Coacervation Phase Separation Method Research Articles

Formulation, Optimization and In vitro / In vivo Characterization of Spray Dried Doxorubicin Loaded Folic Acid Conjugated Gelatin Nanoparticles.

Formulation, optimization and anticancer activity of spray-dried Doxorubicin loaded folic acid conjugated Gelatin nanoparticles (DOX-FA-GN). Doxorubicin loaded gelatin nanoparticles (DOX-GN) were prepared by the Coacervation phase separation method, optimized using DoE and then conjugated with folic acid by covalent coupling to formulate Doxorubicin loaded folic acid conjugated nanoparticles (DOX-FA-GN). The formulated nanoparticles were characterized to evaluate its physicochemical properties. Cellular uptake and cell viability studies were carried out using MTT assay and biodistribution studies were carried out in Wistar rats. Particle size, PDI and entrapment efficiency for optimized DOX-GN were found to be 152.3 ± 9.3 nm 0.294 ± 0.1 and 86.9± 3.4% while for DOX-FA-GN, 193.9 ± 12.3 nm 0.247 ± 0.2 and 84 ± 3.6%. The cytotoxic studies showed a cell viability of 75.1% for DOX-GN and 29.5% DOX-FA-GN. Biodistribution studies were found to be statistically insignificant for conjugated nanoparticles with excellent flow properties. Significantly higher DOX distribution in the lungs was observed in the case of DOX-FA-GN. There was a higher uptake of DOX on HeLa cells with DOX-FA-GN compared to DOX-GN. Also, the biodistribution of Dox in the lungs of Wistar rats was higher in conjugated nanoparticles as compared to unconjugated nanoparticles.

Formulation and Evaluation of Galantamine Hydrobromide Proniosome Gel for Alzheimer’s disease

Galantamine hydrobromide is formulated in tablets and capsules prescribed through oral delivery for the treatment of Alzheimer’s disease. However, oral delivery of drugs can cause severe side effects such as nausea, vomiting, and gastrointestinal disturbance. In the present research work, Galantamine hydrobromide is formulated as proniosome gel by Coacervation phase separation method using different surfactants such as Tweens and Spans. Overall eight formulations were developed and evaluated for various parameters. The prepared gels were viewed by naked eye to observe the colour of gel. Microscopical observations of the gels showed vesicles of optimum size from 3.030 mm (P2) - 3.735 mm (P5). The gel also showed optimum rate of spontaneity in the range 9.60 mm3x1000 (P7) to 11.80 mm3x1000 (P4) and entrapment efficiency of vesicles in the range 66.15% (P5) to 86.92% (P3). The gels had pH in suitable range of skin (5.92-6.9). The in vitro drug diffusion studies revealed that the drug diffusion was affected by the various surfactants used. The rank order of surfactant effect on in-vitro drug diffusion was Tween 80 > Tween 60 > Tween 40 >Tween 20 > Span 80 > Span 60 > Span 40 > Span 20. The proniosomal gel containing Tween 80 showed maximum drug diffusion (99.24%) and the gel containing Span 20 showed minimum drug diffusion (71.74%). FT-IR studies of optimized proniosome gel P8 revealed the absence of any chemical interactions between drug and carriers used.
 Keywords: Galantamine hydrobromide, Proniosome gel, Coacervation phase separation method, Surfactants, in vitro drug diffusion studies.

Formulation and Evaluation of Proniosomal Topical Antifungal Gel of Miconazole Nitrate

Proniosomal gel formulations of miconazole nitrate (MCZ) were prepared by using combinations of different grades of (non-ionic surfactant) span, cholesterol, and lecithin by coacervation phase separation method. Developed 10 proniosomal gel formulations were characterized for particle size, shape, % entrapment efficiency, drug content, in vitro drug permeation, scanning electron microscopy (SEM), DSC, stability study. The fourier transform infrared spectroscopy (FTIR) studies confirmed the compatibility of the drug with excipients. The results showed that all the formulations were pale yellow to pale brown in color, pH was is in the range of 5.60 to 7.20, and encapsulation efficiency was found is in the range of 83 to 91.25% and particle size in between 5.81 ± 0.2 to 07.52 ± 0.07. Among the ten formulations MF2, MF3, MF5, MF6, and MF8 showed maximum drug release in a controlled manner at 12 hours of study and developed into carbopol proniosomal topical gel and evaluated for ex-vivo drug permeation. Formulationoptimized formulation C5MF8 showed higher drug permeation 74.19 ± 0.16% at 12 hr. with a flux valueof 6.829 ± 0.12 μg/cm2 /hr. The permeability coefficient of 0.341 ±0.08 cm2 /hrs., higher correlation coefficient R2 0.9944 for zero-order drug release kinetic model, and follows zero-order release kinetics. Among the 5 formulations, optimized carbopol proniosomal topical gel formulation C5MF8 drug release and in-vitro antifungal activity was compared with marketed formulation cream.C5MF8 showed sustain drug release and zone of inhibition value was very near to marketed preparation. Hence it was concluded that developed carbopol proniosomal topical gel had the potential to act as a controlled release drug carrier,which sustains the drug release for many hours and exhibit good antifungal activity

