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Development and evaluation of antifungal topical niosomal gel formulation
Abstract
Niosome are now widely studied as an alternative delivery system to liposome. An increasing number of non ionic surfactant has been found to form vesicles, capable of entrapping hydrophilic and hydrophobic molecules. In our present study we incorporated Nystatin into niosome by using ether injection method by applying 3 2 factorial design. The niosomes were characterized for size distribution, drug entrapment efficiency, zeta potential and drug release profile. Topical applicability of niosomes was further enhanced by developing niosomal gel formulation using carbomers. Developed niosomal gel was evaluated for pH, spredability, viscosity, drug content, drug release profile and ex vivo deposition study. Microscopic observation and TEM confirmed the uniformity of size and shape and was found to be in the range of 182-219 nm. The entrapment efficiency of the vesicles was determined by ultracentrifugation and was found to be in the range of 62-85%. The release from the niosomal gel was highly prolonged when compared to conventional gel and showed two fold increases in the drug deposition in the skin compared to conventional gel. The stability studies showed that vesicles have greater stability at 4°C followed by 25°C. From the present investigation, it can be concluded that the developed niosomal gel formulation of nystatin has shown great potential in the treatment of fungal infection by providing a prolonged release profile.
... Many factors affect niosome formation such as the method of manufacture, nature of surfactant and drug, temperature at which the lipids are hydrated and the critical packing parameter [2]. Drug deposition, vesicle size and entrapment efficiency are the key parameters involved in formulation of topical niosomes [3]. ...
... Weighed amount of Carbopol 940 (1%) was sprinkled onto the niosomal dispersion containing drug and allowed to hydrate for 1-2 hours. Propylene Glycol (3%) and oleic acid (3%) were added subsequently to the aqueous dispersion with continuous stirring [3]. Methyl paraben (0.1%) was used as preservative. ...
... Millimole of surfactant and cholesterol (X1), time of hydration(X2), hydration temperature (X3) were selected as independent variables and in vitro drug release from formulation was selected as dependent variable. The different levels for the independent variables for the 2 3 factorial design are given in Table 2. Table 3 shows 2 3 factorial design for optimization of developed formulation. ...
... Many factors affect niosomes formation such as the method of manufacture, nature of surfactant and drug, temperature at which the lipids are hydrated and the critical packing parameter [2]. Drug deposition, vesicle size and entrapment efficiency are the key parameters involved in formulation of topical niosomes [3]. ...
... Preparation of carbopol gel: Carbopol 940 (1%) was weighed and sprinkled onto the dispersion containing drug was allowed to hydrate for 1-2 hours. Propylene glycol (3%) and oleic acid (3%) were added subsequently to the aqueous dispersion with continuous stirring [3]. Methyl paraben (0.1%) was used as preservative. ...
... The supernatant was separated, diluted to 100 ml with PBS pH 7.4, filtered using a membrane filter (0.45µm pore size), and measured using a spectrophotometer at 354 nm. EE% was calculated by the following equation [5]. ...
... Figures (3)(4)(5)(6) showed the release profiles of PIR from the investigated niosomes which were occurred in two distinct phases, an initial phase in which rapid drug leakage was observed and stayed for about 8 hours, followed by slow phase stayed for at least 4 hours. The initial phase was due to desorption of drug from the surface of niosomes while the drug release in the slower phase was regulated by diffusion through the swollen niosomal bilayers [10]. ...
Objective: The objective of the present study was to obtain an optimized formula of Piroxicam (PIR) niosomes using central composite design. Method: PIR niosomes were prepared by lipid evaporation method and all vesicles were evaluated for their entrapment efficiency (EE%), and in-vitro drug release. Results: EE% was found to be between 27.24% and 45.27%. The release profiles of PIR niosomes occurred in two distinct phases, an initial phase for about 8 hours, followed by slow phase for at least 4 hours. The in-vitro study suggests that higher EE% was related with slow release. The release pattern shown by these formulations were Higuchi diffusion controlled mechanism. The effects of all the tested independent variables have P-values < 0.05. Conclusion: Central composite design succeeded in optimization of the formulation ingredients on EE% and in vitro release of PIR niosomes. Finally the optimization process provides a formula having optimum level of factors.
... Weight (50 gm) was added to pan. The time required to separate the two slides, i.e. the time in which the upper glass slide moves over the lower plates was taken as measure of Spreadability [16]. Spreadability was calculated by using the formula: ...
... The cotton wool was secured firmly in the place with adhesive plaster. The animal was observed for 7 days for any sign of edema and erythema [16]. ...
