Luliconazole-Loaded Niosomal Gel Formulation Strategies And Optimization And Evaluation Parameter

Celecoxib, a selective COX-2 inhibitor is commonly used in the treatment of arthritis. Recently, cardiotoxic effects associated with conventional modes of delivery of celecoxib have made it pertinent to develop alternate dosage forms capable of selectively delivering the drug topically to affected joints. The aim of the present study was to prepare and characterize niosomal gel formulation for sustained and site-specific delivery of celecoxib. Celecoxib loaded niosomes were prepared and characterized in vitro, ex-vivo and in vivo. The results of organ localization (deep skin layer + muscle) study showed that niosomal gel provided 6.5 times higher drug deposition as compared to carbopol gel (195.2+/-8.7 and 30.0+/-1.5 microg, respectively). The muscle to plasma concentration ratio for niosomal gel formulation was six (2.16+/-0.12 microg/g vs. 0.34+/-0.01 microg/ml) and for carbopol gel it was one (0.36+/-0.01 microg/g vs. 0.43+/-0.02 microg/ml). Biological effectiveness of optimized formulation was evaluated using carrageenan induced rat paw edema model. The application of niosomal gel produced significant reduction of rat paw edema as compared to that after application of conventional gel indicating better skin permeation and deposition of celecoxib from niosomes. The results of the present study demonstrated niosomal gel formulation possess great potential for enhanced skin accumulation, prolonging drug release and improving the site specificity of celecoxib.

Poor aqueous solubility besides extensive hepatic first effect significantly decreases the oral absorption of levosulpiride, which in turn minimizes its therapeutic effectiveness. Niosomes have been extensively investigated as a transdermal vesicular nanocarrier to increase the delivery of low permeable compounds into and across the skin. This research work was to design, develop and optimize levosulpiride-loaded niosomal gel and to evaluate its prospects for transdermal delivery. The Box-Behnken design was used to optimize niosomes by analyzing the impact of three factors (cholesterol; X1, Span 40; X2, and sonication time; X3) on the responses (particle size, Y1, and entrapment efficiency, Y2). Optimized formulation (NC) was incorporated into gel and evaluated for pharmaceutical properties, drug release study, ex vivo permeation, and in vivo absorption. The design experiment data suggest that all three independent variables influence both response variables significantly (p < 0.01). Pharmaceutical characteristics of NC vesicles showed the absence of drug excipient interaction, nanosize (~102.2 nm), narrow distribution (~0.218), adequate zeta potential (−49.9 mV), and spherical shape, which are suitable for transdermal therapy. The levosulpiride release rates varied significantly (p < 0.01) between niosomal gel formulation and control. Greater flux (p < 0.01) was observed with levosulpiride-loaded niosomal gel than with control gel formulation. Indeed, the drug plasma profile of niosomal gel was significantly higher (p < 0.005), with ~3 folds higher Cmax and greater bioavailability (~500% higher; p < 0.0001) than its counterpart. Overall, these findings imply that the use of an optimized niosomal gel formulation can increase the therapeutic efficacy of levosulpiride and may represent a promising alternative to conventional therapy.

The present study was focused on investigating niosomal gels loaded with cholinergic drug; pilocarpine HCl, for prolonged precorneal residence time and improved bioavailability for glaucoma treatment. Pilocarpine HCl niosomes were prepared using various nonionic surfactants (span 20, span 60 and span 80), in the presence of cholesterol in different molar ratios by ether injection method. The selected formulations were incorporated into carbopol 934 and locust bean gum-based gels. TEM analysis confirmed that niosomes formed were spherical in shape and has a definite internal aqueous space with uniform particle size. Formulation F4 composed of span 60 and cholesterol (1:1) gave the highest entrapment (93.26 ± 1.75%) and slower release results after 8 hours (Q8h = 60.35 ± 1.87%) among other formulations. The in-vitro drug permeation studies showed that there was a prolonged release of drug from niosomal gels as compared to niosomes itself. Considering the in-vitro drug release, niosomal gel formulation G2 was the best among the studied formulations. The release data were fitted to an empirical equation, which indicated that the release follows non-Fickian diffusion mechanism. The stability study revealed that incorporation of niosomes in gel increased their stability than the niosome itself. No signs of redness, inflammation, swelling or increased tear production were observed over the study period for tested formulation by Draize’s test. The intraocular pressure (IOP) lowering activity of G2 formulation showed relative bioavailability 2.64 times more than bioavailability of marketed Pilopine HS® gel. These results suggest that the niosomal gels containing pilocarpine HCl are promising ocular carriers for glaucoma treatment.

