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Use of Flory–Huggins Interaction Parameter and Contact Angle Values to Predict the Suitability of the Drug-Polymer System for the Production and Stability of Nanosuspensions

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Abstract

Purpose

Use of Flory–Huggins interaction parameter and contact angle values to predict the suitability of the drug-polymer system for the production and stability of nanosuspensions.

Material and Methods

Melting point depression of the drug was measured using differential scanning calorimetry. Interaction parameter, χ, was calculated using the melting point depression data to elucidate the drug-polymer interaction strength to predict the suitability of the drug-polymer system for the production and stability of nanosuspensions. Contact angle of the drug films were measured with purified water and 0.1%w/w polymer solutions to predict polymer’s suitability for the production and stability of nanosuspension. Nanosuspensions were manufactured to validate the application of the melting point depression approach along with surface property information.

Results

All three polymers, HPMC, Soluplus®, and poloxamer exhibited a negative interaction parameter with naproxen and budesonide. Higher negative interaction parameter values for the naproxen-polymer system indicated stronger drug-polymer interactions, while smaller negative interaction parameter values for the budesonide-polymer system indicated weaker drug-polymer interactions. Interaction parameter was not obtained for fenofibrate with HPMC and Soluplus®, and similarly, no interaction parameter was obtained for carvedilol with HPMC, most likely due to weaker drug-polymer interactions. All three polymers provided lower equilibrium contact angle values when compared to purified water, indicating an affinity for polymers.

Conclusions

Successful production and stability of several nanosuspensions were correlated with Flory–Huggins’s interaction parameter and contact angle values. In the absence of melting point depression, contact angle values can also be used predict the agglomeration tendencies as we have shown for this study.

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Acknowledgements

Thanks to BASF and Ashland for providing the polymer samples free of charge. The author thanks Dr. Shah and Dr. Desai for providing some of the drugs for this research.

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  1. University of the Sciences in Philadelphia, 600 S 43rd Street, Philadelphia, PA, 19104, USA

    Rakesh K. Patel, Sriramakamal Jonnalagadda & Pardeep K. Gupta

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Patel, R.K., Jonnalagadda, S. & Gupta, P.K. Use of Flory–Huggins Interaction Parameter and Contact Angle Values to Predict the Suitability of the Drug-Polymer System for the Production and Stability of Nanosuspensions. Pharm Res 39, 1001–1017 (2022). https://doi.org/10.1007/s11095-022-03269-z

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