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Insights into the Role of Compendial/Biorelevant Media on the Supersaturation Behaviour of Drug Combination (Drug-Drug Interaction) and Precipitation Inhibition by Polymers

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Abstract

Combination drug therapy (CDT) plays an immense role in the treatment of various diseases such as malaria, hypertension, cancer, HIV-AIDS, helminthiasis, and many more. However, in vitro drug-drug interaction (DDI) is not well reported for better efficacy of CDT. In DDI one drug may enhance the precipitation of other drugs thereby reducing the advantage of CDT. Herein, we report DDI in terms of in vitro precipitation of drugs with albendazole and mebendazole. This may be the first report to propensate the possibility of either drug precipitation in the combination. These drugs are categorized into BCS class II weak base and hence have tendency to precipitate in the gastrointestinal tract. The objective of this study is to find precipitation of drug combinations in different compendial and biorelevant media (deionized water, phosphate buffer pH 6.8, FaSSIF, and FeSSIF) and screening of the polymers for precipitation inhibition. Nine polymers were investigated at three different concentrations in terms of their drug-polymer solubility, in vitro precipitation behavior, induction time, SHC, and droplet size. Although, all the polymers inhibit the precipitation of drugs, the extent of precipitation inhibition for Soluplus is high. The obtained drug-polymer precipitates were filtered, dried, and analyzed for amorphous/partial amorphous form using polarised light microscopy (PLM), differential scanning calorimetry (DSC), and powder X-ray diffractometry (PXRD). The drug-polymer interaction was examined using Fourier transform infrared (FTIR) spectroscopy and nuclear magnetic resonance (NMR) revealing the effect of polymers on drug precipitation. These insights may further be used in the formulation of CDT for helminthiasis management.

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Abbreviations

ABZ:

Albendazole

MBZ:

Mebendazole

WHO:

World Health Organization

AMB:

Albendazole-mebendazole

DW:

Deionized water

PB:

Phosphate buffer pH 6.8

FaSSIF:

Fasted state simulated intestinal fluid

FeSSIF:

Fed state simulated intestinal fluid

PVA:

Polyvinyl alcohol

PVP K10:

Polyvinyl pyrolidone K10

PVP K30:

Polyvinyl pyrolidone K30

PVP K90:

Polyvinyl pyrolidone K90

PVP VA64:

Polyvinyl pyrolidone vinyl acetate

SDS:

Sodium dodecyl sulfate

SOL:

Soluplus

POLX:

Poloxamer/Pluronics F68

KOLLI:

Kolliphor/Solutol HS15

PIs:

Precipitation inhibitors

STH:

Soil-transmitted helminths

PLM:

Polarized light microscopy

DLS:

Dynamic light scattering

FTIR:

Fourier transform infrared spectroscopy

NMR:

Nuclear magnetic resonance

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Acknowledgements

The authors would like to acknowledge the Director, NIPER S.A.S. Nagar, for providing the necessary facilities and infrastructure.

Funding

The authors are grateful to NIPER, SAS Nagar for providing financial support for this project.

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Authors and Affiliations

  1. Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Mohali, Punjab, 160062, India

    Prachi Joshi & Abhay T. Sangamwar

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Contributions

Prachi Joshi: conceptualization, data curation, formal analysis, investigation, writing—original draft, and writing—review and editing.

Abhay T Sangamwar: conceptualization, data curation, formal analysis, project administration, validation, and writing—review and editing.

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Correspondence to Abhay T. Sangamwar.

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Joshi, P., Sangamwar, A.T. Insights into the Role of Compendial/Biorelevant Media on the Supersaturation Behaviour of Drug Combination (Drug-Drug Interaction) and Precipitation Inhibition by Polymers. AAPS PharmSciTech 23, 300 (2022). https://doi.org/10.1208/s12249-022-02448-w

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