Delivery of minoxidil encapsulated in cyclodextrins with photoacoustic waves enhances hair growth.

The current pharmacological management of androgenetic alopecia is inconvenient and requires a discipline that patients find difficult to follow. This reduces compliance with treatment and satisfaction with results. It is important to propose treatment regimens that increase patient compliance and reduce adverse effects. This work describes transdermal delivery of minoxidil partially encapsulated in ß-cyclodextrin and assisted by photoacoustic waves. Photoacoustic waves transiently increase the permeability of the skin and allow for the delivery of encapsulated minoxidil. A minoxidil gel formulation was developed and the transdermal delivery was studied in vitro in the presence and absence of photoacoustic waves. A 5-min stimulus with photoacoustic waves generated by light-to-pressure transducers increases minoxidil transdermal delivery flux by approximately 3-fold. The flux of a 1% minoxidil formulation promoted by photoacoustic waves is similar to the passive flux of a 2% minoxidil commercial formulation. Release of minoxidil from ß-cyclodextrin increases dermal exposure without increasing peak systemic exposure. This promotes hair growth with fewer treatments and reduced adverse effects. In vivo studies using encapsulated minoxidil and photoacoustic waves yielded 86% hair coat recovery (vs. 29% in the control group) and no changes in the blood pressure.

Limitations and Innovative Application Methods of Surfactants for Solubilization of Poorly Water-Soluble Drugs.

Poor solubility of drugs leads to poor bioavailability and therapeutic efficiency. A large proportion of drugs that are not developed and marketed for use by patients are due to their extremely low solubility. Therefore, improving the solubility of poorly water-soluble drugs is one of the most important aspects of the field of drug research. With the continuous development of more and more formulation techniques and excipient applications, the solubility of poorly water-soluble drugs can be improved to a certain extent to obtain better pharmacokinetics and pharmacodynamics, including pH microenvironment regulation technology, inclusion complex, solid dispersion, nanotechnology, and application of surfactants. However, the most widely used among them is the application of surfactants. This technique can reduce the surface tension, improve wettability, and have a remarkable solubilizing ability after forming micelles. However, surfactants have also been found to possess certain limitations in solubilization. In this review, the factors affecting the solubilization of surfactants and limiting their application have been summarized from several aspects. These factors include drugs, additives, and media. Some ideas to solve these application limitations have also been put forward, which can lay a foundation for the wider application of surfactants in the future.

Rationalizing Counterion Selection for the Development of Lipophilic Salts: A Case Study with Venetoclax.

The use of lipid-based formulations (LBFs) can be hindered by low dose loading due to solubility limitations of candidate drugs in lipid vehicles. Formation of lipophilic salts through pairing these drugs with a lipophilic counterion has been demonstrated as a potential means to enhance dose loading in LBFs. This study investigated the screening of appropriate counterions to form lipophilic salts of the BCS class IV drug venetoclax. The physical properties, lipid solubility, and in vitro performance of the salts were analyzed. This study illustrated the versatility of alkyl sulfates and sulfonates as suitable counterions in lipophilic salt synthesis with up to ∼9-fold higher solubility in medium- and long-chain LBFs when compared to that of the free base form of venetoclax. All salts formulated as LBFs displayed superior in vitro performance when compared to the free base form of the drug due to the higher initial drug loadings in LBFs and increased affinity for colloidal species. Further, in vitro studies confirmed that venetoclax lipophilic salt forms using alkyl chain counterions demonstrated comparable in vitro performance to venetoclax docusate, thus reducing the potential for laxative effects related to docusate administration. High levels of the initial dose loading of venetoclax lipophilic salts were retained in a molecularly dispersed state during dispersion and digestion of the formulation, while also demonstrating increased levels of saturation in biorelevant media. The findings of this study suggest that alkyl chain sulfates and sulfonates can act as a suitable alternative counterion to docusate, facilitating the selection of counterions that can unlock the potential to formulate venetoclax as an LBF.

Recent advances in nanocrystal-based technologies applied for ocular drug delivery.

