Preparation and Evaluation of Tretinoin Microemulsion Based on Pseudo-Ternary Phase Diagram

Purpose: The aim of the present research was to formulate a transparent microemolsion as a topical delivery system for tretinoin for the treatment of acne. Methods: Microemulsion formulations prepared by mixing appropriate amount of surfactant including Tween 80 and Labrasol, co-surfactant such as propylene glycol (PG) and oil phase including isopropyl myristate – transcutol P (10:1 ratio). The prepared microemolsions were evaluated regarding their particle size, zeta potential, conductivity, stability, viscosity, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), refractory index (RI) and pH. Results: The results showed that maximum oil was incorporated in microemolsion system that was contained surfactant to co-surfactant ratio (Km) of 4:1. The mean droplets size range of microemulsion formulation were in the range of 14.1 to 36.5 nm and its refractory index (RI) and pH were 1.46 and 6.1, respectively. Viscosity range was 200-350 cps. Drug release profile showed 49% of the drug released in the first 8 hours of experiment belong to ME-7. Also, Hexagonal and cubic structures were seen in the SEM photograph of the microemulsions. Conclusion: physicochemical properties and in vitro release were dependent upon the contents of S/C, water and, oil percentage in formulations.Also, ME-7 may be preferable for topical tretinoin formulation

Enhanced Corneal Permeation of Pilocarpine Using Liposome Technology

A novel liposomal pilocarpine formulation as an ophthalmic drug delivery system has been designed to treat patients with glaucoma. The purpose of the present study was to formulate and evaluate liposomes loaded with pilocarpine and to evaluate permeation through rabbit cornea. Liposomes containing pilocarpine were prepared using thin film method. The quantities of soya lecithin and cholesterol were changed to enhance the encapsulation of the drug. The physicochemical properties of the prepared liposomes were evaluated according to their viscosity, pH, particle size, in vitro drug release, and transcorneal rabbit permeation. Dialysis membrane method was utilized to assess drug release profile. The results indicated that the mean particle sizes of liposomes were 120.5-212 nm and the pH and viscosity of formulations were in the range of 6.30-6.63 and 43.85-80.1 cps, respectively. According to the release study results, maximumally 60% of the drug released from liposomal formulations after 24 hours of the experiment. Also, the cumulative percentage of the drug permeated through rabbit cornea was differing from 3.86 to 14.9%. Irrespective from the composition and characteristics of the different liposomal formulations, they significantly increased the drug partitioning, permeability coefficient and flux of pilocarpine in rabbit cornea ex vivo model in comparison to control drug solution. The present study proved that any alteration in composition and nature of pilocarpine liposomal formulations may affect the drug permeability parameters through corneal membrane and also physico-chemical properties. It is probably due to the change in corneal structure in the presence of different liposomes composition

Preparation and Microstructural Characterization of Griseofulvin Microemulsions Using Different Experimental Methods: SAXS and DSC

Purpose: The objective of the present study is to formulate and evaluate a new microemulsion (ME) for topical delivery of griseofulvin. Methods: The solubilities of griseofulvin in different combinations of surfactant to co-surfactant (S/Co ratio) were determined. Accordingly, based on their phase diagrams, eight microemulsions were formulated and then evaluated with respect to their particle size, surface tension, viscosity, conductivity, zeta potential and stability. Their release behavior, Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), refractory index (RI), pH and Small-angle-X-ray scattering (SAXS) were also assessed. Results: The results indicated that the mean droplet size of the MEs ranged from 30.9 to 84.3 nm. Their zeta potential varied from -4.5 to -20.8. Other determined characteristics were viscosity: 254-381 cps, pH: 5.34-6.57, surface tension: 41.16- 42.83 dyne.cm-1, conductivity: 0.0442 – 0.111 ms.cm-1. The drug release was in the range of 22.4 to 43.69 percent. Also, hexagonal, cubic and lamellar liquid crystals were observed in SAXS experiments. Conclusion: It can be concluded that any alteration in MEs constituents directly affects their microstructure, shape, droplet size and their other physicochemical properties

SUPEROXIDE DISMUTASE LOADED NIOSOMES DELIVERY TO HAIR FOLLICLES: PERMEATION THROUGH SYNTHETIC MEMBRANE AND GUINEA PIG SKIN

