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Journal of Pharmaceutical Innovation

, Volume 14, Issue 4, pp 305–315 | Cite as

The Assessment of pH-Induced Supersaturation and Impact of an Additional Drug on the Solution Phase Behavior of Saquinavir

  • Sujata D. Sakhare
  • V. Sai Krishna Anand
  • Aishwarya Karan
  • K. Navya Sree
  • S. G. Vasantharaju
  • Girish Pai
  • Swapnil J. DengaleEmail author
Original Article
  • 113 Downloads

Abstract

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 fixed-dose combination and concomitantly administered drugs but also in formulating supersaturated systems like amorphous solid dispersions and co-amorphous systems.

Keywords

Saquinavir Glass-liquid phase separation pH shift supersaturation Amorphous 

Supplementary material

12247_2018_9357_MOESM1_ESM.pdf (110 kb)
ESM 1 (PDF 109 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical SciencesManipal Academy of Higher EducationManipalIndia
  2. 2.Department of Pharmaceutics, Manipal College of Pharmaceutical SciencesManipal Academy of Higher EducationManipalIndia

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