Microparticulate Based Topical Delivery System of Clobetasol Propionate

Psoriasis is a chronic, autoimmune skin disease affecting approximately 2% of the world's population. Clobetasol propionate which is a superpotent topical corticosteroid is widely used for topical treatment of psoriasis. Conventional dosage forms like creams and ointments are commonly prefered for the therapy. The purpose of this study was to develop a new topical delivery system in order to provide the prolonged release of clobetasol propionate and to reduce systemic absorption and side effects of the drug. Clobetasol propionate loaded-poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres were prepared by oil-in-water emulsion–solvent evaporation technique. Particle size analysis, morphological characterization, DSC and XRD analyses and in vitro drug release studies were performed on the microparticle formulations. Emulgel formulations were prepared as an alternative for topical delivery of clobetasol propionate. In vitro drug release studies were carried out from the emulgel formulations containing pure drug and drug-loaded microspheres. In addition, the same studies were performed to determine the drug release from the commercial cream product of clobetasol propionate. The release of clobetasol propionate from the emulgel formulations was significantly higher than the commercial product. In addition, the encapsulation of clobetasol propionate in the PLGA microspheres significantly delayed the drug release from the emulgel formulation. As a result, the decrease in the side effects of clobetasol propionate by the formulation containing PLGA microspheres is expected.     

Evaluation of Paeonol Skin-Target Delivery from Its Microsponge Formulation: In Vitro Skin Permeation and In Vivo Microdialysis

The aim of the present study was to design a novel topical skin-target drug-delivery system, the paeonol microsponge, and to investigate its drug-release patterns in dosage form, both in vitro and in vivo. Paeonol microsponges were prepared using the quasi-emulsion solvent-diffusion method. In vitro release studies were carried out using Franz diffusion cells, while in vivo studies were investigated by microdialysis after the paeonol microsponges were incorporated into a cream base. In vitro release studies showed that the drug delivered via microsponges increased the paeonol permeation rate. Ex vivo drug-deposition studies showed that the microsponge formulation improved drug residence in skin. In addition, in vivo microdialysis showed that the values for the area under the concentration versus time curve (AUC) for the paeonol microsponge cream was much higher than that of paeonol cream without microsponges. Maximum time (T_max) was 220 min for paeonol microsponge cream and 480 min for paeonol cream, while the half-life (t_1/2) of paeonol microsponge cream (935.1 min) was almost twice that of paeonol cream (548.6 min) in the skin (n = 3). Meanwhile, in the plasma, the AUC value for paeonol microsponge cream was half that of the paeonol cream. Based on these results, paeonol-loaded microsponge formulations could be a better alternative for treating skin disease, as the formulation increases drug bioavailability by lengthening the time of drug residence in the skin and should reduce side-effects because of the lower levels of paeonol moving into the circulation.     

Preparation and evaluation of niosome gel containing acyclovir for enhanced dermal deposition

Niosomes suggest a versatile vesicle delivery system with possible transport of drugs via topical route for skin delivery. The aim of the present research was to optimize niosome gel formulation of acyclovir and to evaluate in both in vitro and in vivo rabbit model. Niosome formulations were formulated by coacervation phase separation technique with different ratios of nonionic surfactants, phospholipids and cholesterol using 3² factorial design. Altering the surfactant concentration has influenced the drug entrapment, but not vesicle size. At high surfactant combinations, the acyclovir release from niosomes was strongly influenced by cholesterol:lecithin ratio. Ex vivo drug permeation data indicate substantial difference in flux values and was influenced by the niosome composition. Ex vivo studies using formulation (B₈) for drug deposition indicate greater amount of niosome being diffused into the skin layers and formed a depot, compared to commercial acyclovir cream (control). Two distinct dermatopharmacokinetic profiles were observed, in vivo, for niosome gel formulation (B₈) and control, which were analog to the profiles observed with ex vivo deposition studies. In vivo plasma drug level suggests low systemic exposure of acyclovir (C_max: 9.44?±?2.27?ng/mL and 14.54?±?3.11?ng/mL for niosome formulation and control, respectively). Comparison of kinetic data of acyclovir in the stratum corneum and plasma signifies that the niosome formulation forms a depot in the epidermis or dermis region. This study concludes that the niosome gel formulation (B₈) could be a viable vesicular system for an impressive transdermal delivery of acyclovir by topical application.     