Development and Evaluation of Optimized Thiolated Chitosan Proniosomal Gel Containing Duloxetine for Intranasal Delivery.

Proniosomes offer excellent potential for improved drug delivery, through versatile routes, by overcoming the permeation barriers faced by several drugs. The study was aimed to develop a thiomer gel containing duloxetine proniosomes for the intranasal delivery, improving its bioavailability and brain delivery through olfactory system. Duloxetine-loaded proniosomes were optimized through Design-Expert Software, prepared by coacervation phase separation method and then characterized in vitro for different vesicle features, and permeation enhancement potential using various techniques. The formulation F2, out of all the trials, fulfilled the maximum requisite of highest entrapment efficiency (76.21 ± 1.24%) and minimum vesicle size (223.91 ± 11.07nm). The F2 was embedded in thiolated chitosan gel rendering it mucoadhesive and further characterized. The in vitro release showed a sustained drug release from the mucoadhesive proniosomal gel with only 54% drug release as compared to that of 71% from proniosome over 8h, following Higuchi drug release model. Ex vivo permeation studies showed the enhancement ratio for the mucoadhesive proniosomal gel to be 1.86-fold greater than proniosomes, indicating a significant improvement in transmucosal permeation. The results suggest that incorporation of proniosomes into thiolated gel can significantly improve its mucoadhesion and retention time in the nasal cavity for providing a sustained drug release. Thus, gel formulation could be considered as a promising approach for efficient intranasal drug delivery of duloxetine. Graphical Abstract.

FORMULATION AND EVALUATION OF PRONIOSOMAL GEL-BASED TRANSDERMAL DELIVERY OF ATORVASTATIN CALCIUM BY BOX–BEHNKEN DESIGN

Objective: The aim of this study was to investigate the combined influence of three independent variables in the preparation of atorvastatin proniosomes by coacervation-phase separation method.
 Methods: On the basis of the preliminary trials, a 3-factor, 3-level Box–Behnken design was employed to study the effect of cholesterol, soya lecithin, and Span 60 independent variable on dependent variables (particle size and % entrapment efficiency). Transmission electron microscopy analysis of optimized formulation has demonstrated the presence of individual proniosomes in spherical shape.
 Results: Atorvastatin optimized proniosomal formulation F2 shown better particle size and % entrapment efficiency, and also, the drug release was 99.72% within 24 h in slow and controlled manner when compared with control. Kinetic analysis of drug release profiles showed that the drug release was followed by zero-order manner with Korsmeyer–Peppas model, which implies super case II release kinetics. The particle size and zeta potential of the optimized atorvastatin proniosomal gel were found to be 65.72 and −10.5, respectively. The optimized batch of proniosomes was used for the preparation of atorvastatin-based proniosomal hydrogel by incorporating hydrated proniosomes to carbopol matrix to enhance the stability and viscosity of the system.
 Conclusion: The enhanced skin permeation, for a prolonged period of time, may lead to improved efficacy and better patient compliance. This study suggests that proniosomal gel-containing atorvastatin could perform therapeutically better effects than the conventional formulations.

