Permeation Amount Research Articles

Osmotic absorption behaviors of imidazolium ILs in digestive system and their effective removal way

Considering the controversial safety and risk solutions of ionic liquids (ILs), more essential basic researches are required as their applied fields become broader and applied scale grows larger. Under this background, the permeation behaviors of six common imidazole ILs on porcine gastric and enteric membranes together with the feasibility of their removal by adsorption with montmorillonite were investigated in vitro. Through the single-factor investigation of different cations, anions and ionic liquid concentrations, the current results show that the IL of 1-ethyl-3-methylimidazolium bromide ([Emim]Br) has the strongest permeation capacity on the gastric membrane during the tests. The cumulative permeation amount of Qn can reach 0.72 mg/cm2, and the cumulative permeation percentage alsoreaches 95.77 %; the whole permeation process conforms to the Hixcon-Crowell model. As comparison, the maximum cumulative penetration percentage of [Emim]Br on enteric member was determined as 89.11 %, and related models was also compared. In order to remove the potential IL in digestive tract, montmorillonite was screened out from those popularily used antidotes in clinic and the adsorption of [Emim]Br in gastric fluid by montmorillonite has been proved more consistent with the second-order kinetics and Langmuir model. The results of molecular simulation, infrared spectrum (IR), X-ray diffraction (XRD) and thermogravimetric (TG) characterization exhibit that [Emim]Br has been successfully adsorbed into the interlayer of montmorillonite. As a whole, the study provided a scientific and effective way to diminish the hidden danger of ionic liquid entering the blood through the digestive system.

Introduction on tritium transport analysis model for HCCP breeding blanket system

In the context of implementing the He-cooled breeding blanket system for a fusion reactor, several crucial aspects need consideration. Among these, the development of a tritium transport model plays a pivotal role in ensuring safety and effective design. Given that tritium release into the environment from the breeding blanket system poses a radioactive risk, accurate calculation and prediction area essential to prevent potential incidents in a fusion reactor. To address this challenge, a collaborative effort between the Korea Institute of Fusion Energy (KFE) and the University of California, Los Angeles (UCLA) resulted in the creation of THETA-FR (Tritium/Hydrogen Enhanced dynamic Transport Analysis Tool for Fusion Reactor). THETA-FR is an integrated analysis tool that combines Matlab Simulink and COMSOL Multiphysics. Its purpose is to model and predict the dynamic transport phenomena of H isotopes (H/D/T) within the breeding blanket system. Specifically, THETA-FR focuses on transient tritium retention, permeation, and release amounts from the breeding blanket system into the environment. In this paper, we introduce the integrated system and components of THETA-FR, shedding light on various tritium behaviors within the HCCP breeding blanket FW/BU component. By leveraging THETA-FR, researchers and engineers can make informed decisions regarding tritium control and safety in fusion reactors.

Dendrimers as Drug Delivery Platforms of the Mechanisms, Benefits, and Use in Anti-Pain: Systematice Literature Review

Background: Efforts to reduce the side effects of long-term NSAID use have prompted exploration of transdermal drug delivery, which offers advantages such as avoiding first-pass metabolism, reducing pain, allowing sustained drug release, and improving patient compliance. Dendrimers, specifically polyamidoamine (PAMAM), are attracting attention for their potential in drug delivery. PAMAM has a three-dimensional structure of monodisperses with high amino group density and internal voids suitable for drug encapsulation. Methods: This research method uses the literature review method which begins with the collection of journals to be reviewed. The article search was conducted on the Pubmed database. Researchers searched with the keyword dendrimer. The two main synthesis methods are convergent and divergent dendrimers. Results: : Drug molecules can be trapped in dendrimers through hydrogen, hydrophobic, or electrostatic bonds. The advantages of dendrimers include improved solubility, permeability, and targeted drug delivery, while the disadvantages are high cost, toxicity and aggregation. This system has been used in several pain medications. Conclusions: Dendrimers are macrostructures with unique characteristics such as nanoscopic size, multifunctional surface, and high branching, making them ideal as drug delivery systems. Ketoprofen with PAMAM-type dendrimers showed that PAMAM dendrimers could significantly increase the accumulative amount of permeation of both drugs after 24 hours, compared with the drug suspension without PAMAM dendrimers. Dendrimers are multi-branched monodisperse macrostructures, derived from Greek.

