Formulation And In Vitro Evaluation Of Fluconazole Niosomal Gel For Topical Drug Delivery

In recent years, treatment of infectious disease through Novel Drug delivery system (NDDS) has undergone a revolutionary shift. Niosomes are a Novel Drug Delivery system which has potential application to treat infectious disease topically. Niosomes are non-ionic surfactant vesicles, in which medication is encapsulated in a vesicle for controlled drug release. Ketoconazole niosomes were prepared by using Cholesterol, Span 60/ Span 40 as surfactants, chloroform, and diethyl ether using rotary vacuum evaporator method. Formulation was then evaluated for particle size, drug content, entrapment efficiency, and in-vitro drug release studies. The Entrapment efficiency and drug content were calculated at 225nm using UV spectrophotometer. The drug content was found to be 70.37% for Span 40 and 72.81% for Span 60.The percentage of drug entrapment in niosomes was 60.3 % for Span 40 and 62.21 % for Span 60. FT-IR studies for niosomes containing Span 40 shows -CH stretching (Aliphatic) at 2891 cm-1and2925 cm-1 for niosomes containing Span 60. Ketoconazole niosomal gel was prepared using Carbopol 940, glycerol, Triethanolamine and distilled water. Evaluation of niosomal gel was determined by Physical appearance, pH, viscosity, drug content, entrapment efficiency and In-vitro diffusion studies.The percentage of the drug release from the niosomal gel was found to be 40.78 % for Span 40 and 33.75% for Span 60 . This delivery system is cost effective and simple to prepare as only the prepared gel of niosomes was introduced in Rotary vacuum evaporator for solvent evaporation.

The present study aimed to investigate the delivery potential of Etodolac (ETD) containing topical niosomal gel. Niosomal formulations were prepared by thin film hydration method at various ratios of cholesterol and Span 60 and were evaluated with respect to particle size, shape, entrapment efficiency, and in vitro characteristics. Dicetyl phosphate (DCP) was also added in the niosomal formulation. Mean particle size of niosomal formulation was found to be in the range of 2 μm to 4 μm. Niosomal formulation N2 (1 : 1) ratio of cholesterol and surfactant displayed good entrapment efficiency (96.72%). TEM analyses showed that niosomal formulation was spherical in shape. Niosomal formulation (N2) displayed high percentage of drug release after 24 h (94.91) at (1 : 1) ratio of cholesterol : surfactant. Further selected niosomal formulation was used to formulate topical gel and was characterized with respect to its various parameters such as pH, viscosity, spreadability, ex vivo study, and in vivo potential permeation. Ex vivo study showed that niosomal gel possessed better skin permeation study than the plain topical gel. Further in vivo study revealed good inhibition of inflammation in case of topical niosomal gel than plain gel and niosomal formulation. The present study suggested that topical niosomal gel formulations provide sustained and prolonged delivery of drug.

ABSTRACTObjectives: Skin drug retention is required in local treatment of skin cancer. This study investigated the interplay effects of ethosomes and microwave in transdermal drug delivery. Skin pre-treatment by microwave and applied with liquified medicine is deemed to ‘cement’ the skin thereby raising skin drug deposition.Methods: 5-fluorouracil-loaded ethosomes were prepared and subjected to size, zeta potential, morphology, drug content, drug release and skin permeation tests. The molecular characteristics of untreated, microwave and/or ethosome-treated skins were examined by Fourier transform infrared and raman spectroscopy, thermal and electron microscopy techniques.Results: The skin drug retention was promoted using larger ethosomes with negative zeta potentials that repelled anionic lipids of skin and hindered vesicle permeation into deep layers. These ethosomes had low ethanol content. They were less able to fluidize the lipid and defluidize the protein domains at epidermis to enlarge aqueous pores for drug permeation. Pre-treatment of skin by 2450 MHz microwave for 2.5 min further increased skin drug penetration and retention of low ethanol ethosomes and provided lower drug permeation than cases treated for 1.15 min and 5 min. A 2.5 min treatment might be accompanied by specific dermal protein fluidization via C=O moiety which translated to macromolecular swelling, narrowing of intercellular spaces at lower skin layers, increased drug retention and reduced drug permeation.Conclusion: Ethosomes and microwave synergized to promote skin drug retention.