FORMULATION AND IN VITRO, IN VIVO EVALUATION OF PRONIOSOMAL GEL OF NEOMYCIN SULPHATE

Objective: The objectives of present investigation were to prepare and evaluate proniosomes of neomycin sulphate (NS) by coacervation phase separation method by using sorbitan monostearate (span 60) and lecithin as a surfactant to increase the penetration through the skin and study the effect of concentration of the same.
 Methods: Proniosomes of neomycin sulphate (NS) were prepared by coacervation phase separation method by using span 60 and lecithin. The effect of concentration of span 60 and lecithin was studied by factorial design. The prepared proniosomes were converted to gel by using carbopol as a gelling agent. The prepared formulations were evaluated for entrapment efficiency, in vitro drug diffusion, in vitro antibacterial activity and in vivo skin irritation test etc.
 Results: All Formulation showed the percentage entrapment efficiency in the range 38.31±0.05% to 77.96±0.06%, good homogeneity and gel was easily spreadable with minimal of shear. Optimized formulation showed enhanced rate of diffusion in vitro, increase in zone of inhibition against staphylococcus aureus, no skin irritation and showed good stability.
 Conclusion: The results of present study indicates that proniosomal gel formulated by using combination of span 60, Lecithin, cholesterol can be used to enhance skin delivery of NS because of excellent permeation of drug. Developed proniosomal gel formulation was promising carrier for NS

FORMULATION DEVELOPMENT AND EVALUATION OF PRONIOSOMAL GEL OF ETHINYLESTRADIOL AND LEVONORGESTREL FOR ANTIFERTILITY TREATMENT

Objective: The purpose of this research was to develop and formulate proniosomal gel drug delivery system of ethinylestradiol and levonorgestrel for antifertility treatment that is capable of efficiently delivering entrapped drug over an extended period of time.Methods: Ethinylestradiol and levonorgestrel are encapsulated in various formulations of proniosomal gel composed of various ratios of span surfactant, cholesterol, soya lecithin, and alcohol as aqueous phase prepared by coacervation-phase separation method. The prepared formulations characterized for drug encapsulation efficiency, size distribution, in vitro release studies, and vesicular stability at different storage conditions were carried. Stability studies for proniosomal gel were carried out for a few weeks. Morphological size and shape of the vesicles are characterized using optical microscopy and scanning electron microscopy (SEM). Stability studies for proniosomal gel were carried out for 3 months.Results: Morphological size and shape of the vesicles are characterized using optical microscopy and SEM, particles are found to be spherical, size of the particles is in the range of 46.4–80.6 nm, and permeation studies showed good control release for prolonged period of time. The encapsulation efficiency of proniosomal gel formulations is in the range of 74–80% and in vitro permeation studies proved that good amount of drug is permeated and has reasonably good stability characteristics as well.Conclusions: The results suggest that proniosomal gel formulations of ethinylestradiol and levonorgestrel may be used for transdermal delivery for antifertility treatment. The dried proniosomal formulation could act as a promising alternative to niosomes.

FORMULATION DEVELOPMENT AND EVALUATION OF PRONIOSOMAL GEL OF ETHINYLESTRADIOL AND LEVONORGESTREL FOR ANTIFERTILITY TREATMENT

Objective: The purpose of this research was to develop and formulate proniosomal gel drug delivery system of ethinylestradiol and levonorgestrel for antifertility treatment that is capable of efficiently delivering entrapped drug over an extended period of time.Methods: Ethinylestradiol and levonorgestrel are encapsulated in various formulations of proniosomal gel composed of various ratios of span surfactant, cholesterol, soya lecithin, and alcohol as aqueous phase prepared by coacervation-phase separation method. The prepared formulations characterized for drug encapsulation efficiency, size distribution, in vitro release studies, and vesicular stability at different storage conditions were carried. Stability studies for proniosomal gel were carried out for a few weeks. Morphological size and shape of the vesicles are characterized using optical microscopy and scanning electron microscopy (SEM). Stability studies for proniosomal gel were carried out for 3 months.Results: Morphological size and shape of the vesicles are characterized using optical microscopy and SEM, particles are found to be spherical, size of the particles is in the range of 46.4–80.6 nm, and permeation studies showed good control release for prolonged period of time. The encapsulation efficiency of proniosomal gel formulations is in the range of 74–80% and in vitro permeation studies proved that good amount of drug is permeated and has reasonably good stability characteristics as well.Conclusions: The results suggest that proniosomal gel formulations of ethinylestradiol and levonorgestrel may be used for transdermal delivery for antifertility treatment. The dried proniosomal formulation could act as a promising alternative to niosomes.

Proniosomal gel-mediated topical delivery of fluconazole: Development, in vitro characterization, and microbiological evaluation.

