Butenafine Research Articles

Formulation and Evaluation of Butenafine Hydrochloride-Incorporated Solid Lipid Nanoparticles as Novel Excipients for the Treatment of Superficial Fungal Infections.

The objective of the present study was to develop natural excipient-based solid lipid nanoparticles (SLN) of butenafine hydrochloride (BUTE) using a modified solvent emulsification technique and to evaluate the competence of aloe vera nanolipidgel in enhancing the penetration of BUTE. BUTE-SLNs were prepared using a 23 factorial design to correlate the effect of formulation components on the BUTE-SLN. Particle size, polydispersity index (PDI), zeta potential, entrapment performance, and drug loading were assessed in the formed SLNs. The fabricated BUTE-SLN was evaluated for transmission electron microscopy, fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction study studies and revealed the encapsulation of BUTE in lipid in the amorphous state. BUTE-SLN-based aloe vera gel was formulated and evaluated compared with the marketed product with respect to primary skin irritation, hydration, skin permeation, and antifungal activity. The BUTE-SLN aloe vera gel, optimized for its formulation, features excellent slip properties and controlled drug release. DSC and XRD studies confirm its amorphous nature with effective drug entrapment. The gel provides enhanced skin deposition, improved antifungal activity, and reduced irritation. This makes it a cost-effective and innovative alternative to traditional dosage forms. BUTE-SLN promisingly showed no irritation, higher hydrating potential, slow and sustained release, and enhanced antifungal activity. With an aim to target deeper skin strata, minimize the side effects of drugs and symptomatic impact of fungal infection, and shorten the duration of therapy, BUTE-SLN was successfully prepared. The mean particle size and PDI were 261.25 ± 2.38 nm and 0.268 ± 0.01, respectively. BUTE-SLN gel offers improved topical delivery of BUTE with significantly higher compatibility and antifungal activity than the marketed formulation.

Novel nanomicelle butenafine formulation for ocular drug delivery against fungal keratitis: In Vitro and In Vivo study

Fungal keratitis (FK) is a serious infectious corneal disease that leads to blindness. Butenafine (BTF) is an allylamine drug with high antifungal activity, but its poor water solubility and low bioavailability limit its clinical application in ophthalmology. To increase its aqueous solubility and corneal permeability, butenafine was encapsulated in d-ɑ-tocopheryl polyethylene glycol succinate (TPGS) polymeric nanomicelles to improve the bioavailability of the drug for the treatment of FK. Butenafine was successfully fabricated into nanomicelles with a high EE of 96.34 ± 1.65 % and DL of 6.71 ± 0.099 %. The BTF-NM showed an average particle size of 13.12 ± 0.24 nm, a zeta potential of -0.56 ± 0.44 mV and a narrow PDI of 0.12 ± 0.02 with a nearly spherical shape. The characterization results of FTIR, XRD and DSC indicated that BTF was encapsulated in the TPGS nanomicelles. The BTF-NM formulation also showed high storage stability, and the in vitro drug release study showed typical biphasic-release characteristics. In addition, the BTF-NM formulation displayed good cellular tolerance and excellent ocular tolerance in rabbits. Significantly elevated in vitro antifungal activity was also observed in the BTF-NM formulation, and remarkable improvements regarding in vivo corneal permeation were observed compared with the BTF suspension formulation. Finally, the in vivo antifungal activity studies indicated that the BTF-NM formulation had a good therapeutic effect on FK and had similar efficacy to that of commercial natamycin suspension eye drops. These results suggest that the BTF-NM ophthalmic formulation could be a promising ocular drug delivery system for the treatment of FK.

Accumulation of squalene in filamentous fungi Trichoderma virens PS1-7 in the presence of butenafine hydrochloride, squalene epoxidase inhibitor: biosynthesis of 13C-enriched squalene.

Squalene is a triterpenoid compound and widely used in various industries such as medicine and cosmetics due to its strong antioxidant and anticancer properties. The purpose of this study is to increase the accumulation of squalene in filamentous fungi using exogeneous butenafine hydrochloride, which is an inhibitor for squalene epoxidase. The detailed settings achieved that the filamentous fungi, Trichoderma virens PS1-7, produced squalene up to 429.93±51.60mg/L after culturing for 7 days in the medium consisting of potato infusion with glucose at pH 4.0, in the presence of 200µm butenafine. On the other hand, no squalene accumulation was observed without butenafine. This result indicated that squalene was biosynthesized in the filamentous fungi PS1-7, which can be used as a novel source of squalene. In addition, we successfully obtained highly 13C-enriched squalene by using [U-13C6]-glucose as a carbon source replacing normal glucose.