Transdermal drug delivery has gained significant attention as a non-invasive and convenient method for administering drugs. However, the stratum corneum, the outermost layer of the skin, poses a significant barrier to drug permeation. To overcome this challenge, vesicular carriers have emerged as promising systems for enhancing drug delivery through the skin. This review highlights recent advances in the development of vesicular carriers for transdermal drug delivery. Liposomes, niosomes, transfersomes, ethosomes, and solid lipid nanoparticles are among the commonly used vesicular carriers. These carriers offer advantages such as improved drug solubility, prolonged drug release, and enhanced drug stability. Additionally, they can encapsulate a wide range of drugs, including hydrophilic and lipophilic compounds. Various strategies have been employed to optimize vesicular carriers for transdermal drug delivery. These include modifying the vesicle composition, size, and surface charge to enhance skin penetration. The incorporation of penetration enhancers, such as surfactants, has also been explored to improve drug permeation across the skin. Furthermore, advancements in nanotechnology have led to the development of novel vesicular carriers, such as nanostructured lipid carriers and elastic liposomes. These carriers offer improved drug loading capacity, sustained release profiles, and enhanced skin penetration. Moreover, the use of vesicular carriers has shown promise in delivering a wide range of therapeutic agents, including small molecules, peptides, proteins, and genetic material. The ability to encapsulate and deliver these diverse drug entities opens new possibilities for transdermal drug delivery in various therapeutic areas.

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.

The present study was aimed on developing and characterizing niosomal gels loaded with adrenergic agonist; dipivefrin HCl for prolonging precorneal residence time and improving bioavailability of drug for glaucoma treatment. Dipivefrin HCl niosomes were prepared using various non-ionic surfactants (span 20, span 60 and span 80) in the presence of cholesterol in different molar ratios by ether injection method. The selected formulations were incorporated into carbopol 934 and locust bean gumbased gels. TEM studies confirmed that niosomes formed were white and spherical in shape and has a definite internal aqueous space with uniform particle size. Formulation F4 composed of span 60 and cholesterol (1:1) gave the highest entrapment (92.16±0.25%) and slower release results after 8 hours (Q8h=61.05±2.87%) among other formulations. The in-vitro drug permeation studies showed that there was a slow and prolonged release of drug from niosomal gel formulations as compared to niosomes itself. Considering the in-vitro release, niosomal gel formulation G2 were the best among the studied formulations. Gel formulation G2 showed higher spreadability (2.21±1.05 g.cm/s), higher bioadhesive strength (2314±1.29 dynes/cm2) but slower drug release (Q8h=52.13±1.81%) due to high gelling capacity. No sign of redness, inflammation, swelling or increased tear production was observed by Draize test. The IOP lowering activity of selected formulation was detected and compared with marketed Pilopine HS® gel. G2 formulation showed relative bioavailability 2.64 times more than bioavailability of marketed Pilopine HS® gel. These results suggest that the niosomal gels containing dipivefrin HCl are promising carriers for glaucoma treatment.

