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Mechanistic Insight of Polymer Effects on the Kinetic of Solution-Mediated Phase Transformation of Nitrofurantoin Anhydrate to Monohydrate

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Abstract

Purpose

Nitrofurantoin is an effective antibacterial drug for the treatment of lower urinary tract infection. However, the anhydrate form can easily transform to the less soluble hydrate form (monohydrate) during dissolution, resulting in a reduction of dissolution rate and oral bioavailability. Therefore, inhibition of phase transformation is vital to stabilize the quality of drugs.

Methods

In this work, the potential of polyethylene glycol (PEG 8000), polyvinyl pyrrolidone (PVP K30), poloxamer 188 and hydroxypropyl methylcellulose (HPMC) to inhibit the hydration of nitrofurantoin during dissolution was investigated by experimental and simulation approaches.

Results

The rates of phase transformation were decreased in the presence of PEG 8000 and poloxamer 188, and PVP K30 and HPMC completely inhibited the phase transformation of anhydrate. The abundant hydrogen bond donor and acceptor groups of PVP and HPMC may easily establish intermolecular interactions with nitrofurantoin molecules, accounting for stronger inhibition of nucleation. Besides, the molecular dynamic simulation further indicated the formation of more extensive interactions between PVP K30 (or HPMC) and the (111) face of monohydrate, suggesting that the strong absorption of polymers on the surface and thus block the sites for incorporation of new growth.

Conclusion

This study provides a mechanistic insight into the inhibition of nitrofurantoin hydration by polymeric additives, which helps design formulations and improve the physical stability of anhydrate.

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Data Availability

Data available on request from the authors.

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Acknowledgements

The authors are grateful for the financial support to this work from the National Natural Science Foundation of China (No. 81872813, 22108313, 82273880), Natural Science Foundation of Jiangsu Province (BK 20200576), Fundamental Research Funds for the Central Universities (No 2632022ZD16).

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Authors and Affiliations

  1. State Key Laboratory of Natural Medicines, Department of Pharmaceutics, College of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China

    Xiyan Wang, Xiaohong Ji, Ting Cai & Minshan Guo

  2. Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing, 210009, China

    Ting Cai

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  1. Xiyan Wang
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Wang, X., Ji, X., Cai, T. et al. Mechanistic Insight of Polymer Effects on the Kinetic of Solution-Mediated Phase Transformation of Nitrofurantoin Anhydrate to Monohydrate. Pharm Res 40, 1587–1598 (2023). https://doi.org/10.1007/s11095-023-03513-0

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  • DOI: https://doi.org/10.1007/s11095-023-03513-0

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