Comparison between Ethylcellulose and Polymethacrylate Topical Nanosponges Loaded with Butenafi ne Hydrochloride

In this study, nanosponges (NS) loaded with butenafi ne hydrochloride (a broad-spectrum benzylamine antifungal agent) were successfully prepared by emulsion solvent diff usion method using ethylcellulose or polymethacrylate as retarder polymers. PVA was used as a stabilizer. NS 18 formulations were formulated with various ratios of 1:1, 1:2, and 1:3 (%, w/w), using diff erent PVA concentrations of 0.25, 0.5, and 0.75 (%, w/w). The prepared formulations were tested for particle size in terms of diameter, which ranged from (73.6 ± 15.4–991 ± 11.2 nm) for ethylcellulose NS, and from (116 ± 0.96–1439.6 ± 237.4 nm) for polymethacrylate NS. The entrapment effi ciency of the selected formulas (F1, F10) were (74.12 ± 2.60%) and (72.89 ± 1.41%). The selected formulas F1 and F10 were also evaluated for their polydispersity, yield, and in-vitro drug release. The release of BFNS powder in F10 (90.42 ± 1.81%) was higher than that of ECNS F1 powder (78.53 ± 3.24%) within 24 hours. Evaluation tests of the scanning electron microscope (SEM), Fourier transform infrared ray (FTIR), and powder X-ray diff raction (PXRD) confi rmed the NS’ spherical and porous features, the absence of any drug polymer interaction, and the stability of the drug in the delivery system. The two formulas of F1 and F10 were found to exhibit prolonged drug release, which minimizes side eff ects and dosing frequency of BF drug application.

Crystal structure of butenafine hydrochloride, C23H28NCl

The crystal structure of butenafine hydrochloride has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional theory techniques. Butenafine hydrochloride crystallizes in space group P21 (#4) with a = 13.94807(5), b = 9.10722(2), c = 16.46676(6) Å, β = 93.9663(5)°, V = 2086.733(8) Å3, and Z = 4. Butenafine hydrochloride occurs as a racemic co-crystal of R and S enantiomers of the cation. The crystal structure is characterized by parallel stacks of aromatic rings along the b-axis. Each cation forms a strong discrete N–H⋯Cl hydrogen bond. The chloride anions also act as acceptors in several C–H⋯Cl hydrogen bonds from methylene, methyl, and aromatic groups. The powder pattern has been submitted to ICDD for inclusion in the Powder Diffraction File™ (PDF®).

Sensitive and effective electrochemical determination of butenafine in the presence of itraconazole using titanium nanoparticles-ionic liquid based nanocomposite sensor

The evaluation of the bioavailability of topically applied medications that act inside or under the skin is a challenging task. Herein, the current study describes a simple, quick, and low-cost electrochemical platform for determining butenafine hydrochloride (BTH) that is mainly prescribed as a treatment of dermatophytosis, applying titanium nanoparticles and an ionic liquid as outstanding mediators. In terms of low detection limits (61.63 nM) and extensive range of 2.21 × 10–7–13.46 × 10–5 M, the established electrochemical technique provided worthy analytical performance for butenafine hydrochloride sensing. The suggested sensor's practical applicability was effectively demonstrated in pharmaceutical preparations, actual stratum corneum samples, and simultaneous detection of butenafine hydrochloride and Itraconazole in pharmaceutical preparation for the first time. All of the experimental factors, like the pH and scan rate, have been investigated and optimized. Diffusion coefficients of butenafine hydrochloride at bare and modified sensors were calculated.