Preparation and Application of Decanoic Acid/Arginine Hydrogels to a Transdermal Formulation.

We prepared a supramolecular hydrogel composed of decanoic acid and arginine (C10/Arg gel) and evaluated its application to a transdermal formulation. C10/Arg gel adjusted to pH 7 with 1 M NaOH aq or 1 M HCl aq provided a translucent hydrogel with a lamellar liquid crystal structure in the concentration region of decanoic acid ≥12% and arginine ≤9%. Rheological measurements showed that C10/Arg gel is a viscoelastic material with both solid and liquid properties, with elasticity being dominant over viscosity in the low shear stress region. The skin permeability of hydrocortisone (HC) and indomethacin (IM) from C10/Arg gels was investigated in vitro using hairless mouse skin and compared to control formulation drug suspensions (IM or HC) in water. The cumulative permeation amount of HC and IM from the C10/Arg gel at 10 h after application was approximately 16 and 11 times higher than that of the control, respectively. On the other hand, the flux of IM decreased with increasing arginine concentration, likely due to the acid-base interaction between Arg and IM in C10/Arg gel. Adequate drug skin permeation enhancement by C10/Arg gel requires optimizing the gel composition for each specific drug.

Solubilization mechanism of α-glycosylated naringin based on self-assembled nanostructures and its application to skin formulation

We previously reported that α-glycosylated naringin (naringin-G), synthesized by enzyme-catalyzed transglycosylation, can enhance the solubility of poorly water-soluble compounds without surface-active property. However, the solubilization mechanism has not been fully elucidated. In this study, the solubilization mechanism of naringin-G was investigated using nuclear magnetic resonance (NMR) spectroscopy, and its application in skin formulations was further investigated. 1H NMR and dynamic light scattering measurements at various concentrations confirmed the self-assembled nanostructures of naringin-G above a critical aggregation concentration of approximately 2.2 mg/mL. Two-dimensional 1H–1H nuclear Overhauser effect spectroscopy and solubility tests revealed that flavone with poor water solubility, could be solubilized in its self-assembled structure with a stoichiometric relationship with naringin-G. When naringin-G was included in the skin formulation, the permeated amount and permeability coefficient (Papp) of flavones improved up to four times with increasing amounts of naringin-G. However, flavone solubilization by adding an excessive amount of naringin-G resulted in a decreased permeated amount and Papp of flavones, indicating the interplay between the apparent solubility and skin permeability of flavones. Naringin-G, which forms a nanoaggregate structure without exhibiting surface-active properties, has the potential to enhance the solubility and skin permeation of poorly water-soluble compounds.

Development and comparison of machine learning models for in-vitro drug permeation prediction from microneedle patch

The field of machine learning (ML) is advancing to a larger extent and finding its applications across numerous fields. ML has the potential to optimize the development process of microneedle patch by predicting the drug release pattern prior to its fabrication and production. The early predictions could not only assist the in-vitro and in-vivo experimentation of drug release but also conserve materials, reduce cost, and save time. In this work, we have used a dataset gleaned from the literature to train and evaluate different ML models, such as stacking regressor, artificial neural network (ANN) model, and voting regressor model. In this study, models were developed to improve prediction accuracy of the in-vitro drug release amount from the hydrogel-type microneedle patch and the in-vitro drug permeation amount through the micropores created by solid microneedles on the skin. We compared the performance of these models using various metrics, including R-squared score (R2 score), root mean squared error (RMSE), and mean absolute error (MAE). Voting regressor model performed better with drug permeation percentage as an outcome feature having RMSE value of 3.24. In comparison, stacking regressor have a RMSE value of 16.54, and ANN model has shown a RMSE value of 14. The value of permeation amount calculated from the predicted percentage is found to be more accurate with RMSE of 654.94 than direct amount prediction, having a RMSE of 669.69. All our models have performed far better than the previously developed model before this research, which had a RMSE of 4447.23. We then optimized voting regressor model’s hyperparameter and cross validated its performance. Furthermore, it was deployed in a webapp using Flask framework, showing a way to develop an application to allow other users to easily predict drug permeation amount from the microneedle patch at a particular time period. This project demonstrates the potential of ML to facilitate the development of microneedle patch and other drug delivery systems.

