The assessment of pH-induced supersaturation and impact of an additional drug on the solution phase behavior of saquinavir

Sakhare, Sujata D and Anand, Sai Krishna V and Karan, Aishwarya and Navya Sree, KS and Vasantharaju, SG and Pai, Girish K and Dengale, Swapnil J (2019) The assessment of pH-induced supersaturation and impact of an additional drug on the solution phase behavior of saquinavir. Journal of Pharmaceutical Innovation, 14 (4). pp. 305-315. ISSN 1872-5120

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Purpose: The goal of this study was to investigate the ability of saquinavir to generate the in vivo supersaturation and the impact of the presence of another solute, i.e., ritonavir, on the phase behavior of the former. Method: The phase behavior of saquinavir alone and in the presence of ritonavir was studied by pH shift supersaturation assay. The generation of drug-rich phase was confirmed by dynamic light scattering (DLS) and UV extinction method. The nature of precipitate generated after pH shift was investigated by employing DSC and XRPD. Further, the flux studies were performed by employing dialysis membrane using Franz diffusion cell. Results: Saquinavir precipitated in the amorphous form exhibiting type-II precipitation behavior generating the drug-rich phase and undergoing glass-liquid phase separation (GLPS) after the shift in pH towards higher side. The supersaturation advantage of saquinavir was marginally lowered in the presence of amorphous ritonavir. However, the free drug concentration of ritonavir was significantly reduced below the saturation solubility generating a subsaturated state. Both the drugs exhibited lowering in the chemical potential in the presence of each other, thereby reducing their flux/diffusion. The decrease in the free drug concentration and chemical potential were found dependent on the mole fraction of the solute present in the binary supersaturated solution. Conclusion: The findings of the phase behavior of weak bases in the presence of other solutes are of great value not only in fixeddose combination and concomitantly administered drugs but also in formulating supersaturated systems like amorphous solid dispersions and co-amorphous systems.

Item Type: Article
Uncontrolled Keywords: Saquinavir; Glass-liquid phase separation; pH shift supersaturation; amorphous.
Subjects: Pharmacy > MCOPS Manipal > Pharmaceutical Quality Assurance
Pharmacy > MCOPS Manipal > Pharmaceutics
Depositing User: KMC Library
Date Deposited: 24 Jan 2020 13:58
Last Modified: 24 Jan 2020 13:58

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