Carbonaceous nanomaterials integrated carbon paste sensors for adsorptive anodic voltammetric determination of butenafine in the presence of its degradation product

Butenafine (BUT) is a new synthetic benzylamine antifungal with an effective inhibitory effect on squalene epoxidase. The present work introduced for the first time a novel sensitive adsorptive differential pulse voltammetric method for sensitive and selective determination of butenafine in pharmaceutical preparations in the presence of its degradation products. Integration of the working carbon paste electrodes with various carbonaceous nanostructures with their enhanced electrocatalytic effect towards the oxidation of butenafine improved the performance of the method. Comprehensive and in-depth studies were performed including the effect of the nature of the nanomaterial, modification mode, and pH under the optimized electroanalytical parameters. Functionalized carbon paste electrodes with multiwall carbon nanotubes (MWCNTs) showed a sharp well-defined oxidation peak for butenafine at 1.119 V following an adsorption electrode reaction mechanism through the participation of one proton/electron, as assumed by the pH, scan rate studies and molecular orbital calculations. Improved sensitivity was recorded within the linear BUT concentration range from 2.0 to 18.0 µg mL−1 with limit of detection 0.477 µg mL−1. A prolonged operational lifetime of more than 4 months and high measurement reproducibility was the promising futures of the fabricated sensors. The selectivity of the proposed method was established in the presence of the BUT degradation product and other interfering species present in pharmaceutical formulations. The achieved selectivity and sensitivity suggested the application of the proposed approach for BUT assay in medicinal creams in the presence of butenafine degradation products.

Formulation and Evaluation of Topical Nano-Lipid-Based Delivery of Butenafine: In Vitro Characterization and Antifungal Activity.

The present research work was designed to prepare butenafine (BN)-loaded bilosomes (BSs) by the thin-film hydration method. BN is a sparingly water-soluble drug having low permeability and bioavailability. BSs are lipid-based nanovesicles used to entrap water-insoluble drugs for enhanced permeation across the skin. BSs were prepared by the thin-film hydration method and optimized by the Box–Behnken design (BBD) using lipid (A), span 60 (B), and sodium deoxycholate (C) as independent variables. The selected formulation (BN-BSo) was converted into the gel using Carbopol 940 as a gelling agent. The prepared optimized gel (BN-BS-og) was further evaluated for the gel characterization, drug release, drug permeation, irritation, and anti-fungal study. The optimized bilosomes (BN-BSo) showed a mean vesicle size of 215 ± 6.5 nm and an entrapment efficiency of 89.2 ± 1.5%. The DSC study showed that BN was completely encapsulated in the BS lipid matrix. BN-BSog showed good viscosity, consistency, spreadability, and pH. A significantly (p < 0.05) high release (81.09 ± 4.01%) was achieved from BN-BSo compared to BN-BSog (65.85 ± 4.87%) and pure BN (17.54 ± 1.37 %). The permeation study results revealed that BN-BSo, BN-BSog, and pure BN exhibited 56.2 ± 2.7%, 39.2 ± 2.9%, and 16.6 ± 2.3%. The enhancement ratio of permeation flux was found to be 1.4-fold and 3.4-fold for the BN-BS-og and pure BN dispersion. The HET-CAM study showed that BN-BSog was found to be nonirritant as the score was found within the limit. The antifungal study revealed a significant (p < 0.05) enhanced antifungal activity against C. albicans and A. niger. The findings of the study revealed that BS is an important drug delivery system for transdermal delivery.

Formulation and Optimization of Butenafine-Loaded Topical Nano Lipid Carrier-Based Gel: Characterization, Irritation Study, and Anti-Fungal Activity.

The present study aims to prepare and optimize butenafine hydrochloride NLCs formulation using solid and liquid lipid. The optimized selected BF-NLCopt was further converted into Carbopol-based gel for topical application for the treatment of fungal infection. Box Behnken design was employed to optimize the nanostructure lipids carriers (NLCs) using the lipid content (A), Tween 80 (B), and homogenization cycle (C) as formulation factors at three levels. Their effects were observed on the particle size (Y1) and entrapment efficiency (Y2). The selected formulation was converted into gel and further assessed for gel characterization, drug release, anti-fungal study, irritation study, and stability study. The solid lipid (Compritol 888 ATO), liquid lipid (Labrasol), and surfactant (tween 80) were selected based on maximum solubility. The optimization result showed a particle size of 111 nm with high entrapment efficiency of 86.35% for BF-NLCopt. The optimized BF-NLCopt converted to gel (1% w/v, Carbopol 934) and showed ideal gel evaluation results (drug content 99.45 ± 2.11, pH 6.5 ± 0.2, viscosity 519 ± 1.43 CPs). The drug release study result depicted a prolonged drug release (65.09 ± 4.37%) with high drug permeation 641.37 ± 46.59 µg (32.07 ± 2.32%) than BF conventional gel. The low value of irritation score (0.17) exhibited negligible irritation on the skin after application. The anti-fungal result showed greater efficacy than the BF gel at both time points. The overall conclusion of the results revealed NLCs-based gel of BF as an ideal delivery system to treat the fungal infection.

