Synthesis and characterisation of novel mutual ester prodrug models   of acyclovir

Dana Ameen Dana Ameen; Sazan Jameel

doi:10.15218/zjms.2019.028

Authors

Dana Ameen Dana Ameen Department of Pharmaceutical Chemistry, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
Sazan Jameel Department of Pharmaceutical Chemistry, College of Pharmacy, Hawler Medical University, Erbil, Iraq.

DOI:

https://doi.org/10.15218/zjms.2019.028

Keywords:

Prodrug, Novel strategy, Acyclovir, Herpes simplex, Ocular delivery, NSAIDs

Abstract

Background and Objective: Ocular herpes is a recurrent viral infection caused by the herpes simplex virus-1. Herpes simplex virus type one HSV-1 is one of the most common ocular viruses causing subsequent inflammatory responses and corneal blindness worldwide. This study aimed to synthesize a series of novel mutual ester prodrug models to treat viral infection and subsequent inflammation at corneal tissue.

Various formulation strategies have been utilized to improve bioavailability by increasing ocular contact time and improving drug permeation. Chemical approaches, such as prodrug, directed to enhance the ocular bioavailability by improving physicochemical properties of the drug molecule, with the goal of improving drug permeation across cornea.

Methods: Steglich esterification method was to design and synthesis a library of novel mutual prodrugs to increase the bioavailability of acyclovir, owing to enhance the lipophilicity compared with acyclovir. In this study a number of non-steroidal anti-inflammatory drugs (NSAIDs) have been conjugated to acyclovir to improve corneal permeation through enhancing lipophilicity and reduce subsequent inflammation.

Results: The synthesized compounds were characterized through FTIR, ¹H-,¹³C –NMR and Mass spectral data. The partition coefficient (logP) of prodrugs were calculated and showed an increment in lipophilicity and permeability in comparison with acyclovir.

Conclusion: The strategy applied to design the novel compound hypothesized to be a novel mutual prodrug, and it may provide a higher absorption than hydrophilic parent (acyclovir) drug with concurrent anti-inflammatory activity.

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