Halobetasol propionate-loaded solid lipid nanoparticles (SLN) for skin targeting by topical delivery

The clinical use of halobetasol propionate (HP) is related to some adverse effects like irritation, pruritus and stinging. The purpose of this work was to construct HP-loaded solid lipid nanoparticles (HP-SLN) formulation with skin targeting to minimizing the adverse side effects and providing a controlled release. HP-SLN were prepared by solvent injection method and formula was optimized by the application of 3² factorial design. The nanoparticulate dispersion was evaluated for particle size and entrapment efficiency (EE). Optimized batch was characterized for differential scanning calorimetry (DSC), scanning electron microscopy, X-ray diffraction study and finally incorporated into polymeric gels of carbopol for convenient application. The nanoparticulate gels were evaluated comparatively with the commercial product with respect to ex-vivo skin permeation and deposition study on human cadaver skins and finally skin irritation study. HP-SLN showed average size between 200?nm and 84–94% EE. DSC studies revealed no drug-excipient incompatibility and amorphous dispersed of HP in SLN. Ex vivo study of HP-SLN loaded gel exhibited prolonged drug release up to 12?h where as in vitro drug deposition and skin irritation studies showed that HP-SLN formulation can avoid the systemic uptake, better accumulative uptake of the drug and nonirritant to the skin compared to marketed formulation. These results indicate that the studied HP-SLN formulation represent a promising carrier for topical delivery of HP, having controlled drug release, and potential of skin targeting with no skin irritation.     

A Review About the Drug Delivery from Microsponges

Microparticulate drug delivery systems have shown a great interest in the pharmaceutical area. They allow the increase of drug therapeutic efficacy and the reduction of side effects. In this context, microsponges represent a new model of porous polymer microspheres, which allow the entrapment of a wide range of active agents. During the development, it is necessary the characterization of the system and among of the most important tests are the release and permeation profile analysis. They can demonstrate the behavior of drug in a specific site with a particular application condition and are related to therapeutic efficacy. Therefore, this review provides an overview of drug delivery profile from microsponges. Methods for determination of in vitro release and ex vivo permeation studies are detailed. Examples of drug delivery from microsponges administered in different sites are also discussed with aim to provide an understanding of the use of this strategy to modify the drug delivery.     

In Vitro and In Vivo Evaluation of Hydroxyzine Hydrochloride Microsponges for Topical Delivery

Hydroxyzine HCl is used in oral formulations for the treatment of urticaria and atopic dermatitis. Dizziness, blurred vision, and anticholinergic responses, represent the most common side effects. It has been shown that controlled release of the drug from a delivery system to the skin could reduce the side effects while reducing percutaneous absorption. Therefore, the aim of the present study was to produce an effective drug-loaded dosage form that is able to control the release of hydroxyzine hydrochloride into the skin. The Microsponge Delivery System is a unique technology for the controlled release of topical agents, and it consists of porous polymeric microspheres, typically 10–50 μm in diameter, loaded with active agents. Eudragit RS-100 microsponges of the drug were prepared by the oil in an oil emulsion solvent diffusion method using acetone as dispersing solvent and liquid paraffin as the continuous medium. Magnesium stearate was added to the dispersed phase to prevent flocculation of Eudragit RS-100 microsponges. Pore inducers such as sucrose and pregelatinized starch were used to enhance the rate of drug release. Microsponges of nearly 98% encapsulation efficiency and 60–70% porosity were produced. The pharmacodynamic effect of the chosen preparation was tested on the shaved back of histamine-sensitized rabbits. Histopathological studies were driven for the detection of the healing of inflamed tissues.KEYWORDS: hydroxyzine HCl, microsponges, oil in oil emulsion solvent diffusion, skin delivery     