Formulation and in vitro evaluation of topical nanosponge-based gel containing butenafine for the treatment of fungal skin infection

In the current study, four formulae (BNS1-BNS4) of butenafine (BTF) loaded nanosponges (NS) were fabricated by solvent emulsification technology, using different concentration of ethyl cellulose (EC) and polyvinyl alcohol (PVA) as a rate retarding polymer and surfactant, respectively. Prepared NS were characterized for particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE) and drug loading (DL). Nanocarrier BNS3 was optimized based on the particle characterizations and drug encapsulation. It was further evaluated for physicochemical characterizations; FTIR, DSC, XRD and SEM. Selected NS BNS3 composed of BTF (100 mg), EC (200 mg) and 0.3% of PVA showed, PS (543 ± 0.67 nm), PDI (0.330 ± 0.02), ZP (−33.8 ± 0.89 mV), %EE (71.3 ± 0.34%) and %DL (22.8 ± 0.67%), respectively. Fabricated NS also revealed; polymer-drug compatibility, drug-encapsulation, non-crystalline state of the drug in the spherical NS as per the physicochemical evaluations. Optimized NS (BNS3) with equivalent amount of (1%, w/w or w/v) BTF was incorporated into the (1%, w/w or w/v) carbopol gel. BTF loaded NS based gel was then evaluated for viscosity, spreadability, flux, drug diffusion, antifungal, stability and skin irritation studies. BNS3 based topical gels exhibited a flux rate of 0.18 (mg/cm2.h), drug diffusion of 89.90 ± 0.87% in 24 h with Higuchi model following anomalous non-Fickian drug release. The BNS3 based-gel could be effective against pathogenic fungal strains.

Formulation and evaluation of butenafine loaded PLGA-nanoparticulate laden chitosan nano gel

The present research work is designed to prepare and optimize butenafine (BT) loaded poly lactic co glycolic acid (PLGA) nanoparticles (BT-NPs). BT-NPs were prepared by emulsification probe sonication method using PLGA (A), PVA (B) as polymer and stabilizer, respectively. The optimum composition of BT-NPs was selected based on the point prediction method given by the Box Behnken design software. The optimized composition of BT-NPop showed a particle size of 267.21 ± 3.54 nm with an entrapment efficiency of 72.43 ± 3.11%. The optimum composition of BT-NPop was further converted into gel formulation using chitosan as a natural polymer. The prepared topical gel formulation (BT-NPopG) was further evaluated for gel characterization, drug release, permeation study, irritation, and antifungal studies. The prepared BT-NPopG formulation showed optimum pH, viscosity, spreadability, and drug content. The release and permeation study results revealed slow BT release (42.76 ± 2.87%) with significantly enhanced permeation across the egg membrane. The irritation study data showed negligible irritation with a cumulative score of 0.33. The antifungal study results conclude higher activity than marketed as well as pure BT. The overall conclusion of the results revealed BT-NPopG as an ideal delivery system to treat topical fungal infection.

Repurposing existing drugs: identification of SARS-CoV-2 3C-like protease inhibitors

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19). Since its emergence, the COVID-19 pandemic has not only distressed medical services but also caused economic upheavals, marking urgent the need for effective therapeutics. The experience of combating SARS-CoV and MERS-CoV has shown that inhibiting the 3-chymotrypsin-like protease (3CLpro) blocks the replication of the virus. Given the well-studied properties of FDA-approved drugs, identification of SARS-CoV-2 3CLpro inhibitors in an FDA-approved drug library would be of great therapeutic value. Here, we screened a library consisting of 774 FDA-approved drugs for potent SARS-CoV-2 3CLpro inhibitors, using an intramolecularly quenched fluorescence (IQF) peptide substrate. Ethacrynic acid, naproxen, allopurinol, butenafine hydrochloride, raloxifene hydrochloride, tranylcypromine hydrochloride, and saquinavir mesylate have been found to block the proteolytic activity of SARS-CoV-2 3CLpro. The inhibitory activity of these repurposing drugs against SARS-CoV-2 3CLpro highlights their therapeutic potential for treating COVID-19 and other Betacoronavirus infections.

