Vertical Diffusion Cells Research Articles

Fabrication of Poly Lactic-co-Glycolic Acid Microneedles for Sustained Delivery of Lipophilic Peptide-Carfilzomib.

Transdermal drug delivery (TDD) is an attractive route of administration, providing several advantages, especially over oral and parenteral routes. However, TDD is significantly restricted due to the barrier imposed by the uppermost layer of the skin, the stratum corneum (SC). Microneedles is a physical enhancement technique that efficiently pierces the SC and facilitates the delivery of both lipophilic and hydrophilic molecules. Dissolving microneedles is a commonly used type that is fabricated utilizing various biodegradable and biocompatible polymers, such as polylactic acid, polyglycolic acid, or poly(lactide-co-glycolide) (PLGA). Such polymers also promote the prolonged release of the drug due to the slow degradation of the polymer matrix following its insertion. We selected carfilzomib, a small therapeutic peptide (MW: 719.924 g/mol, log P 4.19), as a model drug to fabricate a microneedle-based sustained delivery system. This study is a proof-of-concept investigation in which we fabricated PLGA microneedles using four types of PLGA (50-2A, 50-5A, 75-5A, and 50-7P) to evaluate the feasibility of long-acting transdermal delivery of carfilzomib. Micromolding technique was used to fabricate the PLGA microneedles and characterization tests, including Fourier transform infrared spectroscopy, insertion capability using the skin simulant Parafilm model, histological evaluation, scanning electron microscopy, and confocal microscopy were conducted. In vitro release and permeation testing were conducted in vertical Franz diffusion cells. N-methyl pyrrolidone was utilized as the organic solvent and microneedles were solidified in controlled conditions, which led to good mechanical strength. Both in vitro release and permeation testing showed sustained profiles of carfilzomib over 7 days. The release and permeation were significantly influenced by the molecular weight of PLGA and the lipophilic properties of carfilzomib.

Study of xymedone release from hydrogels with zinc oxide nanoparticles

In this work the approaches to assess of the xymedone release from hydrophilic gels with zinc oxide nanoparticles were proposed using a vertical Franz diffusion cell at 37 ℃. A partial validation protocol included the varying of the membrane polarity (lipophilic or hydrophilic cellulose acetate), the acceptor chamber volume (4,35 mL or 12,71 mL), the gel composition (with or without zinc oxide nanoparticles), as well as the metrological characteristics for the xymedone assay when it was released through the membrane in a Franz cell. It was estimated that the Franz cell with the volume of 12,71 mL, and the lipophilic membrane made it possible to estimate the amount of xymedone released with less error (RSD no more than 2%). We showed that the xymedone immobilization into zinc oxide nanoparticles increased the efficiency of xymedone release from the hydrophilic gel by 30%. The xymedone release through the both hydrophilic and lipophilic membranes is described by a pseudo-second-order equation that typical for desorption process from the polymer matrix. The proposed partial validation protocol to assessing the drug release using the Franz cell can be useful for selection of optimal composition of dermal topical dosage forms with hydrophilic pharmaceutical active substances. Keywords: hydrogels, release, xymedone, zinc oxide nanoparticles, partial validation protocol

Evaluation of in vitro Skin Permeation of Clascoterone From Clascoterone Topical Cream, 1% (w/w).