Formulation and Evaluation of Bioadhesive Buccal Drug Delivery of Tizanidine Hydrochloride Tablets

The study aim was concerned with formulation and evaluation of bioadhesive buccal drug delivery of tizanidine hydrochloride tablets, which is extensively metabolized by liver. The tablets were prepared by direct compression using bioadhesive polymers such as hydroxylpropyl methylcellulose K4M, sodium carboxymethyl cellulose alone, and a combination of these two polymers. In order to improve the permeation of drug, different permeation enhancers like beta-cyclodextrin (β-CD), hydroxylpropyl beta-cyclodextrin (HP-β-CD), and sodium deoxycholate (SDC) were added to the formulations. The β-CD and HP-β-CD were taken in 1:1 molar ratio to drug in formulations. Bioadhesion strength, ex vivo residence time, swelling, and in vitro dissolution studies and ex vivo permeation studies were performed. In vitro release of optimized bioadhesive buccal tablet was found to be non-Fickian. SDC was taken in 1%, 2%, and 3% w/w of the total tablet weight. Stability studies in natural saliva indicated that optimized formulation has good stability in human saliva. In vivo mucoadhesive behavior of optimized formulation was performed in five healthy male human volunteers and subjective parameters were evaluated.     

Formulation,Characterization, and Clinical Evaluation of Microemulsion Containing Clotrimazole for Topical Delivery

The objective of the present study was to formulate and evaluate microemulsion systems for topical delivery of clotrimazole (CTM). The solubility of CTM in various oils was determined to select the oil phase of the microemulsion systems. Pseudoternary phase diagrams were constructed to identify the area of microemulsion existence. Five CTM microemulsion formulations (M1–M5) were prepared and evaluated for their thermodynamic stability, pH, refractive index, droplet size, viscosity, and in vitro release across cellulose membrane. Among the prepared microemulsion formulations, M3 (lemon oil/Tween 80/n-butanol/water) and M4 (isopropyl myristate/Tween 80/n-butanol/water) microemulsion systems were found to be promising according to their physical properties and CTM cumulative percentage release. Gel form of M3 and M4 were prepared using 1% Carbopol 940 as the hydrogel matrix. Both formulations were evaluated in the liquid and gel forms for drug retention in the skin in comparison to the marketed CTM topical cream and their stability examined after storage at 40°C for 6 months. Microemulsion formulations achieved significantly higher skin retention for CTM over the CTM cream. Stability studies showed that M4 preparations were more stable than M3. The in vitro anti-fungal activity of M4 against Candida albicans was higher than that of the conventional cream. Moreover, clinical evaluation proved the efficacy and tolerability of this preparation in the treatment of various topical fungal infections.     

Nanoethosomal formulation for skin targeting of amphotericin B: an in vitro and in vivo assessment

Abstract

The present study is envisaged to develop nanoethosomal formulation for enhanced topical delivery of amphotericin B (AmB) for the treatment of cutaneous fungal infections. AmB encapsulated nanoethosomes were prepared using mechanical dispersion method in a strength of 0.1% w/w similar to the strength of marketed topical formulation. Vesicle size of nanoethosomal formulations was found to be in the range of 186?±?2 to 298?±?4?nm. The optimized nanoethosomal formulation was further incorporated in gel base to form AmB nanoethogel formulation. Rheological characterization study of nanoethogel demonstrated its viscoelastic nature with high elasticity and resistance to deformation at 37?°C. The yield stress value was found to be 108.05?±?2.4 and 52.15?±?0.9?Pa for nanoethogel and marketed gel formulation, respectively. The nanoethogel formulation exhibited 2.7- and 3.5-fold higher steady state transdermal flux and skin deposition of AmB, respectively, in comparison to marketed formulation. Confocal laser scanning microscopy (CLSM) study also revealed enhanced skin permeation and deposition with nanoethogel formulation. In vivo study showed that topical application of nanoethogel does not exhibit any skin irritation as tested by Draize test. The developed formulation, in comparison to the marketed gel, demonstrated a remarkable increase in the antifungal activity against Candida albicans. It is thus corroborated from the above results that nanoethosomal formulation represents an efficacious carrier for effective topical delivery of AmB.     