A semi-interpenetrating network acrylic pressure-sensitive adhesive for efficient transdermal application with high cohesion and adhesion

The application of pressure-sensitive adhesives (PSAs) in transdermal drug delivery systems (TDDSs) is limited. Insufficient cohesion in TDDS can lead to cold flow, patch displacement, dose inaccuracies, and the ‘dark ring’ phenomenon. To address these issues, we developed a semi-interpenetrating network (semi-IPN) PSA using a 2-hydroxyethylacrylate-modified acrylic copolymer as the linear polymer and poly[tri(propylene glycol) diacrylate] as the cross-linked network. Semi-IPN PSAs have better mechanical properties compared to traditional PSAs. The cohesion of the semi-IPN PSA was 31 times and 1.6 times that of commercially available DURO-TAK®87-2287 and DURO-TAK® 87–4098, respectively, and the cold flow of the semi-IPN PSA was significantly reduced. Furthermore, the semi-IPN PSA adhered to the human forearm for longer time and did not exhibit the ‘dark ring’ phenomenon after removal. When loaded with flurbiprofen, the semi-IPN PSA was found to maintain high levels of drug release and skin permeation amount, and flurbiprofen loading did not affect its superior cohesive performance. In conclusion, the innovative application of the semi-IPN PSA for TDDS showed excellent mechanical properties, effective adhesion to the skin without irritation, and highly effective drug release. These findings indicate that the use of the semi-IPN is both simple and highly effective for TDDS.

Hydrogen Permeation Properties of Ternary Ni–BaCe0.9Y0.1O3–Ce0.9Gd0.1O2 Cermet Membranes

A ternary Ni–BaCe0.9Y0.1O3 (BCY)–Ce0.9Gd0.1O2 (GDC) cermet involving 40 vol% Ni was fabricated, and its hydrogen permeation characteristics were evaluated when the GDC volume fraction was varied from 0 to 30 vol%. The X-ray diffraction results of the cermet after sintering at 1400 °C revealed that GDC was dissolved in BCY when the GDC volume composition was 20 vol%. Regardless of the BCY and GDC volume fractions, the metal conductivity of the cermet was dominated by Ni. After the addition of only 1 vol% GDC, the particle sizes of Ni and BCY in the cermet significantly decreased, and the particle size decreased as the volume fraction of GDC increased. The hydrogen permeability increased with increasing temperature and for up to 10 vol% GDC, and a maximum permeation rate of 0.142 mL min−1 cm−2 was obtained at 700 °C. This value is comparable to or better than previously reported values for Ni-cermets under the same conditions. The amount of hydrogen permeation decreased above 10 vol% GDC. This study demonstrated that Ni-BCY-GDC cermet is a material that has both high hydrogen permeability and CO2 resistance.

Fabrication of a packaging film based on PLA blends: The evolution of physical, mechanical, and rheological properties

AbstractToday, the use of biodegradable polymers has become widespread in a wide range of industries. This research scrutinized the physical, mechanical, and rheological properties of poly (lactic acid)/poly (ethylene oxide)/carbon nanotube (PLA/PEO/CNTs) blend nanocomposites, as a good candidate for usage in the packaging industry. PEO and CNTs were added at various concentrations to improve the flexibility, toughness, gas permeability, thermal stability, and mechanical properties of PLA via solution blending. Differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Field Emission Scanning Electron Microscope (FESEM), water contact angle (WCA), rheometric mechanical spectrometer (RMS) test, gas permeability, and tensile characterization were performed to characterize the properties of the prepared blends and nanocomposites. The experimental results revealed that the addition of 25 wt% PEO to the PLA matrix made a partially miscible blend with a droplet‐matrix morphology. PEO at this concentration increased the elongation at break (from 2.2% to 18%) while reducing the modulus (from 25 to 6 MPa). Also, the experimental results indicated that the miscibility of PLA and PEO was enhanced by the addition of 1 wt% CNTs to the prepared blend, associated with diminished entropy of mixing in the LCST phase diagram. Theoretical calculations predicted that the CNTs would be localized in the PLA phase which increased the total crystallinity of the sample by 28%, considerably reducing the amount of gas permeation into the nanocomposite. In addition, the introduction of the CNTs to the blend increased the elongation at break and tensile strength by 13% compared to pure PLA and lowered the rate of thermal degradation effectively. Also, the final results showed that the COOH‐CNTs located in the PEO phase caused a decline in the crystallinity and an increase in the gas permeability of the prepared nanocomposite.Highlights Improvement of physical properties of PLA by blending with PEO and CNTs. A deep investigation on rheological behavior of the prepared nanocomposite. Increasing the crystallinity degree of PLA/PEO blend by adding CNTs. Improvement of the miscibility between PLA and PEO in the presence of CNTs. Controlling the CNTs localization by surface modification.