Objective: Alopecia aretea is associated with an increase in free radicals causing damage to hair follicles. Superoxide dismutase (SOD) with sufficient penetration through hair follicles, can prevent their death by its strong antioxidant effects. SOD with high molecular weight underwent limitation in follicular delivery. The aim of this study was the improvement of SOD localization into hair follicles. Methods: SOD-loaded niosomes were prepared by thin layer hydration method and were used as a vehicle for delivery to hair follicles through guinea pig skin and the synthetic membrane. Particle size, entrapment efficiency, drug release, and permeability parameters through hairly and non-hairly pig skin compared with a synthetic membrane were evaluated. Results: Niosomes demonstrated 152-325 nm particle size and the SOD burst and sustained release from niosomes were mainly controlled by diffusion and dissolution phenomena. SOD was protected against degradation by niosomes and after six months, enzyme content and activity decreased less than 5%. In comparison with free SOD, niosomes increased SOD affinity to penetration through follicles by interaction with sebum. Likewise, niosome's characters such as type of surfactant, solid lipid/liquid lipid ratio played critical roles on SOD deposition on hair follicles. Conclusion: Synthetic membrane and hairy guinea pig skin demonstrated similar barrier property against free-SOD thereby implying that free SOD does not interact with guinea pig sebum. Niosomes can introduce a suitable carrier for SOD localization into the hair follicles

Altered Skin Permeation of Finasteride Using Clove Oil, Urea, and Lyophilized Powder of Grape Seed Extract

Purpose: Finasteride is a 5-alpha reductase inhibitor used to treat hair loss and acne. The skin permeation of finasteride is one of the main challenges associated with dermal drug delivery. One way to overcome the skin barrier is to use penetration enhancers. The purpose of this study was to investigate the effect of some penetration enhancers on finasteride permeability on the skin, as well as the effect of pretreatment time on their efficacy. Methods: In order to determine the effect of penetration enhancers on the skin permeability of finasteride, the skin was exposed to clove oil, urea, and lyophilized powder of grape seed extract (LPGSE) at different pretreatment times (2, 4 h), and then the permeability parameters were determined by passing the drug through the skin. Results: The results of this study showed that clove oil, urea, and LPGSE increased the transfer of finasteride from the skin. The highest rate of permeation was observed with clove oil (4 h), and the least permeability was observed with urea (4 h). Conclusion: Increasing the pretreatment time with clove oil and LPGSE increases the permeability of finasteride. Meanwhile, the increase in pretreatment time with urea reduces the penetration of finasteride from the skin due to reversible effects

The Hepatoprotective Effect of Livergol Microemulsion Preparation (Nanoparticle) against Bromobenzene Induced Toxicity in Mice

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Self-Nanoemulsifying Drug Delivery Systems Containing Plantago lanceolata—An Assessment of Their Antioxidant and Antiinflammatory Effects

The most important components of Plantago lanceolata L. leaves are catalpol, aucubin, and acteoside (=verbascoside). These bioactive compounds possess different pharmacological effects: anti-inflammatory, antioxidant, antineoplastic, and hepatoprotective. The aim of this study was to protect Plantago lanceolata extract from hydrolysis and to improve its antioxidant effect using self-nano-emulsifying drug delivery systems (SNEDDS). Eight SNEDDS compositions were prepared, and their physical properties, in vitro cytotoxicity, and in vivo AST/ALT values were investigated. MTT cell viability assay was performed on Caco-2 cells. The well-diluted samples (200 to 1000-fold dilutions) proved to be non-cytotoxic. The acute administration of PL-SNEDDS compositions resulted in minor changes in hepatic markers (AST, ALT), except for compositions 4 and 8 due to their high Transcutol contents (80%). The non-toxic compositions showed a significant increase in free radical scavenger activity measured by the DPPH test compared to the blank SNEDDS. An indirect dissolution test was performed, based on the result of the DPPH antioxidant assay; the dissolution profiles of Plantago lancolata extract were statistically different from each SNEDDS. The anti-inflammatory effect of PL-SNEDDS compositions was confirmed by the ear inflammation test. For the complete examination period, all compositions decreased ear edema as compared to the positive (untreated) control. It can be concluded that PL-SNEDDS compositions could be used to deliver active natural compounds in a stable, efficient, and safe manner

In vitro transdermal delivery of propranolol hydrochloride through rat skin from various niosomal formulations Niosomal formulation of propranolol for transdermal delivery