A niosome based topical gel of adapalene was developed and characterized for the treatment of mild acne. Adapalene is a third generation topical retinoid primarily used in the treatment of mild-moderate acne. Niosomes containing adapalene were prepared by lipid film hydration technique using nonionic surfactants (span 60) and cholesterol at different concentrations. All the niosomal formulations were evaluated for FTIR studies, entrapment efficiency, optical microscopy, stability studies, invitro drug release study, and zeta
potential analysis. Then the optimized niosomal formulation was used for formulating topical gel consisting of carbopol 934. All the formulations were tested for physical properties, in-vitro drug release and skin irritation
test. The result suggests that in all the prepared niosomal formulations as the surfactant concentration increases the entrapment efficiency increases. Lower the cholesterol concentration higher the entrapment efficiency in span 60 formulations. The size of niosomes was found to be uniform and spherical in shape. The entrapment efficiencies of all formulation were calculated. The IR spectral analysis suggested that there was no interaction between the drug and formulation excipients. The drug content was in the range of 95.04±0.57 to 90.68±0.39. The in- vitro release data was calculated using franz diffusion cell. The percentage
drug release of all the formulations was in the range of 68.3 to 46.1. Korsmeyer peppas model indicated that the drug permeation from the niosomal gel followed diffusion and super case ІІ transport. The skin irritation results showed no specific irritation on the skin of rats. Niosomal gel of adapalene offer a promising avenue to fulfill the need for topical drug delivery system that can localize and maintain drug activity at the site of action for a longer period of time thus allowing a sustained action, minimizing frequency of drug administration with patient compliance.
... Although acquired, nanoemulsions are somewhat like micro-emulsions that are solid dispersion like nanometer scale particulate. At the same time, also mechanical power is unlikely to micro-emulsions that also shape instantaneously through exercise; this technique might be an extremely unpredictable complete drop of water recrystallization, as well as a surfactant, is required fully help foster this exact forming of both the micro emulsifying agent as well as to focus on ensuring it's own vibrational stabilization all through memory [3]. Contain the follow-ing elements combined effect like surfactants other than just a single surfactant is being used to document and remain stable these same microemulsions. ...
A Ertapenem is a broad-spectrum carbapenem with an antibacterial agent. It is chemically known as carbapenem carboxylic acid, in which the azetidine and pyrroline rings. The aim and objective of the review on formulation and analytical method of ertapenem active pharmaceutical ingredient. The market formulation available is tablets, dry powder inhalers, injections, nanoemul-sions loaded with the drug ertapenem, and Nanostructure lipid carrier. UV-Visible spectroscopy methods effectively estimate Ertapenem. The pellets were then scanned over a range of 4000-400 cm-1 in an FTIR spectrometer. FTIR spectrum of Ertapenem showed the presence of the peaks, which complies with the reference spectra. This work summarizes the current knowledge of formulation and analytical methods for determining the concentration of ertapenem in different formulations.
... For comparative purpose to elucidate the effect of storage on the characterization of DULloaded elastosomes, portions of the optimum elastosomal dispersions were stored in tightly-sealed glass vials in refrigerator (5 ± 2 • C) and other portions were kept on the shelf at room temperature (25 ± 2 • C) for 3 months (Desai et al., 2011). After the end of the storage period, both portions were compared to freshly prepared elastosomes and were evaluated for E.E.%, PS, PDI, and ZP. ...
... For comparative purpose to elucidate the effect of storage on the characterization of DULloaded elastosomes, portions of the optimum elastosomal dispersions were stored in tightly-sealed glass vials in refrigerator (5 ± 2 • C) and other portions were kept on the shelf at room temperature (25 ± 2 • C) for 3 months (Desai et al., 2011). After the end of the storage period, both portions were compared to freshly prepared elastosomes and were evaluated for E.E.%, PS, PDI, and ZP. ...
Duloxetine hydrochloride (DUL) is a BCS class-II antidepressant drug, acting via serotonin and norepinephrine reuptake inhibition. Despite high oral absorption, DUL suffers limited bioavailability due to extensive gastric and first-pass metabolism. To improve DUL's bioavailability; DUL-loaded elastosomes were developed, via full factorial design, utilizing various span®60: cholesterol ratios, edge activator types and amounts. Entrapment efficiency (E.E.%), particle size (PS), zeta potential (ZP) and in-vitro released percentages after 0.5 h (Q0.5h) and 8 h (Q8h) were evaluated. Optimum elastosomes (DUL-E1) were assessed for morphology, deformability index, drug crystallinity and stability. DUL pharmacokinetics were evaluated in rats following intranasal and transdermal application of DUL-E1 elastosomal gel. DUL-E1 elastosomes [comprising span®60 and cholesterol (1:1) and brij S2 (edge activator; 5 mg)] were optimum with high E.E.% (81.5 ±3.2%), small PS (432 ±13.2 nm), ZP (30.8 ±3.3 mV), acceptable Q0.5h (15.6 ±0.9%), and high Q8h (79.3 ±3.8%). Intranasal and transdermal DUL-E1 elastosomes revealed significantly higher Cmax (251 ±18.6 and 248 ±15.9 ng/mL) at Tmax (2 and 4 h) and improved relative bioavailability (≈2.8 and 3.1 folds) respectively, in comparison to oral DUL aqueous solution. In-vivo histopathological studies were conducted to ensure the safety of DUL-E1. Elastosomes are promising novel nano-carriers, capable of enhancing the bioavailability of DUL via various routes of administration.
