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Evaluation of the rheological and rupture properties of gelatin-based hydrogels blended with polymers to determine their drug diffusion behavior

Polymer Journal volume 54, pages 1477–1487 (2022)Cite this article

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Abstract

In this study, the drug diffusion behavior and kinetics of gelatin hydrogels that were prepared with polymers were evaluated in terms of their rheological and rupture properties. The rheological and rupture properties of polymer-blended hydrogels prepared at pH 5.5 indicated that gelatin was homogeneously mixed with hydroxypropyl methylcellulose phthalate (HPMCP) or methacrylic acid-ethyl acrylate copolymer (Eudragit®) but not with hydroxypropyl methylcellulose or hydroxypropyl methylcellulose acetate succinate. We found that the release rate of nizatidine, a water-soluble drug, from the gelatin/HPMCP hydrogels might be inhibited compared with that from the gelatin/Eudragit® hydrogels at pH 1.2. This was because compared to the gelatin/Eudragit® hydrogels, the gelatin/HPMCP hydrogels had a higher crossover point between the strain-dependent storage and loss moduli. In addition, the gelatin/HPMCP and gelatin/Eudragit® hydrogels showed an increase in rupture stress and strain when the polymer content was increased. The drug diffusion mechanism of the gelatin/HPMCP hydrogel formulations from pH 1.0 to 6.0 was identified using four kinetic models. The findings indicated that the drug diffusion behavior of the gelatin/HPMCP gels below pH 2.0 was governed by diffusion of the drug. These results demonstrate that gelatin-based hydrogels with HPMCP are potential candidates for inhibiting the release of nizatidine in a gastric pH medium.

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Acknowledgements

We would like to thank Dr Hiroki Iwase (Comprehensive Research Organization for Science and Society; CROSS) for providing advice and Misaki Ueda (CROSS) for technical assistance with the viscoelastic measurements. We are also grateful to Shin-Etsu Chemical Co., Ltd. (Tokyo, Japan) for the kind gift of hydroxypropyl methylcellulose (HPMC, TC-5®), hydroxypropyl methylcellulose phthalate (HPMCP, HPMCP®−55), and hydroxypropyl methylcellulose acetate succinate (HPMCAS, Shin-Etsu AQOAT® AS-LF). We are also grateful to Unitec Foods Co., Ltd. (Tokyo, Japan) and Evonik Industries (Essen, Germany) for giving us gelatin (Type B, 250 Bloom) and methacrylic acid-ethyl acrylate copolymer (Eudragit® L100-55), respectively. Satoshi Nogami was supported by Nagai Memorial Research Scholarship from the Pharmaceutical Society of Japan (Tokyo, Japan).

Funding

This research was partially supported by the Hosokawa Powder Technology Foundation (Osaka, Japan).

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Authors and Affiliations

  1. Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan

    Satoshi Nogami, Kazunori Kadota, Hiromasa Uchiyama & Yuichi Tozuka

  2. Neutron Science and Technology Center, Comprehensive Research Organization for Science and Society, Tokai, Ibaraki, 319-1106, Japan

    Hiroshi Arima-Osonoi & Mitsuhiro Shibayama

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  1. Satoshi Nogami
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Correspondence to Kazunori Kadota or Yuichi Tozuka.

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Nogami, S., Kadota, K., Uchiyama, H. et al. Evaluation of the rheological and rupture properties of gelatin-based hydrogels blended with polymers to determine their drug diffusion behavior. Polym J 54, 1477–1487 (2022). https://doi.org/10.1038/s41428-022-00681-5

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