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Ocular Distribution of Papaverine Using Non-aqueous Vehicles

  • Research Article
  • Theme: Ocular Drug Delivery and Ophthalmic Formulations
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Abstract

Papaverine, a poorly soluble opium alkaloid, has recently been shown to reduce retinal inflammation due to which it may have therapeutic application in the management of Leber’s hereditary optic neuropathy. In this study, papaverine eyedrops based on medium chain triglycerides were prepared and the effect of diethyl glycol monoethyl ether (DGME) on their ocular distribution was evaluated using an ex vivo porcine eye model. The route of drug penetration was also studied by orienting the eye to expose either only the cornea or the sclera to the formulation. Furthermore, in vivo studies were performed to confirm ocular tolerability and evaluate ocular drug distribution. Our results showed increased papaverine concentrations in the cornea and sclera in the presence of DGME but with a slight reduction in the retina-choroid (RC) drug concentration when administered via the corneal route, suggesting that DGME enhances drug accumulation in the anterior ocular tissues but with little effect on posterior drug delivery. In vivo, the papaverine eyedrop with DGME showed good ocular tolerability with the highest drug concentration being observed in the cornea (1.53 ± 0.28 μg/g of tissue), followed by the conjunctiva (0.74 ± 0.18 μg/g) and sclera (0.25 ± 0.06 μg/g), respectively. However, no drug was detected in the RC, vitreous humor or plasma. Overall, this study highlighted that DGME influences ocular distribution and accumulation of papaverine. Moreover, results suggest that for hydrophobic drugs dissolved in hydrophobic non-aqueous vehicles, transcorneal penetration via the transuveal pathway may be the predominant route for drug penetration to posterior ocular tissues.

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Acknowledgements

The authors would like to thank Tarnagulla Ventures Pty. Ltd. for funding this study. IDR’s directorship is provided by the Buchanan Charitable Foundation.

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Authors and Affiliations

  1. Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand

    Priyanka Agarwal, Sairam Behera & Ilva Dana Rupenthal

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  1. Priyanka Agarwal
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  2. Sairam Behera
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  3. Ilva Dana Rupenthal
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Correspondence to Ilva Dana Rupenthal.

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Guest Editors: Qingguo Xu and Iok-Hou Pang

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Agarwal, P., Behera, S. & Rupenthal, I.D. Ocular Distribution of Papaverine Using Non-aqueous Vehicles. AAPS PharmSciTech 22, 160 (2021). https://doi.org/10.1208/s12249-021-02050-6

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