Design and <Emphasis Type="Italic">In Vitro</Emphasis> Performance Evaluation of Purified Microparticles of Pravastatin Sodium for Intestinal Delivery

The purpose of research was to develop a mucoadhesive multiparticulate sustained drug delivery system of pravastatin sodium, a highly water-soluble and poorly bioavailable drug, unstable at gastric pH. Mucoadhesive microparticles were formulated using eudragit S100 and ethyl cellulose as mucoadhesive polymers. End-step modification of w/o/o double emulsion solvent diffusion method was attempted to improve the purity of the product, that can affect the dose calculations of sustained release formulations and hence bioavailability. Microparticles formed were discrete, free flowing, and exhibited good mucoadhesive properties. DSC and DRS showed stable character of drug in microparticles and absence of drug polymer interaction. The drug to polymer ratio and surfactant concentration had significant effect on mean particle size, drug release, and entrapment efficiency. Microparticles made with drug: eudragit S100 ratio of 1:3 (F6) exhibited maximum entrapment efficiency of 72.7% and ex vivo mucoadhesion time of 4.15 h. In vitro permeation studies on goat intestinal mucosa demonstrated a flux rate (1,243 μg/cm²/h) that was 169 times higher than the flux of pure drug. The gastric instability problem was overcome by formulating the optimized microparticles as enteric-coated capsules that provided a sustained delivery of the highly water-soluble drug for 12 h beyond the gastric region. The release mechanism was identified as fickian diffusion (n = 0.4137) for the optimized formulation F6. Conclusively, a drug delivery system was successfully developed that showed delayed and sustained release up to 12 h and could be potentially useful to overcome poor bioavailability problems associated with pravastatin sodium.     

<Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Evaluation of Hydroxyzine Hydrochloride Microsponges for Topical Delivery

Hydroxyzine HCl is used in oral formulations for the treatment of urticaria and atopic dermatitis. Dizziness, blurred vision, and anticholinergic responses, represent the most common side effects. It has been shown that controlled release of the drug from a delivery system to the skin could reduce the side effects while reducing percutaneous absorption. Therefore, the aim of the present study was to produce an effective drug-loaded dosage form that is able to control the release of hydroxyzine hydrochloride into the skin. The Microsponge Delivery System is a unique technology for the controlled release of topical agents, and it consists of porous polymeric microspheres, typically 10–50 μm in diameter, loaded with active agents. Eudragit RS-100 microsponges of the drug were prepared by the oil in an oil emulsion solvent diffusion method using acetone as dispersing solvent and liquid paraffin as the continuous medium. Magnesium stearate was added to the dispersed phase to prevent flocculation of Eudragit RS-100 microsponges. Pore inducers such as sucrose and pregelatinized starch were used to enhance the rate of drug release. Microsponges of nearly 98% encapsulation efficiency and 60–70% porosity were produced. The pharmacodynamic effect of the chosen preparation was tested on the shaved back of histamine-sensitized rabbits. Histopathological studies were driven for the detection of the healing of inflamed tissues.     

Brimonidine Tartrate–Eudragit Long-Acting Nanoparticles: Formulation,Optimization, <Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Evaluation

