DESIGNING OF NOVEL TOPICAL IN SITU POLYMERIC FILM-FORMING SOLUTION SPRAY FORMULATION OF ANTIFUNGAL AGENT: IN VITRO ACTIVITY AND IN VIVO CHARACTERIZATION

Objective: Voriconazole (VCZ) is a broad-spectrum antifungal medication that works by inhibiting fungal Cytochrome P450, preventing fungi growth. The current study aims at developing and characterizing an antifungal in situ film-forming polymeric solution spray containing VCZ for use in topical drug delivery systems. Methods: Optimized VCZ in situ polymeric film formulation was evaluated for Fourier transform infrared spectroscopy (FTIR), differential scanning calorimeter (DSC), X-ray diffractometry (XRD), Scanning electron microscope (SEM), in vitro and in vivo, ex-vivo investigation using abdominal rat skin and stability studies. The in vivo antifungal activity of the advanced in situ film was examined in albino Wistar rats. Results: The optimized batch contained 22% Eudragit RS 100 (ERS) and 4% Sorbitol. Based on FTIR, XRD, SEM, and rheological studies. Formulation ingredients of VCZ loaded topical in situ polymeric film spray were observed to be compatible and showed no evidence of precipitation, deformation, or discoloration. Diffusion test (in vitro %), and ex-vivo drug diffusion % obtained 99.22%, and 97.45% respectively. The maximum inhibition zone was measured at 13±0.07 mm. The Wistar rat was employed as an animal model for skin irritation and antifungal studies. A study of short-term stability observed no significant modifications in the physical properties. Conclusion: The findings of the optimized VCZ topical in situ polymeric film spray formulation were satisfactory, demonstrating comparable improvement in superficial antifungal treatment.

In Vitro Antimicrobial Activity Evaluation of a Novel Fitostimoline® Plus Spray Formulation

Wound contaminants are the main cause of healing delay and infection in both chronic and acute wounds; for this reason, the microbial infection management in wound healing is one of the most important components for an effective standard of care. The wound contaminants are most likely to originate from the environment and from the surrounding skin lesion, and to date, the most frequent bacteria isolated are Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae. In order to counteract and control these contaminants, the standard care includes topical antiseptic agents. The most commonly used include iodine-releasing agents (e.g., povidone-iodine), hydrogen peroxide, and polyhexanide. This study aims to investigate the in vitro antibacterial activity of a novel topical spray (Fitostimoline® Plus spray) based on 0.1% polyhexanide and Rigenase® against S. aureus, P. aeruginosa, K. pneumoniae, and the combination of S. aureus and K. pneumoniae. The in vitro antimicrobial activity of Fitostimoline® Plus spray was evaluated by the agar disk diffusion assay, quantitative suspension test, and quantitative carrier test, demonstrating that Fitostimoline® Plus spray is able to kill 99.9% bacteria. These results support the microbiological characterization of Fitostimoline® Plus spray confirming the antibacterial activity of polyhexanide (PHMB).

Protective Effects of Astodrimer Sodium 1% Nasal Spray Formulation against SARS-CoV-2 Nasal Challenge in K18-hACE2 Mice

Strategies to combat COVID-19 require multiple ways to protect vulnerable people from infection. SARS-CoV-2 is an airborne pathogen and the nasal cavity is a primary target of infection. The K18-hACE2 mouse model was used to investigate the anti-SARS-CoV-2 efficacy of astodrimer sodium formulated in a mucoadhesive nasal spray. Animals received astodrimer sodium 1% nasal spray or PBS intranasally, or intranasally and intratracheally, for 7 days, and they were infected intranasally with SARS-CoV-2 after the first product administration on Day 0. Another group was infected intranasally with SARS-CoV-2 that had been pre-incubated with astodrimer sodium 1% nasal spray or PBS for 60 min before the neutralisation of test product activity. Astodrimer sodium 1% significantly reduced the viral genome copies (>99.9%) and the infectious virus (~95%) in the lung and trachea vs. PBS. The pre-incubation of SARS-CoV-2 with astodrimer sodium 1% resulted in a significant reduction in the viral genome copies (>99.9%) and the infectious virus (>99%) in the lung and trachea, and the infectious virus was not detected in the brain or liver. Astodrimer sodium 1% resulted in a significant reduction of viral genome copies in nasal secretions vs. PBS on Day 7 post-infection. A reduction in the viral shedding from the nasal cavity may result in lower virus transmission rates. Viraemia was low or undetectable in animals treated with astodrimer sodium 1% or infected with treated virus, correlating with the lack of detectable viral replication in the liver. Similarly, low virus replication in the nasal cavity after treatment with astodrimer sodium 1% potentially protected the brain from infection. Astodrimer sodium 1% significantly reduced the pro-inflammatory cytokines IL-6, IL-1α, IL-1β, TNFα and TGFβ and the chemokine MCP-1 in the serum, lung and trachea vs. PBS. Astodrimer sodium 1% nasal spray blocked or reduced SARS-CoV-2 replication and its sequelae in K18-hACE2 mice. These data indicate a potential role for the product in preventing SARS-CoV-2 infection or for reducing the severity of COVID-19.