The objective of the present study was to develop niosomal gels loaded with Timolol Maleate (TM), Non-selective beta-adrenergic receptor antagonist, for prolonged duration and improved bioavailability for glaucoma treatment. TM niosomes were prepared by film hydration method with various mixtures of different non-ionic surfactants including Span 20, 40, 60 and Tween 20, 40, along with cholesterol. The prepared vesicles were evaluated for entrapment efficiency, in vitro drug release, particle size, zeta potential and morphology by optical and transmission electron microscopy (TEM). The selected formulations were incorporated into Sodium carboxymethyl cellulose (CMC Na) and Carbopol 934 gels. Gel formulations were characterized for in vitro drug permeation and ex vivo drug permeation through bovine cornea. In addition, stability study, isotonicity test and in-vivo evaluation of the selected formulations were done. The results showed that, the niosomes formed were white and spherical in shape with uniform particle size. Formulations containing span 60 and that containing mixture of span 60 and tween 40 gave the highest entrapment efficiency (94.6% and 98.8%, respectively) and a sustained release of timolol maleate from the niosomes within 24 h (96% and 97.10%, respectively). The in vitro and ex vivo drug release studies showed that there was a slow and prolonged release of drug from niosomal gel formulations. Considering the in-vitro release, niosomal gel formulae GN5 and GN6 (containing CMC Na 3% w/w) were the best among the studied formulations. Draize test was carried out and the intra-ocular pressure lowering activity of prepared formulations were detected and compared with marketed Timogel. Formula containing 3% CMC Na showed relative bioavailability 1.6 times more than bioavailability of marketed Timogel.

Objective: The purpose of the present investigation was to develop and optimize nitrendipine loaded niosomal gel for transdermal delivery using quality by design approach.&#x0D; Methods: Niosomal formulations were developed by application of the thin-film hydration method using different ratios of span 60, cholesterol, temperature, and optimized by three factors-three levels Box-Behnken statistical design. The independent variables were non-ionic surfactant, cholesterol, and temperature, while vesicle size, polydispersity index, and entrapment efficiency were dependent variables. The nitrendipine loaded optimized formulation was incorporated into gel and evaluated for in vitro release, ex-vivo skin permeation, confocal laser scanning microscopy, and histopathological studies.&#x0D; Results: The optimized formulation showed the vesicular size of 226.1±4.36 nm, polydispersity index of 0.282±0.012, and entrapment efficiency of 95.34±3.18% with spherical morphology. The optimized niosomal gel formulation showed transdermal flux 127.60 µg/cm2h through albino Wistar rat skin. Niosomal gel was proved significantly superior by confocal laser scanning microscopy for satisfactory permeation and distribution of gel, deep into the rat skin. Furthermore, dermal safety was confirmed by histopathological studies for transdermal application.&#x0D; Conclusion: It was concluded that the developed niosomal gel overcomes the limitation of low penetration through rat skin and could be a potential nano vesicular system for transdermal delivery.

Niosomes are multilamellar vesicles that effectively transfer active ingredients into the skin's layers. To improve the active substance's penetration across the skin, these carriers are frequently utilized as topical drug delivery systems. Essential oils (EOs) have garnered significant interest in the field of research and development owing to their various pharmacological activities, cost-effectiveness, and simple manufacturing techniques. However, these ingredients undergo degradation and oxidation over time, leading to a loss of functionality. Niosome formulations have been developed to deal with these challenges. The main goal of this work was to create a niosomal gel of carvacrol oil (CVC) to improve its penetration into the skin for anti-inflammatory actions and stability. By changing the ratio of drug, cholesterol and surfactant, various formulations of CVC niosomes were formulated using Box Behnken Design (BBD). A thin-film hydration technique using a rotary evaporator was employed for the development of niosomes. Following optimization, the CVC-loaded niosomes had shown: 180.23 nm, 0.265, -31.70 mV, and 90.61% of vesicle size, PDI, zeta potential, and EE%. An in vitro study on drug release discovered the rates of drug release for CVC-Ns and CVC suspension, which were found to be 70.24 ± 1.21 and 32.87 ± 1.03, respectively. The release of CVC from niosomes best fit the Higuchi model, and the Korsmeyer-Peppas model suggests that the release of the drug followed the non-Fickian diffusion. In a dermatokinetic investigation, niosome gel significantly increased CVC transport in the skin layers when compared to CVC-conventional formulation gel (CVC-CFG). Confocal laser scanning microscopy (CLSM) of rat skin exposed to the rhodamine B-loaded niosome formulation showed a deeper penetration of 25.0 µm compared to the hydroalcoholic rhodamine B solution (5.0 µm). Additionally, the CVC-N gel antioxidant activity was higher than that of free CVC. The formulation coded F4 was selected as the optimized formulation and then gelled with carbopol to improve its topical application. Niosomal gel underwent tests for pH determination, spreadability, texture analysis, and CLSM. Our findings imply that the niosomal gel formulations could represent a potential strategy for the topical delivery of CVC in the treatment of inflammatory disease.

