Diffusion in Metallic Glasses and in Oxide Glasses - An Overview

We remind the reader to some common features of metallic and oxide glasses. We then introduce the radiotracer method for diffusion studies, which can be applied for both types of glasses. We provide an overview on diffusion in metallic glasses in which we consider both types of metallic glasses – conventional and bulk metallic glasses. In the last part we discuss diffusion and ionic conduction in oxide glasses. For ionic glasses, conductivity measurements are an important complement to tracer diffusion studies. We remind the reader to the method of impedance spectroscopy. We discuss results for soda-lime silicate glasses, single alkali borate glasses and mixed alkali borate glasses and present evidence for collective jump processes in glasses.

Formulation and Evaluation of Luliconazole Microsponges Loaded Gel for Topical Delivery

Microsponge containing Luliconazole (LCZ) with different proportion of drug:polymer (Ethyl cellulose and Eudragit RS 100) were obtained efficiently using Quasi-emulsion solvent diffusion method. Luliconazole is an anti-fungal drug used for the topical delivery. The purpose of the microsponge formulation is to control the release of LCZ drug to the skin through Microsponge Delivery System (MDS) known to be the novel technique which overcome the maximum concentration of active ingredient, frequency doses, and skin irritation. The prepared microsponges were examined using drug content, % production yield, % entrapment efficiency and in-vitro drug release. The formulation were subjected to in-vitro drug release studies for 6 hr in which it was concluded that Ethyl cellulose microsponges formulated by drug:polymer (1:1) and Eudragit RS 100 microsponges formulated by drug:polymer (1:3) showed maximum controlled release i.e., Increase in drug:polymer ratio (1:1 to 1:9) increased the production yield and entrapment efficiency of microsponges using Ethyl cellulose with no significant effect for Eudragit RS 100.Therefore, both formulation F1 and F2 was dispersed in carbopol gel preparation for controlled delivery of LCZ to the skin. Various physical parameters like pH, spreadability, viscosity and in-vitro drug diffusion studies were evaluated for the prepared gel formulations. Microsponge gel formulation i.e., FG1 showed better results for controlled release of 89.40% as compared to FG2 i.e., 92.18% over the period of 12 hrs which is performed in Franz Diffusion Cell. On basis of in-vitro diffusion studies for LCZ gel formulation, microsponges using Ethyl cellulose (FG1) was found to be best for its controlled release of LCZ for 12 hrs and followed zero order kinetics. Hence, formulated LCZ loaded gel have potential to treat fungal infections i.e., tinea pedis, tinea cruris and tinea corporis.

1287. Double Disk Diffusion Study to Evaluate the Synergistic Effect Between Cefiderocol and Ceftazidime-Avibactam Against Cefiderocol-Non-susceptible Acinetobacter baumannii

Background Cefiderocol (CFDC), a siderophore cephalosporin, has broad coverage of Gram-negative bacteria and has been approved for clinical use in USA and Europe. The SIDERO-WT surveillance studies showed that CFDC shows >95% susceptibility against Acinetobacter baumannii. Against many of CFDC non-susceptible isolates, most of which had blaPER gene, the combination use of avibactam significantly decreased the MIC by broth microdilution (BMD). In this study, we evaluated the appropriate methodology to evaluate the synergistic effect by disk diffusion studies. Methods The susceptibility testing was conducted as recommended by the CLSI using CFDC non-susceptible isolates (MIC of >4 µg/mL based on CLSI breakpoint). The MIC by BMD was determined using iron-depleted cation-adjusted Mueller-Hinton broth, in the presence or absence of 4 µg/mL of avibactam. The disk diffusion was evaluated using Mueller-Hinton agar, and the synergy was evaluated by using disk stacking methods. For disk stacking methods, CFDC disk was placed on agar on which bacterial suspension of 0.5 McFarland units was spread, then the ceftazidime-avibactam (CZA) disks was stacked on the top, followed by adding a drop (30 µL) of saline on the stacked disks. As an alternative method, CZA was immersed in saline for 1 second instead of adding a drop of saline, followed by the stacking on the top. The disk zone size was determined after 24-hour incubation at 37°C. Results Against blaPER-positive A. baumannii which showed >64 µg/mL MIC of CFDC and CZA, CFDC MIC decreased to 0.25 µg/mL in the presence of avibactam. The disk diffusion methods also showed isolates resistant to CFDC and CZA and showed susceptiblilty disk zone to CFDC by stacking both disks. On the other hand, against blaNDM-positive A. baumannii which showed 64 µg/mL MIC of CFDC and CZA, the disk diffusion methods showed resistance even when stacking both disks. Against multiple isolates, the MIC of CFDC without or with avibactam was correlated well with the disk zone produced by CFDC disk alone or stacked with CZA disks, respectively (Figure). Conclusion The synergistic effect between CFDC and avibactam by BMD methods could be detected by disk stacking methodology using CFDC and CZA disks. Disclosures Yoshinori Yamano, PhD, Shionogi (Employee) Miki Takemura, MS, SHIONOGI & CO., LTD. (Employee) Roger Echols, MD, Shionogi (Consultant) Christopher Longshaw, PhD, Shionogi (Employee)