... Sorbitan esters are also widely employed in the development of both lipid and polymeric nystatin's delivery systems [10,125,133,[138][139][140][141][142][143][144]. Other nonionic commercial surfactants successfully employed in nystatin's delivery systems are Procetyl TM AWS (PPG-5-ceteth-20) [145], Solutol Ò HS-15 (polyethylene glycol 12-hydroxystearate) [146], Labrafil Ò M 1944 (polyoxyethylated kernel oil) [124], Labrasol Ò (caprylocaproyl macrogolglyceride) and Plurol Ò oleique (polyglyceryl-3 oleate) [126,127]. ...
Nystatin is an antifungal molecule with a remarkable yet squandered versatility. In this review, its mechanism of action is explored, along with its extensive action spectrum and toxicity. A multitude of methodologies to tackle the drug's physical and chemical hurdles are outlined along with some proven-effective strategies to increase its activity and/or decrease its toxicity. A separate detailed section focused on micro and nanotechnology solutions addresses new drug delivery systems made of polymeric, metallic or lipid materials. Although the topical route depicts greater representativeness amongst these formulations, the intravenous, dental, oral, vaginal and inhalation routes are also mentioned. The unsuccessful previous attempts at developing parenteral formulations of nystatin or even the withdrawal of a nystatin-loaded multilamellar liposome should not divert research away from this drug. In fact, the interest in nystatin ought to be reawakened with the ongoing clinical trials on the promising nystatin-like genetically engineered derivate BSG005.
... The absorbance was measured spectrophotometrically at 207nm after appropriate dilution 14 . ...
Clarithromycin is macrolide antibiotic used as against various susceptible bacteria. In the present study
erythromycin was entrapped into niosomes by ether injection technique with the optimization of various process
parameters. The niosomal formulations were prepared using a polymer Span 80 and Cholesterol in different ratio
(2:1, 2:2, 3:1, 3.5:1, 4:1, 4.5:2). Dicetly phosphate (DCP) was added in the niosomal formulation. The niosomal
formulation was used to formulate topical gel and evaluated for various parameters such as pH, spreadability,
Rheological study and In vitro release in diffusion cells. All the formulations were found to release
clarithromycin in a controlled manner for a prolonged period over 8 hours. It was observed that niosomes
prepared using an span 80 and cholesterol in 4.5:2 ratio exhibited the best release profile and able to sustain the
drug release for 8 hours. The results demonstrate that the entrapment of drug into niosomes leads to prolongation
of drug release, enhanced drug retention into skin and improved permeation across the skin after encapsulation.
... The top plate was then removed and the time (in sec) required by the top plate to separate out from above plate should be noted. A shorter the time interval indicates better spreadability 31 . ...
The research investigated the modification of nano-emulsion by using transesterfied soyabean oil, to enhanced solubility and diffusion of voriconazole. Ternary phase diagrams of soyabean oil, acid / base esters of soyabean oil, Tween 80: PEG 400 (S/CoS) and water were developed. Ester value of soyabean oil increased from 214.04 to 261.5mg KOH/1g for acid ester and 293.58mg KOH/1g for base ester confirmed transesterification. The modified nanoemulsion batches E 4 , E 5 , E A4 , E A5 , E B2 and E B3 showed thermodynamic stability. Nanoemulsion of Soyabean oil (E 3 and E 4), acid ester (E A4 and E A5) , and base ester (E B2 and E B3) were selected for in-vitro drug diffusion studies. The globule size of batch E 4 , E A4 and E B2 nanoemulsion was found to be 185.6, 162.8 and 115.4 nm, respectively. Zeta potential of batch E 4 , E A4 , and E B2 was observed-35,-27 and-9mV respectively. The in vitro release release profiles from the E 4 , E A4 and E B2 batches of nanoemulsion gel were fitted into Peppas kinetic model. Moreover, 'n' value of batch E 4 , E A4 , and E B2 was 0.8844, 0.8284, 0.8475 non-fickian diffusion. The soyabean oil and soyabean acid ester oil nanoemulsion found to be stable and a promising vehicle to enhance the permeation of voriconazole for topical delivery.
... For performing the stability study storage condition was determined based on ICH Guidelines. The selected F9 batch was subjected to stability study [12][13][14][15]. ...
Objective: The present study was aimed to develop of the Guanfacine Hydrochloride Extended-release tablets for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). The dosage regimen of Guanfacine Hydrochloride is 4 mg at every 6 h. The concentration of Guanfacine in plasma is fluctuating. Hence, to control the plasma fluctuation and to avoid toxicity problem, Guanfacine Hydrochloride was chosen as a drug with an aim to develop an extended release system for 20 to 24 h. Methods: The design of the system was based on the use of pH-dependent polymer (Hydroxypropyl Methyl Cellulose), pH-independent polymer (Eudragit L 100-55), along with microenvironment modifiers such as organic acid (Fumaric acid) were used in the formulation. Drug-excipient compatibility was studied by FTIR. Before compression, the granules were evaluated for precompression parameters such as bulk density, tapped density, an angle of repose, compressibility index and Hausner’s ratio. After compression, evaluation tests of tablets such as general appearance, hardness, thickness, weight variation, friability, content uniformity, in vitro release studies and stability studies were performed. Results: Out of 9 formulations, the drug release was found to be within the innovator formulation F9. The stability study of formulation F9 revealed there was no significant change in physical and chemical properties of drug stored at 40 °C/75 % RH, 30 °C/65 % RH, 25 °C/60 % RH for 2 mo. Conclusion: Optimized formulation batch F9 showed highest F2 value which indicates similarity with innovator product. The study indicates that Guanfacine Hydrochloride Extended-release tablet was successfully developed.