Winlevi® (clascoterone) topical cream (1%, w/w) was approved by the U.S. FDA for the treatment of acne vulgaris in patients 12years of age and older. The active ingredient, clascoterone, is not stable in physiological solutions and can hydrolyze to cortexolone at body temperature. Instability of clascoterone poses a significant challenge in accurately assessing the rate and extent of clascoterone permeation in vitro. Therefore, the purpose of this study was to develop an in vitro skin permeation test (IVPT) method, and a robust analytical method, that can minimize hydrolyzation of clascoterone during the study for quantification of clascoterone. Two IVPT methods, using either vertical diffusion cells or flow-through cells, were developed and compared to evaluate in vitro permeation of clascoterone from Winlevi. A liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was developed to monitor the level of clascoterone and cortexolone in the IVPT samples. The analytical method features a 2-min high-throughput analysis with good linearity, selectivity, and showed a lower limit of quantitation (LLOQ) of 0.5ng/mL for both clascoterone and cortexolone. The in vitro skin permeation of clascoterone and cortexolone was observed as early as 2h in both IVPT methods. A substantive amount of clascoterone was found to hydrolyze to cortexolone when using the vertical static diffusion cells with aliquot sampling. Conversely, degradation of clascoterone was significantly minimized when using the flow-through diffusion cells with fractional sampling. The data enhanced our understanding of in vitro permeation of clascoterone following topical application of the Winlevi topical cream, 1% and underscores the importance of IVPT method development and optimization during product development.

Development of ocular delivery systems for macitentan and ex vivo study of intraocular permeation

Macitentan is a drug that acts as a non-selective antagonist of endothelin receptors. It has been officially approved for the treatment of cases of pulmonary arterial hypertension. There are studies in animal models that indicate a therapeutic potential for this drug in the treatment of glaucoma, a degenerative eye disease marked by a progressive reduction in the visual field that can progress to irreversible blindness. In the present work, ophthalmic formulations of macitentan were developed with the aim of evaluating their potential to deliver the active ingredient to therapeutically relevant sites. An HPLC-DAD method was adapted from the literature and validated to quantify macitentan in each step. Physicochemical characterization studies of the formulations were performed, and a Franz vertical diffusion cell was used in an analysis of the in vitro/ex vivo permeation using cornea and sclera of porcine eyes to represent biological membranes. The developed formulations presented different permeation profiles according to the presence or absence of water in the base formulation and the type of viscosity promoting agent used. The formulations that showed the highest percentage of permeation were evaluated for mucus adhesiveness and the most promising were further analyzed for stability that included measuring drug content, pH, and viscosity. One formulation was developed for the ocular release of macitentan with a high percentage of drug permeation, adequate viscosity and stability that could represent an advancement in the treatment of glaucoma with a high potential for patient adherence.

A Comparative Study and Prediction of the Ex Vivo Permeation of Six Vaginally Administered Drugs across Five Artificial Membranes and Vaginal Tissue.

The theoretical interpretation of the vaginal permeability phenomenon, the evaluation of the suitability of five artificial membranes, and the prediction of the behaviors of vaginal drugs were the main objectives of this study. Franz vertical diffusion cells and different validated HPLC methods were used to measure the permeability of six vaginally administered drugs (econazole, miconazole, metronidazole, clindamycin, lidocaine, and nonoxynol-9). This study was performed (in vitro) on different membranes of polyvinylidene fluoride (PVDF), plain cellulose or cellulose impregnated with isopropyl myristate (IPM), and cellulose combined with PVDF or IPM. The results were compared with those obtained from cow vaginal tissue (ex vivo), where cellulose was proven to be the best simulant. According to the permeability profiles (Papp), the water solubility of the drugs was considered a necessary criterion for their transport in the membranes or in the tissue, while the size was important for their penetration. Furthermore, it was found that polar compounds show clear superiority when penetrating cellulose or tissue, while non-polar ones show superiority when penetrating the lipophilic PVDF membrane. Finally, a successful attempt was made to predict the Papp values (|Papp-predPapp| < 0.005) of the six drugs under study based on a PLS (Partial Least Squares) in silico simulation model.

