Effect of Solid Forms on Physicochemical Properties of Valnemulin

Jinbo Ouyang,Fangze Han,Xin Huang,Limin Zhou,Jian Chen

doi:10.3390/cryst9120675

Jinbo Ouyang, Fangze Han + Show 3 more

Open Access

https://doi.org/10.3390/cryst9120675

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Journal: Crystals	Publication Date: Dec 16, 2019
Citations: 5	License type: CC BY 4.0

Affiliation: East China University of Technology, Tianjin University

Abstract

To improve the physicochemical properties of valnemulin (VLM), different solid forms formed by VLM and organic acids, including tartaric acid (TAR), fumaric acid (FUM), and oxalic acid (OXA), were successfully prepared and characterized by using differential scanning calorimetry (DSC), scanning electron microscope (SEM), X-ray powder diffraction (XRPD), and Fourier-transform infrared spectroscopy (FT-IR). The excess enthalpy Hex between VLM and other organic acids was calculated by COSMOthermX software and was used to evaluate the probability of forming multi-component solids between VLM and organic acids. By thermal analysis, it was confirmed that multi-component solid forms of VLM were thermodynamically more stable than VLM itself. Through dynamic vapor sorption (DVS) experiments, it was found that three multi-component solid forms of VLM had lower hygroscopicity than VLM itself. Furthermore, the intrinsic dissolution rate of VLM and its multi-component forms was determined in one kind of acidic aqueous medium by using UV-vis spectrometry. It was found that the three multi-component solid forms of VLM dissolved faster than VLM itself.

Highlights

Many pharmaceuticals fail clinical trials, mostly due to pure physicochemical properties, including poor dissolution rate, low crystallinity, and strong hygroscopicity [1,2]
The above results demonstrated that the solubility and dissolution rate of active pharmaceutical ingredient (API) could be significantly increased by the formation of multi-component solid forms of API with other acids
Three multi-component solid forms of VLM with organic acids were successfully prepared by solution crystallization method

Summary

Introduction

Many pharmaceuticals fail clinical trials, mostly due to pure physicochemical properties, including poor dissolution rate, low crystallinity, and strong hygroscopicity [1,2]. The discovery of methods that can improve the dissolution rate and stability of active pharmaceutical ingredient (API) is an important challenge in the pharmaceutical industry. 50% of all active pharmaceutical ingredients (APIs) have been developed as multi-component solid forms, such as pharmaceutically acceptable salts [9,10]. Pharmaceutical cocrystals are multi-component crystalline forms made of neutral molecular components, usually involving an API and one cocrystal former, exhibiting a definite stoichiometry ratio, often leading to a hydrogen-bonded molecular complex [15,16]. To improve the physicochemical properties of the drug, it is important to develop multi-component solid forms of VLM and to compare their physicochemical properties with the physicochemical properties of VLM itself.

Materials

COSMO-RS Calculation

FT-IR Spectroscopy

Intrinsic Dissolution Rate

Conclusions