Preparation and characterization of co-amorphous Ritonavir–Indomethacin systems by solvent evaporation technique: Improved dissolution behavior and physical stability without evidence of intermolecular interactions

Dengale, Swapnil J and Ranjan, Om Prakash and Hussen, Syed Sajjad and Krishna, BSM and Musmade, Prashant B and Shenoy, Gautham G and Bhat, Krishnamurthy (2014) Preparation and characterization of co-amorphous Ritonavir–Indomethacin systems by solvent evaporation technique: Improved dissolution behavior and physical stability without evidence of intermolecular interactions. European Journal of Pharmaceutical Sciences, 62. pp. 57-64. ISSN 0928-0987

[img] PDF
RTV_EJPS_Final version.pdf - Published Version
Restricted to Registered users only

Download (937kB) | Request a copy

Abstract

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 FTIR. 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 amorpho s 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.

Item Type: Article
Uncontrolled Keywords: Amorphous forms ; Solubility ; Dissolution ; Indomethacin ;Ritonavir.
Subjects: Pharmacy > MCOPS Manipal > Pharmaceutical Chemistry
Pharmacy > MCOPS Manipal > Pharmaceutical Quality Assurance
Pharmacy > MCOPS Manipal > Pharmaceutics
Depositing User: KMC Manipal
Date Deposited: 19 Jun 2014 07:39
Last Modified: 19 Jun 2014 07:39
URI: http://eprints.manipal.edu/id/eprint/139832

Actions (login required)

View Item View Item