Development and quality assessment of glutathione tripeptide loaded niosome containing carbopol emulgels as nanocosmeceutical formulations.

This study focuses on the preparation, physicopharmaceutical and mechanical characterization of reduced glutathione tripeptide loaded niosome containing emulgels as a novel nanocosmeceutical product. Prepared emulgel formulations were mainly composed of oily phase containing different lipids such as glycerine dibehenate, cetyl alcohol, cetearyl alcohol, etc., and aqueous phase containing Carbopol934® as gelling agent. Niosomal lipidic vesicles prepared from Span 60 and cholesterol were subsequently incorporated into optimum emulgel formulations. The pH, viscosity, and textural/mechanical properties of emulgels were examined before and after the incorporation of niosomes. The viscoelasticity and morphological characterization were performed on the final formulation before the packed formulation's microbiological stability test. The hardness and compressibility results ensured easy removal of the emulgel from the container. Due to the carboxyl groups of Carbopol934®, moderate adhesiveness with good cohesiveness was achieved. The rheological characteristics of the emulgels were estimated by oscillatory testing and the data fitted with the Herschel-Bulkley model. Thus, the viscoelastic properties and shear-thinning flow of emulgels were demonstrated. The final formulation was microbiologically stable, and pathogens or skin-irritating allergens were not detected. An anti-aging cosmeceutical preparation containing glutathione tripeptide loaded lipid-based niosome dispersion, suitable for topical use due to its textural and viscosity properties, was successfully produced.

SLN enriched hydrogels for dermal application: Full factorial design study to estimate the relationship between composition and mechanical properties.

When considering dermal administration of cosmeceuticals and/or drugs, the stratum corneum layer of the skin, has a barrier function that limits the penetration of active substances to the targeted skin tissues. Solid lipid nanoparticles/SLNs are colloidal carrier systems, which show superiority in dermal administration of cosmeceuticals/drugs. This superiority results from the ability of the SLNs to penetrate the skin layers easily. However, the main problem in dermal administration of colloidal drug systems is the need for a suitable semisolid vehicle for application as well as patient compliance. The main purpose of this study is to investigate the relationship between hydrogels and SLNs by using 32 full factorial design which simplifies the process by establishing the relationship between variables. Two different types of gel forming agent, hydroxypropyl methylcellulose or Carbopol 934 P, in three different polymer concentration used for preparation of SLN-enriched hydrogels. Formulations evaluated for their hardness and cohesiveness by using 32 full factorial design and the optimum formulations obtained for both gelling agents. As a result, mechanical properties of hydrogels consisting either hydroxypropyl methylcellulose or Carbopol 934 P revealed promotive results for dermal application of SLNs. The type and concentration of the gel-forming agent which is selected as a semisolid carrier for lipid nanoparticles are basic parameters affecting the dermal behavior of the system.

Development and In vitro Evaluation of Nifedipine Gel Formulations for Anorectal Applications.

OBJECTIVE: Current study focuses on the formulation and characterization of lipophilic and hydrophilic gel formulations of nifedipine to treat anal fissure via anodermal application. METHODS: Lipophilic gels were prepared with Aerosil grades as gelling agents in bulk oils. Polyethylene glycols, hydroxypropyl methylcellulose, and Carbopol® 974P were used as gelling agents in water and propylene glycol for forming hydrophilic gels. The effect of repeated Freeze-Thaw Cycles (FT-C) on microstructures of the gels was investigated by examining viscosity, rheology and textural properties. Aerosil 200 containing lipophilic gels exhibited thixotropic behavior with plastic flow properties and higher viscosities. RESULT: Accordingly, their compressibility and adhesiveness increased. FT-C caused notable changes in microstructures and textural properties of the lipophilic gels excluding the formulation containing Aerosil 200-in-isopropyl myristate. Among the hydrophilic gels, the viscosity of Carbopol® 974P gels increased depending on the amount of polymer, triethanolamine and water; these gels featured plastic flow without thixotropic behavior. Their compressibility and adhesiveness were higher than other gel formulations with stable post-FT-C characteristics. The higher flux values of nifedipine were observed from water containing Carbopol® 974P gel. CONCLUSION: The results of the stability tests showed that the Carbopol® 974P gel had a longer shelf life than the Aerosil 200-in-isopropyl myristate gel.

Preparation and evaluation of clindamycin phosphate loaded chitosan/alginate polyelectrolyte complex film as mucoadhesive drug delivery system for periodontal therapy.

In this study, Clindamycin phosphate loaded adhesive polyelectrolyte complex films for local periodontal therapy were prepared with alginate and chitosan. The thickness, drug content, structure, swelling, adhesion and in vitro drug release with release kinetics of formulations were evaluated. The effects of the varying concentration and molecular weight of polymers used and the volume of the polymer solutions on the characteristics of the films were investigated. Increasing the concentration of sodium alginate in total content of polymer mixture caused to higher adhesiveness. Chitosan molecular weight also affected to adhesiveness of complex films. The release rate of drug and release kinetics was affected from the complexation. The best complexation was obtained with the three times higher concentration and volume of alginate in combination with low molecular weight chitosan. Thus polyelectrolyte films that have delayed release together with high swelling ability and adhesiveness and high drug content were formed. Due to the heterogeneous structure of complex film, the release profiles of the formulations fitted to the anomalous transport mechanism. 3D structure of the drug loaded complex film was analyzed by Micro-CT imaging in this study and it was showed that using this method would be very advantageous for further studies about the investigation of complexation than the other imaging methods in order to determine the volume and the size of the formed complexes within the structure at the same time.

