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Abstract
Objective
To investigate the in-situ physicochemical interaction of Rifampicin and Ritonavir - Lopinavir Solid dispersion administered for the treatment of comorbid conditions i.e. Tuberculosis and HIV/AIDS.
Methods
pH-shift dissolution of Rifampicin (RIF) in presence of Ritonavir-Lopinavir solid dispersion (RL-SD) was carried out in USP phosphate buffer 6.8 and FaSSIF. Equilibrium and amorphous solubility were determined for the drugs. Pure drugs, their physical mixtures, and pH-shifted co-precipitated samples were characterized using DSC, PXRD, and FTIR. Fluorescence spectroscopy was used to investigate drug-rich and drug-lean phases. In-vitro and ex-vivo flux studies were also carried out.
Results
The results showed significant differences in the solubility and dissolution profiles of RTV and LOP in the presence of RIF, while RIF profile remained unchanged. Amorphicity, intermolecular interaction and aggregate formation in pH-shifted samples were revealed in DSC, XRD and FTIR analysis. Fluorescence spectroscopy confirmed the formation of drug-rich phase upon pH-shift. In-vitro and ex-vivo flux studies revealed significant reduction in the flux of all the drugs when studied in presence of second drug.
Conclusion
RIF, RTV and LOP in presence of each other on pH-shift, results in co-precipitation in the amorphous form (miscible) which leads to reduction in the highest attainable degree of supersaturation. This reduction corresponds to the mole fraction of the RIF, RTV and LOP within the studied system. These findings suggest that the concomitant administration of these drugs may lead to physicochemical interactions and possible ineffective therapy.
Acknowledgments
The authors would like to acknowledge Lupin Limited and Hetero Drugs Limited for providing gift samples of drugs for the research. The authors would also like to acknowledge that this research work was presented as poster in Manipal Research Colloquium (MRC 2023), Manipal Academy of Higher Education, Manipal by the same authors.
Authors’ contributions
Athira R Nair: investigation, experimentation, data curation, conceptualization, and writing of original draft; Vullendula Sai Krishna Anand, Dani Lakshman Yarlagadda, Bheemisetty Brahmam: experimentation, reviewing, Swapnil J. Dengale: conceptualization, and supervision, Krishnamurthy Bhat: conceptualization, reviewing, and supervision.
Disclosure statement
The authors declare that there are no conflicts of interest regarding the publication of this article.