Design Development and Optimization of Econazole Nitrate AntiFungal Emulgel by Using Factorial Design Approach

ABSTRACT: Econazole nitrate, an imidazole ring-containing broad-spectrum antifungal drug, is used to treat Dermatomycosis furfuracea, Foot mycosis and Groin dermatophytosis. This work focuses on the formulation and assessment of nanoemulgels generated from Nano emulsions using high-speed homogenization. Nanoemulgel has various benefits over creams and ointments, one of which is that the drug is delivered to intended location more quickly. Mycosis for skin belong to the most common dermatological syndrome in the globe. Topical treatment improves efficacy and permeability. The characterization of the econazole was done by physical appearance , melting point , UV , IR , DSC. Solubility of Econazole in different oils and surfactants like Almond oil , Oleic acid , Olive oil, Tween 80,Tween 40, Span 80 and PEG 400 , Ethanol. According to solubility the surfactant, oil and co-surfactant was chosen. The nanoemulsion of Econazole with oleic acid, tween 80, PEG400 was made . Nanoemulsion was then characterized by entrapment efficiency, Globular size(particle size),zeta potential, drug content . After getting optimized batch the corbopol 940 use as gelling agent , was encorporated into the nanoemulsion , and nanoemulgel was formed . The nanoemulgel properties were assessed by measuring drug content, viscosity pH. Drug release from nanoemulgel was done by franze diffusion cell . The melting point of the Econazole was found to be 1630C. UV Spectroscopy of Econazole gives wavelength 218 nm for the topical formulation . FTIR gives the functional groups present in pure Econazole structure.. The solubility of Econazole is highest in oleic acid was 66 mg/ml , surfactant Tween 80 was 11.23 mg/ml, and co surfactant PEG400 was 3.8 mg/ml . The Particle size of the nanoemulsion was found to be 192.4 nm with PDI is 0.209. The zeta potential is -30.96 mV and the % drug release is 94.2% over 24 Hrs which results in sustained and controlled drug release from the formulation. And follows higuchi order kinetics. The DSC of pure drug and final formulation of nanoemulgel was obtained which explains that decrease in melting point from pure drug(167.950C) to nanoemulgel ( 104.230 C)that the crystallinity decreases and goes toward amorphous which increase solubility. Potential Amorphization or interaction of Econazole with nanoemulgel matrix. Drug content was 96.08% and spreadability was 29.41 gm.cm/sec, and gel was easily spreads through skin. Antifungal study gives the larger zone of inhibition of the optimized formulation batch of nanoemulgel compared to the marketed formulation. Stability study was done at different temperature conditions and changes in pH, viscosity, drug content, gelling capacity was noted.

Tranylcypromine (logP = 1.34, MW = 133.19g/mol) is a monoamine oxidase inhibitor used in treating major depressive disorder and is available only as oral tablets. Transdermal delivery of tranylcypromine minimizes hepatic and gastrointestinal side effects associated with oral dosing and prevents systemic side effects improving patient compliance. A two-day suspension-based transdermal delivery method was developed in this study, and the delivery of tranylcypromine across dermatomed porcine ear skin was evaluated. Different penetration enhancers were screened, namely, isopropyl myristate, oleyl alcohol, oleic acid, and a combination of oleic acid and oleyl alcohol. Isopropyl myristate was chosen as the penetration enhancer, and suspension-based transdermal patches were formulated with acrylate and polyisobutylene pressure-sensitive adhesives by the solvent evaporation method. The release liner and backing membrane were chosen, and the drying time for each patch was optimized. The optimized patches were characterized for their adhesive properties, drying time, peel test, shear strength, and uniformity in drug content. In vitro permeation studies were performed on dermatomed porcine ear skin using vertical static Franz diffusion cells, and the receptor samples were collected at predetermined time points for 48h. The samples were analyzed in a validated UPLC method. Acrylate-based suspension patch delivered a significantly higher amount of drug (712 ± 21.46μg/cm2) as compared to passive delivery from drug dissolved in propylene glycol (461.49 ± 75.55μg/cm2), reaching the two-day therapeutic target. However, the PIB-based suspension patch delivered 559.25 ± 12.37μg/cm2 of tranylcypromine across the skin but did not reach the required target.