INTRODUCTION: The intricate physiological barriers of the eye and the limited volume of eye drops impede efficient delivery of poorly water-soluble drugs. In the last decade, nanocrystals have emerged as versatile drug delivery systems in various administration routes from bench to bedside. The unique superiorities of nanocrystals, mainly embodied in high drug-loading capacity, good mucosal adhesion and penetration, and greatly improved drug solubility, reveal a promising prospect for ocular delivery of poorly water-soluble drugs. AREAS COVERED: This article focuses on the ophthalmic nanocrystal technologies and products that are in the literature, clinical trials, and even on the market. The recent research progress in the preparation, ocular application, and absorption of nanocrystals are highlighted, and the pros and cons of nanocrystals in overcoming the physiological barriers of the eye are also summarized. EXPERT OPINION: Nanocrystals have demonstrated success as glucocorticoid eye drops in the treatment of anterior segment diseases. However, the thermodynamic stability of nanocrystals remains the major challenge in product development. New technologies for efficiently optimizing stabilizers and sterilization processes are still expected. Strategies to confer more diverse functions via surface modification are also worth exploration to improve the potential of nanocrystals in delivering poorly water-soluble drugs to posterior segment of the eye.

Drug-drug co-amorphous systems: An emerging formulation strategy for poorly water-soluble drugs.

Overcoming the poor water solubility of small-molecule drugs is a major challenge in the development of clinical pharmaceuticals. Amorphization of crystalline drugs is a highly effective strategy to improve their aqueous solubility. However, amorphous drugs are thermodynamically unstable and likely to crystallize during manufacturing and storage. Recently, drug-drug co-amorphous systems have emerged as a novel strategy to not only enable enhanced dissolution and physical stability of the individual drugs within the system but also to provide a strategy for combination therapy of the same or different clinical indications. This review serves to highlight advances in the methods used to manufacture and characterize drug-drug co-amorphous systems, summarize drug-drug co-amorphous applications reported in recent decades, and provide an outlook on future possibilities and perspectives.

A Synergistic Approach Therapy for Colorectal Cancer Based on Exosomes and Exploitation of Metabolic Pathways.

In order to reduce the side effects of traditional chemotherapy in the treatment of colorectal cancer (CRC), a new drug delivery system has been developed in this work, based on exosomes that can host two drugs that act synergistically: farnesol (that stops the cell cycle) and paclitaxel (prevents microtubule system depolymerization). Firstly, exosomes were isolated from different cell cultures (from colorectal cancer and from fibroblast as example of normal cell line) by different methods and characterized by western blot, TEM and DLS, and results showed that they express classical protein markers such as CD9 and HSP-70 and they showed spherical morphology with sizes from 93 nm to 129 nm depending on the source. These exosomes were loaded with both drugs and its effect was studied in vitro. The efficacy was studied by comparing the viability of cell cultures with a colorectal cancer cell line (HCT-116) and a normal cell line (fibroblast HS-5). Results showed that exosomes present a specific effect with more reduction in cell viability in tumour cultures than healthy ones. In summary, exosomes are presented in this work as a promising strategy for colorectal cancer treatment.

Stability of Rapidly Crystallizing Sulfonamides Glasses by Fast Scanning Calorimetry: Crystallization Kinetics and Glass-Forming Ability.

Production and evaluation of the kinetic stability of the amorphous forms of active pharmaceutical ingredients are among the current challenges of modern pharmaceutical science. In the present work, amorphous forms of several sulfonamides were produced for the first time using Fast Scanning calorimetry. The parameters, characterizing the glass-forming ability of the compounds, i.e. the critical cooling rate of the melt and the kinetic fragility, were determined. The cold crystallization kinetics was studied using both isothermal and non-isothermal approaches. The results of the present study will contribute to the development of approaches for producing amorphous forms of rapidly crystallizing active pharmaceutical ingredients.

The Development of Lipid-Based Sorafenib Granules to Enhance the Oral Absorption of Sorafenib.

Sorafenib (SFN) is an anticancer multi-kinase inhibitor with great therapeutic potential. However, SFN has low aqueous solubility, which limits its oral absorption. Lipids and surfactants have the potential to improve the solubility of water-insoluble drugs. The aim of this study is thus to develop novel lipid-based SFN granules that can improve the oral absorption of SFN. SFN powder was coated with a stable binary lipid mixture and then absorbed on Aeroperl 300 to form dry SFN granules with 10% drug loading. SFN granules were stable at room temperature for at least three months. Compared to SFN powder, SFN granules significantly increased SFN release in simulated gastric fluid and simulated intestinal fluid with pancreatin. Pharmacokinetics and tissue distribution of SFN granules and SFN powder were measured following oral administration to Sprague Dawley rats. SFN granules significantly increased SFN absorption compared to SFN powder. Overall, the lipid-based SFN granules provide a promising approach to enhancing the oral absorption of SFN.

