title: Preparation and characterization of co-amorphous Ritonavir-Indomethacin systems by solvent evaporation technique: improved dissolution behavior and physical stability without evidence of intermolecular interactions.
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 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.
authors.affiliation: Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104, India. Electronic address: swapnil.jd@manipal.edu.
authors.forename: Swapnil J
authors.initials: SJ
authors.lastname: Dengale
authors.affiliation: Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104, India.
authors.forename: Om Prakash
authors.initials: OP
authors.lastname: Ranjan
authors.affiliation: Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104, India.
authors.forename: Syed Sajjad
authors.initials: SS
authors.lastname: Hussen
authors.affiliation: Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104, India.
authors.forename: B S M
authors.initials: BS
authors.lastname: Krishna
authors.affiliation: Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104, India.
authors.forename: Prashant B
authors.initials: PB
authors.lastname: Musmade
authors.affiliation: Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104, India.
authors.forename: G
authors.initials: G
authors.lastname: Gautham Shenoy
authors.affiliation: Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104, India.
authors.forename: Krishnamurthy
authors.initials: K
authors.lastname: Bhat
mesh_terms: D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004355:Drug Stability; D005898:Glass; D007213:Indomethacin / Q000737:chemistry*; D033362:Powder Diffraction; D019438:Ritonavir / Q000737:chemistry*; D012995:Solubility; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared; D044366:Transition Temperature; D014961:X-Ray Diffraction
chemical_list: D012997:Solvents; D019438:Ritonavir; D007213:Indomethacin
keywords: Amorphous forms; Dissolution; Indomethacin; Ritonavir; Solubility