The aim of this study was to explore the potential of proniosomal gel for topical delivery of fluconazole, an antifungal drug used in fungal infections caused by pathogenic fungi. Fluconazole-loaded proniosomal gels were prepared by the coacervation phase separation method using different nonionic surfactants (spans and tweens). The prepared fluconazole proniosomal gels were evaluated for various parameters such as particle size (PS), drug entrapment efficiency percentage (EE%), and in vitro drug release. The experimental results showed that the EE% for the prepared formulae are acceptable (85.14%–97.66%) and they are nanosized (19.8–50.1 nm) and the diffusion from the gels gave the desired sustaining effect. F4, which was prepared from span 60, tween 80 (1:1), and cholesterol showed highest EE% and gave slow release (40.50% ± 1.50% after 6 h), was subjected to zeta potential (ZP) test, transmission electron microscopy as well as microbiological study. The results showed a well-defined spherical vesicle with sharp boundaries with good physical stability of fluconazole within the prepared gel. Moreover, F4 showed an excellent microbiological activity represented by a greater zone of inhibition (5.3 cm) compared to control gel (fluconazole in 2% hydroxy propyl methyl cellulose (HPMC) gel formula) (4.2 cm) and plain gel with no drug (0 cm) against Candida albicans. This study showed the suitability of the proniosomal gel in attaining the desired sustainment effect for topical delivery of fluconazole for the management of fungal infection. The physical stability study showed that there was no significant change in EE%, PS, and ZP of fluconazole proniosomal gel after storage for 6 months.

Characterization and Release of Ibuprofen in Proniosome System (Ibuprofen-Span 60-Cholesterol)

The aim of this research was to determine influence of proniosome system which consists of ibuprofen-span 60-cholesterol with molar ratio of 2:1:0.75. The proniosome system was made by Coacervation Phase Separation Method,using ethanol 96% as solvent and glycerol 0.1% as aqueous phase. There were two formulas in this research formula I was ibuprofen non proniosome in HPMC gel base and formula II was ibuprofen proniosome in HPMC gel base. Characterization of formulas included organoleptic and pH of ibuprofen gel. Drug release was determined using diffusion cell and cellophane membrane in phosphate buffer pH 6.0 ± 0.05 at temperature 32 ± 0.5 oC for 7 hours. The drug release (flux) of ibuprofen from formula I and II were 28.3067 ± 3.0852 µg/cm2/min½ and 23.1900 ± 1.7658 µg/cm2/min½, respectively. The statistical result using independent sample T-test on degree of confident of 95% (α = 0.05) concluded that there was significant value of their fluxs. Research result revealed that release of ibuprofen proniosome system was lower than ibuprofen nonproniosome system in HPMC 4000 gel base..

DESIGN OF PRONIOSOMAL GEL CONTAINING EUGENOL AS AN ANTIFUNGAL AGENT FOR THE TREATMENT OF ORAL CANDIDIASIS

The objective of this study was to design and investigate the antifungal activity of proniosomal gel of eugenol for the treatment of oral candidiasis. The proniosomal gel was prepared by coacervation phase separation method using different surfactants like spans 20, 60, 80, soya lecithin and cholesterol. The proniosomal gel formulations were evaluated for visual inspection, pH detection, viscosity, spreadability, in vitro drug release and kinetics study, and in vivo studies. The compatibility study indicated that the drug and the excipients were compatible with each other. The results showed that pH, viscosity and spreadability were all acceptable for topical preparation. In vitro drug release study and drug release kinetics were conducted to check the release study and drug release patterns of the formulation. Amongst the formulations, an optimized formulation was selected to conduct an in vivo study. Candida albicans was used to induce oral candidiasis for the evaluation of therapeutic efficacy of proniosomal gel in immunosuppressed rats. Activity was analysed by microbiological and histopathological techniques and was compared with the marketed product. It is evident from the study that the proniosomal gel shows sustained release trend with strong antifungal activity.