Effect of chemical penetration enhancers on the transdermal delivery of olanzapine in human skin in vitro

This research study involves the development of an olanzapine (OLZ) formulation using various chemical penetration enhancers (CPEs) for transdermal delivery. The aim of this study was to obtain the initial data needed about the effects of various CPEs on the skin permeation of OLZ. The effects of the selected CPEs were examined by studying the permeation profiles of OLZ from formulations applied to human cadaver skin samples. A control formulation of OLZ in propylene glycol (PG) was prepared and compared against formulations containing chemical penetration enhancers. Five different CPEs (oleic acid (OA), cineole (Cin), isopropyl alcohol (IPA), Tween 80 (T80), and N-methyl pyrrolidone (NMP)) at 5% w/w were individually added to the formulation containing OLZ in PG. The in vitro permeation study was carried out using vertical Franz diffusion cells mounted with human cadaver skin. Samples from the receptor compartment of the cell were collected at 2 h, 4 h, 8 h, 12 h, and 24 h at room temperature. The amount (µg/cm2) of permeated drug (OLZ) was measured using a validated HPLC method, and the percentage (%) of OLZ permeated was calculated. Based on the data obtained, different CPEs were found to have a significant impact on OLZ permeability compared to the control formulation. The most effective chemical penetration enhancer was shown to be 5% w/w OA with a 3.3-fold increase in enhancement ratio (ER). The rank of order for the highest concentration of OLZ permeated from each of CPE containing formulation was as follows: OA > Cin > IPA > T80 > NMP. The most effective chemical penetration enhancer was OA but the cytotoxic study using human fibroblast cells suggests that OA may not be safe due to its cytotoxic effects.

A Validated IVRT Method to Evaluate Semisolid Dosage Form Containing Ximenynic Acid Using a Novel Approach

Purpose: Ximenynic acid (XMA) holds significant potential in the market, especially due to its widespread application in the cosmetics sector. As its various biological activities continue to be discovered, there is a sharp rise in demand for ximenynic acid. A novel analytical approach has been devised for an in-house product, comparable to the reference listed drug (Softalia, containing 30% ximenynic acid), utilized in gel formulations. This method is designed to conduct in-vitro release studies employing Franz vertical diffusion cell apparatus and analytical quantification via high-performance liquid chromatography (HPLC). Methods: The methodology has been assessed concerning specificity, linearity, the limit of quantitation (LoQ), limit of detection (LoD), inter-day precision, intermediate precision, accuracy, and solution stability. Following method development, the reference product containing 30% ximenynic acid underwent testing against the in-house XMA semisolid dosage form to accurately demonstrate “equivalence”, with results aligning with the applicable acceptance criteria falling within the range of 75 to 133.33%, as outlined in the FDA’s SUPAC-SS guidance. The in-vitro release assay has proven valuable for quality assurance, batch comparison, and monitoring the impacts of different formulations, scales, scaling up/down, methods, locations, and other variables. Results: This research fabricates specific IVRT techniques for performing assessments of semisolid dosage forms, which are required for many regulatory purposes.

Formulation and optimisation of Ozenoxacin topical nano-emulgel including a comprehensive methodology to qualify and validate the critical parameters of an in-vitro release test method and ex-vivo permeation test

Objective The purpose of this study was to formulate, optimize Ozenoxacin topical nano-emulsion using factorial design followed by to prepare and evaluate nano-emulgel using validated in-vitro release testing (IVRT) technique for determination of Ozenoxacin release rate along with ex-vivo permeation testing (EVPT). Significance: Nano-emulgel is a proven delivery system for poorly soluble substances works by enhancing the solubility and bioavailability. Factorial design provides a systematic and efficient means to study the effect of multiple factors on responses. IVRT is an USP compendia technique utilized for performance analysis of semi-solid formulations. Methods Nano-emulsion formulation optimization was done with factorial design, evaluated for globule size and % entrapment efficiency (EE). Nano-emulgels were characterized for assay, organic impurities, rheological behavior, IVRT, EVPT, and skin retention studies. IVRT validation was executed using vertical diffusion cells (VDCs). Results Ozenoxacin nano-emulsion was optimized with 1:1 ratio of Oil: Smix, 3:1 ratio of Surfactant:Co-Surfactant, and 15000 RPM of homogenization speed which resulted 414.6 ± 5.2 nm globule size and 92.8 ± 2.1% entrapment efficiency. Results confirmed that IVRT and Reversed Phase – High Performance Liquid Chromatographic techniques were validated as per regulatory guidelines. In-vitro, ex-vivo drug release, and skin retention from the optimized nano-emulgel formulation was comparatively higher (∼1.5 times) than that from the innovator (OZANEXTM) formulation. Conclusions Based on these results, Ozenoxacin nano-emulgel can be considered an effective alternative and was found to be stable at 40 °C/75% RH and 30 °C/75% RH storage condition for 6 months.