Abstract: Background/Aim: Inflammation typically occurs when infectious microorganisms enter the body, settle in specific tissues, and/or circulate in the blood. Asparagus racemosus extract contains various saponins and flavonoids and plant-origin drugs have fewer side effects and toxicity. The phytoconstituents have less permeability through the skin; to enhance their permeability and effectiveness it was loaded in niosomes. Therefore, the study aimed to formulate and characterize the niosomal gel loaded with Asparagus racemosus extract for anti-inflammatory activity. Materials and Methods: The niosomes containing saponins in the extract were prepared using thin film hydration method and 23 full factorial design was employed to assess the influence of independent variables span 60 and cholesterol on vesicle size, PDI, zeta potential, and percentage entrapment efficiency. 10% of niosomal and conventional gels were prepared by incorporating optimized niosomes and extract containing total saponin in 1% carbopol gel. Ex vivo permeability studies of prepared gels were performed through goat skin using Franz diffusion cell. An anti-inflammatory study was conducted on albino rat. Results: The statistical analysis revealed the significant effect of independent variables on vesicle size, PDI, entrapment efficiency and zeta potential. SEM image shows vesicles are spherical in shape and uniform in size. The niosomal gel provided a significantly higher amount of steady-state flux and permeability coefficient into the skin than conventional gel. The animal model proved that niosomal gel loaded with total saponins in extract showed significant anti-inflammatory compared to the control. Conclusion: It was concluded that the niosomal gel had better efficacy than the conventional gel. Keywords: Asparagus racemosus, Niosomes, Span 60, Cholesterol, Factorial design, Carbopol 934.

Delivery of drug through topical route, delivers most convenient and novel approach. The Skin can offer several advantages as a route of drug administration although its barrier nature makes it difficult for most drugs to penetrate in to and permeate through it. During the past decades there has been a lot of interest in lipid vesicles as a tool to improve topical drug delivery. Vesicular system such as liposomes, niosomes, ethosomes and elastic deformable vesicles provide an alternative for improved skin drug delivery. In fact vesicles can act as drug carriers controlling drug release. The Research findings were intended to develop sustained release of aceclofenac niosomes formulations in order to reduce gastrointestinal disturbances and to provide better effect when applied topically. Niosomes of aceclofenac was prepared by modified ether injection method using different ratio of surfactants (Tween 20, 40, 60 & 80) with cholesterol and drug. The developed formulations were optimized based on the high entrapment efficiency and in-vitro release studies. Optimized batch was selected and made in to topical niosomal gel using gelling agents like carbopol and sodium carboxy methyl cellulose. Formulation were evaluated for various parameters like vesicle shape, vesicle size, entrapment efficiency, drug content, compatibility studies, in-vitro release studies and stability studies. Ether injection method was found to be most satisfactory in terms of niosome particle size, drug entrapment efficiency was found to be 88.68 ±0.64 % and in-vitro release studies showed 40% of sustain drug release at the end of 8 hrs of study when compared with marketed formulation. Hence, the formulated niosomal topical gel was found to be a better alternative when compared to the marketed formulation in terms of better efficacy, bioavailability and permeation.

In the past few decades, considerable attention has been focused on the development of new drug delivery system (NDDS). The NDDS should ideally fulfill two prerequisites. Firstly, it should deliver the drug at a rate directed by the needs of the body, over the period of treatment. Secondly, it should channel the active entity to the site of action. Conventional dosage forms including prolonged release dosage forms are unable to meet none of these. At present, no available drug delivery system behaves ideally, but sincere attempts have been made to achieve them through various novel approaches in drug delivery. The aim of present work is to develop a niosomal drug delivery system of aceclofenac. To perform drug-polymer compatibility FT-IR studies were carried out and observed that there was no interaction between the APl and excipients. 8 niosomal formulations are prepared by the thin film hydration method using the cholesterol as the phospholipid. Prepared niosomal formulations were characterized by vesicle size, shape, surface charge, entrapment efficiency, drug content and invitro drug release studies. The vesicle size, size distribution and zeta potential of the optimized formulation (F5) was found to be 65.6 nm and zeta potential was found to be -1.5mV. Size distribution curve confirms the normal size distribution of the vesicles. The % entrapment efficiency of niosomal vesicles formulations were found to be in the range of 54.18±0.59 to 92.71±0.56 and optimized formulation was found to be 92.71±0.56 and drug content of niosomes formulations (F1to F8) were determined to be in the range of 94.6 -97.8%. The pH of all topical niosomal gels were found to be in the range of 7.4±0.02 to 7.4±0.08.The best fit with higher correlation (r2> 0.99) was found with the Zero Order Release and follows Korsemeyer peppas equation for all the formulations, which means that release of Aceclofenac from the lipid bilayer vesicles were due to diffusion. The stability studies were carried out and there was no significant change found in the formulations.

