Solubility Data and Computational Modeling of Baricitinib in Various (DMSO + Water) Mixtures.

Saad M Alshahrani,Faiyaz Shakeel

doi:10.3390/molecules25092124

Saad M Alshahrani, Faiyaz Shakeel

Open Access

https://doi.org/10.3390/molecules25092124

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Abstract

The solubility and thermodynamic analysis of baricitinib (BNB) in various dimethyl sulfoxide (DMSO) + water mixtures were performed. The “mole fraction solubilities (xe)” of BNB in DMSO and water mixtures were determined at “T = 298.2–323.2 K” and “p = 0.1 MPa” using an isothermal saturation technique. “Hansen solubility parameters (HSPs)” of BNB, pure DMSO, pure water and “DMSO + water” mixtures free of BNB were also estimated. The xe data of BNB was regressed well by five different thermodynamics-based co-solvency models, which included “Apelblat, Van’t Hoff, Yalkowsky-Roseman, Jouyban-Acree and Jouyban-Acree-Van’t Hoff models” with overall deviations of <5.0%. The highest and lowest xe value of BNB was computed in pure DMSO (1.69 × 10−1 at T = 323.2 K) and pure water (2.23 × 10−5 at T = 298.2 K), respectively. The HSP of BNB was found to be closer to that of pure DMSO. Based on activity coefficient data, maximum solute–solvent molecular interactions were observed in BNB-DMSO compared to BNB-water. The results of “apparent thermodynamic analysis” indicated endothermic and entropy-drive dissolution of BNB in all “DMSO + water” combinations including mono-solvents (water and DMSO). “Enthalpy-entropy compensation analysis” showed enthalpy-driven to be the main mechanism of solvation of BNB.

Highlights

Baricitinib (BNB; Figure 1) is a potent orally active drug that has recently been approved for commercialization by the United States Food and Drug Administration (USFDA) [1,2].It is a selective irreversible inhibitor of Janus kinase-1 and Janus kinase-2 and shows many therapeutic effects such as anti-inflammatory, immunomodulatory and antineoplastic effects [2,3].It shows potential results in the treatment of rheumatoid arthritis [3,4]
The “mole fraction solubility” values of BNB in mono-solvents were soluble in water, which creates a lot of problems in its formulation development [2]
The “mole fraction solubility” values of BNB in mono‐solvents were computed using Equation (1) and its xe values in different “dimethyl sulfoxide (DMSO) + water” combinations were calculated by applying Equation (2)

Summary

Introduction

Baricitinib (BNB; Figure 1) is a potent orally active drug that has recently been approved for commercialization by the United States Food and Drug Administration (USFDA) [1,2].It is a selective irreversible inhibitor of Janus kinase-1 and Janus kinase-2 and shows many therapeutic effects such as anti-inflammatory, immunomodulatory and antineoplastic effects [2,3].It shows potential results in the treatment of rheumatoid arthritis [3,4]. Baricitinib (BNB; Figure 1) is a potent orally active drug that has recently been approved for commercialization by the United States Food and Drug Administration (USFDA) [1,2]. It is a selective irreversible inhibitor of Janus kinase-1 and Janus kinase-2 and shows many therapeutic effects such as anti-inflammatory, immunomodulatory and antineoplastic effects [2,3]. BNB is reported to be very slightly soluble in water, which creates a lot of problems in its formulation development [2]. Co-solvency and formulation techniques for solubilization of BNB are poorly reported in the literature. Solubility and thermodynamics data of poorly soluble drugs in neat solvents and water-co-solvent mixtures have greater impact in various fields which includes “medical sciences (preclinical and clinical studies), pharmaceutical sciences (pre-formulation studies and dosage form design), chemical sciences (purification and recrystallization) and physical pharmacy (physicochemical characterization)” [5,6,7,8]

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