Lovastatin, a BCS class II drug, exhibits poor aqueous solubility and variable therapeutic performance, limiting its clinical effectiveness. The present study aimed to develop and optimize a lovastatin-loaded nanoemulsion and further incorporate it into a nanoemulgel system to enhance solubility and achieve controlled topical drug delivery. Preformulation studies were conducted to evaluate the physicochemical properties and solubility behavior of the formulation. Suitable oils, surfactants, and co-surfactants were selected based on solubilization capacity and emulsification efficiency. A pseudo-ternary phase diagram was constructed to identify the nanoemulsion region. A 3² full factorial design was employed to optimize formulation variables, namely, oil concentration (X₁) and Smix concentration (X₂), with percent transmittance, viscosity, and drug release as responses. The optimized nanoemulsion exhibited high clarity (99.45% transmittance), appropriate viscosity (~140 cP), nanoscale droplet size with uniform distribution, and enhanced drug release (~86% over 8 h). The optimized system was incorporated into a carbopol-based gel to obtain a nanoemulgel with a suitable pH, good spreadability, and homogeneity. The nanoemulgel demonstrated sustained drug release (~92% over 12 h), indicating its potential for prolonged topical delivery. Statistical analysis confirmed that oil concentration significantly influenced formulation performance, whereas Smix improved drug release and clarity. Short-term stability studies indicated no significant changes in the physicochemical properties. Overall, the developed nanoemulsion-based nanoemulgel represents a promising approach for enhancing the solubility and controlled topical delivery of lovastatin, warranting further investigation using ex vivo and in vivo studies. Design, Optimization, and Evaluation of a Lovastatin-Loaded Nanoemulsion-Based Nanoemulgel for Enhanced Solubility and Controlled Topical Drug Delivery Highlights • Developed a lovastatin-loaded nanoemulsion using a systematic Design of Experiments (3² factorial design) approach • Optimized formulation demonstrated high clarity, nanoscale droplet size, and enhanced drug release • Nanoemulsion was successfully incorporated into a Carbopol-based nanoemulgel for topical delivery • Nanoemulgel exhibited suitable physicochemical properties with sustained drug release up to 12 h • Oil and Smix concentrations were identified as critical factors influencing formulation performance • The developed system offers a promising strategy for improving solubility and controlled topical delivery of poorly water-soluble drugs

The aim of the present research work was to investigate the potential of emulgel in enhancing the topical delivery of Itraconazole. Emulgel formulations of Itraconazole were prepared using two types of gelling agents namely: Carbopol 934 and Carbopol 940. The influence of the type of the gelling agent and the concentration of both the oil phase and emulsifying agent on the drug release from the prepared emulgel was investigated using a 23 factorial design. The prepared formulations were evaluated for their physical appearance, viscosity, drug release, globule size, skin irritation test, antifungal activity, transmission electron microscopy and stability. Commercially available Itraconazole cream was used for comparison. All the prepared emulgel showed acceptable physical properties concerning color, homogeneity, consistency, spreadability, and pH value. The antifungal activity and drug release were found to be higher for optimized formulation as compared to the marketed Itraconazole cream. The result of studied revealed that the optimized batch shows 95.08% release in 48 hours and stable for around three. The result of microbial assay compared with marketed product, the result shows46.6% inhibition of optimized batch where as marketed preparation shows only 32.3% inhibition. While result of skin irritation test shows no edema and erythema. No irritation was observed on the skin of the rabbits. Stability studies showed that the physical appearance, rheological study, in vitro drug release, and antifungal activity in all the prepared emulgel remained unchanged upon storage for 3 months. In general conclusion, it was suggested that the emulgel formulation succeed the drug release for sustained drug delivery in a controlled manner in comparison with cream.