In the present study, an effort was made to design prolonged release Eudragit nanoparticles of brimonidine tartrate by double emulsion–solvent evaporation technique for the treatment of open-angle glaucoma. The effect of various formulation variables like initial drug amount, lecithin proportion, phase volume and pH, secondary emulsifier and polymer proportion were studied. Various process variables like energy and duration of emulsification, lyophilization on the characteristics of nanoparticles and in vitro drug release profile were studied. The selected formulations were subjected to in vivo intraocular pressure-lowering efficacy studies by administering aqueous dispersion of nanoparticles into the lower cul de sac of glaucomatous rabbits. The prepared Eudragit-based nanoparticles were found to have narrow particle size range and improved drug loading. The investigated process and formulation variables found to have significant effect on the particle size, drug loading and entrapment efficiency, and in vitro drug release profile of nanoparticles. The selected formulations upon in vivo ocular irritability and tolerability tests were found to be well tolerated with no signs of irritation. In vivo pharmacodynamic efficacy studies revealed that the selected nanoparticle formulations significantly improved the therapy as area under the ∆IOP vs. time curve [AUC_{(∆IOP vs.t)}] showed several fold increase in intensity and duration of intraocular pressure (IOP) decrease. All the selected nanoparticle formulations were found to prolong the drug release in vitro and prolong IOP reduction efficacy in vivo, thus rendering them as a potential carrier in developing improved drug delivery systems for the treatment of glaucoma.     

Nanostructured lipid carriers as semisolid topical delivery formulations for diflucortolone valerate

Context: Topical treatment of skin disease needs to be strategic to ensure high drug concentration in the skin with minimum systemic absorption.

Objective: The aim of this study was to produce semisolid nanostructured lipid carrier (NLC) formulations, for topical delivery of the corticosteroid drug, diflucortolone valerate (DFV), with minimum systemic absorption.

Method: NLC formulations were developed using a high shear homogenization combined with sonication, using Precirol® ATO5 or Tristearin® as the solid lipid, Capryol? or isopropyl myristate as the liquid lipid and Poloxamer® 407 as surfactant. The present study addresses the influence of different formulations composition as solid lipid, liquid lipid types and concentrations on the physicochemical properties and drug release profile from NLCs.

Results and discussion: DFV-loaded NLC formulations possessed average particle size ranging from 160.40?nm to 743.7?nm with narrow polydispersity index. The encapsulation efficiency was improved by adding the lipid-based surfactants (Labrasol® and Labrafil® M1944CS) to reach 68%. The drug release from the investigated NLC formulations showed a prolonged release up to 12?h. The dermatopharmacokinetic study revealed an improvement in drug deposition in the skin with the optimized DFV-loaded NLC formulation, in contrast to a commercial formulation.

Conclusion: NLC provides a promising nanocarrier system that work as reservoir for targeting topical delivery of DFV.     

Multiunit Floating Drug Delivery System of Rosiglitazone Maleate: Development, Characterization, Statistical Optimization of Drug Release and In Vivo Evaluation

A multiunit floating drug delivery system of rosiglitazone maleate has been developed by encapsulating the drug into Eudragit® RS100 through nonaqueous emulsification/solvent evaporation method. The in vitro performances of microspheres were evaluated by yield (%), particle size analysis, drug entrapment efficiency, in vitro floating behavior, surface topography, drug–polymer compatibility, crystallinity of the drug in the microspheres, and drug release studies. In vitro release was optimized by a {3, 3} simplex lattice mixture design to achieve predetermined target release. The in vivo performance of the optimized formulation was evaluated in streptozotocin-induced diabetic rats. The results showed that floating microspheres could be successfully prepared with good yields (69–75%), high entrapment (78-97%), narrow size distribution, and desired target release with the help of statistical design of experiments from very small number of formulations. In vivo evaluation in albino rats suggested that floating microspheres of rosiglitazone could be a promising approach for better glycemic control.     

Microemulsion for topical delivery of fenoprofen calcium: in vitro and in vivo evaluation

The aim of this study was to investigate microemulsion (ME) based topical delivery system for fenoprofen calcium (FPCa) to eliminate its oral gastrointestinal adverse effects. ME was prepared by the water titration method using oleic acid as oil phase, tween 80 as a surfactant and propylene glycol as a cosurfactant. Oleic acid was selected as oil phase due to its good solubilizing capacity. ME existence region was determined using pseudo-ternary phase diagrams for preparing different formulations. Six different formulations were selected with various values of oil (25–68%), water (2–3%), and the mixture of surfactant and cosurfactant (1:1) (24–67%). The selected ME formulae were characterized for optical birefringence, transmission electron microscopy (TEM), pH, % transmittance, electronic conductivity, drug content, droplet size, rheological properties and stability evaluation. In vitro release study of FPCa from ME s through the synthetic membrane and hairless rat skin were evaluated. The optimized formula ME5 consisting of 5% w/w FPCa, 60% w/w oleic acid as oil phase, 3% w/w aqueous phase, and 32% w/w of surfactant phase containing Tween 80 and propylene glycol (1:?1) showed the highest transdermal flux and highest skin permeation rate. Finally, the % inhibition of carrageenan-induced rat paw edema of the optimized formula ME5 was highly significant (p?0.001) as compared to plain gel of FPCa. In conclusion, ME is a promising technique for topical delivery of FPCa.     

