Search Results (254)

Background/Objectives: This study aimed to develop and evaluate an anti-pollution film-forming spray (FFS) containing coffee cherry pulp extract (FFS-CCS). The formulation was designed to create a protective skin barrier, improving skin health while defending against environmental pollutants. Its physical properties, dust resistance, stability, skin penetration, and clinical effectiveness were assessed to ensure optimal performance and safety. Methods: Various polymers and a ternary solvent system were used to enhance the stability and solubility of bioactive compounds from the coffee cherry pulp extract. The formulations were characterized based on appearance, film formation, viscosity, pH, spray uniformity, spray pattern, angle, film thickness, and particle adhesion. Stability testing was conducted under different storage conditions. Skin penetration was assessed using Franz diffusion cells with Strat-M^® membranes to simulate human skin. A single-blind, placebo-controlled trial with 42 participants was conducted over 60 days to evaluate the effects of FFS-CCS on skin hydration, tone, and wrinkle reduction. Clinical assessments were performed using a Corneometer, Mexameter, and Skin Visioscan. Results: The FFS1-CCS formulation, incorporating PVP K90 and a ternary solvent system, significantly improved the solubility, stability, and bioavailability of key bioactive compounds (chlorogenic acid, caffeine, and theophylline). Physical characterization confirmed uniform, transparent films with optimal viscosity and sprayability. Stability testing showed minimal degradation. Skin penetration and retention studies revealed enhanced retention of bioactive compounds with minimal systemic absorption. PVP K90, along with ethanol and propylene glycol, extended the compounds’ residence time on the skin, ensuring localized delivery. Clinically, FFS1-CCS significantly improved skin hydration, reduced roughness, lightened skin tone, and decreased erythema. Conclusions: The FFS1-CCS formulation utilizing PVP K90 significantly enhanced the stability, bioavailability, and skin retention of coffee cherry pulp extract, resulting in improved skin hydration, wrinkle reduction, and skin tone enhancement. These findings highlight the potential of coffee cherry pulp extract as a multifunctional, sustainable cosmeceutical ingredient, offering both anti-aging and environmental protection benefits, making it a promising solution for skincare applications. Full article

This study focuses on analyzing the in vitro release characteristics, as well as improving the penetration rate and stability of hydrocortisone acetate and pramoxine. This medication combination (hydrocortisone and pramoxine) is the first generic drug product utilized to alleviate minor pain, itching, swelling, and discomfort associated with anorectal conditions such as hemorrhoids. Background/Objectives: The developed novel formulations contain hydrocortisone acetate and pramoxine HCl as active ingredients, at least one solvent, at least one penetrating agent, at least one emulsifying agent, at least one surfactant, and at least one antimicrobial preservative, and pH values between 3.0 and 5.0, preferably between 3.5 and 4.5. Methods: Typical semi-solid dosage form quality control tests included appearance, identification, content homogeneity, pH, viscosity, assay, compounds of interest, microbiological testing, and in vitro release testing. In in vitro release testing, a series of formulations containing hydrocortisone acetate and pramoxine were tested for in vitro release across the Strat-M membrane using Franz diffusion cells methodology in comparison to a reference product (Pramosone Cream 2.5%). Results: Quantitative content of the release tests of the active ingredients in the cream, assay tests, antimicrobial preservative efficacy, and stability tests were carried out by high-sensitivity liquid chromatography. Conclusions: In conclusion, the cream formulations developed in this study have the potential to offer more effective treatment compared to reference products in terms of both in vitro release rates, and their reliability and validity were confirmed through validation studies. Full article