Bentonite as a water-insoluble amorphous solid dispersion matrix for enhancing oral bioavailability of poorly water-soluble drugs.

Bentonite (BT), an orally administrable natural clay, is widely used for medical and pharmaceutical purposes due to its unique properties, including swelling, adsorption and ion-exchange. However, its application as a matrix of amorphous solid dispersion (ASD) formulations is rarely reported, despite the fact that drugs can adsorb to BT in an amorphous state. The objective of this study was to explore the feasibility of BT as a water-insoluble ASD matrix for enhancing the oral bioavailability of poorly water-soluble drugs, including sorafenib (SF). We prepared a novel BT-based ASD of an SF-BT composite (SFBTC) by adsorbing SF onto BT under acidic conditions using the ionic interaction between cationic SF and negatively charged BT. Scanning electron microscopy (SEM), powder X-ray diffractometry (pXRD), and differential scanning calorimetry (DSC) analyses revealed that SF adsorbed to BT in an amorphous state at SF:BT ratios from 1:3 to 1:10. In pharmacokinetic studies in rats, SFBTC (1:3) significantly improved the oral bioavailability of SF, and the AUClast of SFBTC (1:3) was 3.3-fold higher than that of NEXAVAR®, a commercial product of SF. An in vitro release study under sink conditions revealed that SFBTC (1:3) completely released SF in a pH-dependent manner, while a nonsink condition study indicated the generation of supersaturation under intestinal pH conditions. A kinetic solubility study showed that the release of SFBTC (1:3) followed the diffusion-controlled mechanism, which is a typical characteristic of water-insoluble matrix-based ASDs. The pharmacokinetic studies of drug-BT composites of various drugs belonging to BCS class II indicated that the pKa value of the adsorbed drugs is one of the most important factors determining their dissolution and oral bioavailability. These results suggest that BT could be a promising water-insoluble ASD matrix for improving the oral bioavailability of poorly water-soluble drugs, including SF.

Quality attributes for printable emulsion gels and 3D-printed tablets: Towards production of personalized dosage forms.

3D-printing technology offers a flexible manufacturing platform with the potential to address the need of personalized dosage forms. However, quality aspects of such small-scale, on-demand production of pharmaceutical products intended for personalization is still limited. The aim of this study was therefore to study critical quality control attributes of lipid tablets produced by semi-solid extrusion (SSE) 3D printing from emulsion gels incorporating a poorly water-soluble drug. Quality attributes for both the printable emulsion gel and the printed dosage forms were assessed. The emulsion gel was shown to be printable with accurate dosing for at least one month of storage at 4 °C. Tablets were 3D printed in different sizes and a correlation, R2 value of 0.99, was found between the weight and the drug content. The 3D-printed tablets complied with the mass and drug content uniformity requirements described in the European Pharmacopoeia.. Solid-state characterization of the tablets during short-term storage revealed no signs of crystallinity of the drug. Lastly, the lipid digestion and drug release were unchanged after short-term storage of the tablets. This study demonstrates the potential of SSE 3D printing for personalized dosing of a lipid-based formulation strategy and discusses central quality attributes for the printable formulation and the 3D-printed dosage form.

Preclinical Investigation of Transdermal Route for Enhanced Bio-performance of Duloxetine HCl.

The aim of the study was to develop and optimise drug-in-adhesive (DIA) transdermal patch of duloxetine HCl for enhanced drug delivery. DIA patch so developed reduced the dose and dosing frequency by enhancing bio-performance of the drug. A transdermal DIA patch having Duro-Tak 87-2287 as DIA polymer and Transcutol P as permeation enhancer loaded with 40% drug previously complexed with MeßCD duly characterised (FTIR, DSC, and SEM) was developed for in vivo study. Pharmacokinetic parameters of developed formulation were assessed and compared with oral route of administration. Among various permeation enhancers (PEs), Transcutol P exhibited most enhanced permeation (ER ≈ 1.99) in terms of flux and Q24 compared to control group having. Mean of maximum plasma concentration (Cmax) and area under time-concentration curve (AUC0-72) in Wistar rats (n = 6) for transdermal patch (10 mg/kg) was found to be 70.31 ± 11.2 ng/ml and 2997.29 ± 387.4 ng/ml*h, respectively, and were considerably higher than oral dose of DLX (20 mg/kg and 10 mg/kg). Albeit, T1/2 was higher in case of transdermal delivery, but this was due to sustained behaviour of delivery system. These findings highlight the significance of both inclusion complexation and transdermal delivery of DLX using DIA patch for efficient drug absorption.

