A Novel Desloratadine-Benzoic Acid Co-Amorphous Solid: Preparation, Characterization, and Stability Evaluation.

Ahmad Ainurofiq,Diky Mudhakir,Rachmat Mauludin,Sundani Soewandhi

doi:10.3390/pharmaceutics10030085

Ahmad Ainurofiq, Diky Mudhakir + Show 2 more

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https://doi.org/10.3390/pharmaceutics10030085

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Abstract

Low physical stability is the limitation of the widespread use of amorphous drugs. The co-amorphous drug system is a new and emerging method for preparing a stable amorphous form. Co-amorphous is a single-phase amorphous multicomponent system consisting of two or more small molecules that are a combination of drugs or drugs and excipients. The co-amorphous system that uses benzoic acid (BA) as an excipient was studied to improve the physical stability, dissolution, and solubility of desloratadine (DES). In this study, the co-amorphous formation of DES and BA (DES–BA) was prepared by melt-quenching method and characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), and polarized light microscopy (PLM). Dissolution, solubility, and physical stability profiles of DES–BA were determined. The DES crystals were converted into DES–BA co-amorphous form to reveal the molecular interactions between DES and BA. Solid-state analysis proved that the co-amorphous DES–BA system (1:1) is amorphous and homogeneous. The DSC experiment showed that the glass transition temperature (Tg) of tested DES–BA co-amorphous had a higher single Tg compared to the amorphous DES. FTIR revealed strong interactions, especially salt formation. The dissolution rate and solubility of co-amorphous DES–BA (1:1) obtained were larger than the DES in crystalline form. The PXRD technique was used to assess physical stability for three months at 40 °C with 75% RH. The DES–BA co-amorphous system demonstrated better physical stability than a single form of amorphous DES. Co-amorphous DES–BA has demonstrated the potential for improving solid-state stability, as the formation of DES–BA co-amorphous salt increased solubility and dissolution when compared to pure crystalline DES. This study also demonstrated the possibility for developing a DES–BA co-amorphous system toward oral formulations to improve DES solubility and bioavailability.

Highlights

A crystal engineering strategy was applied to modify the physicochemical properties of drugs through the formation of salts, polymorphs, solvates, hydrates, amorphous and newer forms, co-crystal and co-amorphous systems [1,2]
The amorphous form of naproxen made by ball milled, cryo-milled, and spray-dried methods was unstable and recrystallized rapidly compared to melt-quenching
benzoic acid (BA) was successfully used as a small molecule excipient to create a co-amorphous system from DES to stabilize amorphous DES as well as to increase the solubility and dissolution of DES over its crystalline form

Summary

Introduction

A crystal engineering strategy was applied to modify the physicochemical properties of drugs through the formation of salts, polymorphs, solvates, hydrates, amorphous and newer forms, co-crystal and co-amorphous systems [1,2]. Amorphous drugs have become interesting subjects because of their favorable properties, such as higher solubility, faster dissolution rate, and greater bioavailability when compared to their crystalline form. This is because the amorphous compound is in the highest internal energy state of the solid material and has a higher molecular motion than the crystal compound [3,4]. Pure amorphous drugs often show rapid recrystallization kinetics to low energy crystal states (low solubility) [5,6]. It is necessary to stabilize the amorphous form to take advantage of the benefits provided by drugs in an irregular state

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