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Management and control of intraocular pressure applying macitentan hydrogel film formulation: improved effect of surfactant and cosurfactant system

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Abstract

Background

Macitentan blocks endothelin receptors in order to control the pulmonary arterial hypertension (PAH). Oral administration of macitentan is associated with painful urination and troubled breathing.

Objectives

Formulated macitentan hydrogel film was used for examining the control of intraocular pressure, and the effect of surfactant and cosurfactant was studied.

Methods

Macitentan ocular film formulation has been prepared in hydroxypropyl methylcellulose (HPMC) matrix system using different surfactant/co-surfactant system, and intraocular pressure was monitored on normotensive rabbit eyes after application in the cul-de-sac.

Results

The solid state characterization of the film indicated amorphisation of macitentan and no issues regarding major incompatibility was observed. Combination of surfactant, co-surfactant and hydrophilic co-solvent systems in the said films markedly improved the drug release and mucosal tissue permeation. Presence of PEG and Transcutol significantly improved ex vivo corneal permeation of MP and MT respectively compared to other films. Transcutol (MT) exhibited greatest difference among the formulations by improving the vesicular bilayer fluidity and reducing the mucosal tissue barrier facilitating the transcorneal diffusion. A combination of diffusion and erosion control behavior was observed in drug release and corneal permeation of the films due to the balanced liquid penetration and polymeric chain relaxation rate. MP and MT films were used for further in vivo studies to achieve possible effective and prolonged control of intraocular pressure. In vivo study has revealed the reduction in intraocular pressure upto about 23 % when tested on normotensive rabbit model. The films has managed to lower the IOP upto 3 h.

Conclusion

Developed macitentan hydrogel film containing Transcutol (MT) could have a high potential for the control and management of ocular hypertension after topical application.

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The authors confirm that the data supporting the findings of this study are available within the article

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Acknowledgements

The authors are grateful to the Department of Science & Technology, Ministry of Science & Technology, New Delhi, India, for providing INSPIRE fellowship to Souvik Nandi (IF 180534). The authors are grateful to the Honorable Prof. Manojranjan Nayak, President, Siksha ‘O’ Anusandhan (Deemed to be University) for facilitating and encouraging the research. The authors are also thankful to Dr. (Ms) Barsha Dash, Senior Scientist, CSIR-Institute of Minerals and Materials Technology, Bhubaneswar, for facilitating the other analytical facilities for the research.

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmaceutical Sciences, Siksha ‘O’ Anusandhan (Deemed to be University), Bhubaneswar- 751003, Odisha, India

    Sidhartha Sankar Hota, Souvik Nandi & Subrata Mallick

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  1. Sidhartha Sankar Hota
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  2. Souvik Nandi
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  3. Subrata Mallick
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Contributions

SSH was responsible for the laboratory works and in preparing the primary manuscript. SN took care of the software analysis and made the final draft of the manuscript. SM was responsible for the study design and final approval of the manuscript as the supervisor.

Corresponding author

Correspondence to Subrata Mallick.

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The animal studies has been approved by the institutional ethical committee (Regd. No.: 1171/PO/RE/S/08/CPCSEA) bearing protocol number IAEC/SPS/SOA/13/2018.

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Hota, S.S., Nandi, S. & Mallick, S. Management and control of intraocular pressure applying macitentan hydrogel film formulation: improved effect of surfactant and cosurfactant system. DARU J Pharm Sci 30, 39–47 (2022). https://doi.org/10.1007/s40199-021-00428-2

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