Formulation and Evaluation of Topical Microemulgel Containing Terbinafine Hydrochloride

The purpose of this study is to create and test a Terbinafine hydrochloride microemulgel. Terbinafine hydrochloride is an FDA-approved antifungal medication used to treat fungal infections on the skin. It's a BCS class II medication with little bioavailability. In the realm of pharmaceutical sciences, microemulgel has evolved into one of the most intriguing topical preparations. Microemulgel as a delivery technique has several advantages over simple traditional formulations, including simplicity of administration, increased residence duration at the application site, consistent drug release with improved bioavailability, superior thermodynamic stability, and excellent transdermal permeability. Terbinafine hydrochloride microemulgels were made with carbopol 940 and HPMC as gelling agents, oleic acid as an oil, parabens as a preservative, and tween 20 as an emulgent and penetration enhancer. The appearance, spreadability, homogeneity, viscosity, pH, percent drug content, and in vitro diffusion studies of the generated microemulgel formulation were all visually checked. The findings show that developing a terbinafine-containing microemulgel is more effective, but clinical efficacy must be determined through clinical trials.

Gelation and Yielding Behavior of Polymer-Nanoparticle Hydrogels

Polymer-Nanoparticle hydrogels are a unique class of self-assembled, shear-thinning, yield-stress fluids which have demonstrated potential utility in many impactful applications. Here we present a thorough analysis of the gelation and yielding behavior of these materials with respect to the polymer and nanoparticle component stoichiometry. Through comprehensive rheological and diffusion studies, we reveal insights into the structural dynamics of the polymer nanoparticle network which identify that stoichiometry plays a key role in gelation and yielding, ultimately enabling the development of hydrogel formulations with unique shear-thinning and yield-stress behaviors. Access to these materials opens new doors for interest- ing applications in a variety of fields including tissue engineering, drug delivery, and controlled solution viscosity.

FORMULATION AND EVALUATION OF ANTIFUNGAL CREAM OF CHLORPHENESIN

Objective: The main aim of our research was to develop an Antifungal cream formulation consisting of Chlorphenesin for the treatment of Fungal infections. Topical route is the most suitable route for skin infections. Methods: The development of topical drug delivery systems designed to have systemic effects appears to be beneficial for a number of drugs on account of several advantages over conventional dosage forms(or) routes of drug administration. An Antifungal cream formulation consisting of Chlorphenesin was prepared. Results: The formulation was subjected to in vitro diffusion studies. Microbiological studies were performed to find out the safety of materials used in the formulation. Conclusion: The developed cream consisting of Cholrphnesin was found to be safe and effective for the treatment of fungal infection.

Formulation and Evaluation of Hydrogels containing Liposomes Entrapped with Antifungal Agent

Background: The main aim of the present study was to formulate and evaluate prolonged release Fluconazole liposomal gel for the transdermal delivery. Fluconazole, α-(2.4-diflurofenil)-α-(1H-triazole-1-methyl)-1H-1, 2, 4-triazole-1-ethanol, is a class of antifungal of triazole. It shows the action against species of Candida sp., and it is specified in cases of or pharyngeal candidiasis, esophageal, vaginal, and deep infection. Materials and Method: Fluconazole liposomal gel was prepared by thin film hydration method using phosphatidyl choline and cholesterol. Liposomes were characterized for entrapment efficiency, particle size, and surface charge. Liposomes were then dispersed into a Carbopol gel base to form liposomal gel and evaluated for drug content, pH, spreadability, viscosity and in-vitro drug release. Results: The results indicated that concentration of cholesterol in the formulations affected the particle size and entrapment efficiency. When the concentration of cholesterol increased particle size was also increased but decrease in entrapment efficiency. The viscosity of Fluconazole liposomal gel decreases with increasing rate of shear. Hence it was showed that with non-Newtonian flow. In-vitro diffusion studies were carried out using cellophane membrane, results showed that liposomal gel formulation F1 (91.36%) showed highest cumulative percent of drug release and formulation F8 (76.98%) showed lowest cumulative percent of drug release. Conclusion: Therefore, Fluconazole liposomal gel sustained the drug release for the longer duration, hence decreases the number of application of drugs and also improves patient compliance.