The leaf extract of Tectona grandis L.f. has shown potential as a 5α-reductase inhibitor, with two bioactive markers, namely (+)-eperua-8,13-dien-15-oic acid (1) and (+)-eperua-7,13-dien-15-oic acid (2), used for extract standardization. The purpose of this research was to investigate the in vitro skin penetration behavior of 1 and 2 in T. grandis leaf ethanolic extract solution and ready-to-use extract in propylene glycol (PG), and secondly, to determine their physicochemical properties, including partition coefficients and solubility. The appropriate vehicle for the in vitro skin penetration study was evaluated using the shake-flask method. The in vitro skin penetration study was conducted using the Franz diffusion cell model, and the amounts of the two active compounds in the extracts were analyzed using the HPLC method. Compounds 1 and 2 showed poor solubility in distilled water, whereas their solubility in HEPES buffer with 2% w/v of Tween 20 was significantly greater. The partition coefficient (log P_o/w) value for 1 was 5.77 ± 0.07, and for 2, it was 5.66 ± 0.02, indicating that both compounds are hydrophobic. After 24 h of an in vitro skin penetration study, 1 in both extracts showed significantly higher cumulative amounts (%) compared to 2. These findings suggest that 1 is more hydrophobic and readily penetrates the stratum corneum. When a PG enhancer was added, high cumulative amount trends of 1 and 2 in the ethanolic extract and extract in PG in the receiver compartment were detected after 24 h. These studies provide important insights that will guide the further development of products with T. grandis extracts for treating hair loss. Full article

Lidocaine is an analgesic agent frequently incorporated in topical formulations intended for application in minor surgical procedures or relieving neuropathic pain associated with numerous conditions, including post-herpetic neuralgia or diabetic peripheral neuropathy. In this study, Pickering o/w emulsions with halloysite nanotubes as a stabilizing agent and lidocaine incorporated in the internal phase were formulated with the use of the Quality by Design (QbD) approach. The selected emulsions were transformed into semisolid gels with poloxamer 407 as a thickening agent, and investigated for rheological and textural properties, indicating the mechanical features of the obtained gels. Moreover, the obtained formulations were tested for lidocaine release with the use of vertical Franz diffusion cells in order to assess the relationship between the applied composition and potential clinical applicability of the analyzed gels. The obtained results indicate that the emulsion droplet diameter is affected mostly by the oil and halloysite contents. The yield stress points, hardness and cohesiveness values of the obtained gels increased with the oil content. The drug release rate seems to be affected mostly by the concentration of the active ingredient in the oil phase. Full article

Background: Due to their antibacterial activities, essential oils can be potential alternatives to antibiotics in certain cases. West Indian lemongrass (Cymbopogon citratus) essential oil (LEO) is effective against a broad range of bacteria by inhibiting spore formation, and is considered safe. In this study, we demonstrated its therapeutical potential in the treatment of pitted keratolysis (PK), a superficial skin infection affecting the pressure-bearing areas of plantar surfaces. Methods: For in vitro antibacterial efficacy testing, LEO was mixed into different ointment bases, including Hydrogelum methylcellulose FoNo VIII., Ungentum oleosum FoNo VIII. (Ung. oleoso), Unguentum stearini FoNo VIII. (Ung. stearin), and Vaselinum cholesterinatum FoNo VIII. (Vasel. cholest.), at different concentrations of 1, 3, and 5%. These formulations were tested on representatives of three bacterial species associated with PK: Kytococcus sedentarius, Dermatophilus congolensis, and Bacillus thuringiensis. Results: In the in vitro tests, Hydrogelum methylcellulose (HM) gel best supported the antibacterial effects of LEO, reducing the number of living bacteria on agar plates by 4–5 orders of magnitude in a concentration-dependent manner during the 30 min exposure times. This was also confirmed by the Franz diffusion cell drug release test; after 30 min, several active compounds could be detected in the HM samples, in contrast to the other bases. Shelf-life experiments showed that the HM base supported the antibacterial features of 3% LEO for at least 2 years without significant loss of efficacy. Conclusions: Our study highlights that ointments containing essential oils potentially have a place in the treatment of PK. Therefore, antibiotics may potentially be replaced for the treatment of PK, thereby reducing environmental antibiotic pressure, which is one of the driving forces behind the spread of antibiotic resistance. Full article