To formulate and evaluate the hydrogels containing meloxicam for topical application and also compare the effect of penetration enhancers on release of drug. Meloxicam gels were prepared by dispersion method using carbopol-940 and 934 (1%w/w) as rate controlling polymer and drug penetration enhancers such as tween 80, oleic acid and sesame oil in the concentration of 1% and 2% . The formulated gels were evaluated for drug content, pH, viscosity, spreadability, extrudability, in vitro drug permeation, drug release kinetics, bioadhesion test, accelerated stability of selected gel formulation. The in vitro drug permeation through pig's skin was carried out by using Keshary-Chein diffusion cell and viscosity was determined by brookfield viscometer (Modle No. LVDVE). All the gel formulations were found to be very clear and homogeneous. Drug content of all formulations was found to be above 93%. Formulation F(14) containing carbopol-934(1%w/w) and sesame oil 2% gave 99% release as compared to other formulations obeying zero order kinetic with a good bioadhesion quality. The permeability coefficient of all formulations was found in the range of 0.2 to 0.4×10(-3)cm(2)/hr. The results were compared statistically and found with satisfactory correlation and it was observed that the rate of drug release increased with increase in concentration of penetration enhancers.

Purpose: To prepare and characterize buccal transmucosal delivery system of enalapril maleate for overcoming its low bioavailability, and hence provide improved therapeutic efficacy and patient compliance.Methods: Transmucosal drug delivery systems of enalapril maleate were formulated as buccal films by solvent casting technique using polyvinylpyrrolidone K90, hydroxypropyl methylcellulose, sodium carboxymethylcellulose (high viscosity). The films were evaluated for film weight, thickness, folding endurance, drug content uniformity, surface pH, in vitro residence time, in vitro drug release and ex-vivo permeation.Results: All the formulations showed high drug content (96.45 to 98.49 %). Those with good swelling showed good residence time. In vitro drug release was highest for films prepared with high viscosity grade sodium carboxymethylcellulose (SCMC- HV,F2), releasing 92.24 % of drug in 1.5 h) followed by F4 (containing polyvinyl pyrrolidone K-90 1 % w/v and SCMC (HV) 1 % w/v). Ex-vivo drug permeation at the end of 10 h was 82.24 and 89.9 % for F2 and F4, respectively.Conclusion: Prompt drug release was obtained from the formulation (F2) containing SCMC 2 % w/v with 10 mg enalapril. However, on the basis of the highest swelling and residence time, and controlled drug release, formulation F4 (containing PVP K-90 and SCMC HV) would be suitable for the development of buccal film for effective therapy of cardiac diseases.Keywords: Cardiac disease, Transmucosal, Buccal films, Enalapril maleate, Drug release, Ex-vivo permeation

In the present research work an attempt was made to prepare and evaluate the transdermal patches of Tramadol HCl, a centrally acting opiod analgesic drug. Formulations were made by using different ratios of rate controlling polymers like Eudragit RL100, hydroxyl propyl methyl cellulose 6 cps and ethyl cellulose. Poly ethylene glycol 400 is used as plasticizer and Tween 80 as penetration enhancer. The patches were prepared by solvent evaporation technique using liquid paraffin as lubricant. The study examines the influence of polymers ratio on physicochemical properties and drug release potential of transdermal films. In the pre formulation studies, solubility, partition coefficient and melting point were determined to assess its application for transdermal delivery. The FTIR studies confirmed that there is no incompatibility present between drug and excipients. The patches were evaluated for their appearance, weight uniformity, and thickness uniformity, drug content uniformity, folding endurance, invitro diffusion and stability studies. Based on the evaluation studies F10 formulation was optimised. The drug release was extended for 12 hrs showing drug release of 94.19%. The release kinetics data for optimised formulation has revealed that the patch is best fit in to higuchi model with fickian type of diffusion. The optimised formulation was subjected to accelerated stability studies for 6 months and the results found to be stable with respect to drug content, drug release as well as physical changes.