... In the other study, the researchers first prepared niosomal nystatin with a size range of 182-219 nm, and then prepared gel formulation using carbomers. The niosomal nystatin resulted in a prolonged drug release profile and a two-fold increase in drug deposition in the skin, compared to the conventional gel [39]. ...
Skin is an important organ of the body due to offering an accessible and convenient site for drug administration. One of the disadvantages of transdermal drug delivery is the low penetration rate of drugs through the skin. Over the past decades, nanoparticles have been used as drug delivery systems to increase therapeutic effects or reduce toxicity. Encapsulation of drugs in nanoparticulate vesicles simplifies the transports of drugs into and across the skin.
Niosome nanoparticles are among these drug delivery systems, which have numerous applications in drug delivery and targeting. Niosomes are frequently used for loading drugs serving different purposes (e.g., anticancer, antiviral, and antibacterial agents). In recent years, there has been much research on the use of niosomal systems for the delivery of fungal drugs. A review of the literature investigating the advantages of niosomes in antifungal drug delivery can elucidate the efficiency and superiority of this nanocarrier over other nanocarriers.
... While increasing (X2) resulted in firstly decreasing vesicle size then increased. The decrease in the size firstly was because of a decrease in cholesterol content relative to a surfactant which contributed to increase the hydrophobicity then further increase in surfactant/lipid ratio led to an increase in vesicle size which was substantiated by the increase in the overall degree of hydrophilicity [27]. Also, increasing lecithin content (X3) led to increase in mean vesicle size because of the long hydrocarbon chain of lecithin molecules (18C) [15]. ...
Objective: The aim of the present study was to obtain an optimized formula of itraconazole (ITC) proniosomes using Box Behnken design.Methods: Itraconazole proniosomes were prepared using span 60 and/or brij 35 as surfactants, cholesterol and lecithin as a penetration enhancer by slurry method. Various trials have been carried out for investigation of proniosomes. Parameters such as entrapment efficiency (EE%), in vitro drug release, zeta potential, vesicle size and Transmission Electron Microscope were assessed for evaluation of proniosomes.Results: Entrapment efficiency (EE%) was found to be between 78.56% and 95.46%. The release profile of itraconazole proniosomes occurred in two distinct phases, an initial phase for about 8 h, followed by a slow phase for 16 h. The release pattern shown by these formulations was Higuchi diffusion controlled mechanism. The zeta potential values for all itraconazole proniosomes were in the range of-21.71 to-34.53 mV which confirms their stability. All itraconazoleproniosomes formula was found to be nano-sized and were appeared to be spherical in shape with sharp boundaries. One way analysis of variance (ANOVA) study showed that HLB (X1) had the main effects on most responses (Y).Conclusion: Box behnken design facilitates optimization of the formulation ingredients on entrapment efficiency, in vitro release of itraconazole proniosomes, zeta potential and vesicle size. Finally, an optimum level of factors was provided by the optimization process.
... The antifungal activity was created by the drug incorporated in the niosome [39].Smallest zone produced by pure ITC may be due to the minimal solubility of the drug in an aqueous media. Antifungal activity of niosomal dispersion was greater compared to proniosmal gel because the drug release from gel formulation was retarded compared to niosomal dispersion [40]. ...
... Nystatin release from niosomal gel was highly prolonged when compared with conventional gel. Further, the niosomal gels showed 2-fold enhancement in nystatin deposition in porcine skin compared with conventional gel (Desai et al., 2011). The in vitro antifungal activity against Candida albicans was higher for the niosomal dispersion compared with the niosomal gel, probably due to the faster nystatin release from the dispersion. ...
Invasive fungal infections are becoming a major health concern in several groups of patients leading to severe morbidity and mortality. Moreover, cutaneous fungal infections are a major cause of visits to outpatient skin clinics. Despite the availability of several effective agents in the antifungal drug arena, their therapeutic outcome is less than optimal due to limitations related to drug physicochemical properties and toxicity. For instance, poor aqueous solubility limits the formulations options and efficacy of several azole antifungal drugs while toxicity limits the benefits of many other drugs. Nanoparticles hold great promise to overcome these limitations due to their ability to enhance drug aqueous solubility, bioavailability and antifungal efficacy. Further, drug incorporation into nanoparticles could greatly reduce its toxicity. Despite these interesting nanoparticle features, there are only few marketed nanoparticle-based antifungal drug formulations. This review discusses different classes of nanoparticles used in antifungal drug delivery, such as lipid-based vesicles, polymeric micelles, solid lipid nanoparticles, nanostructured lipid carriers and dendrimers with emphasis on their advantages and limitations. Translation of these nanoformulations from the lab to the clinic could be facilitated by focusing the research on overcoming problems related to nanoparticle stability, drug loading and high cost of production and standardization.