Background Despite many studies on polymer-incorporated nanocarriers for ophthalmic drug delivery, few have thoroughly explored the relationship between coating composition and performance. This study aimed to evaluate the effects of three commonly used cationic polymers—distearoyl phosphatidylethanolamine-polyethylene glycol 1000-poly(amidoamine) (DSPE-PEG1000-PAMAM), trimethyl chitosan (TMC), and (2,3-dioleoyloxypropyl) trimethylammonium chloride (DOTAP)—on the corneal behaviors and anti-cataract efficacy of diosmetin (DIO)-loaded micelles (D-M-P, D-M-T, and D-M-D, respectively). Methods The DIO-loaded micelles were prepared using the thin-film dispersion method and incorporated with the three polymers through hydrophobic interactions and electrostatic adsorption. Structural characterization was demonstrated by TEM imaging and particle size analyzer. In vitro release behavior was detected by the dialysis method. Cell viability of D-M-P, D-M-T, and D-M-D on L929 cells was detected by CCK-8 assays, with cellular uptake performed using coumarin 6 as the fluorescence indicator. Precorneal retention behaviors of these three vesicles were observed by In Vivo Imaging System. Transcorneal permeability was determined by modified Franz diffusion method and the permeation routes of the vesicles are investigated. Selenite-induced cataract model was established. The anti-cataract effects of three different DIO-loaded micelles were evaluated by the observation of lens opacity and antioxidant enzyme activities. Eye Irritation of the DIO in different preparations was estimated using the Draize test, along with H&E staining of the corneas. Results Structural characterization of DIO-loaded micelles revealed that the vesicles were spherical, with a uniform size distribution of around 28 nm, a similar surface potential of approximately 6.0 mV, and a high DIO entrapment efficiency of about 95%. Compared to the DIO suspension, all three formulations exhibited a significant sustained-release effect. They showed no signs of irritation and demonstrated increased IC50 values in L929 cells, indicating improved biocompatibility. Cellular uptake in human lens epithelial cells (HLECs) was assessed using confocal laser scanning microscopy. C-M-T displayed the highest fluorescence signals, with a cellular internalization 3.2 times greater than that of the solution group. Both C-M-T and C-M-P enhanced vesicle retention on the corneal surface by at least 47.8% compared to the Cou-6 solution. Furthermore, TMC facilitated the paracellular transport of vesicles into the deepest layers of the cornea and delivered DIO across the cornea, with a P_app value 3.11 times and 1.49 times those of D-M-D and D-M-P, respectively. In terms of therapeutic efficacy, D-M-T demonstrated the most significant attenuation of lens opacity, along with enhanced antioxidant enzyme activities and inhibition of lipid peroxidation. Conclusion The modification of micelle vesicles with different cationic polymers significantly influences their performance in ocular drug delivery. Among the tested formulations, D-M-T stands out due to its multiple advantages, including enhanced transcorneal drug delivery, therapeutic efficacy for DIO, and safety, making it the most promising candidate for ophthalmic applications. Full article

The compositions based on Pentravan^® vehicle were prepared with (S)-naproxen, and its salt —(S)-naproxenate of L-prolinium isopropyl ester as active pharmaceutical ingredients, and two penetration enhancers from the group of sensates—menthol and Capsicum Tincture. Thermophysical properties of the mixtures of each naproxen form with enhancers were determined by DSC method. The stability of the prepared compositions after one- and three-month storage and the rheological properties were investigated. The permeation of active ingredients through the human skin was evaluated based on the in vitro study in Franz diffusion cells using the prepared compositions with each naproxen form. Increase in the permeability of the naproxen salt, especially in the presence of Capsicum Tincture, provides much faster and greater penetration of the skin by the drug. It seems to be promising the use of the developed composition in the form of pain relief and anti-inflammatory creams, occlusive compresses or topical patches. Moreover, the developed compositions can be crucial for the topical compositions made in compounding pharmacies by physicians’ recipes in individual pain pharmacotherapy. Full article