Introduction: Dutasteride, a synthetic 4-azasteroid belonging to the class of 5-α-reductase, a BCS class II drug, is used in treating Androgenetic Alopecia and Benign Prostatic Hyperplasia. Aims: The study aims to formulate, evaluate and perform stability studies of Dutasteride-loaded topical niosomal gel. Methodology: Formulation components such as, surfactants and cholesterol were tested for any drug/excipient interactions. Ether injection method was employed to prepare Niosomes. Five formulations were prepared and then assessed for their particle size, SEM, zeta potential, PDI, entrapment efficiency, drug content and in vitro diffusion studies. The optimized formulation F3 Consisted of Dutasteride, span 40 and cholesterol in the ratio 1:4:2. The optimized formulation (F3) was incorporated into a gel. Three gel formulations (FG1, FG2 and FG3) were prepared and were assessed for pH, viscosity, spreadability, drug content and in vitro diffusion studies. The optimized niosomal gel (FG2) consisted of 0.3% Optimized Niosomes and 0.75% Carbopol 934. The drug release kinetics studies were performed for the optimized gel. Finally, stability studies were performed at 30°C ± 2°C / 65% RH ± 5%. Results: The optimized niosomes showed an Entrapment efficiency of 63.2%, zeta potential -22.7 mV, particle size 300.4 nm, drug content 86.23% and 96.23% drug release in 8 hours. The optimized niosomal gel (FG2) consisted of 0.3% Optimized Niosomes and 0.75% Carbopol 934. The gel showed pH 4.7, viscosity 66213 cps, spreadability 15.7g.cm/sec, drug content 91.4% and percent drug release 91.45% in 24 hours. The drug release kinetics studies showed that the optimized gel formulation (FG2) followed Higuchi model with R2 value of 0.9975. The stability studies indicated that the optimized niosomal gel was stable for 90 days. Conclusion: The stability studies confirmed the drug content and the physical nature of the gel for 90 days. Thus, the formulation can be regarded as stable and effective for drugs meant for topical application. Dutasteride gel formulations have the potential to enhance drug bioavailability by facilitating greater penetration of drugs with restricted permeability.

Objective: The purpose of the present study was to develop a novel elastic bilayer vesicle entrapped with Flurbiprofen (FLB) for transdermal use to avoid adverse effect associated with oral administration of the drug. Encapsulation of drug in vesicle prolongs the existence of the drug in the systemic circulation and thus enhances penetration into the target site and reduces toxicity. Method: Niosomes were prepared using surfactants (span 40 and span 60) and cholesterol in the molar ratio of 1:1, 2:1, 3:1 and 3:2. Vesicles prepared by thin film hydration method were characterized for morphology, vesicle size and zeta potential, thermal analysis and Entrapment Efficiency (EE). Results: Results revealed that the EE and size of niosomes were influenced by surfactant type and cholesterol ratio. F8 (span 60: cholesterol in 3:2) exhibited the highest encapsulation of FLB (76.77 ± 0.55) with vesicle size of 154 ± 2.96 nm and Polydispersity Index (PDI) of 0.09. The optimized formulation F8 was selected for incorporation into the gel. Niosomal gel was evaluated for homogeneity, pH, spreadability and in-vitro drug release. Conclusion: All the parameters of niosomal gel were found to be satisfactory and in-vitro release study revealed prolonged and complete release of entrapped FLB (93.23±0.65%) in comparison to FLB hydrogel (42.65±0.29%). The results suggested that niosomes may serve as promising vehicles for the transdermal delivery of FLB.

Background: Berberine is an isoquinoline alkaloid with potent anti-inflammatory effects. However, its therapeutic efficacy is often restricted by its poor solubility, absorption, and permeability, especially in topical applications. Transferosomes are elastic vesicular carriers with high skin permeability values and retention, making them suitable for encapsulating hydrophilic and lipophilic actives. Objective: The objective of this research was to develop a transferosome-based topical gel formulation of Berberine hydrochloride (BER) to improve its skin permeability and anti-inflammatory efficacy. Methods: The thin film hydration method was used to formulate the BER transferosomes. The effects of independent variables, amount of BER in lipid phase (X1), and lipid (Phospholipon 90G) to surfactant ratio (X2) on BER entrapment and vesicle size were studied using face-centered central composite design. The characterization was performed using differential scanning calorimetry, transmission electron microscopy, and X-ray diffraction. The optimized batch (F5) was incorporated in Carbopol gel and further investigated for viscosity, in vitro and ex-vivo diffusion, skin retention by tape stripping, and in-vivo anti-inflammatory efficiency. Results: The formulation optimized with 50 mg of drug and a 5:1 lipid-to-surfactant ratio (F5) demonstrated higher drug entrapment efficiency (72.11%) and lower vesicle size (77.9 nm). TEM validated the spherical vesicle morphology, whereas DSC and XRD analysis confirmed the molecular entrapment of BER within the phospholipid vesicles. The transferosomal gel demonstrated improved BER diffusion (0.63 mg/cm2) confirmed by in vitro and ex-vivo diffusion experiments that revealed a 6-fold increase in flux and permeability coefficient (0.1053 mg. cm-2.h-1). The drug release from transferosome gel was non-Fickian in nature (n = 0.6575), indicating an integration of diffusion and erosion processes. Furthermore, BER transferosomal gel displayed substantial anti- inflammatory activity in rats (p < 0.001). Conclusion: The findings demonstrated the potential of transferosomal gel as a promising approach for efficient drug delivery and therapeutic efficacy.