Development and Validation of Simple, Rapid and Sensitive High- Performance Liquid Chromatographic Method for the Determination of Butenafine Hydrochloride

Aims: The current paper reports a simple, rapid, sensitive, accurate, and precise Reverse-phase high performance liquid chromatography (RP-HPLC) method with wide range of estimation to determine butenafine hydrochloride in nanosponges. This method has been validated as per ICH norms.&#x0D; Study Design: Experimental design with influence of variables such as mobile phase composition, flow rate, temperature and wavelength on the chromatographic peaks.&#x0D; Place and Duration of Study: Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia between Jan 2020 and March 2020.&#x0D; Methodology: Separation was achieved by utilizing the most commonly used reverse phase column (C-18, 5 μm, 150 mm x 4.6 mm) set at 30ºC and quantified by UV detection at 280 nm after isocratic elution from a mobile phase (70:30 v/v of methanol: phosphate buffer pH 3.0) flowing at 1 ml/min.&#x0D; Results: A sharp and symmetrical peak was observed at 4.08 ± 0.01 minutes. The low variation in peak area and retention time (1.12% and 0.29%, respectively) and a high number of theoretical plates (&gt;2000) indicated this method’s efficiency and suitability. The least square linear regression analysis (Y = 9265.5 X + 1961.4) showed excellent correlation (r2 = 0.999 ± 0.0003) between concentration and peak area of butenafine hydrochloride through a wide concentration range of 1–50 µg/ml. The limits of detection and quantification (LOD and LOQ) were 0.18 µg/ml and 0.57 µg/ml, respectively. The assay or determinations were accurate, precise and reproducible with mean accuracy and mean relative standard deviation of precision of 101.53 ± 0.43% and 0.51 ± 0.11% respectively.&#x0D; Conclusion: The developed RP-HPLC method was simple, sensitive, reproducible with wide range of estimation of butenafine hydrochloride in the nanosponges. The proposed method could be used for the analysis of butenafine hydrochloride in the conventional pharmaceutical formulations such as tablets, syrup, creams including novel formulations such as nanoparticles, nanosponges, nanoemulsions. The proposed method overcomes the specificity, sensitivity and reproducibility related issues of ultraviolet-visible spectroscopy.

Selective potentiometric sensors for the determination of butenafine hydrochloride in a cream formulation

In situ screen printed (ISPE) and in situ carbon paste (ICPE) electrodes have been developed for the selective determination of butenafine hydrochloride (BF.HCl) in pharmaceutical preparation. The construction and potentiometric characteristics of the proposed sensors were described. The proposed sensors exhibited Nernstian slopes of 60.30 ± 0.79 and 59.80 ± 0.96 mV decade−1 for ISPE (electrode I) and ICPE (electrode II), respectively, within a linear concentration range of 1.0 × 10−6–1.0 × 10−2 mol L−1 of BF.HCl drug solution and performed satisfactorily over wide pH ranges 3.0–8.5 and 2.5–7.0 with a relatively fast response time 3–4 and 7–8 s for ISPE (electrode I) and ICPE (electrode II), respectively. Also the proposed electrodes exhibited a relatively long operational lifetime of 72 and 42 days, for ISPE (electrode I) and the paste of ICPE (electrode II), respectively and they showed good discrimination ability for BF.HCl relative to numbers of interfering materials. The morphology of the surface of the proposed sensors was investigated using scanning electron microscopy to study the effect of in situ modification on the surface structure of the developed electrodes.

