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Stable Atropine Loaded Film As a Potential Ocular Delivery System For Treatment Of Myopia

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Abstract

Purpose

The objective of the present study was to prepare stable and high bioavailability ocular atropine loaded films (ATR-films) as potential ocular drug delivery systems for the treatment of myopia.

Methods

ATR-films were prepared by the solvent casting method and the physical properties of films were evaluated including thickness, water content, light transparency, disintegration time, and mechanical properties. FT-IR, DSC, XRD, TGA, AFM, and Raman spectroscopy were performed to characterize the film. The stability test was conducted under different conditions, such as high humidity, high temperature, and strong light. The pharmacokinetic study and irritation assessment were conducted in rabbits. The efficacy of ATR-films was evaluated by refraction and ocular biometry in myopia guinea pigs.

Result

After optimizing the formulation, the resulting ATR-film was flexible and transparent with lower water content (8.43% ± 1.25). As expected, the ATR-film was stable and hydrolysate was not detected, while the content of hydrolysate in ATR eye drops can reach up to 8.1867% (limit: < 0.2%) in the stability study. The safety assessment both in vitro and in vivo confirmed that the ATR-film was biocompatible. Moreover, the bioavailability (conjunctiva 3.21-fold, cornea 2.87-fold, retina 1.35-fold, sclera 2.05-fold) was greatly improved compared with the ATR eye drops in vivo pharmacokinetic study. The pharmacodynamic study results showed that the ATR-film can slow the progress of form-deprivation myopia (~ 100 ± 0.81D), indicating that it has a certain therapeutic effect on form-deprivation myopia.

Conclusion

The ATR-film with good stability and high bioavailability will have great potential for the treatment of myopia.

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Acknowledgements

This work was supported by the National Mega-project for Innovative Drugs [2019ZX09721001], National Key R&D Program of China [2020YFE0201700], Liaoning Revitalization Talents Program [XLYC1907111, XLYC1908031], Liaoning Province Doctoral Start-up Fund Program [2019-BS-226], Liaoning BaiQianWan Talents Program [(2020)78], Career Development Program for Young and Middle-aged Teachers of Shenyang Pharmaceutical University [ZQN2019004] and Dual Service Program of University in Shenyang.

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, China

    Muse Ji, Hongbing Liu, Shuting Ma, Jingxin Gou, Haibing He, Yu Zhang & Xing Tang

  2. Department of Ophthalmology, the Fourth Affiliated Hospital of China Medical University, Shenyang, 110016, Liaoning, China

    Jun Kong

  3. Affiliated Hospital of Inner Mongolia University for the Nationalities, Tongliao, 028000, Neimenggu, China

    Yannan Jia

  4. School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, China

    Tian Yin

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  1. Muse Ji
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Correspondence to Yu Zhang.

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Ji, M., Liu, H., Ma, S. et al. Stable Atropine Loaded Film As a Potential Ocular Delivery System For Treatment Of Myopia. Pharm Res 38, 1931–1946 (2021). https://doi.org/10.1007/s11095-021-03135-4

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