The present study was aimed to investigate the delivery potential of vancomycin containing topical niosomal gel. Niosomal formulations were prepared by thin film hydration method at various ratios of Soya PC: Span 80 and were evaluated with respect to particle size, shape, entrapment efficiency, and in vitro characteristics. Average vesicle size of optimized formulation F9 was 158.85 nm. The Zeta potential was found 38.25%. Entrapment efficiency of optimized Niosome formulation (F9) was found as 78.85%. Further, niosomes were incorporated into gel base and characterized for viscosity, % entrapment, extrudability, spreadability and drug release study. It was found that viscosity of prepared gel was 3310±25 cps, % assay was 98.95±0.2 %, extrudability was 175±4 g and spreadibility (g/cm/sec) was found that 8.56±0.25 (g/cm/sec) respectively. In vitro drug release from niosome gel was carried out using franz diffusion cell method. The percentage drug release of optimized formulation was found to be 96.65±0.14 after 12 hrs.

The purpose of this study was to load diacerein (DCR) in niosomes by applying response surface methodology and incorporate these niosomes in gel base for topical delivery. Box–Behnken design was used to investigate the effect of charge-inducing agent (X1), surfactant HLB (X2) and sonication time (X3) on the vesicle size (Y1), entrapment efficiency (Y2) and cumulative drug released (Y3). DCR niosomal formulations were prepared by thin film hydration method. The optimized formula was incorporated in different gel bases. DCR niosomal gels were evaluated for homogeneity, rheological behavior; in vitro release and pharmacodynamic activity by carrageenan-induced hind paw edema method in the rat compared with DCR commercial gel. The results revealed that the mean vesicle sizes of the prepared niosomes ranged from 7.33 to 23.72 µm and the entrapment efficiency ranged from 9.52% to 58.43% with controlled release pattern over 8 h. DCR niosomal gels exhibited pseudoplastic flow with thixotropic behavior. The pharmacodynamic activity of DCR niosomal gel in 3% HPMC showed significant, 37.66%, maximum inhibition of edema size in comparison with 20.83% for the commercial gel (p < 0.05). These results recommended the incorporation of DCR niosomes in 3% HPMC for topical application as a potent anti-inflammatory drug for the treatment of osteoarthritis.

Rutin is a natural flavonoid that has many effects on human health and beauty. However, rutin has low solubility and bioavailability. Niosomes are drug delivery system that enhance drug permeation of drug through the skin. Aloe is widly used in cosmetic preparations due to its anti-aging, moisturizing and essential skin nutrients. Therefore, the aim of study is preparation of nano niosomes, loaded with rutin and aloe gel extraction (rutin-aloe niosomes) by thin film hydration method. Rutin niosomes was reduced size by ultrasonic method. The size and distribution of vesicles were determined by dynamic light scattering method. Drug content in niosomal suspension was determined by UV-Vis absorption spectroscopy. The results showed that rutin-aloe niosomes were prepared by thin-film hydration method using Span 60, cholesterol and rutin in molar ratio of 7:3:4 using aloe gel extract as hydration solvent. Mixture of methanol-chloroform (volume ratio 1:1) was used as solvent for solution of membrane companents for evaporation. The manufactured rutin-aloe niosomes had size of about 160 nm, the entrapment efficiency was 95,57% and drug loading was 32,06%.&#x0D; Keywords&#x0D; Rutin, aloe, niosomes, nano, entrapment efficiency, drug loading.&#x0D; References&#x0D; [1] A. Ganeshpurkar, A.K. Saluja, The Pharmacological Potential of Rutin, Saudi pharmaceutical journal 2 (2017) 149-164. https://doi.org/10.1016/j.jsps.2016.04.025.[2] N.B. Mahale, P.D. Thakkar, Niosomes: novel sustained release nonionic stable vesicular systems—an overview, Advances in colloid and interface science 183 (2012) 46-54. https://doi.org/10.1016/j.cis.2012.08.002[3] V.B. Junyaprasert, P. Singhsa, Physicochemical properties and skin permeation of Span 60/Tween 60 niosomes of ellagic acid, International journal of pharmaceutics 2 (2012) 303-311. https://doi.org/10.1016/j.ijpharm.2011.11.032.[4] A. Manosroi, P. Jantrawut et al, In vitro and in vivo skin anti-aging evaluation of gel containing niosomes loaded with a semi-purified fraction containing gallic acid from Terminalia chebula galls, Pharmaceutical biology 11 (2011) 1190-1203.https://doi.org/10.3109/13880209.2011.576347.[5] A. Surjushe, R. Vasani et al, Aloe vera: a short review, Indian journal of dermatology 4 (2008) 163 - 166. https://doi.org/10.4103/0019-5154.44785.[6] M. Takahashi, D. Kitamoto et al, Liposomes encapsulating Aloe vera leaf gel extract significantly enhance proliferation and collagen synthesis in human skin cell lines, Journal of oleo science 12 (2009) 643-650. https://doi.org/ 10.5650/jos.58.643.&#x0D; &#x0D; &#x0D;