An Analytical Target Profile for the Development of an In Vitro Release Test Method and Apparatus Selection in the Case of Semisolid Topical Formulations.

This study focuses on how to define an Analytical Target Profile (ATP) which is intended for use in practice and on facilitating the selection of in vitro release test (IVRT) technology for diclofenac sodium topical hydrogel and cream. The implementation involves incorporating the new draft guidelines of the International Council for Harmonisation (ICH Q14) and USP (United States Pharmacopeia) Chapter 1220. Four IVRT apparatuses were compared (USP Apparatus II with immersion cell, USP Apparatus IV with semisolid adapter, static vertical diffusion cell, and a new, in-house-developed flow-through diffusion cell) with the help of the ATP. Performance characteristics such as accuracy, precision, cumulative amount released at the end of the IVRT experiment, and robustness were investigated. We found that the best apparatus for developing IVRT quality control (QC) tests in both cases was USP II with an immersion cell. All four different IVRT apparatuses were compared with each other and with the data found in the literature.

Reverse‐phase high‐performance liquid chromatography methodology for film‐forming mafenide spray: Compatibility, assay, and in‐vitro release evaluation using Franz vertical diffusion cell apparatus

AbstractThis paper described a short and precise reverse‐phase high‐performance liquid chromatography (HPLC) method for quantifying mafenide in a film‐forming spray and preliminary in‐vitro release study. Following the International Council for Harmonization guidelines Q2 (R1), the method was validated. The chromatographic separation was achieved using a 10 mM potassium dihydrogen phosphate solution (mobile phase A) mixed with HPLC‐grade methanol (mobile phase B) in an 85:15 v/v ratio. Inert Sustain C8 (4.6 × 250 mm), 5 μm column was selected as the stationary phase. The flow rate was set as 0.8 mL/min, and detection was carried out at a wavelength of 222 nm. The developed HPLC method showed an accuracy between 98% and 102%. The primary diffusion study of film‐forming spray was performed using the Franz vertical diffusion cell apparatus. It was observed that an average of 26.94% of drug releases at 24 h. This indicates the drug has a slower release rate and shows local pharmacological action. The Weibull dissolution model was more fitting with regression square 0.9953. Furthermore, the drug excipient compatibility study revealed no interactions as the only drug peak was found in the chromatographic method, indicating that the chosen excipients were appropriate for a stable formulation.

Understanding the impact of formulation design on microstructure and drug release from porous microparticle-based tretinoin topical gels

For proportionally formulated intermediate strengths of a topical product, the relationship of drug release across multiple strengths of a given product is not always well understood. The current study aims to assess the proportionality of tretinoin release rates across multiple strengths of tretinoin topical gels when manufactured using two different methods to understand the impact of formulation design on drug product microstructure and tretinoin release rate. Two groups of tretinoin gels of 0.04 %, 0.06 %, 0.08 % and 0.1 % strengths were manufactured. Gels in Group I were prepared by incorporating 4–10 % g/g of 1 % w/w tretinoin-loaded microparticles into a gel base. Gels in Group II were manufactured using 10 % g/g of the microparticles that were loaded with increasing amounts (0.4–1 % w/w) of tretinoin. The two groups of gels were characterized by evaluating microstructure using a polarized microscope, rheology using an oscillatory rheometer, and drug release using Vison® Microette™ Hanson vertical diffusion cells. The microscopic images were used to discriminate between the two groups of gels based on the abundance of microparticles in the gel matrix observed in the images. This abundance increased across gels of Group I and was similar across gels of Group II. The rheology parameters, namely viscosity at a shear rate of 10 s−1, shear thinning rate, storage, and loss modulus, increased across gels of Group I, and were not significantly different across gels of Group II. The release rate of tretinoin from the drug products was proportional to the nominal strength of the drug product in both Group I and Group II, with a correlation coefficient of 0.95 in each case, although the absolute release rates differed. Overall, changing the formulation design of tretinoin topical gels containing porous microparticles may change the physicochemical and structural properties, as well as the drug release rate of the product. Further, keeping the formulation design consistent across all strengths of microparticle-based topical gels is important to achieve proportional release rates across multiple strengths of a given drug product.