Influence of Lactobacillus Biosurfactants on Skin Permeation of Hydrocortisone

One of the most widely used strategies to improve drug diffusion through the skin is the use of permeation enhancers. The aim of this work was to investigate the effect of two biosurfactants (BS), produced by Lactobacillus crispatus BC1 and Lactobacillus gasseri BC9, on the skin permeation profile of hydrocortisone (HC, model drug). HC aqueous solubility and in vitro diffusion studies through porcine skin were performed in the presence of BC1-BS and BC9-BS at concentrations below and above critical micellar concentrations (CMC). Moreover, skin hydration tests and differential scanning calorimetry (DSC) analysis were performed to further investigate BS interaction with the outermost layer of the skin. Both BS increased HC solubility, especially at concentrations above their CMC. At concentrations below the CMC, drug permeation through the skin was improved, as the result of a dual effect: a) the formation of a superficial lipophilic environment, as confirmed by the reduction in skin hydration and b) the interaction between BS and the stratum corneum (SC), as demonstrated by the DSC curves. From the obtained data, it appears that BC1-BS and BC9-BS could represent new promising green excipients for drug permeation enhancement through the skin.

Diffusion Processes in International Political Economy

This article provides an overview of recent literature on diffusion within the field of International Political Economy (IPE). It considers some of the more significant channels through which diffusion can occur, as well as the major causal processes that are likely to be responsible for the diffusion. After providing a brief overview of the modeling strategy adopted by many of the more influential diffusion studies, it goes on to discuss a number of promising directions for future research. It suggests that the literature has moved away from answering the question of whether diffusion is occurring in different contexts and is now more focused on understanding the conditions under which diffusion is more or less likely to occur. It argues that the study of diffusion within IPE tends to be problem-centered in its approach and stands to benefit from more engagement between quantitative and qualitative research.

In Vitro–In Vivo Correlation in Dermal Delivery: The Role of Excipients

The composition of topical and transdermal formulations is known to determine the rate and the extent of drug delivery to and through the skin. However, to date, the role of excipients in these formulations on skin delivery of actives has received little attention from scientists in the field. Monitoring skin absorption of both drug and vehicle may provide insights into the mechanism by which excipients promote permeation and may facilitate the design of effective and safer products. Previously, we have investigated the use of quantitative Confocal Raman Spectroscopy (CRS) to investigate the delivery of an active to the skin, and we also reported the first fully quantitative study that compared this method with the well-established in vitro permeation test (IVPT) model. To further explore the potential of quantitative CRS in assessing topical delivery, the present work investigated the effects of commonly used excipients on the percutaneous absorption of a model drug, ibuprofen (IBU). Permeation of IBU and selected solvents following finite dose applications to human skin was determined in vitro and in vivo by Franz diffusion studies and quantitative CRS, respectively. The solvents used were propylene glycol (PG), dipropylene glycol (DPG), tripropylene glycol (TPG), and polyethylene glycol 300 (PEG 300). Overall, the cumulative amounts of IBU that permeated at 24 h in vitro were similar for PG, DPG, and TPG (p > 0.05). These three vehicles outperformed PEG 300 (p < 0.05) in terms of drug delivery. Concerning the vehicles, the rank order for in vitro skin permeation was DPG ≥ PG > TPG, while PEG 300 did not permeate the skin. A linear relationship between maximum vehicle and IBU flux in vitro was found, with a correlation coefficient (R2) of 0.95. When comparing in vitro with in vivo data, a positive in vitro–in vivo (IVIV) correlation between the cumulative permeation of IBU in vitro and the total amount of IBU that penetrated the stratum corneum (SC) in vivo was observed, with a Pearson correlation coefficient (R2) of 0.90. A strong IVIV correlation, R2 = 0.82, was found following the linear regression of the cumulative number of solvents permeated in vitro and the corresponding skin uptake in vivo measured with CRS. This is the first study to correlate in vivo permeation of solvents measured by CRS with data obtained by in vitro diffusion studies. The IVIV correlations suggest that CRS is a powerful tool for profiling drug and vehicle delivery from dermal formulations. Future studies will examine additional excipients with varying physicochemical properties. Ultimately, these findings are expected to lead to new approaches for the design, evaluation, and optimization of formulations that target actives to and through the skin.