Microemulsion-Based Topical Hydrogels of Tenoxicam for Treatment of Arthritis

Tenoxicam (TNX) is a non-steroidal anti-inflammatory drug (NSAID) used for the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, backache and pain. However, prolonged oral use of this drug is associated with gastrointestinal adverse events like peptic ulceration, thus necessitating its development as topical formulation that could obviate the adverse effects and improve patient compliance. The present study was aimed at development of microemulsion-based formulations of TNX for topical delivery at the affected site. The pseudoternary phase diagrams were developed and microemulsion formulations were prepared using Captex 300/oleic acid as oil, Tween 80 as surfactant and n-butanol/ethanol as co-surfactant. Optimized microemulsions were characterized for drug content, droplet size, viscosity, pH and zeta potential. The ex vivo permeation studies through Laca mice skin were performed using Franz diffusion cell assembly, and the permeation profile of the microemulsion formulation was compared with aqueous suspension of drug and drug incorporated in conventional cream. Microemulsion formulations of TNX showed significantly higher (p?<?0.001) mean cumulative percent permeation values in comparison to conventional cream and suspension of drug. In vivo anti-arthritic and anti-inflammatory activity of the developed TNX formulations was evaluated using various inflammatory models such as air pouch model, xylene-induced ear edema, cotton pellet granuloma and carrageenan-induced inflammation. Microemulsion formulations were found to be superior in controlling inflammation as compared to conventional topical dosage forms and showed efficacy equivalent to oral formulation. Results suggest that the developed microemulsion formulations may be used for effective topical delivery of TNX to treat various inflammatory conditions.     

Development and Evaluation of New Microemulsion-Based Hydrogel Formulations for Topical Delivery of Fluconazole

The aim of the present investigation was to develop and evaluate microemulsion-loaded hydrogels (MEHs) for the topical delivery of fluconazole (FZ). The solubility of FZ in oils, surfactants and cosurfactants was evaluated to identify the components of the microemulsion. The pseudo-ternary phase diagrams were constructed using the novel phase diagram by micro-plate dilution method. Carbopol EDT 2020 was used to convert FZ-loaded microemulsions into gel form without affecting their structure. The selected microemulsions were assessed for globule size, zeta potential and polidispersity index. Besides this, the microemulsion-loaded hydrogel (MEH) formulations were evaluated for drug content, pH, rheological properties and in vitro drug release through synthetic membrane and excised pig ear skin in comparison with a conventional hydrogel. The optimised MEH FZ formulations consisting of FZ 2%, Transcutol P 11.5% and 11%, respectively, as oil phase, Lansurf SML 20-propyleneglycol 52% and 50%, respectively, as surfactant–cosurfactant (2:1), Carbopol EDT 2020 1.5% as gelling agent and water 34.5% and 37%, respectively, showed highest flux values and high release rate values, and furthermore, they had low surfactant content. The in vitro FZ permeation through synthetic membrane and excised pig ear skin from the studied MEHs was best described by the zero-order and first-order models. Finally, the optimised MEH FZ formulations showed similar or slightly higher antifungal activity as compared to that of conventional hydrogel and Nizoral® cream, respectively. The results suggest the potential use of developed MEHs as vehicles for topical delivery of FZ, encouraging further in vitro and in vivo evaluation.KEY WORDS: fluconazole, in vitro skin permeation, microemulsion, microemulsion-loaded hydrogel, topical     