Development and Optimization of Lovastatin-loaded Trans-dermal Proniosomal Gel using Box-Behnken Design

In this study, a proniosome-based transdermal drug delivery system of lovastatin was developed by coacervation phase separation method. On the basis of the pilot trials, a 3-factor, 3-level Box–Behnken design was employed to characterize the effect of Cholesterol, soya lecithin and Tween 80 on dependent variables (particle size, entrapment efficiency, and drug release). TEM analysis of optimized formulation has demonstrated the presence of individual Proniosomes in spherical shape. Lovastatin optimized proniosomal formulation F1 shown better particle size and percentage entrapment efficiency and drug release of 99.49% within 24h in slow and controlled manner when compared with control. Kinetic analysis of drug release profiles showed that the systems predominantly released Lovastatin in a zero-order manner with a strong correlation coefficient (R2= 0.9990). The particle size and Zeta potential of the optimized lovastatin proniosomal gel was found to be 138.82 nm and -11.4 mV respectively. Optimized batch of Proniosomes was used for the preparation of Lovastatin - based proniosomal hydrogel by incorporating hydrated Proniosomes to Carbopol matrix to enhance the stability and viscosity of the system. The enhanced skin permeation for prolonged time may lead to improved efficacy and better patient compliance. 

FORMULATION AND EVALUATION OF TOPICAL FORMULATION FOR CUTANEOUS TUBERCULOSIS

Cutaneous Tuberculosis is also known as dermal tuberculosis or tuberculosis cutis (extrapulmonary tuberculosis) which can occur in any age group and patients who may or may not be suffering from pulmonary tuberculosis. The current treatment given for the disease is oral therapy of anti-tubercular drugs which has many side effects such as hepatotoxicity, headache, anxiety, euphoria, insomnia, eosinophilia, hepatitis. Hence to avoid these side effects and to increase efficiency of current therapy a topical proniosomal gel of isoniazid was formulated. Coacervation phase separation method was used and proniosomal gel was formulated by using Span 20, soya lecithin, and cholesterol. Optimum concentration of 3 factors Span 20, soya lecithin, and cholesterol were determined using Box Behnken design with at 2 levels and vesicle size and entrapment efficiency as responses. The optimized proniosomal gel was characterized by vesicle size, entrapment efficiency, transmission electron microscopy (TEM), in vitro drug release, skin retention studies, skin irritation studies and stability studies. The optimised batch showed vesicle size of 2.27±1.82 µ, and entrapment efficiency of 98.15±0.25 %. The optimised formulation was stable under refrigeration condition (5°C) in amber coloured bottle, was non-irritating and showed 98.10±1.28 % release and 85±1.53 % permeation after 6 h and 436±12 µg drug was retained in the skin after 3 hrs. Keywords: Cutaneous tuberculosis, isoniazid, proniosomal gel, stabilityÂ

FORMULATION AND EVALUATION OF ANTIFUNGAL PRONIOSOMAL GEL FOR ORAL CANDIDIASIS

Fluconazole is a synthetic antifungal drug, belonging to triazole group and mostly used to treat oral candidiasis caused by the yeast Candida albicans. Fluconazole commercially available in tablets that offer poor bioavailability, due to hepatic first pass effect and gastric instability leads to frequent dosing. Buccal drug delivery can bypass such problems of tablet and leads to increase in bioavailability. Due to low molecular weight, fluconazole can suitably administered by buccal route, hence local and targeted action can achieve. The present study was conducted to develop proniosomal gel of fluconazole by coacervation phase separation method using Span 20, cholesterol, soya lecithin, ethanol and aqueous vehicle. Based on preliminary studies surfactant and aqueous vehicle was selected. The Box Behnken design was employed to optimized proniosomes by evaluating responses like entrapment efficiency, vesicle size and drug release. The optimized proniosomes were evaluated with entrapment efficiency (96.83%), vesicle size (2µm), in-vitro drug release 85.66 % (3 h) and ex vivo mucosal permeation (85.67 %) with flux (394.09 μg/cm2h). The optimized proniosomes were incorporated into 2% w/w Carbopol gel 934 (1:1) to obtain proniosomal gel. This optimized proniosomal gel was found with good viscosity, good spreadability and adhesiveness, also it shows maximum drug release and permeation as compared to plain gel of fluconazole. In microbiological studies, optimized formulation shows the maximum inhibitory effect as compared to plain gel of drug, which concluded that optimized proniosomal gel exerted local and targeted buccal delivery with good fungistatic effect than plain gel of fluconazole against Candida albicans. Keywords: proniosomal gel, oral candidiasis, fluconazole, mucoadhesion, Candida albicans.