Synergistic stabilization of emulsion gel by nanoparticles and surfactant enables 3D printing of lipid-rich solid oral dosage forms.

Pharmaceutical formulation of oral dosage forms is continuously challenged by the low solubility of new drug candidates. Pickering emulsions, emulsions stabilized with solid particles, are a promising alternative to surfactants for developing long-term stable emulsions that can be tailored for controlled release of lipophilic drugs. In this work, a non-emulsifying lipid-based formulation (LBF) loaded with fenofibrate was formulated into an oil-in-water (O/W) emulsion synergistically stabilized by stearic acid and silica (SiO2) nanoparticles. The emulsion had a droplet size of 341 nm with SiO2 particles partially covering the oil-water interface. In vitro lipid digestion was faster for the emulsion compared to the corresponding LBF due to the larger total surface area available for digestion. Cellulose biopolymers were added to the emulsion to produce a gel for semi-solid extrusion (SSE) 3D printing into tablets. The emulsion gel showed suitable rheological attributes for SSE, with a trend of higher viscosity, yield stress, and storage modulus (G'), compared to a conventional self-emulsifying lipid-based emulsion gel. The developed emulsion gel allows for a non-emulsifying LBF to be transformed into solid dosage forms for rapid lipid digestion and drug release of a poorly water-soluble drug in the small intestine.

Personalizing oral delivery of nanoformed piroxicam by semi-solid extrusion 3D printing.

Semi-solid extrusion (SSE) 3D printing enables flexible designs and dose sizes to be printed on demand and is a suitable tool for fabricating personalized dosage forms. Controlled Expansion of Supercritical Solution (CESS®) is a particle size reduction technology, and it produces particles of a pure active pharmaceutical ingredient (API) in a dry state, suspendable in the printing ink. In the current study, as a model API of poorly water-soluble drug, nanoformed piroxicam (nanoPRX) prepared by CESS® was accommodated in hydroxypropyl methylcellulose- or hydroxypropyl cellulose-based ink formulations to warrant the printability in SSE 3D printing. Importantly, care must be taken when developing nanoPRX formulations to avoid changes in their polymorphic form or particle size. Printing inks suitable for SSE 3D printing that successfully stabilized the nanoPRX were developed. The inks were printed into films with escalating doses with exceptional accuracy. The original polymorphic form of nanoPRX in the prepared dosage forms was not affected by the manufacturing process. In addition, the conducted stability study showed that the nanoPRX in the prepared dosage form remained stable for at least three months from printing. Overall, the study rationalizes that with nanoparticle-based printing inks, superior dose control for the production of personalized dosage forms of poorly water-soluble drugs at the point-of-care can be achieved.

Control of Dissolution and Supersaturation/Precipitation of Poorly Water-Soluble Drugs from Cocrystals Based on Solubility Products: A Case Study with a Ketoconazole Cocrystal.

This study demonstrates in vitro and in vivo control of cocrystal dissolution with drug supersaturation/precipitation based on the solubility product of a cocrystal. As a cocrystal model, KTZ-4ABA (ketoconazole, KTZ, a poorly water-soluble drug cocrystal, with 4-aminobenzoic acid, 4ABA, a coformer) was used. The presence of 4ABA in the dissolution media dramatically reduced the dissolution rate of KTZ-4ABA and regulated the supersaturation/precipitation of KTZ, supported by the solubility product of KTZ-4ABA. In the in vitro dissolution study, the combined solid form of KTZ-4ABA and a ten-fold amount of 4ABA significantly lowered the degree of KTZ supersaturation without precipitation and further cocrystal dissolution. To confirm cocrystal dissolution control in the gastrointestinal tract with the same composition as the in vitro study, an in vivo oral administration study with rats was conducted. When KTZ was coadministered to rats in the cocrystal form, an excess of 4ABA coadministered with KTZ-4ABA in the solid form reduced the maximum plasma KTZ concentration (Cmax), prolonged the time to reach the Cmax, but did not influence the area under the plasma concentration-time curve. These results demonstrate that both in vitro and in vivo cocrystal dissolution can be regulated by adding an appropriate amount of coformer based on the solubility product, which can be one of the promising strategies for the oral use of cocrystal formulations.