Cilostazol, an anti-platelet aggregation medicine, is also known to have vasodilation properties and is commonly used for treating muscle soreness and cramps by increasing the muscle oxygen supply. The medication has limited oral bioavailability, is prone to pre-systemic metabolism, and is poorly soluble in aqueous media. A transdermal administration was planned to increase the drug’s solubility and therapeutic efficacy. The current work intended to develop cilostazol niosome-loaded transdermal gel, which was prepared, and with the use of Fourier transform infrared and differential scanning calorimetry analyses, drug-excipient interactions were observed. The medication was formulated utilizing Carbopol-934, Pluronic-F-127, and HPMC gel bases for the transdermally delivered niosomal gels. The produced niosomes had a maximum percentage of drug entrapment at 96.4%, with a particle size of 102 ± 11.30 nm and polydispersity index of 0.29 ± 0.069. The highest percentage of the medication that was entrapped was 96.4%, and the Carbopol-934 gel basis released the major part of the drug under in vitro conditions. A maximum transdermal flux was recorded at 3850.92 μg after 4 h, indicating a 10% increase in cilostazol permeation through rat skin. The flux rate for the niosomal preparation containing the drug ranged from 14.85 to 28.02 μg/cm 2 h −1 . In comparison to the pure cilostazol-loaded gels, the pharmacokinetics investigation showed that the niosomal gel formulations had considerably greater C max , T max , and AUC 0 . The niosomes loaded with cilostazol exhibited greater solubility, higher bioavailability, and improved effectiveness. Better therapeutic results may be achieved with systemic and site-directed delivery of cilostazol using the designed transdermal niosomal gel with appropriate molecular tagging modification/(s).

Objective: In this study, niosomal hydrogel formulation was investigated as a promising carrier for piroxicam sustained release ocular delivery.Methods: Piroxicam loaded niosomes were prepared by thin film hydration technique using various proportions of span and cholesterol. Optimized formulation was selected depending on the highest percent drug entrapment. Morphology, mean size, encapsulation efficiency (EE) and in vitro drug release from niosomes in phosphate buffer pH 7.4, were evaluated. Drug‐cholesterol interaction was studied by FTIR spectroscopy. Drug retention in niosomes was performed at refrigerated temperature and room temperature for the period of two months. The optimized niosomal formulation was incorporated into 1% carbopol gel and evaluated for the ex vivo transocular drug permeation comparing to a plain drug gel through excised albino rabbit cornea using Franz diffusion cell.Results: Maximum drug EE was obtained with Span 80: cholesterol niosomes of µmolar ratio (300:200). Also they were stable during the storage time. No significant interaction between the drug and cholesterol was detected. The optimized niosomal gel formulation showed prolonged drug release and enhanced drug ocular bioavailability comparing to the plain gel.Conclusion: piroxicam niosomal formulation was prepared successfully and is useful as a sustained release preparation.