Preparation and characterization of a curcumin nanoemulsion gel for the effective treatment of mycoses

Fungal infections of skin including mycoses are one of the most common infections in skin or skins. Mycosis is caused by dermatophytes, non-dermatophyte moulds and yeasts. Various studies show different drugs to treat mycoses, yet there is need to treat it with applied drugs delivery. This study was designed to prepare a bio curcumin (CMN) nanoemulsion (CMN-NEs) for transdermal administration to treat mycoses. The self-nanoemulsification approach was used to prepare a nanoemulsion (NE), utilizing an oil phase consisting of Cremophor EL 100 (Cre EL), glyceryl monooleate (GMO), and polyethylene glycol 5000 (PEG 5000). Particle size (PS), polydispersity index (PDI), zeta potential (ZP), Fourier transform infrared (FTIR) spectrophotometric analysis, and morphological analyses were performed to evaluate the nanoemulsion (NE). The in vitro permeation of CMN was investigated using a modified vertical diffusion cell with an activated dialysis membrane bag. Among all the formulations, a stable, spontaneously produced nanoemulsion was determined with 250 mg of CMN loaded with 10 g of the oil phase. The average droplet size, ZP, and PDI of CMN-NEs were 90.0 ± 2.1 nm, − 7.4 ± 0.4, and 0.171 ± 0.03 mV, respectively. The release kinetics of CMN differed from zero order with a Higuchi release profile as a result of nanoemulsification, which also significantly increased the flux of CMN permeating from the hydrophilic matrix gel. Overall, the prepared nanoemulsion system not only increased the permeability of CMN but also protected it against chemical deterioration. Both CMN-ME (24.0 ± 0.31 mm) and CMN-NE gel (29.6 ± 0.25 mm) had zones of inhibition against Candida albicans that were significantly larger than those of marketed Itrostred gel (21.5 ± 0.34 mm). The prepared CMN-NE improved the bioavailability, better skin penetration, and the CMN-NE gel enhanced the release of CMN from the gel matrix on mycotic patients.

Analysis of the permeable and retainable components of Cayratia japonica ointment through intact or broken skin after topical application by UPLC-Q-TOF-MS/MS combined with in vitro transdermal assay

Cayratia japonica ointment has been used for many years to promote wound healing after perianal abscess surgery. This study aimed to determine the skin-permeable and skin-retainable components of Cayratia japonica ointment after topical application to intact or broken skin via UPLC-Q-TOF-MS/MS analysis and in vitro transdermal assay. Moreover, a combination of semi-quantitative and molecular docking analyses was performed to identify the main active components of the Cayratia japonica ointment and the probable phases of the wound healing process that they act on. Modified vertical Franz diffusion cells and abdominal skin of rats were selected for the in vitro transdermal study. Mass spectrometry data were collected in both positive and negative ion modes. A total of 7 flavonoids (schaftoside, luteolin-7-O-glucuronide, luteolin-7-O-glucoside, apigenin-7-O-glucuronide, luteolin, apigenin, and chrysin) and 1 coumarin (esculetin), were found to permeate and/or retained by intact or broken skin. Among them, the flavonoids were more permeable through intact/broken skin and exhibited stronger binding affinities for targets related to the inflammatory and proliferative phases of wound healing. This study suggests that the flavonoids in Cayratia japonica ointment are most likely the main active components and are crucial at the inflammatory and proliferative phases of wound healing.