Abstract Objective(s): The purpose of the present study was to prepare and to evaluate a novel niosome as transdermal drug delivery system for propranolol hydrochloride and to compare the in vitro efficiency of niosome by either thin film hydration or hand shaking method. Materials and Methods: Niosomes were prepared by Thin Film Hydration (TFH) or Hand Shaking (HS) method. Propranolol niosomes were prepared using different surfactants (span20, 80) ratios and a constant cholesterol concentration. In vitro characterization of niosomes included microscopical observation, size distribution, laser light scattering evaluation, stability of propranolol niosomes and permeability of formulations in phosphate buffer (pH=7) through rat abdominal skin. Results: The percentage of entrapment efficiency (%EE) increased with increase in surfactant concentration in all formulations. Among them, F3 formulation (containing span80:cholesterol ratio of 3:1) showed the highest entrapment efficiency (86.74±2.01%), Jss (6.33µg/cm 2 .h) and permeability coefficient (7.02 × 10 −3 cm/h). By increasing the percentage of entrapment efficiency (resulting in increase in surfactant concentration), the drug released time is not prolonged. Among all the formulations, F4 needed more time for maximum drug release. Among these formulations, F4 was also found to have the maximum vesicle size as compared to other formulations. It was observed that niosomal suspension prepared from span 80 was more stable than span 20. Conclusion: This study demonstrates that niosomal formulations may offer a promise transdermal delivery of propranolol which improves drug efficiency and can be used for controlled delivery of propranolol

Preparation and Evaluation of Polymeric Nanofibers Containing Griseofulvin –Microemulsion by Electrospinning Process: Polymeric Nanofibers Loaded with Microemulsion: Preparation and Evaluation

In this study, the purpose of preparing CS/PVA nanofibers loaded GRF microemulsion is to increase the solubility of Low soluble drug griseofulvin by using microemulsion nanocarrier, and nanofiber was used as a technique for a new product. This drug is one of the antifungal drugs, and its uses are for skin diseases. Therefore, a topical route can be a good option. Chitosan /polyvinyl alcohol (CS/PVA) nanofiber containing griseofulvin (GRF) loaded microemulsion was obtained. The microemulsion comprised oleic acid and Transcutol P as the oil phase, Span20 and Labrasol as the surfactant, and Plurol oleique as the cosurfactant. Formulations were prepared with a ME(GRF): polymer ratio (30: 70) and (40: 60) and a polymeric solution containing chitosan (2%) and polyvinyl alcohol (10%) at two weight ratio (20: 80) and (10: 90), respectively. The physicochemical characteristics of the GRF-CS/PVA nanofibers were evaluated. The differential scanning calorimetry (DSC) study showed the amorphous state of the GRF-loaded microemulsions and PVA polymer embedded into the nanofibers. The entrapment efficiency percentage of GRF in the mats was approximately 66.67% - 88.89%. Drug release behavior showed controlled and slow release of drugs that are affected by the type of microemulsion formulation and the ratio of polymers used in nanofibers

The Effect of Various Vehicles on the Naproxen Permeability through Rat Skin: A Mechanistic Study by DSC and FT-IR Techniques

Purpose: The purpose of the present investigation was to evaluate the effectiveness of different vehicles on drug permeability and microstructure of intercellular or lipids in SC layer of skin. Methods: Pre-treated skin of rat using some vehicles including Labarac PG ,Transcutol P, tween 80, span 80 and propylene glycol (PG), were mounted on specialized design franz-diffusion cell was used to assess naproxen permeation and parameters such as permeability coefficients and state flux (Jss) were evaluated. Any differences in peak position and also change in symmetric and asymmetric stretching of C-H bond, lipid ester carbonyl stretching in SC, C=O stretching (Amide I) and C-N stretching of keratin (Amide II) absorbance using Fourier transform infrared spectroscopy (FTIR) were considered to investigate the enhancing mechanism. DSC method was utilized to compare their mean transition temperature (Tm) and enthalpies (ΔH). Results: Steady-state flux (Jss), permeability coefficient (Kp) and diffusion coefficient (D) were significantly (p<0.05) increased by using their span80 showed the biggest enhancement ratio (ERflux) and Transcutol P, Labrafac PG, Tween 80 and Propylene glycol were at the next levels. In comprised to hydrated rat skin the maximum increase in diffusion coefficient was for Tween 80(p<0.05), Lipid fluidization, lipid disruption structure and the irreversible denaturation of proteins in the SC layer of skin by span 80, Tween 80, Labrafac PG, Transcutol P and propylene glycol, were indicated by FT-IR and DSC techniques. Conclusion: It is concluded that naproxen permeation through rat skin may be facilitated by utilizing the vehicle systems. Lipid fluidization and lipid extraction are among suggested mechanisms