Fluconazole-loaded niosomal gels as a topical ocular drug delivery system for corneal fungal infections

Etodolac is used in the treatment of rheumatoid arthritis, osteoarthritis, and other inflammatory diseases. Upon oral administration, it is reported to cause ulcerative colitis, gastrointestinal irritation, edema and peptic ulcer. Hence, an alternative delivery system has been designed in the form of transethosome. The present study describes the preparation, optimization, characterization, and ex vivo study of etodolac-loaded transethosomal gel using the central composite design. Transethosomes (TELs) are elastic vesicles composed of phospholipid, ethanol and edge activator (surfactant). TELs were prepared by thin film hydration method and characterized by Scanning electron microscopy (SEM), entrapment efficiency, vesicle size, Zeta potential and the transethosomal gel was characterized by clarity, pH, viscosity, spread ability, drug content and in vitro drug release. Microscopic examination of transethosomes showed soft, malleable and spherical vesicles with a smooth surface within the range. Vesicle size and % entrapment efficiency of the optimized transethosomal formulation was found to be 268.1nm and 83.75 0.61% respectively. Zeta potential of the optimized transethosomal formulation was found to be -18.0 mv. The ex-vivo study showed spread ability of transethosomal gel 26± 0.03.Drug content was found to be 98.24 0.024%.In Vitro Drug Release Study of optimised formulations for 12 hrs was found to be 97.35± 0.43%.

The transdermal route of drug delivery has received significant attention in pharmaceutical research due to its ability to overcome many challenges associated with oral medication administration, including the ability to bypass first-pass metabolism, ensuring a more predictable and prolonged period of action, as well as minimizing the occurrence of adverse reactions. Transferosomes are a type of ultra-deformable lipid-based vesicles, that have the potential to offer several benefits compared to the traditional lipid-based vesicles such as liposome. The major goal of this research was to prepare (for the first time) dapagliflozin-loaded transferosomes for the purpose of minimizing the potential risk of hyperglycemia associated with oral administration for the treatment of diabetes. The transferosomes were prepared by the thin film hydration method with 5 mg of drug and different proportions of phospholipid and edge activators. The transferosomes were characterized for entrapment efficiency (EE), drug content, pH, vesicle size, PDI, zeta potential,viscosity, in vitro drug release, ex vivo permeation, FTIR and SEM. Tween 80-based transferosomes (F6) at a 95:5% w/w phospholipid:edge activator ratio yielded the highest EE (93±0.77%), drug content (99.7±1.68%), in vitro drug release within 24 hours (99±1.4%), vesicle size (105.8±1.61nm), PDI (0.436±0.01), viscosity (155±1.95 cP), and zeta potential (-35.15mV), which was selected as the optimum formula. The formula had good ex vivo permeation after 24 hours (289.8±5.2 µg/cm2, 91% drug permeated), compatible drug-excipients according to FTIR, and nano-sized spherical shape vesicles according to SEM. Three months of stability testing according to the ICH guidelines revealed that the formula was stable at 4±2C° and 25±2C°. As a conclusion, this research suggested that transferosomes can be prepared as a transdermal drug delivery system with suitable properties to be given once daily as transdermal patch for the antidiabetic drug dapagliflozin.