Assessment of Apple Peel Barrier Effect to Pesticide Permeation Using Franz Diffusion Cell and QuEChERS Method Coupled with GC-MS/MS.

In this study, a new approach to pesticide permeation through the apple peel into the pulp is discussed. The tested compounds can be classified, based on mode of action, as systemic (boscalid, cyprodinil, pirimicarb, propiconazole and tebuconazole) or contact (captan, cypermethrin and fludioxonil) pesticides. The barrier effect was assessed using a Franz flow-type vertical diffusion cell system. A residue analysis was performed using a modified quick, easy, cheap, efficient, rugged and safe (QuEChERS) extraction method coupled to gas chromatography with tandem mass spectrometry (GC-MS/MS). The limits of detection (LODs) ranged between 2.6 µg kg-1 (pirimicarb) and 17 µg kg-1 (captan), with the coefficient of variability (CV) lower than 6%, while recoveries ranged from 85% (boscalid) to 112% (captan) at 0.1 and 1 mg kg-1 spiked levels. The highest peel penetration was observed for pirimicarb, captan and cyprodinil, with cumulative permeations of 90, 19 and 17 µg cm-2, respectively. The total absorption was in the range from 0.32% (tebuconazole) to 32% (pirimicarb). Only cypermethrin was not quantitatively detected in the pulp, and its use can be recommended in crop protection techniques. The obtained results indicate that molecular weight, octanol-water partition coefficient and water solubility are important parameters determining the process of pesticide absorption.

Topical Micro-Emulsion of 5-Fluorouracil by a Twin Screw Processor-Based Novel Continuous Manufacturing Process for the Treatment of Skin Cancer: Preparation and In Vitro and In Vivo Evaluations.

5-Fluorouracil (5-FU), a BCS class III drug, has low oral bioavailability and is cytotoxic in nature causing severe systemic side effects when administered through the intravenous route. Topical drug delivery could potentially mitigate the systemic side-effects. Microemulsions (MEs) would be an apt solution due to enhanced partitioning of the drug to the skin. However, conventional methods for preparing MEs are inefficient since they are not continuous and are very tedious and time-consuming processes hence revealing the need for the development of continuous manufacturing technology. In our study, 5-FU MEs were prepared using a continuous manufacturing Twin Screw Process (TSP) and its efficiency in the treatment of skin cancer was evaluated. Water-in-oil MEs were prepared using isopropyl myristate as the oil phase and Aerosol OT and Tween 80 as the surfactants. The average particle size was observed to be 178 nm. Transmission electron microscopy was employed to confirm the size and shape of the MEs. FTIR study proved no physical or chemical interaction between the excipients and the drug. In vitro drug release using vertical diffusion cells and ex vivo skin permeation studies showed that the drug was released sustainably and permeated across the skin, respectively. In in vitro cytotoxicity studies, 5-FU MEs were accessed in HaCat and A431 cell lines to determine percentage cell viability and IC50. Skin irritation and histopathological examination implied that the 5-FU MEs did not cause any significant irritation to the skin. In vivo pharmacodynamics studies in rats suggested that the optimised formulation was effective in treating squamous cell carcinoma (SCC). Therefore, 5-FU MEs efficiently overcame the various drawbacks faced during oral and intravenous drug delivery. Also, TSP proved to be a technique that overcomes the various problems associated with the conventional methods of preparing MEs.

A Study of Microemulsion Systems for Transdermal Delivery of Risperidone Using Penetration Enhancers

