Assessing the Solubility of Baricitinib and Drug Uptake in Different Tissues Using Absorption and Fluorescence Spectroscopies

Abstract

The low water solubility of baricitinib (BCT) limits the development of new formulations for the topical delivery of the drug. The aims of this study were to assess the solubility of BCT in different solvents, including Transcutol, a biocompatible permeation enhancer that is miscible in water, to evaluate the drug uptake in human skin and porcine tissues (sclera, cornea, oral, sublingual, and vaginal), and to subsequently extract the drug from the tissues so as to determine the drug recovery using in vitro techniques. Analytical methods were developed and validated for the quantification of BCT in Transcutol using absorption and fluorescence spectroscopies, which are complementary to each other and permit the detection of the drug across a broad range of concentrations. Results show that Transcutol permits an increased drug solubility, and that BCT is able to penetrate the tissues studied. The solutions of BCT in Transcutol were stable for at least one week. Hence, Transcutol may be a suitable solvent for further development of topical formulations.

Local and Sustained Baricitinib Delivery to the Skin through Injectable Hydrogels Containing Reversible Thioimidate Adducts

“…This was consistent with prior methods for measuring baricitinib in solution. [ 40,41 ] Next, we assembled hydrogels with varying baricitinib loading (0.2 mg mL⁻ 1 , 2 mg mL⁻ 1 , corresponding to 40‐fold or fourfold thiol excess, respectively), hydrogel concentration (% w/v), and thiol modification (30% or 50%). Baricitinib hydrogels were incubated in PBS at room temperature with releasates collected and replaced regularly over six weeks.…”

A novel MTORC2-AKT-ROS axis triggers mitofission and mitophagy-associated execution of colorectal cancer cells upon drug-induced activation of mutant KRAS

“…Last, we made use of a simple and sensitive spectroscopic method for the determination of organic compounds that have a characteristic absorption peak in the UV-visible region [ 32 ] to measure intracellular accumulation of C1. The absorption spectra of C1 solutions at defined concentrations (25–200 μM) were used for establishing the calibration curve, as well as the spectra from the supernatants of drug-treated cells ( Figure 7F-H ).…”

Gel Formulations with an Echinocandin for Cutaneous Candidiasis: The Influence of Azone and Transcutol on Biopharmaceutical Features

“…Azone increases the fluidity of the skin lipids by disrupting the lipid bilayers of the skin [ 44 ]. Transcutol-P is widely used in topical and oral formulations to improve the solubility of poorly soluble drugs; it disrupts the stratum corneum of the skin [ 45 , 46 ].…”

“…Azone increases the fluidity of the skin lipids by disrupting the lipid bilayers of the skin [44]. Transcutol-P is widely used in topical and oral formulations to improve the solubility of poorly soluble drugs; it disrupts the stratum corneum of the skin [45,46]. The permeation parameters, such as the flux and the cumulative amount of drug permeated at a given time, characterize the rate and extent of the drug through the skin.…”