The relevance of co-amorphous formulations to develop supersaturated dosage forms

In-vitro, and ex-vivo investigation of Ritonavir-Lopinavir co-amorphous materials

V. Sai Krishna Anand, Sujata D. Sakhare, K. S. Navya Sree, Athira R. Nair, K. Raghava Varma, Karthik Gourishetti, Swapnil J. Dengale

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 co-amorphous 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 co-amorphous material of 2:1 M 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.

Original languageEnglish
Pages (from-to)124-134
Number of pages11
JournalEuropean Journal of Pharmaceutical Sciences
Volume123
DOIs
Publication statusPublished - 15-10-2018

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Lopinavir
Ritonavir
Dosage Forms
Solubility
Pharmaceutical Preparations
Fourier Transform Infrared Spectroscopy
Buffers
Phosphates
Membranes
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

Sai Krishna Anand, V. ; Sakhare, Sujata D. ; Navya Sree, K. S. ; Nair, Athira R. ; Raghava Varma, K. ; Gourishetti, Karthik ; Dengale, Swapnil J. / The relevance of co-amorphous formulations to develop supersaturated dosage forms : In-vitro, and ex-vivo investigation of Ritonavir-Lopinavir co-amorphous materials. In: European Journal of Pharmaceutical Sciences. 2018 ; Vol. 123. pp. 124-134.
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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 co-amorphous 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 co-amorphous material of 2:1 M 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.",
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The relevance of co-amorphous formulations to develop supersaturated dosage forms : In-vitro, and ex-vivo investigation of Ritonavir-Lopinavir co-amorphous materials. / Sai Krishna Anand, V.; Sakhare, Sujata D.; Navya Sree, K. S.; Nair, Athira R.; Raghava Varma, K.; Gourishetti, Karthik; Dengale, Swapnil J.

In: European Journal of Pharmaceutical Sciences, Vol. 123, 15.10.2018, p. 124-134.

Research output: Contribution to journalArticle

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T2 - In-vitro, and ex-vivo investigation of Ritonavir-Lopinavir co-amorphous materials

AU - Sai Krishna Anand, V.

AU - Sakhare, Sujata D.

AU - Navya Sree, K. S.

AU - Nair, Athira R.

AU - Raghava Varma, K.

AU - Gourishetti, Karthik

AU - Dengale, Swapnil J.

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