Highly sensitive electrochemical sensor determination of drug in pharmaceutical analysis

Modified carbon paste electrodes and screen printed electrodes were developed for the potentiometric determination of butenafine hydrochloride (BTFHC) in urine, serum and pharmaceutical preparations. Two modified carbon paste electrodes (electrodes A and C) and two modified screen printed electrodes (electrodes B and D) using tricresylphosphate (TCP) and o-nitrophenyloctyl ether (o-NPOE) plasticizers, respectively, were used. The electrodes showed a linear concentration range from 1.57×10-7 to 1.0 × 10-2 and 1.0 × 10-7 to 1.0 × 10-2 mol L-1 with detection limit of 1.57×10-7 and 1.0 × 10-7 mol L-1 for modified carbon paste (MCPEs; electrodes A and B) and modified screen printed (MSPEs; electrodes C and D), respectively. The calibration graphs have slope values of 56.95±0.56, 58.22±0.78, 56.18±0.66 and 57.69±0.39 mV decade-1 for electrodes A, B, C and D, respectively. The response time was relatively quick in the whole concentration range and was found to be 12s for electrodes (A and B) and 7s for electrodes (C and D). The electrodes were found to have life time of 82, 99, 160 and 185 days without showing any deviations in a pH range of 5.0–9.0 and 4.0–9.0 for MCPEs (electrodes A and B) and MSPEs electrodes (C and D), respectively. The fabricated electrodes displayed good selectivity for BTFHC with respect to number of common foreign inorganic cations, sugar species, organic and glycine as the fillers that may be added to the pharmaceutical preparation or biological fluids. Fortunately, such materials mostly do not interfere. The potential application of the sensors (A-D) was accomplished as a result of good recoveries made from real samples fortified with BTFHC. Results indicated the proficiency of the sensors reliable for rapid, onsite monitoring of BTFHC in pharmaceutical preparation and in biological samples.

Use of an in vitro human skin permeation assay to assess bioequivalence of two topical cream formulations containing butenafine hydrochloride (1%, w/w)

The primary objective of this work was to investigate, using an in vitro human skin permeation study, whether changes in the excipients of butenafine hydrochloride cream would have any effect on bioperformance of the formulation. Such in vitro data would be a surrogate for any requirement of a bioequivalence (BE) study to demonstrate formulation similarity. A LC-MS/MS method for quantitation of butenafine in various matrices was developed and validated. A pilot study was performed to validate the in vitro skin permeation methodology using three cream formulations containing butenafine hydrochloride at concentrations of 0.5, 1.0 and 1.5% (w/w). Finally, a definitive in vitro human skin permeation study was conducted, comparing the extent of butenafine hydrochloride permeation from the new formulation to that from the current formulation. The results of the study comparing the two formulations showed that there was no statistically significant difference in the extent of butenafine permeation into human skin. In conclusion, these in vitro data demonstrated that the formulation change is likely to have no significant impact on the bioperformance of 1% (w/w) butenafine hydrochloride cream.

Vehicle effects on human stratum corneum absorption and skin penetration.

This study evaluated the effects of three vehicles-ethanol (EtOH), isopropyl alcohol (IPA), and isopropyl myristate (IPM)-on stratum corneum (SC) absorption and diffusion of the [14C]-model compounds benzoic acid and butenafine hydrochloride to better understand the transport pathways of chemicals passing through and resident in SC. Following application of topical formulations to human dermatomed skin for 30 min, penetration flux was observed for 24 h post dosing, using an in vitro flow-through skin diffusion system. Skin absorption and penetration was compared to the chemical-SC (intact, delipidized, or SC lipid film) binding levels. A significant vehicle effect was observed for chemical skin penetration and SC absorption. IPA resulted in the greatest levels of intact SC/SC lipid absorption, skin penetration, and total skin absorption/penetration of benzoic acid, followed by IPM and EtOH, respectively. For intact SC absorption and total skin absorption/penetration of butenafine, the vehicle that demonstrated the highest level of sorption/penetration was EtOH, followed by IPA and IPM, respectively. The percent doses of butenafine that were absorbed in SC lipid film and penetrated through skin in 24 h were greatest for IPA, followed by EtOH and IPM, respectively. The vehicle effect was consistent between intact SC absorption and total chemical skin absorption and penetration, as well as SC lipid absorption and chemical penetration through skin, suggesting intercellular transport as a main pathway of skin penetration for model chemicals. These results suggest the potential to predict vehicle effects on skin permeability with simple SC absorption assays. As decontamination was applied 30 min after chemical exposure, significant vehicle effects on chemical SC partitioning and percutaneous penetration also suggest that skin decontamination efficiency is vehicle dependent, and an effective decontamination method should act on chemical solutes in the lipid domain.

