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KMID : 1146920220520050639
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Journal of Pharmaceutical Investigation
2022 Volume.52 No. 5 p.639 ~ p.648
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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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Lei Fang
Zhang Huimin
Luo Rui
Fei Qingsong
Bai Luyu
He Ning
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Abstract
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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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KEYWORD
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Desmopressin acetate, In situ gel, Intraocular, Administration, Pharmacokinetics, Pharmacodynamic
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