... The supernatant was separated, diluted to 100 ml with PBS Ph 7.4, filtered using a membrane filter (0.45µm pore size), and measured using a spectrophotometer at 354 nm. EE% was calculated by the following equation 3 . ...
Objective: The objective of the present study was incorporation PIR niosomes in different gel bases to develop (PIR) gel for tansdermal delivery. Method: PIR niosomes were prepared by lipid evaporation method and all vesicles were evaluated for their entrapment efficiency (EE%), and in-vitro drug release. PIR gels were prepared using sodium alginate, methyl cellulose (MC), hydroxyl propyl methyl cellulose (HPMC), carboxy methyl cellulose (CMC), and xanthan gum. The effect of type and concentration of the employed gel bases on the permeation was tested. The viscosity of gel formulae and also the shelf life were evaluated. Results: The results showed that polymers type affect the drug permeation and rheological properties of PIR niosomal gel. F3 containing 4% MC showed the best permeation through rat skin (87.73 ± 2.06) and the lowest viscosity. Conclusion: All the studied gels are of acceptable physical properties and drug content. They exhibited pseudoplastic flow with thixotropic behavior. Considering in-vitro permeation, rheological properties, and shelf life, F3 (4% MC) formula was the best.
... Triplicate experiments were conducted for each study and sink conditions were always maintained through out the experiment. All samples were analyzed for NYS content spectrophotometrically at a wavelength of 306 nm against PBS (pH 6.4) as a blank [15]. ...
Objective: Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. Various new technologies have been developed for the transdermal delivery of some important drugs. Physical and chemical means of crossing the lipophilic stratum corneum, the outermost layer of the skin, are being explored. The goal of the present study was to formulate and evaluate the potential use of transfersomal vesicles as a transdermal drug delivery system for poorly soluble drug, Nystatin. Methods: It was investigated by encapsulating the drug in various transfersomal formulations composed of various ratios of Phospholipone H 100, Span 80, Tween 80 and sodium deoxycholate prepared by lipid film hydration by rotary evaporation sonication method. The prepared formulations were characterized for light microscopy, and evaluated for particle shape, entrapment efficiency (EE%), stability, and in vitro skin permeation. Results: The vesicles were spherical in structure as confirmed by Transmission Electron Microscopy. The EE% of nystatin in the vesicles was in the range of 50-70%. The result revealed that Nystatin in all of the formulations was successfully entrapped with uniform drug content. In vitro skin permeation studies were carried by abdominal rabbit skin using a dissolution-dialysis apparatus fabricated in our laboratory. The amount of drug deposited in the skin and the amount permeated were higher in case of transfersomes with an enhancement ratio of 2.59, when compared to liposomes and the commercial product. Conclusion: It is evident from this study that transfersomes are a promising prolonged delivery system for Nystatin and have reasonably good stability characteristics. This research suggests that nystatin loaded transfersomes can be potentially used as a transdermal drug delivery system.
Migraine is a disabling neurovascular polygenic disorder affecting life quality with escorted socioeconomic encumbrances. Herein, we investigated the consolidated amalgamation of passive lipomer approach alongside active sonophoresis assisted transdermal delivery of zolmitriptan (ZT) using high frequency ultrasound pre-treatment protocol to mitigate migraine attacks. A modified nanoprecipitation technique was utilized to prepare zolmitriptan loaded lipomers (ZTL) adopting 23 factorial design. Three factors were scrutinized namely lipid type, ZT: lipid ratio and ZT: Gantrez® ratio. The prepared systems were characterized regarding particle size, zeta potential, polydispersity index, entrapment efficiency and in-vitro release studies. The best achieved ZTL system was evaluated for ZT- Gantrez® intermolecular interactions, drug crystallinity, morphology, ex-vivo permeation and histopathological examination. Finally, a comparative in-vivo biodistribution study through radiotracking technique using Technetium-99m was adopted. L2 was the best-achieved ZTL system with respect to spherical particle size (390.7 nm), zeta-potential (-30.8 mV), PDI (0.2), entrapment efficiency (86.2%), controlled release profile, flux (147.13 μg/cm2/hr) and enhancement ratio (5.67). Histopathological studies proved the safety of L2 system upon application on skin. L2 revealed higher brain Cmax (12.21 %ID/g), prolonged brain MRT (8.67 hr), prolonged brain .23 hr), significantly high relative bioavailability (2929.36%) and similar brain Tmax (0.5 hr) compared to I.V. route with higher brain/blood ratio. Thus, sonophoresis assisted transdermal delivery of ZTL offers a propitious alterative to alleviate migraine symptoms.
This article to investigate the effectiveness of using Niosomes in a transdermal drug delivery system for Econazole. Topically applied Niosomes can increase the longer action on the skin (stratum corneum and epidermis), while reducing the systemic absorption of the drug. Econazole is a imidazole antifungal agent used in the treatment of Candida infections, fungal infections. Econazole Niosome was prepared by Thin Film Hydration Technique by varying the cholesterol and surfactant ratios as 1:1, 1:2, 1:3, 1:4 Each formulation was evaluated for drug release. The release showing required amount of drug release per day as well as extended for the required day is the optimized formulation. Hence, B formulation is the optimized one.