Oral administration is the most preferred route for drug delivery due to its convenience, non-invasiveness, and patient compliance. However, it is challenged by gastrointestinal barriers, enzymatic degradation, and first-pass metabolism, which reduce drug bioavailability. Lipid nanoparticles (LNPs), including solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), offer a promising strategy to overcome these limitations by enhancing drug stability, permeability, and absorption. The Quality by Design (QbD) framework provides a systematic approach for LNP development to ensure consistent product quality. By promoting process understanding and control, QbD not only supports scientific formulation development but also enhances industrial scalability by reducing the experimental workload, shortening the development time, and lowering the production costs. This review highlights key QbD elements such as the quality target product profile (QTPP), critical quality attributes (CQAs), critical material attributes (CMAs), critical process parameters (CPPs), and design of experiments (DoE) and their roles in guiding formulation and process optimization. The effects of various CMAs and CPPs on the CQAs such as particle size, polydispersity index, encapsulation efficiency, zeta potential, and drug release are discussed. Furthermore, the in vitro, in vivo, and ex vivo performances of optimized LNPs were explored in detail. Overall, QbD offers a robust platform for the rational design and scalable production of high-quality lipid-based drug delivery systems for oral administration.

Atazanavir (ATV) is widely used as anti-HIV agent having poor aqueous solubility needs to modulate novel drug delivery system to enhance therapeutic efficiency and safety. The main objective of the present work was to fabricate ATV-loaded nanostructured lipid carriers (NLCs) employing quality by design (QbD) approach to address the challenges of bioavailability and their safety after oral administration. Herein, the main objective was to identify the influencing variables for the production of quality products. Considering this objective, quality target product profile (QTPP) was assigned and a systematic risk assessment study was performed to identify the critical material attributes (CMAs) and critical process parameter (CPP) having an influence on critical quality attributes (CQAs). Lipid concentrations, surfactant concentrations, and pressure of high-pressure homogenizer were identified as CMAs and CPP. ATV-NLCs were prepared by emulsification-high pressure homogenization method and further lyophilized to obtain solid-state NLCs. The effect of formulation variables (CMAs and CPP) on responses like particle size (Y1), polydispersity index (Y2), and zeta potential (Y3) was observed by central composite rotatable design (CCRD). The data were statistically evaluated by ANOVA for confirmation of a significant level (p < 0.05). The optimal conditions of NLCs were obtained by generating design space and desirability value. The lyophilized ATV-NLCs were characterized by DSC, powder X-ray diffraction, and FT-IR analysis. The morphology of NLCs was revealed by TEM and FESEM. In vitro study suggested a sustained release pattern of drug (92.37 ± 1.03%) with a mechanism of Korsmeyer-Peppas model (r2 = 0.925, and n = 0.63). In vivo evaluation in Wistar rats showed significantly higher (p < 0.001) plasma drug concentration of ATV-NLCs as compared to ATV-suspension using chylomicron flow block model. The relative bioavailability of ATV-NLCs was obtained to be 2.54 folds. Thus, a safe and promising drug targeting system was successfully developed to improve bioavailability and avoiding first-pass effect ensures to circumvent the acute-toxicity of liver.

The aim of the present study was to formulate and evaluate the nonionic surfactant vesicles of frusemide in order to enhance its skin permeation. The process variables which could affect the preparation and properties of the niosome formulation studied included type of spans, ratio of span and cholesterol, ratio of cholesterol and dicetylphosphate (DCP), concentration of drug, type of solvent, hydration media and time of hydration. The formulated niosomes thus were characterized for various parameters such as surface morphology, size, entrapment efficiency, skin permeation, etc. Stability of the niosomes in terms of drug holding capacity was assessed for a period of 30 days on storage under defined conditions. The maximum entrapment efficiency of 77.73±2.36% was obtained with niosomes formulated from Span 60∶Cholesterol∶DCP (47.5∶47.5∶5) using chloroform:methanol (4∶1) as the solvent system at the hydration time of 1 hr. A direct relationship was observed between the percentage leaching of the drug out of the vesicles and temperature. Higher transdermal flux was obtained with niosomal gel (9.2±0.5 μg/cm2/hour) in comparison to conventional gel (6.4±0.3 μg/cm2/hour).

Niosomes based formulation containing tenoxicam: A newer solution for the rheumatic diseases