Overcoming the Hydrophobic Nature of Zinc Phenylacetate Through Co-Crystallization with Isonicotinamide.

Zinc phenylacetate (Zn-PA), a substitute for sodium phenylacetate as an ammonia-scavenging drug is hydrophobic, which poses problems for drug dissolution and solubility. We were able to co-crystallize the zinc phenylacetate with isonicotinamide (INAM) and produce a novel crystalline compound (Zn-PA-INAM). The single crystal of this new crystal was obtained, and its structure is reported here for the first time. Zn-PA-INAM was characterized computationally by ab initio, Hirshfeld calculations, CLP-PIXEL lattice energy calculation, and BFDH morphology analysis, and experimentally by PXRD, Sc-XRD, FTIR, DSC, and TGA analyses. Structural and vibrational analyses showed a major modification in intermolecular interaction of Zn-PA-INAM compared to Zn-PA. The dispersion-based pi-stacking in Zn-PA is replaced by coulomb-polarization effect of hydrogen bonds. As a result, Zn-PA-INAM is hydrophilic, improving the wettability and powder dissolution of the target compound in an aqueous solution. Morphology analysis revealed, unlike Zn-PA, Zn-PA-INAM has polar groups exposed on its prominent crystalline faces, reducing the hydrophobicity of the crystal. The shift in average water droplet contact angle from 128.1° (Zn-PA) to 27.1° (Zn-PA-INAM) is strong evidence of a marked decrease in hydrophobicity of the target compound. Finally, HPLC was used to obtain the dissolution profile and solubility of Zn-PA-INAM compared to Zn-PA.

Development of Robust Tablet Formulations with Enhanced Drug Dissolution Profiles from Centrifugally-Spun Micro-Fibrous Solid Dispersions of Itraconazole, a BCS Class II Drug.

Fibre-based oral drug delivery systems are an attractive approach to addressing low drug solubility, although clear strategies for incorporating such systems into viable dosage forms have not yet been demonstrated. The present study extends our previous work on drug-loaded sucrose microfibres produced by centrifugal melt spinning to examine systems with high drug loading and investigates their incorporation into realistic tablet formulations. Itraconazole, a model BCS Class II hydrophobic drug, was incorporated into sucrose microfibres at 10, 20, 30, and 50% w/w. Microfibres were exposed to high relative humidity conditions (25 °C/75% RH) for 30 days to deliberately induce sucrose recrystallisation and collapse of the fibrous structure into powdery particles. The collapsed particles were successfully processed into pharmaceutically acceptable tablets using a dry mixing and direct compression approach. The dissolution advantage of the fresh microfibres was maintained and even enhanced after humidity treatment for drug loadings up to 30% w/w and, importantly, retained after compression into tablets. Variations in excipient content and compression force allowed manipulation of the disintegration rate and drug content of the tablets. This then permitted control of the rate of supersaturation generation, allowing the optimisation of the formulation in terms of its dissolution profile. In conclusion, the microfibre-tablet approach has been shown to be a viable method for formulating poorly soluble BCS Class II drugs with improved dissolution performance.

Preparation and evaluation of astaxanthin-loaded 2-hydroxypropyl-beta-cyclodextrin and Soluplus® nanoparticles based on electrospray technology.