This article to investigate the effectiveness of using Niosomes in a transdermal drug delivery system for
Econazole. Topically applied Niosomes can increase the longer action on the skin (stratum corneum and epidermis),
while reducing the systemic absorption of the drug. Econazole is a imidazole antifungal agent used in the treatment of
Candida infections, fungal infections. Econazole Niosome was prepared by Thin Film Hydration Technique by varying
the cholesterol and surfactant ratios as 1:1, 1:2, 1:3, 1:4 Each formulation was evaluated for drug release. The release
showing required amount of drug release per day as well as extended for the required day is the optimized formulation.
Hence, B formulation is the optimized one
Occurrence of skin fungal infections is increasing nowadays and their presence is more prominent in patients suffering from immunocompromised diseases like AIDS. Skin fungal infections are a major cause of visits by patients to dermatology clinics. Although, a large number of antifungal agents are available for treatment of skin fungal infections, but, their toxic profile and physicochemical characteristics reduce therapeutic outcome. When these antifungal agents are delivered topically using conventional formulations like creams and gels, they may cause various side effects like redness, burning, and swelling at the site of application. Therefore, various vesicular formulations (phospholipid based or non phospholipid based) have been explored by pharmaceutical scientists to treat skin fungal infections topically. Vesicular formulation explored for the purpose are liposomes, ethosomes, transfersomes, transethosomes, niosomes, spanlastics, oleic acid vesicles, and nanoparticles. These formulations show various advantages like bioavailability enhancement of bioactives, high skin permeation power, no side effects at application site, dosing frequency reduction, and sustained drug release. Therefore, in the present article, we have discussed about the utility of various vesicular nanocarrier systems to treat skin fungal infections.
The main Objective of the work was encapsulating of Doxorubicin hydrochloride in liposomal formulation for treatment of cancer chemotherapy. Conventional compositions of Doxorubicin hydrochloride were available as freeze-dried product or as a solution of doxorubicin hydrochloride in water. Both these products have been associated with a number of toxicities when administered intravenously. To overcome these problems, in the present study, inclusion of Doxorubicin hydrochloride in liposomal formulation has proved to be good approach to eliminate the toxicities and improve drug antitumor activity. In this study, Doxorubicin hydrochloride liposomes containing Hydrogenated Soy Phosphatidyl Choline, Cholesterol, various stabilizers and ammonium sulphate prepared by dried thin film hydration method. The characterization of liposomes was carried out by vesicle size, zeta potential, %free drug and in-vitro dissolution. The formulation having negative stabilizer, Phosphotidyl glycerol shown minimum % free drug, optimum particle size and least percent drug release when compared to the formulations having positive stabilizer, Stearylamine. The release kinetics of formulations containing neural, negative and positive stabilizers followed zero-order release kinetics. Hence it could be concluded that stabilizes like Stearylamine and Phosphotidyl glycerol along with Hydrogenated Soy Phosphatidyl Choline (HSPC) and Cholesterol were suitable carriers for the preparation of Doxorubicin HCl liposomes.
The main objective of the work was encapsulating of Doxorubicin hydrochloride in liposomal formulation for treatment of cancer chemotherapy. Conventional compositions of Doxorubicin hydrochloride were available as freeze-dried product or as a solution of doxorubicin hydrochloride in water. Both these products have been asso-ciated with a number of toxicities when administered intravenously. To overcome these problems, in the present study, inclusion of Doxorubicin hydrochloride in liposomal formulation has proved to be good approach to elimi-nate the toxicities and improve drug antitumor activity. In this study, Doxorubicin hydrochloride liposomes con-taining Hydrogenated Soy Phosphatidyl Choline, Cholesterol, various stabilizers and ammonium sulphate prepared by dried thin film hydration method. The characterization of liposomes was carried out by vesicle size, zeta poten-tial, %free drug and in-vitro dissolution. The release kinetics of formulations containing neural, negative and posi-tive stabilizers followed zero-order release kinetics. Hence it could be concluded that stabilizers like Stearylamine and Phosphotidyl glycerol along with Hydrogenated Soy Phosphatidyl Choline (HSPC) and Cholesterol were suita-ble carriers for the preparation of Doxorubicin HCl liposomes.
