps.2014.05.015
DO - 10.1016/j.ejps.2014.05.015
M3 - Article
C2 - 24878386
AN - SCOPUS:84902345480
SN - 0928-0987
VL - 62
SP - 57
EP - 64
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
ER -