Topical drug delivery of licorice flavonoids and their structure-affinity relationship with the porcine skin

Traditional Chinese medicine (TCM) possesses a long history of clinical application in the transdermal prescriptions, however, their transdermal mechanisms had not been clearly elucidated ascribing to their complex ingredients and different content. In this work, we firstly provide insights reports on the transdermal mechanisms of licorice flavonoids (LFs) extracts and the structure-affinity relationship between LFs compounds and the skin. The permeation properties of LFs extracts were conducted on the porcine skin and rat skin. It was highlighted that chalones and flavanone molecules were easier to permeate through the skin from LFs extracts than isoflavone. Differ from other LFs compounds, insoluble licochalcone A and licoflavone A obtained a higher permeation amount from LFs extracts than its corresponding monomer ingredients affirmed through molecular dynamics simulation study. In the stratum corneum (SC), among 33 kinds of flavonoids, glabridin possessed the highest compatibility with the skin lipids. Furthermore, interaction parameters (χ) values between the drugs and ceramide were negatively correlated with the number of hydrogen bond donor (HBD), polarizability and polar surface area of LFs compounds. The HBD of LFs molecules could help drugs bind to the skin lipids and then formed appropriate hydrogen bond interactions with the skin lipids, further improving the affinity between the drugs and the skin. Moreover, LFs components permeated through the porcine skin by disturbing the lipids arrangement in the SC. In the epidermis and dermis, the positive number and absorption rate of LFs extracts by HaCaT cells was significantly higher than melanocytes and HSF cells after 6 h. This study provided a new approach to unveil the molecular mechanisms of LFs permeation, which gave a reference for permeation of other TCM extracts.

Exploring the therapeutic potential of sodium deoxycholate tailored deformable-emulsomes of etodolac for effective management of arthritis

The current piece of research intends to evaluate the potential of combining etodolac with deformable-emulsomes, a flexible vesicular system, as a promising strategy for the topical therapy of arthritis. The developed carrier system featured nanometric dimensions (102 nm), an improved zeta potential (− 5.05 mV), sustained drug release (31.33%), and enhanced drug deposition (33.13%) of DE-gel vis-à-vis conventional system (10.34% and 14.71%). The amount of permeation of the developed nano formulation across skin layers was demonstrated through CLSM and dermatokinetics studies. The safety profile of deformable-emulsomes has been investigated through in vitro HaCaT cell culture studies and skin compliance studies. The efficacy of the DE-gel formulation was sevenfold higher in case of Xylene induced ear edema model and 2.2-folds in CFA induced arthritis model than that of group treated with conventional gel (p < 0.01). The main technological rationale lies in the use of phospholipid and sodium deoxycholate-based nanoscale flexible lipoidal vesicles, which effectively encapsulate drug molecules within their interiors. This encapsulation enhances the molecular interactions and facilitates the transportation of the drug molecule effectively to the target-site. Hence, these findings offer robust scientific evidence to support additional investigation into the potential utility of flexible vesicular systems as a promising drug delivery alternative for molecules of this nature.

The implications of lipid mobility, drug-enhancers (surfactants)-skin interaction, and TRPV1 activation on licorice flavonoid permeability.