Objective: Use of povidone-iodine (PVP-I) as a microbicidal agent is complicated by contact burns and other adverse reactions attributed to its sudden concentrated release from absorbent skin bandages. The current investigation examines the potential of niosomes or non-ionic surfactant vesicles to aid in the slow sustained release of the topical antiseptic in order to overcome this major drawback. Method: Candida albicans, a fungus commonly associated with cutaneous infections was selected as the test organism since PVP-I has broad spectrum properties and been reported to be an effective antimycotic agent. After evaluating the antimicrobial effect of unencapsulated PVP-I on Candida cells, niosomes were developed by the thin film hydration technique, with a stoichiometric proportion of antiseptic: cholesterol: sorbitane monooleate of 1:1:2. The formulated vesicles were characterized for their particle size, zeta potential and drug entrapment efficiency. Further, in vitro agar cup tests and studies on the sustained release profile of the entrapped medicament were performed. Results: The minimum inhibitory concentration of PVP-I for Candida was found to be 0.45% w/v available iodine and complete killing of cells was achieved at this concentration within 180 seconds. The average size of loaded vesicles was recorded to be 338.4 nm, with a drug entrapment efficiency of 80%. Subsequent to its encapsulation, PVP-I showed good permeability, retention of the fungicidal activity and the slow sustained effect lasted for almost 35 hours. Conclusion: This is the first report of a study that has developed and characterized the in vitro efficacy and sustained drug delivery of PVP-I using niosomal carriers. The results demonstrate that niosomes can act as microreservoirs prolonging the release of PVP-I. They could thus help to prevent contact burns associated with the immediate release of the antiseptic when used for topical application.
Life threatening invasive fungal infections is a major problem in immunocompromised patients. Standard antifungal agents so far have been quite successful, but some of them have limited use because of toxicity and drug resistance and even their clinical efficacy in some invasive fungal infections, such as aspergillosis and fusariosis, is not optimal. Among the several widely used antifungal drugs, azoles are most frequently prescribed in various types of fungal infections. Some new antifungal agents have demonstrated therapeutic potential and may provide additional options for the treatment of fungal infections and may help to overcome the limitations of current drugs. This review briefly discusses currently available antifungal agents and primarily concerns with recent developments in antifungal agents including lipid formulation of polyenes, novel azoles, echinocandins, sordarins, nikkomycins, monoclonal antibody, aminocandin and interferon-γ-1b.
Topical drug administration is a localized drug delivery system anywhere in the body through ophthalmic, rectal, vaginal and skin as topical routes. Skin is one of the most readily accessible organs on human body for topical administration and is main route of topical drug delivery system. There are various skin infections caused by fungus. An antifungal medication is a pharmaceutical fungicide used to treat mycoses such as athlete's foot ringworm, candidasis. Antifungal works by exploiting differences between mammalian and fungal cells to kill the fungal organism without dangerous effect on host. kitoconazole is an imidazoles antifungal derivative and used for the treatment of local and systemic fungal infection. When administered orally, ketoconazole is best absorbed at highly acidic levels, so antacids or other causes of decreased stomach acid levels will lower the drug's absorption. Absorption can be increased by taking it with an acidic beverage, such as cola. Ketoconazole is very lipophilic and tends to accumulate in fatty tissues.
The purpose of the present investigation is to formulate and evaluate proniosomal transdermal carrier systems for flurbiprofen. Proniosomes were prepared using various non-ionic surfactants, namely span 20 (Sp 20), span 40 (Sp 40), span 60 (Sp 60) and span 80 (Sp 80) without and with cholesterol at percentages ranging from 0% to 50%. The effect of surfactant type and cholesterol content on drug release was investigated. Drug release was tested by diffusion through cellophane membrane and rabbit skin. Drug release from the prepared systems was compared to that from flurbiprofen suspensions in distilled water and HPMC (hydroxypropylmethylcellulose) gels. In case of Sp 20 and Sp 80, the added amount of cholesterol affected the preparation type to be either proniosomal alcoholic solutions or liquid crystalline gel systems. On the other hand, both Sp 40 and Sp 60 produced gel systems in presence or absence of cholesterol. Microscopic observations showed that either proniosomal solutions or gel formulations immediately converted to niosomal dispersions upon hydration. Due to the skin permeation barrier, rabbit skin showed lower drug diffusion rates compared to cellophane membrane. The proniosomal composition controlled drug diffusion rates to be either faster or slower than the prepared flurbiprofen suspensions in HPMC gels or distilled water, respectively. In conclusion, this study demonstrated the possibility of using proniosomal formulations for transdermal drug delivery.
Ketoconazole niosomes were prepared by ether injection technique using surfactant (Tween 40 or 80), cholesterol and drug in five different ratios by weight, 1:1:1, 1.5:1:1, 2:1:1, 2.5:1:1 and 3:1:1. The niosomes were characterized for size, shape, entrapment efficiency and in vitro drug release (by exhaustive dialysis).The formulations were also tested for in vitro (cup-plate method) and in vivo antifungal activity (in rabbits) and compared with free ketoconazole. The results of the present study indicate that niosomes have the potential to reduce the therapeutic dose of ketoconazole by improving its performance.
Gellified emulsion (Emulsion in gel) have emerged as one of the most interesting topical drug delivery system as it has dual release control system i.e. emulsion and gel. Also the stability of emulsion is increased when it is incorporated in gel. Itraconazole is an orally or topically active antifungal agent with a broad spectrum of activity. The objective of this project was to develop a Gellified emulsion for control delivery for Itraconazole. In present work we prepare emulsion and then incorporated in carbapol gel. The prepared formulation was evaluated on basis of pH, spreadability, Viscosity, drug content, in vitro release and Stability Studies. The microbial assay and Skin irritation studies on rabbit was also performed. The result of studied reveled 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 shows 46.6% inhibition of optimized batch where as marketed preparation shows only 32.3% inhibition. While result of skin irritation test shows no edema and erythema. Hence it can be concluded that emulsion based system is more effective and safe system for sustain delivery of antifungal agent(s).