Background/Objectives: The present study focused on the formulation and evaluation of novel topical systems containing Salvia officinalis (sage), emphasizing their antioxidant and anti-inflammatory properties. Sage, rich in carnosol, offers considerable therapeutic potential, yet its low water solubility limits its effectiveness in traditional formulations. The aim of our experimental work was to improve the solubility and thus bioavailability of the active ingredient by developing self-nano/microemulsifying drug delivery systems (SN/MEDDSs) with the help of Labrasol and Labrafil M as the nonionic surfactants, Transcutol HP as the co-surfactant, and isopropyl myristate as the oily phase. Methods: The formulations were characterized for droplet size, zeta potential, polydispersity index (PDI), encapsulation efficacy, and stability. The composition exhibiting the most favorable characteristics, with particle sizes falling within the nanoscale range, was incorporated into a cream and a gel, which were compared for their textural properties, carnosol penetration, biocompatibility and efficacy. Results: Release studies conducted using Franz diffusion cells demonstrated that the SNEDDS-based cream achieved up to 80% carnosol release, outperforming gels. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) test and enzyme-linked immunosorbent assays (ELISA) showed strong efficacy, with an in vivo carrageenan-induced rat paw edema model revealing that the SNEDDS-based cream significantly reduced inflammation. Conclusions: These findings highlight the potential of SNEDDS-enhanced topical formulations in improving therapeutic outcomes. Further research is warranted to confirm their long-term safety and efficacy. Full article

Background/Objectives: Since 2008, following clinical studies conducted on children that revealed the ability of the β-adrenergic antagonist propranolol to inhibit capillary growth in infantile hemangiomas (IHs), its oral administration has become the first-line treatment for IHs. Although oral propranolol therapy at a dosage of 3 mg/kg/die is effective, it can cause systemic adverse reactions. This therapy is not necessarily applicable to all patients. Topical skin applications could help maintain a high drug concentration at local sites and also represent a characteristically easy method of administration for pediatric patients. Because no topical propranolol dosage forms are commercially available, such formulations may be prepared at hospitals and pharmacies. Methods: In the present study, we identified a simple method for preparing topical propranolol hydrochloride formulations at 1% w/w with five commercial ready-to-use bases and evaluated the pharmaceutical profiles. The physical stability of the extemporaneous formulations was predicted by performing an accelerated centrifuge test and assessed by visual inspection after one month storage at 25 °C. The chemical stability of the drug in the five formulations was assessed by using a high-performance liquid chromatography (HPLC) method. In vitro drug-release and permeability experiments were conducted through synthetic membranes and the outer pavilion of a pig’s ear by utilizing Franz-type diffusion cells. Results: The results indicated that the release of the drug was significantly influenced by the internal structure and physicochemical properties of each base. Conclusions: Specifically, the formulations prepared with the hydrophilic bases could be easily prepared and yield satisfactory results, representing a potential effective therapy for IHs in pediatric patients. Full article

Background/Objectives: This study is an attempt to reveal the potential of two types of interpenetrating polymer network (IPN) hydrogels based on poly(2-hydroxyethyl methacrylate) (PHEMA) and poly(N,N-dimethylacrylamide) (PDMAM). These IPNs were evaluated for their potential for dermal delivery of the hydrophobic drug dexamethasone (DEX). Methods: The two types of IPNs were analyzed for their rheological behavior, swelling characteristics, and drug-loading capacity with DEX. Drug release profiles were studied in Franz diffusion cells in PBS media. Finally, the cytotoxicity of the PHEMA/PDMAM-based IPNs was studied against T-cell lymphoma cells (HUT-78) and a normal murine fibroblast cell line (CCL-1). Results: The rheological properties of these hydrogels show suitable mechanical properties for dermal application, with G′ values of ~10 kPa. From the rheological data, the mesh size of these hydrogels was found to be influenced by the type of the IPN and its composition, varying between 6.5 and 50 nm. The loading capacity of both IPN types and DEX entrapment efficiency were highly influenced by the IPN’s composition. The loading capacity of the IPNs can reach ~3.5%, with a DEX entrapment efficiency of ~35%. The PHEMA/PDMAM IPNs demonstrate an extended release profile with up to ~95% DEX released in 24 h, while PDMAM/PHEMA IPNs release no more than ~25% DEX in 24 h. The drug release profiles follow either non-Fickian diffusion (n~0.6) or case-II transport (n~0.9–1), depending on the IPN’s composition. The PHEMA/PDMAM-based materials were found to be non-cytotoxic against HUT-78 and CCL-1 cells. Conclusions: The study reveals that the IPNs of PHEMA and PDMAM appear to be suitable platforms for dermal delivery of dexamethasone as they have appropriate mechanical properties, providing tools to control drug loading and release, and they are biocompatible with human skin cells. Full article

