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Virtual Cocrystal Screening of Adefovir Dipivoxyl: Identification of New Solid Forms with Improved Dissolution and Permeation Profiles.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Fael, Hanan 
Lee, Samuel 
Ruiz, Rebeca 
Hunter, Christopher A  ORCID logo  https://orcid.org/0000-0002-5182-1859

Abstract

The application of a computational screening methodology based on the calculation of intermolecular interaction energies has guided the discovery of new multicomponent solid forms of the oral antiviral Adefovir Dipivoxyl. Three new cocrystals with resorcinol, orcinol and hydroquinone have been synthesized and thoroughly characterized. They show improved dissolution profiles with respect to the single solid form, particularly the cocrystals of orcinol and resorcinol, which have 3.2- and 2-fold faster dissolution rates at stomach conditions (pH 1.5). Moreover, dynamic dissolution experiments that simultaneously mimic both the pH variation along the gastrointestinal tract and the partition into biological membranes show that, in addition to the faster initial dissolution, Adefovir Dipivoxyl also penetrates faster into the organic membranes in the form of resorcinol and orcinol cocrystals.

Description

Keywords

Adefovir Dipivoxyl, cocrystal, cocrystallization, computational screening, dissolution rate, permeability, polyphenols

Journal Title

Pharmaceutics

Conference Name

Journal ISSN

1999-4923
1999-4923

Volume Title

14

Publisher

MDPI AG
Sponsorship
Catalan Government (2017 SGR 1074)
Ministerio de Ciencia e Innovación (PID2020- 115374GB-100)
European Union (Erasmus-Mundus Action-2 program, Avempace II project)