BOX–BEHNKEN METHOD TO OPTIMIZE LORNOXICAM PRONIOSOMES: PREPARATION, IN VITRO CHARACTERIZATION AND ANALGESIC ACTIVITY

The objective of present investigation was to develop and evaluation of proniosomes as the carrier of lornoxicam for topical delivery. lornoxicam-loaded proniosomes were prepared by coacervation phase separation method. The Box–Behnken design used in this study helped in identifying the factors affecting drug entrapment efficiency and drug diffusion. Proniosomes were evaluated for appearance, pH, viscosity, entrapment efficiency and in vitro drug diffusion studies. The optimized formulations were further evaluated to vesicle size, shape, zeta potential, percutaneous permeation and analgesic effect. The vesicles were found to be unilamellar, spherical in shape. The analgesic effect of lornoxicam proniosomal gel showed better therapeutic activity.

Development, characterization &invivo evaluation of proniosomal based transdermal delivery system of Atenolol

The potential of proniosomes as a transdermal drug delivery system for Atenolol was investigated by encapsulating the drug in various formulations of proniosomal gel composed of various ratios of sorbitan fatty acid esters, cholesterol, lecithin prepared by Coacervation-phase separation method. The objectives of the present study were to define effects on the antihypertension activity and pharmacokinetics of a novel transdermal Proniosomal gel incorporating Atenolol. The formulated systems were characterized in vitro for size, drug entrapment, In vitro and in vivo drug permeation profiles and vesicular stability at different storage conditions. The optimized Atenolol proniosomes (AT8) showed nanometric vesicle size, high entrapment efficiency and marked enhancement in transdermal permeation. The prepared Proniosomal gel showed the relative bioavailability of 365.38 fold increased for AT8 than oral. The maximal concentrations (Cmax), of drug were significantly reduced while the areas under the plasma concentration–time curve (AUC), and mean residence times (MRT), t1/2 were evidently increased and extended, respectively. The results suggest that proniosomes can act as promising carrier which offers an alternative approach for transdermal delivery of Atenolol.

Sustained ocular delivery of Dorzolamide-HCl via proniosomal gel formulation: in-vitro characterization, statistical optimization, and in-vivo pharmacodynamic evaluation in rabbits

Glaucoma is the second cause of blindness worldwide. Frequent administration of traditional topical dosage forms may lead to patient incompliance and failure of treatment. Our study aims to formulate proniosomal gel formulations that sustain the release of the water-soluble anti-glaucoma drug Dorzolamide-HCl (Dorz). Proniosomal gel formulations were prepared using coacervation phase separation method according to a 52 full factorial design. The effects of Cholesterol and surfactant (Span 40) amounts (independent variables) on the percentage entrapment efficiency (EE%), particle size (PS), and the percent of drug released after 8 h (Q8h) (dependent variables (DVs)) were investigated. An optimized formulation (OF) was chosen based on maximizing EE% and Q8h and minimizing PS. An intraocular pressure (IOP) pharmacodynamic study was performed in rabbits to evaluate the in-vivo performance of the OF-gel compared to the marketed Trusopt® eye drops. The results showed that the independent variables studied significantly affected EE%, PS, and Q8h. OF was the one containing 60 mg Cholesterol and 540 mg Span 40. It had desirability of 0.885 and its actually measured DVs deviated from the predicted ones by a maximum of 4.8%. The in-vivo pharmacodynamic study showed that OF could result in higher reduction in IOP, significantly sustain that reduction in IOP and increase Dorz bioavailability compared to Trusopt® eye drops. Thus the OF-gel is very promising for being used in glaucoma treatment.