Formulation and in vitro evaluation of ketoprofen fast-dissolving tablets.

Drugs exhibiting satisfactory absorption from the oral mucosa or intended for immediate pharmacological action can be advantageously formulated as orally fast-disintegrating tablets (FDTs or ODTs). Therefore, taste masking of active ingredients becomes essential in these systems because the drug is entirely released in the mouth. Despite advances in the FDT technologies, formulation of drugs with a bitter taste is still a challenge, especially when the amount of drug is high. In this study, a new solution is being developed to incorporate higher doses of a model bitter taste drug; ketoprofen, without affecting the fast-disintegrating properties of the formulation. The unpleasant taste of the active drug usually masked by adding flavoring ingredients and sweeteners to improve taste and palatability but in this study a novel approach of using a polymer; Eudragit EPO and a granulation procedure of this polymer with the active drug was applied to mask the bitter taste of ketoprofen. In order to produce ketoprofen FDT formulations, a two-stepped procedure was followed; granulation process with the taste-masking agent (Eudragit EPO) and then direct compression (F3 and F4). In F1 and F2 formulations, granulation process was not implemented in order to observe the effect of application method of Eudragit EPO. As well as observing the effect of taste-masking agent, crospovidone and sodium starch glycolate were used in different concentrations (2, 4 and 8wt%) to examine the influence of superdisintegrants on FDT properties. All the FDTs containing 30 mg ketoprofen (F1, F2, F3 and F4) were evaluated by means of in vitro quality control tests.

Studies on transdermal delivery enhancement of zidovudine.

The purpose of this study was to investigate physicochemical characteristics and in vitro release of zidovudine from monolithic film of Eudragit RL 100 and ethyl cellulose. Films included 2.5% or 5% (w/w) zidovudine of the dry polymer weight were prepared in various ratios of polymers by solvent evaporation method from methanol/acetone solvent mixture. The release studies were carried out by vertical Franz cells (2.2 cm(2) area, 20 ml receptor fluid). Ex vivo studies were done on Wistar rat skin within the films F6 (Eudragit RL100) and F7 (Eudragit RL100/Ethylcellulose, 1:1) consisting 5% (w/w) zidovudine in comparison with the same amount of free drug. Either iontophoresis (0.1 and 0.5 mA/cm(2) direct currents, Ag/AgCl electrodes) or dimethyl sulfoxide (pretreatment of 1% and 5%, w/w, solutions) were used as enhancers. Films consisting of ethyl cellulose under the ratio of 50% (w/w) gave similar release profiles, and the highest in vitro cumulative released amount was achieved with F6 film which gave the closest results with the free drug. This result could be due to the high swelling capacity and re-crystallization inhibition effect of RL 100 polymer which also influenced the film homogenization. All the films were fitted to Higuchi release kinetics. It was also observed that both 0.5-mA/cm(2) current and 5% (w/w) dimethyl sulfoxide applications significantly increased the cumulative permeated amount of zidovudine after 8 h; however, the flux enhancement ratio was higher for 0.5-mA/cm(2) current application, especially within F6 film. Thus, it was concluded that Eudragit RL100 film (F6) could be further evaluated for the transdermal application of zidovudine.

In vitro and in vivo transdermal studies of atenolol using iontophoresis.

Matrix formulations of Eudragit E 100: NE 40D polymers (100:0, 70:30, 60:40, 50:50% w/w) with 20% w/w of triacetine and 5% w/w of atenolol were prepared by film casting method with different solvents (methanol, 2-propanol and acetone). In vitro release of atenolol from the films were studied by vertical Franz diffusion cells in HEPES buffer (pH 7.4) for 78 h. Direct currents of 0.1 and 0.5 mA/cm2 were applied for 6 h to the formulations with Ag/AgCl electrodes. Also, transdermal application for the Eudragit E 100: NE 40 D (70:30% w/w) formulation was compared by iontophoresis or oleic acid (2.5% w/v) with control group on Wistar rats. As a result, the in vitro release rate of atenolol from films were increased with iontophoresis by increasing the current density (from 0.240 to 0.424 mg/cm2 for 70:3% w/w formulation) and also increased with the amount of Eudragit NE 40D (from 0.646 to 1.30 mg/cm2 at the end of 78 h). It is obtained from the in vivo studies that oleic acid provided a higher plasma and skin concentration (0.825 mg/mL and 12.5 mg/cm2, respectively) than iontophoresis treatment (0.399 mg/mL and 1.81 mg/cm2, respectively) due to the different mechanisms. However, the results showed that iontophoresis is a good alternative for enhancing the transdermal delivery of atenolol.