Optimization and Evaluation of the In Vitro Permeation Parameters of Topical Products with Non-Steroidal Anti-Inflammatory Drugs through Strat-M® Membrane

Pharmaceutical products containing non-steroidal anti-inflammatory drugs (NSAIDs) are among the most prescribed topical formulations used for analgesic and antirheumatic properties. These drugs must overcome the skin barrier to cause a therapeutic effect. Human skin has been widely used as a model to study in vitro drug diffusion and permeation, however, it suffers from many limitations. Therefore, to perform in vitro permeation test (IVPT), we used a Strat-M® membrane with diffusion characteristics well-correlated to human skin. This study’s objective was to optimize the IVPT conditions using Plackett–Burman experimental design for bio-predictive evaluation of the in vitro permeation rates of five non-steroidal anti-inflammatory drugs (diclofenac, etofenamate, ibuprofen, ketoprofen, naproxen) across Strat-M® membrane from commercial topical formulations. The Plackett–Burman factorial design was used to screen the effect of seven factors in eight runs with one additional center point. This tool allowed us to set the sensitive and discriminative IVPT final conditions that can appropriately characterize the NSAIDs formulations. The permeation rate of etofenamate (ETF) across the Strat-M® membrane was 1.7–14.8 times faster than other NSAIDs from selected semisolids but 1.6 times slower than the ETF spray formulation.

Quantitative proton nuclear magnetic resonance method for simultaneous analysis of fluticasone propionate and azelastine hydrochloride in nasal spray formulation

A facile, rapid, accurate and selective quantitative proton nuclear magnetic resonance ( 1 H-qNMR) method was developed for the simultaneous determination of fluticasone propionate (FLP) and azelastine hydrochloride (AZH) in pharmaceutical nasal spray for the first time. The 1 H-qNMR analysis of the studied analytes was performed using inositol as the internal standard and dimethyl sulfoxide- d 6 (DMSO- d 6 ) as the solvent. The quantitative selective proton signal of FLP was doublet of doublet at 6.290, 6.294, 6.316 and 6.319 ppm, while that of AZH was doublet at 8.292 and 8.310 ppm. The internal standard (inositol) produced a doublet signal at 3.70 and 3.71 ppm. The method was rectilinear over the concentration ranges of 0.25–20.0 and 0.2–15.0 mg ml −1 for FLP and AZH, respectively. No labelling or pretreatment steps were required for NMR analysis of the studied analytes. The proposed 1 H-qNMR method was validated efficiently according to the International Council on Harmonisation guidelines in terms of linearity, limit of detection, limit of quantification, accuracy, precision, specificity and stability. Moreover, the method was applied to assay the analytes in their combined nasal spray formulation. The results ensured the linearity ( r 2 > 0.999), precision (% RSD < 1.5), stability, specificity and selectivity of the developed method.

The Spray of Pegagan Leaf Extract as an Antifungal of Vulvovaginal Candidiasis: A Narrative Review

Vulvovaginal Candidiasis (VVC) is a type of infection caused by the fungus Candida spp. The treatment of candidiasis usually uses antifungal drugs on Candida albicans. Pegagan (Centella asiatica (L.) Urban) is one of wild plants that have been used by the community as a drug. The content of secondary metabolite compounds found in pegagan, such as triterpenoids, alkaloids, flavonoids, and saponins can act as antifungal agents. A literature review in the form of national, international journals and digital books originated from various sites is carried out online. The result of the narrative analysis shows that the ethanol extract of pegagan leaves with a concentration of 75 x 103 ppm can inhibit the growth of C. albicans by up to 17.5 mm. The results of the toxicity prediction with three parameters shows that the active compounds of pegagan leaves are weak inhibitors, non-carcinogenic and in the toxicity test, it at most belongs to category III. Other than that, the spray formulation with a concentration of 1% (w/w) of pegagan leaf extract is found to be safe and non-irritant to skin.

Application of DoE in polymers screening and optimization of in situ topical ϑilm-forming solution for spray formulation

DoE is a structured and organised method to determine the relationship between the effect of change in the concentration of the independent variables and its impact on the formulation, through establishing a mathematical model. Since the acceptance of the QbD approach by the regulatory authorities across the world, DoE has been widely implemented in the areas of screening and optimisation of the formulations by the pharmaceutical industries. The topical delivery of API still posses' limitations such as insufficient contact time, odd hours of application time, sticking to fabrics, formulation washing off, etc. To address these limitations, the researcher planned to develop an in situ polymeric sprays that will form a transparent and flexible film, & will not interfere with the applicant's routine. Polymers such as HPMC, Eudragit RS100, PVP K30, PVP K90, Carbopol, Propylene glycol, Soluplus, and pullulan whereas the plasticisers selected were sorbitol. Voriconazole, a second-generation triazole, was used as a model drug. The article is a technological demonstration, in which the screening of polymers as well as the optimised concentration of the polymeric will be selected through 32 factorial design. The aim of the present article is also to establish the relationship between the software response and experimental values. The experiments were designed using 32 factorial design which resulted in 9 trial runs. Each run was evaluated for drying time, viscosity, and stickiness. The resultant response surface Later the optimisation, to yield an optimised polymeric solution that can deliver a desired in situ films. Based on ANOVA comparison of variability due to treatment, the significance of the regression model was evaluated. Other procedures such as DSC, FRIR, Stickiness, pH, diffusion studies were also performed on the selected formulation.