The relevance of co-amorphous formulations to develop supersaturated dosage forms: In-vitro, and ex-vivo investigation of Ritonavir-Lopinavir coamorphous materials

Anand, Sai Krishna V and Sakhare, Sujata D and Navya Sree, KS and Nair, Athira R and Varma, Raghava K and Gourishetti, Karthik and Dengale, Swapnil J (2018) The relevance of co-amorphous formulations to develop supersaturated dosage forms: In-vitro, and ex-vivo investigation of Ritonavir-Lopinavir coamorphous materials. European Journal of Pharmaceutical Sciences, 123. pp. 124-134. ISSN 0928-0987

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Abstract

Ritonavir and Lopinavir have previously been demonstrated to decrease the maximum solubility advantage and flux in the presence of each other. The present study investigated the ability of Ritonavir and Lopinavir coamorphous materials to generate a supersaturated state. Further, it explored the precipitation and flux behavior of co-amorphous materials. The co-amorphous materials of Ritonavir and Lopinavir were prepared by quench cool method and characterized in the solid state using XRPD, DSC, FTIR. The solubility studies were conducted in USP phosphate buffer (pH 6.8) for 12 h. The supersaturation potential and precipitation behavior were studied employing pH shift method. Further, the diffusion behavior was explored in vitro and ex-vivo using a semipermeable membrane and intestinal everted sac method, respectively. The results showed that the co-amorphous materials have the potential to generate a supersaturated state. However, the reduction in the amorphous solubility was observed for both the drug(s) and the degree of reduction was found proportionate with the mole fraction of the compound in the co-amorphous material. Interestingly, the flux of both the drugs from coamorphous material of 2:1M ratio (Ritonavir 2: Lopinavir 1) was found exceeding the flux of the individual drugs in the amorphous form. The significant increase in the flux was attributed to the improved drug release properties due to precipitation of drug rich phase of nano/micro dimensions.

Item Type: Article
Uncontrolled Keywords: Ritonavir ; Lopinavir ; Co-amorphous ; Liquid-liquid phase separation ; Solubility ;Flux.
Subjects: Pharmacy > MCOPS Manipal > Pharmaceutical Quality Assurance
Pharmacy > MCOPS Manipal > Pharmacology
Depositing User: KMC Library
Date Deposited: 17 Sep 2018 04:50
Last Modified: 17 Sep 2018 04:50
URI: http://eprints.manipal.edu/id/eprint/151982

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