The main objective of present investigation to formulate and evaluate mucoadhesive buccal patches of Lisinopril using solvent casting method. Sodiumalginate combined with Sodium carboxyl methyl cellulose, HPMC, and Carbopol934 in different proportions were used as a mucoadhesive polymer and Propyleneglycol used as a plasticizer as well as penetration enhancers. The formulated Buccal patches of Lisinopril were evaluated on the basis of Thickness, Weight uniformity, folding endurance, swelling Studies, Surface pH Determination, Percentage Moisture loss, Drug content Uniformity, Ex-Vivo Mucoadhesive strength, In Vitro Drug Release, Ex- vivo permeation study. By compatibility study there is no chemical interaction between drug and excipients used. All prepared buccal patches were transparent, smooth, consistent and flexible. The surface pH of all formulations was found to be almost in neutral pH and no mucosal irritation was expected. Among all the formulations, F6 showed maximum swelling index as 25.01%. The optimized formulation F6 also showed satisfactory, Mucoadhesive strength (5.1kg/cm2), drug content (98.75), and Ex-Vivo permeation (82.03%). In-Vitro drug release of optimised formulation (F6) was found to be 75.12 at the end of 8 hrs. Drug release mechanism was determined by plotting release data to Higuchi and Korsmeyer-Peppas model. All the formulations are best fitted to Korsmeyer-Peppas model and according to this model the drug releases from theses patches may be controlled by diffusion with super case-II transport.

This study focused on the development and optimization of a chrysin-loaded emulgel for enhanced topical delivery using a 32 factorial design. Preformulation and compatibility studies, including FTIR and DSC, confirmed the chemical stability of chrysin with selected excipients, carbopol 934, tween 80, and light liquid paraffin. By using 32 factorial design, a total 9 formulations were prepared (F1–F9), employing different concentrations of carbopol 934 and tween 80 as independent variables. The prepared formulation was evaluated for drug content, viscosity, in-vitro drug release, globule size, pH, spreadability, and stability. The optimized formulation was identified through statistical analysis, response surface methodology (RSM), and overlay plots of independent variables versus dependent responses. In the results, drug content uniformity (96.34%–98.25%) viscosity (553.25–736.38 cP), globule size (7.57–13.7 µm), drug release (78.34%–86.26%), pH (6.44–6.82) and spreadability (17–22 g cm/s) were all within the acceptable range for emulgel. The RSM and overlay plots identified F3 as an optimized formulation with a desirability score of 0.986. The optimized formulation demonstrated ideal performance with the viscosity of 647.38 cP, globule size of 10.23 µm, drug release of 82.57%, drug content of 98.25%, pH of 6.68, and spreadability of 20 g·cm/s. The optimized formulation composed of chrysin (1%), light liquid paraffin (7.5%), mentha oil (4%), tween 80 (1.5%), carbopol 934 (3%), and methylparaben (0.03%). In-vitro permeation studies showed sustained drug diffusion over 12 h (112.72 µg/cm2), without an initial burst, indicating controlled release behavior. The developed emulgel system presents a promising approach for the effective topical delivery of chrysin.

Vonoprazan fumarate, a potassium-competitive acid blocker used for the treatment of gastroesophageal reflux disease, is classified as a BCS Class II drug with low solubility and high permeability. The present study aimed to enhance the solubility Vonoprazan fumarate by preparing an inclusion complex with HP-β-Cyclodextrin. Compatibility studies conducted via FT-IR spectroscopy confirmed no significant interaction between the drug and excipients. Sublingual tablets were formulated using the direct compression method, with Crospovidone as a superdisintegrant. Pre compression parameters indicated good powder flow properties, while post-compression evaluations showed tablets with acceptable hardness, friability, uniform drug content, and mechanical strength. A 3² factorial design was employed to optimize the formulation, evaluating the effects of Drug:HP-β-Cyclodextrin ratio (X₁) and Crospovidone concentration (X₂) on in vitro disintegration time (Y₁), wetting time (Y₂), and cumulative drug release (% CDR) at 2 min (Y₃) and cumulative drug release at 12 min (Y₄). Among the formulations, batch VF8 demonstrated superior performance with 99.33 ± 1.46% drug content, rapid dissolution (99.75% in 12 min), minimum wetting time (11.10 ± 0.30 sec), and disintegration time (15.18 ± 0.52 sec). Design Expert software and ANOVA analysis confirmed that independent variables were within acceptable limits, and overlay contour plots validated VF8 as the optimized batch. Stability studies revealed no significant changes in tablet properties or drug release after one month under accelerated conditions 40 ± 2 °C/75 ± 5 % RH. The study concludes that sublingual tablets of Vonoprazan fumarate can be successfully formulated using superdisintegrants and inclusion complexation via direct compression, achieving rapid drug release and potentially enhanced bioavailability.