Licorice flavonoids (LFs) are derived from perennial herb licorice and have been attaining a considerable interest in cosmetic and skin ailment treatments. However, some LFs compounds exhibited poor permeation and retention capability, which restricted their application. In this paper, we systematically investigated and compared the enhancement efficacy and mechanisms of different penetration enhancers (surfactants) with distinct lipophilicity or "heat and cool" characteristics on ten LFs compounds. Herein, the aim was to unveil how seven different enhancers modified the stratum corneum (SC) surface and influence the drug-enhancers-skin interaction, and to relate these effects to permeation enhancing effects of ten LFs compounds. The enhancing efficacy was evaluated by enhancement ratio (ER)permeation, ERretention, and ERcom, which was conducted on the porcine skin. It was summarized that heat capsaicin (CaP) and lipophilic Plurol® Oleique CC 497 (POCC) caused the most significance of SC lipid fluidity, SC water loss, and surface structure alterations, thereby resulting in a higher permeation enhancing effects than other enhancers. CaP could completely occupied drug-skin interaction sites in the SC, while POCC only occupied most drug-skin interactions. Moreover, the enhancing efficacy of both POCC and CaP was dependent on the log P values of LFs. For impervious LFs with low drug solubility, enhancing their drug solubility could help them permeate into the SC. For high-permeation LFs, their permeation was inhibited ascribed to the strong drug-enhancer-skin strength in the SC. More importantly, drug-surfactant-skin energy possessed a good negative correlation with the LFs permeation amount for most LFs molecules. Additionally, the activation of transient receptor potential vanilloid 1 (TRPV1) could enhance LFs permeation by CaP. The study provided novel insights for drug permeation enhancement from the viewpoint of molecular pharmaceutics, as well as the scientific utilization of different enhancers in topical or transdermal formulations.

The impact of surface area per volume (SA/V) ratio on drug transport from supersaturated solutions of ketoconazole

The purpose of this study aimed to evaluate the impact of the surface area per volume (SA/V) ratio on drug transport from two supersaturated solutions (SSs) of ketoconazole with and without hydroxypropyl methylcellulose (HPMC), used as a precipitation inhibitor. In vitro dissolution, membrane permeation with two SA/V ratios, and in vivo absorption profiles for both SSs were determined. For the SS without HPMC, a two-step precipitation process due to the liquid–liquid phase separation was observed; the constant concentration with approximately 80 % of the dissolved amount was maintained for the first 5 min and subsequently decreased between 5 and 30 min. For the SS with HPMC, a parachute effect was observed; the constant concentration with approximately 80 % dissolved amount was maintained for more than 30 min and decreased very slowly thereafter. Assessment of the SA/V ratio using in vitro and in vivo models demonstrated that when the SA/V ratio was small, the SS with HPMC resulted in a significantly higher permeated amount than the SS without HPMC. In contrast, when the SA/V ratio was large, the HPMC-mediated parachute effect on drug transport from SSs was attenuated, both in vitro and in vivo. The parachute effect by HPMC decreased as the SA/V ratio increased, and the performance of supersaturating formulations would be overestimated by in vitro studies with small SA/V ratios.

Remote-controllable dosage management through a wearable iontophoretic patch utilizing a cell phone.

With regard to medical treatment through operations, remote control is possible, however, the area of remote-controllable drug treatment is yet to be established. In this study, a prototyped remote-controllable dosage management system that allows patients and caregivers to administer therapeutic drugs via an internet line without touching the dosage device or formulation was developed. This system consists of a transmitter (System A) located away from the patient, and a dosage device (System B) equipped with a receiver (B1), dosage management unit (B2), and a drug treatment unit (B3) that can be installed on the patient. Additionally, Bluetooth® is adopted to communicate from System A to System B. In the present study, System A was incorporated into a cell phone, and System B was a constant-current iontophoresis (IP) device, which was applied on excised pig skin. Sodium salt of betamethasone phosphate (BP-Na+) was selected as a model drug, and the in vitro skin permeation of BP- was evaluated. As a result, by transmitting the administration information incorporated in System A through B1 to B2, the optimal current was passed between the IP electrodes in B3, and the skin permeation of BP- was obtained by remote control. That is, the skin permeation of BP- was obtained by the current flowing from the IP device. The permeation amount decreased when the voltage load was stopped. These results suggested that remote control from System A enables dosing management of bioactive substances from dosage devices applied on the skin, intracutaneously, or subcutaneously without being near the patient. Although various trials are still required to complete the remote-controlled system, the patient does not have to go to the hospital except to take injections. Such drug administrations would lead to decreased medical expenses and increased quality of life for patients.

