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Sustained ocular delivery of desmopressin acetate via thermoreversible in situ gel formulation: preparation and in vitro/in vivo evaluation

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Abstract

Purpose

The present study was designed to formulate a thermoreversible in situ gel system for sustained ocular delivery of desmopressin acetate (DDAVP) for the treatment of polyuria.

Methods

The cold method was employed for the preparation of in situ gel formulations using different levels of poloxamer 407 (F-127) and carboxymethyl chitosan (CMCTS). The optimal formulation was selected based on gelation temperature, rheological behavior, and in vitro drug release, and further evaluated by thermal, ocular irritation, residence time, in vivo pharmacokinetics, and pharmacodynamic analyses.

Results

The optimal formulation, composed of F-127 (20%) and CMCTS (1.5%), showed appropriate fluidity at room temperature (25 °C) and transitioned to semisolid gels at physiological temperature (34 °C). The optimal gels showed pseudoplastic fluid properties and favorable thixotropy characteristics in rheological tests. Differential scanning calorimetry analysis revealed even dispersal of DDAVP in the matrix of gels. Results from in vivo studies demonstrated that the newly prepared gel successfully prolonged the residence time of DDAVP, improved ocular bioavailability, and exerted the same antidiuretic effect as ophthalmic drops.

Conclusion

The developed thermoreversible ophthalmic in situ gel of DDAVP presents a promising formulation for the treatment of polyuria.

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Authors and Affiliations

  1. Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, 350 Longzihu Road, Hefei, 230012, China

    Fang Lei, Huimin Zhang, Rui Luo, Qingsong Fei, Luyu Bai & Ning He

  2. Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Hefei, 230012, China

    Ning He

  3. Institute of Pharmaceutics, Anhui Academy of Chinese Medical Sciences, Hefei, 230012, China

    Ning He

  4. Engineering Technology Research Center of Modern Pharmaceutical Preparation, Anhui Province, Hefei, 230012, China

    Ning He

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  1. Fang Lei
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Correspondence to Ning He.

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All authors (F. Lei, H. Zhang, R. Luo, Q. Fei, L. Bai, and N. He) declare no conflict of interest.

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This article does not contain any studies with human subjects performed by any of the authors; all animal experiments were conducted following the guidelines of the Anhui University of Chinese Medicine Animal Care and Use Committee (Document number AHUCM-rabbits-2021132).

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Lei, F., Zhang, H., Luo, R. et al. Sustained ocular delivery of desmopressin acetate via thermoreversible in situ gel formulation: preparation and in vitro/in vivo evaluation. J. Pharm. Investig. 52, 639–648 (2022). https://doi.org/10.1007/s40005-022-00592-w

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