Enhanced Dissolution of Naproxen by Combining Cocrystallization and Eutectic Formation.

Hakyeong Kim,Il Won Kim,Soeun Jang

doi:10.3390/pharmaceutics13050618

Hakyeong Kim, Il Won Kim + Show 1 more

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https://doi.org/10.3390/pharmaceutics13050618

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Journal: Pharmaceutics	Publication Date: Apr 25, 2021
Citations: 8	License type: CC BY 4.0

Affiliation: Soongsil University

Abstract

Improving dissolution properties of active pharmaceutical ingredients (APIs) is a critical step in drug development with the increasing occurrence of sparingly soluble APIs. Cocrystal formation is one of the methods to alter the physicochemical properties of APIs, but its dissolution behavior in biorelevant media has been scrutinized only in recent years. We investigated the combined strategy of cocrystallization and eutectic formation in this regard and utilized the cocrystal model system of naproxen and three pyridinecarboxamide isomers. Binary melting diagrams were constructed to discover the eutectic compositions of the three cocrystals with excess amounts of pyridinecarboxamides. The melt–crystallized eutectics and cocrystals were compared in their dissolution behaviors with respect to neat naproxen. The eutectics enhanced the early dissolution rates of the cocrystals in both the absence and presence of biologically relevant bile salt and phospholipid components, whereas the cocrystal dissolution was expedited and delayed, respectively. The combined strategy in the present study will be advantageous in maximizing the utility of the pharmaceutical cocrystals.

Highlights

Improving dissolution properties of active pharmaceutical ingredients (APIs) is a critical step in drug development with the increasing occurrence of sparingly soluble APIs
When the solubility of an active pharmaceutical ingredient (API) is too low for the dose required for the intended efficacy, the API is categorized as class II or IV of the biopharmaceutical classification system (BCS) depending on its permeation characteristic: II for proper and IV for improper gastrointestinal permeability [3,4]
All differential scanning calorimeter (DSC) thermograms for the construction of melting diagrams are shown in Figure S1, and those for cocrystals and eutectic compositions are presented in Figure 3 along with the neat compounds

Summary

Introduction

Improving dissolution properties of active pharmaceutical ingredients (APIs) is a critical step in drug development with the increasing occurrence of sparingly soluble APIs. Enhancing the API solubility by altering the nature of the solids is the thermodynamic approach, employing salts, metastable polymorphs, amorphous phases, and cocrystals [4,7,8,11]. Among these solids, cocrystals take a unique place due to the diverse possibilities for the coformer selection and the stability arising from the strong hydrogen bonding often found in the cocrystal structures [9,11,12]. Noteworthy are the cocrystal solubilities defined in both simple buffers and lipid–based media, which are physiologically more relevant [14,15,16]

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