Genitourinary syndrome of menopause (GSM) affects a significant percentage of postmenopausal women and manifests as vaginal dryness, irritation, and urinary discomfort, typically treated with vaginal estrogens. Hydrogels are preferred over creams due to their superior comfort and mucoadhesive properties. This study introduces a novel vaginal gel formulation containing hydroxyethyl cellulose (HEC) and estriol-hydroxypropyl-β-cyclodextrin complex (E3-HPBCD) for the treatment of GSM. The estriol (E3) release profile of the gel was evaluated using a Franz diffusion cell system, and its permeability was tested on reconstructed human vaginal epithelium. Biocompatibility was assessed using (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) (MTT), lactate dehydrogenase (LDH) assays, and real-time cell analysis (RTCA) on human skin keratinocyte (HaCaT) cells, which showed increased cell viability and no obvious cytotoxicity. The results indicated that efficient E3 release and satisfactory epithelial permeability with HPBCD provide the bioavailability of E3. These results suggest the potential of the gel as a biocompatible and effective alternative for the treatment of GSM. Further studies are required to assess the long-term safety and clinical efficacy. Full article

Sinomenine (SIN) is a drug for the treatment of rheumatoid arthritis, most of which is administered orally, but it is prone to adverse gastrointestinal effects. Gel can overcome the gastrointestinal adverse effects caused by oral administration. In this paper, a multiscale computational pharmaceutics strategy was developed to guide the systematic study of formulation factors of a SIN gel and, further, to guide the formulation design. A molecular dynamics (MD) simulations method was utilized to successfully screen the optimal prescription of SIN gel and to elucidate the molecular mechanisms affecting the quality of SIN gel. The optimal prescription was 3.0% of SIN, 1.0% of Carbopol (Cp), 30% of Ethanol (Eth), 5.0% of Glycerine (Gly) and 10.0% of Menthol (Men). The influence mechanism can be explained by the combination of multiple parameters, such as the microstructure diagram, the radius of gyration (Rg) and the radial distribution function (RDF). In vitro transdermal studies were carried out using a modified Franz diffusion cell method to evaluate the quality of the screened and reference prescriptions. The results showed that the cumulative penetration and penetration rate of the screening of prescription were better than the reference formulation. Most important of all, the simulation results are in good agreement with the in vitro release experiment, indicating that the strategy has good applicability. This study was able to accurately optimize the formulation and elucidate the molecular mechanism, which would provide a reference for further research on SIN and gel. Full article