Effects of Masks Containing 0.5% Tranexamic Acid‐Loaded Ethosomes on Melasma in the Asian Skin: A Randomized Controlled Clinical Trial

Background. Tranexamic acid (TA) has emerged as a promising treatment for melasma without serious adverse effects. Ethosomes have been reported as the carriers for transdermal drug delivery systems to increase the amount of drug permeation through the skin. However, few studies of the local usage of TA‐loaded ethosomes exist. Objectives. To evaluate the efficacy of a mask containing 0.5% TA‐loaded ethosomes in the treatment of melasma in the Asian skin. Methods. In a double‐blind, placebo‐controlled, randomized, prospective study, 88 Asian participants with melasma were randomized 1 : 1 to two groups as follows: the TA or control. The TA group was treated with moisturizing masks with 0.5% TA‐loaded ethosomes, and the control was treated with moisturizing masks only. Masks were applied once daily for the first two weeks and once every other day for the third and fourth weeks. The primary outcome was measured by the modified melasma area and severity index (mMASI) and a visual analog scale (VAS) for vessels. The secondary outcomes were VAS for skin texture and satisfaction. Results. The reduction of VAS vessel scores at the end of treatment in the TA group was significantly greater than that in the control group (P &lt; 0.001). The mMASI scores and skin texture scores decreased over time in both groups, but no significant differences were found between the two groups (P &gt; 0.05). The score of participant satisfaction in the TA group was significantly higher than that in the control group (P &lt; 0.01). Conclusions. Masks containing TA‐loaded ethosomes appear to be an effective treatment for Asian melasma in terms of angiogenesis and skin texture. It improves the pigmentation to some extent but has no significance. This trial is registered with ChiCTR1900024257.

Variation of the collective drainage pipelines parameters when passing the transit flow

Simple and convenient dependences for calculating basic hydraulic and design characteristics of pressure collecting horizontal drainage pipelines operating in the presence of transit flow, in which the fluid collection along the path occurs in the filtration mode, are presented in the paper. They are based on the analysis of a system of differential equations that describe the fluid motion in such pipes. The solutions are based on the assumption that the member, which takes into account the effect of the flow variation along the pass, is neglected. The concept of a fictitious infinitely long collecting drainage pipeline or a pipeline with an infinitely large amount of the pipe walls permeation is used in the analysis. It is assumed that the actual flow at the end of this pipelines is replaced by a conditional flow, which is collected at the fictitious end section of the pipeline. The flow in the end section of the fictitious pipes is assumed to be zero. The introduced assumptions allow to use formulas for calculation of the mentioned pipelines with a certain approximation which are applied at calculation of pipelines operation without transit. These dependences allow to calculate the effect of transit flow on the hydraulic characteristics of the collecting drainage pipelines.

Enhancing effects of chemical permeation enhancer propylene glycol and ultrasonic technology on transdermal permeation of Baimai Ointment

This study aimed to improve the transdermal permeation quantity of Baimai Ointment by investigating the enhancing effects of physical and chemical permeation promoting methods on transdermal permeation of Baimai Ointment. The improved Franz diffusion cell method was used for in vitro transdermal experiment. The abdominal skin of mice was used, and the skin was treated with 3% propylene glycol in the chemical enhancement group. Ultrasonic technology was introduced in the physical enhancement group. The conditions of ultrasonic technology were optimized by single factor trial. Taking Q_(EF) and ER as the indexes of penetration promotion performance, the enhancing effects of the two methods were compared. The results showed that the promotion performance of 3% propylene glycol for ammonium glycyrrhizinate, nardosinone and curcumin of the chemical enhancement group were 1.74, 1.60, and 3.73 times higher than those of the blank group, respectively. The overall permeation efficiency of the Baimai Ointment was significantly improved. The comprehensive promoting effect on each component was curcumin&gt;ammonium glycyrrhizinate&gt;nardosinone. In the physical enhancement group, the penetration promoting effect of ultrasonic power 1.0 W was better than that of 2.0 W and 0.5 W, ultrasonic time 5 min was better than 3 min and 8 min, and the ultrasonic frequency 1 MHz was better than 3 MHz. Therefore, the optimal ultrasonic condition was 1.0 W-5 min-1 MHz. Under this condition, in terms of the transdermal permeation for ammonium glycyrrhizinate, the Q_(EF) and ER of the ultrasonic technology were better than those of 3% propylene glycol. In terms of the transdermal permeation for nardosinone and curcumin, the QEF and ER of 3% propylene glycol were better than those of the ultrasonic technology. Therefore, 3% propylene glycol combined with ultrasonic technology can be used to promote permeation of Baimai Ointment that contains both water-soluble and fat-soluble components in the clinical application. This study provides a theoretical basis for the clinical application of Baimai Ointment and other transdermal preparations.

Preparation and Characterization of Aprepitant Solid Dispersion with HPMCAS-LF.