The aim of this study was to develop and characterize microemulsion formulations using penetration enhancers as potential transdermal delivery systems for risperidone. Initially, a simple formulation of risperidone in Propylene Glycol (PG) was prepared as a control formulation, together with formulations incorporating various penetration enhancers, alone and/or in combination, and also microemulsion formulations with various chemical penetration enhancers, were prepared and all were evaluated for risperidone transdermal delivery. An ex-vivo permeation study was carried out using human cadaver skin and vertical glass Franz diffusion cells to compare all the microemulsion formulations. The microemulsion prepared from oleic acid as the oil (15%), Tween 80 (15%) as the surfactant and isopropyl alcohol (20%) as the co-surfactant, and water (50%) showed higher permeation with a flux value of 32.50±3.60 ug/hr/sq.cm, a globule size of 2.96±0.01 nm, a polydispersity index of 0.33±0.02 and pH of 4.95. This novel in vitro research disclosed that an optimized microemulsion formulated using penetration enhancers was able to increase permeation of risperidone by 14-fold compared to the control formulation. The data suggested that microemulsions may be useful in the delivery of risperidone via the transdermal route.

Study of factors affecting the in vitro release of dexpanthenol from solutions and topical semi-solid preparations

The aim. To identify the factors influencing the in vitro release of dexpanthenol (DP) from solutions and semi-solid preparations.&#x0D; Materials and methods. Dispersed systems containing 5.0 % DP were studied: solutions that were Newtonian liquids and semi-solid preparations (creams, gels and ointment) with non-Newtonian flow behaviour. Rheological studies were performed by rotational viscometry. In vitro release tests were performed using vertical diffusion cells. The content of DP in the receptor medium was determined by liquid chromatography.&#x0D; Results. It has been shown that the greatest values of release parameters of DP were characteristic of its aqueous solution; they decreased when propylene glycol (PG), macrogol 400 (M400), and poloxamer 338 (P338) were added but remained at a high enough level. The inclusion of cationic surfactant and cetostearyl alcohol (CSA) (0.5 : 4.5 % m/m) into the Newtonian liquid led to the formation of disperse system with a plastic flow behaviour and to significant decrease in the DP release. In the case of a cream containing a non-ionic surfactant and CSA, the release parameters of DP were also at a low level. The release of DP from the w/o emulsion-based ointment was minimal. Compared to DP aqueous solution, the rate of DP release from a carbomer-based gel decreased by 2.8 times; when 20 % of a mixture of PG and M400 (10 : 10 % m/m) was added to such a gel, the rate of drug release decreased by another 1.5 times. The fastest and most complete release of DP was observed in the case of the P338-based disperse system, which transformed from a Newtonian liquid into a gel at 32 °C.&#x0D; Conclusions. In vitro release of DP depended on the type of base; rapid and complete release of DP was characteristic of its aqueous solution, and minimal release was observed in the case of hydrophobic ointment. The use of CSA in combination with a surfactant or carbomer to create bases for semi-solid preparations with plastic flow behaviour was a considerable factor that significantly slowed down the release of DP from them. The greatest values of the release parameters of DP were observed in the case of a gel based on P338

A Preliminary Study on the Release of Bioactive Compounds from Rice Starch Hydrogels Produced by High-Pressure Processing (HPP).

This work aimed to carry out a preliminary study on the release of bioactive compounds loaded into starch-based hydrogels produced by high-pressure processing (HPP). As a study case, the experiments were carried out on rice starch HPP hydrogels. Rice starch (20% w/w) and green tea extract (2% w/w), suspended in distilled water, were treated by HPP at processing conditions enabling starch gelatinisation, namely 600 MPa for 15 min at room temperature. Additional experiments were carried out on samples that were further loaded with glycerol (5% w/w). Gel formation was assessed by analysing the gelatinisation extent, structuring level, and swelling power of the samples. At the processing conditions utilised, stable hydrogels were obtained even in the presence of the extract and/or the glycerol in the starch suspension. As expected, the colour of the hydrogels formed was affected by the addition of green tea extract in the starch solution. HPP starch hydrogels were characterised by Fourier transform infrared spectroscopy (FT-IR) to determine the interactions between the different compounds utilised in the formulation. Moreover, the release kinetics of bioactive compounds from HPP rice starch hydrogels was evaluated using a vertical Franz diffusion cells system, simulating a transdermal pattern. The diffusion of bioactive compounds was measured spectrophotometrically and via HPLC analysis. A controlled release of bioactive compounds from the hydrogel structure was detected, suggesting that small molecules, such as polyphenols, positively interacted with the rice starch HPP hydrogel network that allowed a smooth and constant release of these bioactive compounds over time.