Transdermal drug delivery is an attractive approach for both local and systemic therapeutics of various diseases. Transdermal drug delivery systems show various advantages like reduction of local irritation, prevention of first-pass hepatic metabolism, and bioavailability enhancement of bioactive molecules over conventional drug delivery systems. The main objective of the present research work was to develop and characterize (in-vitro and ex-vivo) econazole nitrate loaded transethosomes and their comparison with marketed cream of econazole nitrate [Ecoderm, Brown and Burk Pharmaceutical (Pvt.) Ltd., Bengaluru, India] for effective transdermal delivery. Transethosomes loaded with econazole nitrate were developed by homogenization method and evaluated for entrapment (%), vesicular size, zeta potential, polydispersity index (PDI), and invitro drug release. Furthermore, optimized econazole nitrate loaded transethosomes were added to Carbopol 934 gel and this gel was evaluated for viscosity, pH, drug content, ex-vivo skin permeation and retention studies followed by in-vitro antifungal activity against C. albicans fungus. The optimized transethosomes loaded with econazole nitrate showed vesicle size of 159.3 ± 4.3 nm, entrapment efficiency about 78.3 ± 2.8%, acceptable colloidal properties like (zeta potential = -27.13 ± 0.33 mV, PDI = 0.244 ± 0.045), approximately 57.56 ± 2.33% drug release up to 24 h. Results of DSC analysis confirmed the encapsulation of econazole nitrate inside transethosomes. Optimized transethosomes showed drug release following zero order through diffusion mechanism. Transethosomal gel showed high drug content (92.35 ± 0.63%) and acceptable values of pH (5.68 ± 0.86) or viscosity (10390 ± 111 cPs). Transethosomal gel showed less ex-vivo skin penetration (17.53 ± 1.20%), high ex-vivo skin retention (38.75 ± 2.88%), and high in-vitro antifungal activity compared to the marketed cream of econazole nitrate. Therefore, it can be concluded that econazole nitrate loaded transethosomes are effective to deliver econazole nitrate transdermally in a controlled fashion for effective elimination of cutaneous candidiasis.

ObjectiveThe aim of this study was to formulate and evaluate the oral fast-dissolving film of lisinopril for the effective management of hypertension and cardiac diseases.Materials and methodsFast-dissolving films were prepared by the solvent-casting method using a combination of different polymers, HPMC E5 LV, HPMC E 3 and HPMC 4KM, along with PEG as a plasticizer. The Fourier-transform infrared study for the drug-polymer interaction was carried out. Evaluation of physical parameters such as physical appearance, surface texture, uniformity of weight, uniformity of strip thickness, surface pH, folding endurance, uniformity of drug content and percentage of moisture absorption were performed. Kinetic data analysis for the release study and the stability study were also performed.Result and conclusionResults of uniformity of weight, thickness, folding endurance, surface pH, tensile strength, percentage drug content, swelling index, tensile strength and percentage elongation of all the films were found to be satisfactory with respect to variation of these parameters between films of same formulation. The Fourier-transform infrared study indicated that there was no interaction between the drug and the polymers. The in-vitro drug release study showed that a better rate of drug release was achieved by formulations FA3, FB1, FB4 FC8 and FD10 compared with other formulations. The stability study did not show any significant difference in the external appearance, the drug content and the in-vitro drug release. The ex-vivo study indicated that the drug has a better ability to cross the sublingual barrier at a faster rate, and hence the delivery system was found to be promising as it has the potential of overcoming the drawbacks associated with tablet formulations available in the market presently.