This study focused on improving the physicochemical characteristics of aprepitant with poor water solubility by preparing solid dispersion (SD). To prepare the SD with HPMCAS-LF, the solvent evaporation method was applied. Based on dissolution analysis, the dissolution rate of SD increased by five times compared with aprepitant. In addition, scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC) results suggested the presence of amorphous-form aprepitant inside SD. According to Fourier transform infrared (FTIR) spectroscopy, intermolecular hydrogen bonds were detected between polymer and aprepitant. The Caco-2 cell experiment proved that SD did not lower the transepithelial electrical resistance (TEER) values but improved the permeation amount of aprepitant. Additionally, the SD of aprepitant displayed excellent stability.

A study on the molecular mechanisms underlying the compatibility of traditional Chinese medicines: Development of ferulic acid-tetramethylpyrazine compound patch

Chuanxiong Rhizome (known as Chuanxiong in Chinese), is widely used in traditional Chinese medicines (TCMs) compounding patches. Ferulic acid (FA) and tetramethylpyrazine (TMP) are the main components of Chuanxiong. This paper aimed to prepare an FA-TMP compound patch with proven anti-inflammatory activity and elucidate the molecular mechanisms of transdermal behaviors of compounds. As confirmed by an anti-inflammatory study, the formulation was optimized by the employment of in vitro skin permeation. The addition of TMP increased the skin permeation amount of FA by approximately 1.9 times. Through FT-IR, XPS, and thermal analysis, it was demonstrated that FA mainly formed hydrogen bonds with TMP, which depressed the melting point (ΔM.P. = 14.6 °C) and hydrophilicity (Δlog Do/w = 0.44) of FA. As revealed by ATR-FTIR and 13C NMR, compounds increased the degree of skin lipid perturbation (ΔνasCH2 = 3.28 cm−1) and attenuated FA binding to ceramides and keratin. To sum up, the hydrogen bonding site of FA was competed by TMP, which enhanced the ability of FA to penetrate the stratum corneum (SC) and partition into the hydrophilic dermal layer, increasing the amount of skin permeation of FA. This study is the first investigation on the combined citation of FA and TMP in patches. It will not only provide a valuable reference for research on the molecular mechanism of transdermal behaviors concerning compounds but will also help to provide a theoretical basis at the molecular level for the scientific design of TCMs formulations.

Oral transmucosal delivery of eletriptan for neurological diseases

Migraine is a highly prevalent neurological disease affecting circa 1 billion patients worldwide with severe incapacitating symptoms, which significantly diminishes the quality of life. As self-medication practice, oral administration of triptans is the most common option, despite its relatively slow therapeutic onset and low drug bioavailability. To overcome these issues, here we present, to the best of our knowledge, the first study on the possibility of oral transmucosal delivery of one of the safest triptans, namely eletriptan hydrobromide (EB). Based on a comprehensive set of in vitro and ex vivo experiments, we highlight the conditions required for oral transmucosal delivery, potentially giving rise to similar, or even higher, drug plasma concentrations expected from conventional oral administration. With histology and tissue integrity studies, we conclude that EB neither induces morphological changes nor impairs the integrity of the mucosal barrier following 4 h of exposure. On a cellular level, EB is internalized in human oral keratinocytes within the first 5 min without inducing toxicity at the relevant concentrations for transmucosal delivery. Considering that the pKa of EB falls within the physiologically range, we systematically investigated the effect of pH on both solubility and transmucosal permeation. When the pH is increased from 6.8 to 10.4, the drug solubility decreases drastically from 14.7 to 0.07 mg/mL. At pH 6.8, EB gave rise to the highest drug flux and total permeated amount across mucosa, while at pH 10.4 EB shows greater permeability coefficient and thus higher ratio of permeated drug versus applied drug. Permeation experiments with model membranes confirmed the pH dependent permeation profile of EB. The distribution of EB in different cellular compartments of keratinocytes is pH dependent. In brief, high drug ionization leads to higher association with the cell membrane, suggesting ionic interactions between EB and the phospholipid head groups. Moreover, we show that the chemical permeation enhancer DMSO can be used to enhance the drug permeation significantly (i.e., 12 to 36-fold increase). Taken together, this study presents important findings on transmucosal delivery of eletriptan via the oral cavity and paves the way for clinical investigations for a fast and safe migraine treatment.