Formulation Development and Evaluation of Topical Film-Forming Lotion Containing Butenafine Hydrochloride

Many agents are applied to the skin deliberately with beneficial outcomes. Conventional formulations intended for topical and dermatological administration of drugs such as creams, foams, gels and lotions are considered to reside for a relatively short period of time at the targeted site. The localized treatment of body tissues, diseases and wounds requires that the particular pharmaceutical component be maintained at the site of treatment for an effective period of time. Sweat, clothing, movements and getting washed away easily on contact with water are some of the problems that have limited the effectiveness and residence time of conventional topical formulations for treatment of fungal infections of skin. This necessitates longer treatment duration. Hence, a composition that adheres to skin surface afflicted and provides localized delivery of an antifungal agent is needed. The present work aims at designing and formulating a 'film- forming lotion' which on application will form a thin transparent film on the skin. Eudragit RL 100 and HPMC K4M was used to form a matrix film. The formulations were prepared using 32 full factorial design. They were tested for drying time, drug release, antifungal activity, skin irritation and stability studies. The gel was characterised for pH, viscosity, drug content, effective dosage volume and mechanical properties of the film formed after application; bioadhesion and water vapour permeability were also tested. All the formulations showed results within acceptable range for various tests. The optimized formulation showed drug release of 99.64% and antifungal activity in terms of efficacy as 98.72%. Such a formulation can be claimed to decrease duration of therapy, will be more accepted by the patients and be a breakthrough in treating fungal infections of the skin.

Formulation, optimization and evaluation of microemulsion based gel of Butenafine Hydrochloride for topical delivery by using simplex lattice mixture design

The aim of the present investigation was to develop and evaluate Butenafine Hydrochloride loaded microemulsion based gel for treatment of fungal infection. Pseudo ternary phase diagrams were constructed for different microemulsion formulations composed of Capmul MCM as oil, Cremophor RH 40 as surfactant and Transcutol HP as co-surfactant. Composition of microemulsion system was optimized using simplex lattice mixture design including the concentration of oil, Surfactant co-surfactant ratio (Smix) and water (independent variables) and the % transmittance and globule size of microemulsion (response variables). The physicochemical properties of the optimized microemulsion were investigated. Microemulsion was incorporated into 1 % carbopol 934P gel and the ex vivo drug permeation of gel was also investigated. The results showed that the optimized microemulsion formulation was composed of Capmul MCM oil (5 %, w/w), Cremophor RH 40/Transcutol HP (43.333 %, w/w) and water (51.667 %, w/w). The mean globule diameter was 108.8 nm. The conclusion was that the release controlling ability of microemulsion containing gel formulation was significantly improved in comparison to commercial cream. Skin irritation study was also performed and it shows no irritation on rat skin after 24 h of application. Microbiological assay of Butenafine Hydrochloride was performed where it shows better zone of inhibition than marketed formulation.

Microemulsion-loaded hydrogel formulation of butenafine hydrochloride for improved topical delivery

Topical microemulsion systems for the antifungal drug, butenafine hydrochloride (BTF) were designed and developed to overcome the problems associated with the cutaneous delivery due to poor water solubility. The solubility of BTF in oils, surfactants and co-surfactants was evaluated to screen the components of the microemulsion. Isopropyl palmitate was used as the oil phase, aerosol OT as the surfactant and sorbitan monooleate as co-surfactant. The pseudoternary diagrams were constructed to identify the area of microemulsion existence and optimum systems were designed. The systems were assessed for drug-loading efficiency and characterized for pH, robustness to dilution, globule size, drug content and stability. Viscosity analysis, spreadability, drug content assay, ex vivo skin permeation study and antifungal activity assay were performed for the optimized microemulsion-loaded hydrogel. The optimized BTF microemulsion had a small and uniform globule size. The incorporation of microemulsion system into Carbopol 940 gel was found to be better as compared to sodium alginate or hydroxyl propyl methyl cellulose (HPMC K4M) gel. The developed gel has shown better ex vivo skin permeation and antifungal activity when compared to marketed BTF cream. Thus, the results provide a basis for the successful delivery of BTF from microemulsion-loaded hydrogel formulation, which resulted in improved penetration of drug and antifungal activity in comparison with commercial formulation of BTF.