The effect of particle size of liposomes on the deposition of drugs into the strata of skin was evaluated using hairless mice, hamster and pig skin. In vitro diffusion studies were performed in an attempt to find an optimum formulation for topical drug delivery as well as to try to explain the mechanism of topical drug delivery by liposomes. The results indicate that an optimum particle size for optimal drug delivery exists. The study proved that the follicular route play an important role in determining the kinetics of drug transfer from liposomes into the skin. Peer Reviewed http://deepblue.lib.umich.edu/bitstream/2027.42/31700/1/0000636.pdf
A transdermal patch for the OTC antihistamine, triprolidine (TP), might provide benefits in terms of increased efficacy and reduced sedative side effects. However, concerns over potential irritant or allergic contact sensitization (ACS) skin reactions necessitated through skin toxicity testing before and during initial clinical development. Initial effort was expended on development of a binary vehicle delivery system comprised of TP in 0.5% oleic acid (OA) in propylene glycol (PG). Rabbit skin irritation and Buehler guinea pig skin sensitization testing indicated that this TP/OA/PG formula had both skin irritation and ACS potential. Both tests underestimated, to some degree, the skin toxicities observed in later clinical testing. In clinical tests, skin irritation was due mainly to the OA/PG vehicle, but was enhanced in the presence of high TP concentrations. Of 26 subjects enrolled in a rising dose clinical pharmacokinetics study, one subject exposed twice to TP/OA/PG presented with delayed skin reactions suggestive of ACS. Positive diagnostic patch test results for this subject and four out of five other twice-exposed study subjects suggested that the TP/OA/PG formula had a very high ACS potential. Subsequent predictive clinical patch testing was conducted with a buffered aqueous TP formula which provided in vitro skin penetration of the drug equivalent to the TP/OA/PG formula. These clinical studies demonstrated that TP itself had no significant irritation potential but still induced ACS reactions in a high proportion of test subjects. The incidence of adverse skin reactions to TP was considered to be too high relative to the degree of improved therapeutic benefit of this delivery form. On this basis, all technology development effort was discontinued.
The permeation of estradiol from vesicular formulations through human stratum corneum was studied in vitro. The vesicles were composed of nonionic n-alkyl polyoxyethylene ether surfactants (CnEOm). The thermodynamic activity of estradiol present in each formulation was kept constant by saturating all formulations with estradiol. The effects of both the particle size and the composition of the formulation on estradiol permeation across excised human stratum corneum were investigated. Stratum corneum that was pretreated with empty surfactant carriers allowed for significantly higher estradiol fluxes compared with untreated stratum corneum. However, estradiol fluxes obtained in these pretreatment experiments appeared to be significantly lower than those obtained by the direct application of the estradiol-saturated carrier formulation on top of the stratum corneum. Furthermore, in the case of pretreatment of the stratum corneum, an increase in carrier size resulted in a decrease in estradiol flux. For direct application the opposite was found. Two mechanisms are proposed to play an important role in vesicle-skin interactions, i.e., the penetration enhancing effect of surfactant molecules and the effect of the vesicular structures that are most likely caused by adsorption of the vesicles at the stratum corneum-suspension interface.
In order to quantitatively investigate the importance of transfollicular pathway for drug delivery, drug penetration through human scalp skin was investigated using liquid formulations containing lipophilic and hydrophilic drugs in vitro. The penetration pathway for drugs through the scalp skin was examined using fluorescent probes. Additionally, the drug penetration through the scalp skin was compared with that via human abdominal skin to clarify the usefulness of intrafollicular delivery. Lipophilic melatonin (MT) and ketoprofen (KP) showed high permeabilities through the scalp skin, although the flux of KP was much higher. Absorption enhancers, N-methyl-2-pyrrolidone and isopropylmyristate, only slightly increased the fluxes. Hydrophilic fluorouracil (5FU) and acyclovir (ACV) penetrated through the scalp skin with relatively large fluxes. However, there was large variability in the fluxes of these drugs across scalp skin from different sources. When the relationship between the flux and hair follicle density was estimated, there was good correlation between the two (r = 0.651 for MT and r = 0.666 for ACV, P < 0.05). The histologic examination of the scalp skin, following application of the formulation with nile red or sodium fluorescein, indicated that the probes permeated into the junction of the internal and external root sheath of follicles and diffused into the dermis via the outer root sheath at the initial times. The penetration of nile red, a lipophilic probe, via the stratum corneum of scalp skin was later than that via the follicles. The permeation of MT and 5FU through the scalp skin was much higher than that via the abdominal skin, being 27 and 48 times as high as the abdominal skin, respectively. These results indicate that the drug delivery through the scalp skin will offer an available delivery means for drugs, particularly for hydrophilic drugs.