BACKGROUND: Astaxanthin is a type of food-derived active ingredient with antioxidant, antidiabetic and non-toxicity functions, but its poor solubility and low bioavailability hinder further application in food industry. In the present study, through inclusion technologies, micellar solubilization and electrospray techniques, we prepared astaxanthin nanoparticles before optimizing the formulation to regulate the physical and chemical properties of micelles. We accomplished the preparation of astaxanthin nanoparticle delivery system based on single needle electrospray technology through use of 2-hydroxypropyl-ß-cyclodextrin and Soluplus® to improveme the release behavior of the nanocarrier. RESULTS: Through this experiment, we successfully prepared astaxanthin nanoparticles with a particle size of approximately 80 nm, which was further verified with scanning electron microscopy and transmission electron microscopy. Furthermore, the encapsulation of astaxanthin molecules into the carrier nanoparticles was verified via the results of attenuated total reflectance intensity and X-ray powder diffraction techniques. The in vitro release behavior of astaxanthin nanoparticles was different in media that contained 0.5% Tween 80 (pH 1.2, 4.5 and 6.8) buffer solution and distilled water. Also, we carried out a pharmacokinetic study of astaxanthin nanoparticles, in which it was observed that astaxanthin nanoparticle showed an effect of immediate release and significant improved bioavailability. CONCLUSION: 2-hydroxypropyl-ß-cyclodextrin and Soluplus® were used in the present study as a hydrophilic nanocarrier that could provide a simple way of encapsulating natural function food with repsect to improving the solubility and bioavailability of poorly water-soluble ingredients. © 2023 Society of Chemical Industry.

Electrospun self-emulsifying core-shell nanofibers for effective delivery of paclitaxel.

The poor solubility of numerous drugs pose a long-existing challenge to the researchers in the fields of pharmaceutics, bioengineering and biotechnology. Many "top-down" and "bottom-up" nano fabrication methods have been exploited to provide solutions for this issue. In this study, a combination strategy of top-down process (electrospinning) and bottom-up (self-emulsifying) was demonstrated to be useful for enhancing the dissolution of a typical poorly water-soluble anticancer model drug (paclitaxel, PTX). With polyvinylpyrrolidone (PVP K90) as the filament-forming matrix and drug carrier, polyoxyethylene castor oil (PCO) as emulsifier, and triglyceride (TG) as oil phase, Both a single-fluid blending process and a coaxial process were utilized to prepare medicated nanofibers. Scanning electron microscope and transmission electron microscope (TEM) results clearly demonstrated the morphology and inner structures of the nanofibers. The lipid nanoparticles of emulsions after self-emulsification were also assessed through TEM. The encapsulation efficiency (EE) and in vitro dissolution tests demonstrated that the cores-shell nanofibers could provide a better self-emulsifying process int terms of a higher EE and a better drug sustained release profile. Meanwhile, an increase of sheath fluid rate could benefit an even better results, suggesting a clear process-property-performance relationship. The protocols reported here pave anew way for effective oral delivery of poorly water-soluble drug.

When Interactions Between Bile Salts and Cyclodextrin Cause a Negative Food Effect: Dynamic Dissolution/Permeation Studies with Itraconazole (Sporanox®) and Biomimetic Media.

The marketed oral solution of itraconazole (Sporanox®) contains 40% (259.2 mM) of 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD). The obvious role of HP-ß-CD is to solubilize itraconazole and to overcome its poor aqueous solubility that restricts its absorption. In this study, we investigated the biorelevance of in vitro experiments by the influence of biomimetic media (containing bile salts and phospholipids) on the predicted itraconazole absorption from the commercial HP-ß-CD-based Sporanox® solution. We performed phase-solubility studies of itraconazole and dynamic 2-step-dissolution/permeation studies using a biomimetic artificial barrier, Sporanox® solution, and fasted state simulated intestinal fluid (FaSSIF_V1). Both FaSSIF_V1 and HP-ß-CD increased the apparent solubility of itraconazole when used individually. In combination, their solubility-enhancing effects were not additive probably due to the competition of bile salts with itraconazole for the hydrophobic cavity of HP-ß-CD. Our combined dissolution/permeation experiments indicated the occurrence of a transient supersaturation from Sporanox® upon two-step dissolution. Through systematic variation of bile salt concentrations in the biomimetic media, it was observed that the extent and the duration of supersaturation depend on the concentrations of bile salts: supersaturation was rather stable in the absence of bile salts and phospholipids. The higher the bile salt concentration, the faster the collapse of the transient supersaturation occurred, an effect which is nicely mirrored by reduced in vitro permeation across the barrier. This is an indication of a negative food effect, which in fact correlates well with what earlier had been observed in clinical studies for Sporanox® solution. In essence, we could demonstrate that in vitro two-stage dissolution/permeation experiments using an artificial barrier and selected biomimetic media may predict the negative effects of the latter on cyclodextrin-based drug formulations like Sporanox® Oral Solution and, at the same time, provide a deeper mechanistic insight.

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

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.