PREPARATION AND CHARACTERIZATION OF TOLTERODINE TARTRATE PRONIOSOMES

Objective: Proniosomes are dry free flowing, granular products that are water soluble carrier particles, coated with surfactants and can be hydrated to form niosomal dispersion immediately before use in hot aqueous media. Tolterodine, is medication used to treat frequent urination, urinary incontinence, or urinary urgency. It acts on M2 and M3 subtypes of muscarinic receptors. Methods: Tolterodine tartrate proniosome formulations were prepared by coacervation phase separation method by using different surfactants in different ratios. The prepared proniosomal formulations were evaluated for vesicle size, rate of spontaneity, encapsulation efficiency, drug content, In vitro release study and stability studies. Results: The size range was found to be 15.28±0.33 to 16.43±0.22 µm. Viscosity of all formulations lies in the range of 7244-9314 cp. Maximum release was shown by formulations of batch PG4 (87.45 %), and minimum for formulations of batch PG4 (50%), after 12 h. Optimized formulations PG4 shows stability at different temperatures. Conclusion: Tolterodine tartrate proniosome formulations prepared by using coacervation phase separation method are capable of releasing drug for the extended period of time. Peer Review History: Received 2 April 2017; Revised 5 May; Accepted 10 May, Available online 15 May 2017 Academic Editor: Dr. DANIYAN Oluwatoyin Michael, Obafemi Awolowo University, ILE-IFE, Nigeria, toyinpharm@gmail.com UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 3.0/10 Average Peer review marks at publication stage: 7.0/10 Reviewer(s) detail: Dr. Mohammed Abdel-Wahab Sayed Abourehab, Umm Al-Qura University; Makkah Al-Mukarramah, Saudi Arabia, mohawahab2002@yahoo.com Dr. Sally A. El-Zahaby, Pharos University in Alexandria, Egypt, sally.elzahaby@yahoo.com Similar Articles: INVESTIGATION OF PRONIOSOMES GEL AS A PROMISING CARRIER FOR TRANSDERMAL DELIVERY OF GLIMEPIRIDE FORMULATION AND EVALUATION OF ETODOLAC NIOSOMES BY MODIFIED ETHER INJECTION TECHNIQUE

Performance evaluation of non-ionic surfactant based tazarotene encapsulated proniosomal gel for the treatment of psoriasis

The study aims to explore the potential of non-ionic surfactant based proniosomal gel (PNG) in improving the topical delivery of tazarotene by in vitro and in vivo studies. The PNG was prepared using coacervation phase separation method composed of span, stearylamine, cholesterol, and lecithin. The PNG demonstrated favorable vesicle size (3.26±0.22μm) and percent encapsulation efficiency (49.50±2.3%). The PNG was evaluated for viscosity which indicated that the ratio of span:cholesterol:stearylamine (64.5:30.5:5mM) demonstrated no any fluctuations in viscosity. The scanning electron micrographs exhibited spherical vesicles with sharp boundaries. The in vitro drug release through cellulose membrane and rat's skin were found to be in the following order of the formulation code A2>A4>A3>A5 and A4>A2>A3>A5, respectively, which showed the prolonged release of entrapped tazarotene. Further, in vitro drug permeation and retention studies revealed that formulations A2 and A4 showed the higher percent of drug permeation whereas formulations A3 and A5 showed the higher percent of drug retention through rat's skin. Moreover, PNG A2 and A4 formulations demonstrated good stability characteristics at different temperature conditions. The stability in the presence of detergent revealed that no any abrupt change in turbidity. The skin irritation studies performed with formulations A2 and A4 showed no erythema compared with the plain PNG. The male Albino NMRI mice tail model was used to performed in vivo skin histological examination which revealed that an increase in the orthokeratosis strengthened. Thus, all the results concluded that surfactant, Span 60 based PNG formulations have shown a good ability to increase drug accumulation in the various skin layers and more potential carrier for topical delivery of tazarotene for an effective therapy of psoriasis.

Proniosomal gel-mediated transdermal delivery of bromocriptine: in vitro and ex vivo evaluation

ABSTRACTVesicular systems endow large opportunities for the transdermal delivery of therapeutics. The present study was designed to investigate the potential of a novel class of vesicular system ‘proniosome’ as a carrier for transdermal delivery of bromocriptine (BCT). Proniosome formulations were prepared by the coacervation-phase separation method and the influence of factors like surfactant type and its amount, lipid concentration, cholesterol amount and drug content were studied. Span 60 was the most appropriate surfactant, and yielded vesicle size and percentage encapsulation efficiency of 1.3 µm and 98.9%, respectively. The developed system was characterised w.r.t. morphology, transition temperature, drug release, skin permeation and skin irritancy. Proniosomes exhibited a sustained release pattern of BCT in vitro. Skin permeation study revealed high penetration of proniosomes with sustained release of BCT through rat skin. The optimised proniosomal formulation showed enhanced transdermal flux of 16.15 μg/cm2/h as compared to 3.67 μg/cm2/h for drug dispersion. The developed formulations were observed as non-irritant to the rat skin and were found as quite stable at 4 and 25 °C for 90 days w.r.t. vesicle size and drug content. The dried proniosomal formulation could act as a promising alternative to niosomes and preferably for transdermal delivery of BCT.