Enhanced skin deposition and delivery of voriconazole using ethosomal preparations

Despite its broad-spectrum antifungal properties, voriconazole has many side effects when administered systemically. The aim of this work was to develop an ethosomal topical delivery system for voriconazole and test its potential to enhance the antifungal properties and skin delivery of the drug. Voriconazole was encapsulated into various ethosomal preparations and the effect of phospholipid and ethanol concentrations on the ethosomes properties were evaluated. The ethosomes were evaluated for drug encapsulation efficiency, particle size and morphology and antifungal efficacy. Drug permeability and deposition were tested in rat abdominal skin. Drug encapsulation efficiency of up to 46% was obtained and it increased with increasing the phospholipid concentration, whereas the opposite effect was observed for the ethanol concentration. The ethosomes had a size of 420–600?nm and negative zeta potential. The particle size of the ethosomes increased by increasing their ethanol content. The ethosomes achieved similar inhibition zones against Aspergillus flavus at a 2-fold lower drug concentration compared with drug solution in dimethyl sulfoxide. The ex vivo drug permeability through rat abdominal skin was ～6-fold higher for the ethosomes compared with the drug hydroalcoholic solution. Similarly, the amount of drug deposited in the skin was higher for the ethosomes and was dependent on the ethanol concentration of the ethosomes. These results confirm that voriconazole ethosomal preparations are promising topical delivery systems that can enhance the drug antifungal efficacy and improve its skin delivery.     

Encapsulation of Vincristine in Liposomes Reduces its Toxicity and Improves its Anti-Tumor Efficacy

Abstract

Vincristine is a potent therapeutic agent with activity against a variety of tumor types. It is a cell-cycle specific agent which has exhibited enhanced anti-tumor activity when delivered in liposomal form. Vincristine can be encapsulated into large unilamellar vesicles in response to a transmembrane pH gradient with trapping efficiencies approaching 100%. The extent of vincristine encapsulation, and the subsequent retention of the drug within the liposomes, both in vitro and in vivo, are strongly dependent on the lipid composition of the liposome and on the magnitude of the transmembrane pH gradient. Liposomal formulations of vincristine have been optimized for both liposome circulation longevity, drug retention characteristics and in vivo antitumor activity. When compared to free vincristine, these formulations significantly increase the levels of vincristine remaining in the plasma after i.v. administration. These formulations also significantly increase the delivery of vincristine to tumor sites. As a consequence of the improved accumulation of vincristine at tumor sites, liposomal formulations of vincristine exhibit dramatically improved efficacy against a variety of ascitic and solid murine and human tumors than does free vincristine. Liposomal vincristine is expected to be of wide utility in a variety of human malignancies.     

Development and Evaluation of Ethyl Cellulose-Based Transdermal Films of Furosemide for Improved In Vitro Skin Permeation

Transdermal films of the furosemide were developed employing ethyl cellulose and hydroxypropyl methylcellulose as film formers. The effect of binary mixture of polymers and penetration enhancers on physicochemical parameters including thickness, moisture content, moisture uptake, drug content, drug–polymer interaction, and in vitro permeation was evaluated. In vitro permeation study was conducted using human cadaver skin as penetration barrier in modified Keshary–Chein diffusion cell. In vitro skin permeation study showed that binary mixture, ethyl cellulose (EC)/hydroxypropyl methylcellulose (HPMC), at 8.5:1.5 ratio provided highest flux and also penetration enhancers further enhanced the permeation of drug, while propylene glycol showing higher enhancing effect compared to dimethyl sulfoxide and isopropyl myristate. Different kinetic models, used to interpret the release kinetics and mechanism, indicated that release from all formulations followed apparent zero-order kinetics and non-Fickian diffusion transport except formulation without HPMC which followed Fickian diffusion transport. Stability studies conducted as per International Conference on Harmonization guidelines did not show any degradation of drug. Based on the above observations, it can be reasonably concluded that blend of EC–HPMC polymers and propylene glycol are better suited for the development of transdermal delivery system of furosemide.