The aim of this study was to formulate and evaluate the oral fast-dissolving film of Vitamin B6 for the effective management of motion sickness and vomiting during pregnancy. Fast-dissolving films were prepared by the solvent-casting method using different polymers, HPMC-15 and Pullulan, along with Propylene glycol as a plasticizer. The Fourier-transform infrared study for the drug-polymer interaction was carried out. Evaluation of physical parameters such as physical appearance, surface texture, uniformity of weight, uniformity of strip thickness, surface pH, folding endurance, uniformity of drug content and percentage of moisture absorption were performed. Kinetic data analysis for the release study and the stability study were also performed. Results of uniformity of weight, thickness, folding endurance, surface pH, percentage drug content, tensile strength and percentage elongation of all the films were found to be satisfactory. The Fourier-transform infrared study indicated that there was no interaction between the drug and the polymers. The in-vitro drug release study showed that a better rate of drug release was achieved by formulations F4 and F8 compared with other formulations. The stability study did not show any significant difference in the external appearance, the drug content and the in-vitro drug release. In conclusion present study suggested that fast dissolving films has a better ability to cross the sublingual barrier at a faster rate, and hence the delivery system was found to be promising as it has the potential of overcoming the drawbacks associated with tablet formulations available in the market presently.
 Keywords: Fast-dissolving film, Vitamin B6, HPMC-15, Pullulan gum, Mango peel pectin, Crospovidone, solvent casting

This study focused on the development and evaluation of etoricoxib-loaded transdermal patches for sustained drug delivery to enhance bioavailability and patient compliance. The patches were formulated using polymeric matrices to achieve controlled drug release and improved skin permeability. Various physicochemical characterizations, including surface morphology, thickness, weight uniformity, folding endurance, tensile strength, and moisture content, were conducted to ensure uniformity and mechanical stability. In vitro drug release studies demonstrated a sustained release profile over 24 hours, preventing burst release while maintaining therapeutic drug levels. Ex vivo permeation studies using Wistar rat skin confirmed efficient drug penetration, enhanced by penetration enhancers. A six-month accelerated stability study (40°C ± 2°C, 75% ± 5% RH) showed no significant changes in drug content or release profile. The optimized formulation (F6) exhibited superior mechanical properties, enhanced skin permeation, and controlled drug release, making it a promising alternative to oral etoricoxib for long-term pain management and anti-inflammatory therapy.

Aim: This study aimed to develop and evaluate a novel emulgel formulation of ketoconazole to overcome its poor solubility and limited skin permeability, thereby enhancing its topical delivery and antifungal efficacy. Methodology: Ketoconazole was incorporated into an oil-in-water emulsion, which was then combined with a suitable gelling agent to form the emulgel. Various oils, emulsifiers, and gelling agents were optimized to achieve better drug release and skin permeation. The formulations were evaluated for physical appearance, pH, spreadability, viscosity, and drug content uniformity. In vitro skin permeation studies were conducted using excised rat skin to compare the permeation profile of the emulgel with a conventional ketoconazole cream. Ex vivo antifungal efficacy was assessed against Candida albicans to determine the therapeutic potential of the emulgel. Results: The optimized ketoconazole emulgel exhibited ideal physicochemical properties, including an appropriate pH, superior spreadability, and viscosity suitable for topical application. In vitro permeation studies revealed a 3-fold increase in skin penetration compared to the conventional cream. Ex vivo antifungal studies demonstrated enhanced antifungal activity, with the emulgel showing significantly higher efficacy against Candida albicans than the conventional cream. Conclusion: The development of a ketoconazole emulgel offers a promising strategy for improved topical delivery and antifungal efficacy. By enhancing skin penetration and providing sustained drug release, this emulgel system addresses the limitations of traditional formulations. Further clinical studies are recommended to explore its potential for treating superficial fungal infections.