Species of the genus Kalanchoe have a long history of therapeutic use in ethnomedicine, linked to their remarkable medical properties. These species include Kalanchoe blossfeldiana succulents, which grow in tropical regions. Despite the great interest in this plant, there are no reports about its therapeutic effects on the skin. In this study, the antioxidant properties of K. blossfeldiana ethanol extracts and the skin permeation of a topical hydrogel containing the extract (HKB) were assessed. Additionally, the content of active compounds in the K. blossfeldiana extract was evaluated by UHPLC-MS and HPLC-UV. The extract was analyzed with three antioxidant assays: ABTS, DPPH, and FRAP. Furthermore, the antielastase and antihialuronidase properties of the tested extract were assessed. Ex vivo penetration studies were performed using the Franz diffusion cells. The estimation of the cytotoxicity of HKB was performed by using an MTT assay ((4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) on the human fibroblasts HFF-1. The results obtained show that the antioxidant properties of K. blossfeldiana extract were similar to those of ascorbic acid, while antielastase and antihialuronidase tests indicated the strong antiaging and anti-inflammatory activity of the extract (IC₅₀ was 26.8 ± 0.13 and 77.31 ± 2.44 µg/mL, respectively). Moreover, active ingredients contained in K. blossfeldiana extract penetrated through the human skin and accumulated in it. The cytotoxicity test showed that HKB had no significant effect on human fibroblasts at a concentration up to 0.5%. In conclusion, the hydrogel containing the K. blossfeldiana extract can be considered as an interesting and new alternative to dermatologic and cosmetic preparations. Full article

Imipramine hydrochloride (IMP), a tricyclic antidepressant used for major depression, enuresis, and neuropathic pain, is limited by gastrointestinal complications, low oral bioavailability (44%), and complex dosing requirements. This study aimed to explore a novel non-invasive nasal delivery system using chitosan nanoparticles (Cs NPs) embedded in an in situ gel to address the limitations of oral IMP administration. Cs NPs loaded with IMP were synthesized via ionic gelation and assessed for precision in drug concentration using a validated HPLC method. The particles were integrated into a thermoresponsive polymer, Pluronic F127, to form an in situ gel suitable for nasal administration. The formulation was characterized for gelation temperature, duration, viscosity, mucoadhesive strength, and overall gel robustness. Drug release kinetics and the controlled release mechanism were studied using ex vivo permeation tests with Franz diffusion cells and nasal sheep mucosa. The optimized nanoparticle formulation (F4-50) exhibited a consistent PS of 141.7 ± 2.2 nm, a zeta potential (ZP) of 16.79 ± 2.1 mV, and a high encapsulation efficiency of 67.71 ± 1.9%. The selected in situ gel formulation, F4-50-P1, demonstrated a gelation temperature of 33.6 ± 0.94 °C and a rapid gelation time of 48.1 ± 0.7 s. Transform-attenuated total reflectance infrared spectroscopy (ATR-IR) confirmed the compatibility and effective encapsulation of IMP within the formulation. The release profile of F4-50 included an initial burst release followed by a sustained release phase, with F4-50-P1 showing improved control over the burst release. The flux rates were 0.50 ± 0.01 mg/cm²/h for F4-50 and 0.33 ± 0.06 mg/cm²/h for F4-50-P1, indicating effective permeation. The developed chitosan nanoparticle-based in situ gel formulation provides a promising approach for the controlled release of IMP, enhancing therapeutic efficacy and patient compliance while mitigating the disadvantages associated with oral delivery. Full article

Background: Skin and soft tissue infections (SSTIs) present significant treatment challenges. These infections often require systemic antibiotics such as vancomycin, which poses a risk for increased bacterial resistance. Topical treatments are hindered by the barrier function of the skin, and microneedles (MNs) offer a promising solution, increasing patient compliance and negating the need for traditional needles. Methods: This study focused on the use of sodium alginate MNs for vancomycin delivery directly to the site of infection via a cost-effective micromolding technique. Dissolving polymeric MNs made of sodium alginate and loaded with vancomycin were fabricated and evaluated in terms of their physical properties, delivery ability, and antimicrobial activity. Results: The MNs achieved a 378 μm depth of insertion into ex vivo skin and a 5.0 ± 0 mm zone of inhibition in agar disc diffusion assays. Furthermore, in ex vivo Franz cell experiments, the MNs delivered 34.46 ± 11.31 μg of vancomycin with around 35% efficiency, with 9.88 ± 0.57 μg deposited in the skin after 24 h. Conclusions: These findings suggest that sodium alginate MNs are a viable platform for antimicrobial agent delivery in SSTIs. Future in vivo studies are essential to confirm the safety and effectiveness of this innovative method for clinical use. Full article