Anti-Photoaging Effects of Nanocomposites of Amphiphilic Chitosan/18β-Glycyrrhetinic Acid.

Improving the transdermal absorption of weakly soluble drugs for topical use can help to prevent and treat skin photoaging. Nanocrystals of 18β-glycyrrhetinic acid (i.e., NGAs) prepared by high-pressure homogenization and amphiphilic chitosan (ACS) were used to form ANGA composites by electrostatic adsorption, and the optimal ratio of NGA to ACS was 10:1. Dynamic light scattering analysis and zeta potential analysis were used to evaluate the nanocomposites' suspension, and the results showed that mean particle size was 318.8 ± 5.4 nm and the zeta potential was 30.88 ± 1.4 mV after autoclaving (121 °C, 30 min). The results of CCK-8 showed that the half-maximal inhibitory concentration (IC50) of ANGAs (71.9 μg/mL) was higher than that of NGAs (51.6 μg/mL), indicating that the cytotoxicity of ANGAs was weaker than that of NGAs at 24 h. After the composite had been prepared as a hydrogel, the vertical diffusion (Franz) cells were used to investigate skin permeability in vitro, and it was shown that the cumulative permeability of the ANGA hydrogel increased from 56.5 ± 1.4% to 75.3 ± 1.8%. The efficacy of the ANGA hydrogel against skin photoaging was studied by constructing a photoaging animal model under ultraviolet (UV) irradiation and staining. The ANGA hydrogel improved the photoaging characteristics of UV-induced mouse skin significantly, improved structural changes (e.g., breakage and clumping of collagen and elastic fibers in the dermis) significantly, and improved skin elasticity, while it inhibited the abnormal expression of matrix metalloproteinase (MMP)-1 and MMP-3 significantly, thereby reducing the damage caused by UV irradiation to the collagen-fiber structure. These results indicated that the NGAs could enhance the local penetration of GA into the skin and significantly improve the photoaging of mouse skin. The ANGA hydrogel could be used to counteract skin photoaging.

In Vitro Performance Analysis of a Minoxidil Thermosensitive Gel with Reduced Runoff for Eyebrow Hair Growth.

There is a growing interest in innovative products for eyebrow hair loss treatment with fewer adverse effects. Nevertheless, a fundamental formulation aspect of preventing the fragile skin from the ocular region from being irritated is that the formulations remain restricted to the application region and do not run off. Consequently, the methods and protocols in drug delivery scientific research must be adapted to fulfill such performance analysis demand. Thus, this work aimed to propose a novel protocol to evaluate the in vitro performance of a topical gel formulation with a reduced runoff for minoxidil (MXS) delivery to eyebrows. MXS was formulated with 16% poloxamer 407 (PLX) and 0.4% of hydroxypropyl methylcellulose (HPMC). The sol/gel transition temperature, viscosity at 25 °C, and formulation runoff distance on the skin were evaluated to characterize the formulation. The release profile and skin permeation were evaluated in Franz vertical diffusion cells for 12 h and compared to a control formulation (4% PLX and 0.7% HPMC). Then, the formulation's performance at promoting minoxidil skin penetration with minimum runoff was evaluated in a vertical custom-made permeation template (divided into three areas: superior, middle, and inferior). The MXS release profile from the test formulation was comparable to that from the MXS solution and the control formulation. There was also no difference in the MXS amount that penetrated the skin in the permeation experiments in Franz diffusion cells using the different formulations (p > 0.05). However, the test formulation demonstrated a localized MXS delivery at the application site in the vertical permeation experiment. In conclusion, the proposed protocol could differentiate the test formulation from the control, attesting to its better performance in efficiently delivering MXS to the site of interest (middle third of application). The vertical protocol can be easily employed to evaluate other gels with a drip-free appeal.