Nanocomposite Gels for Controlled Topical Delivery of Simvastatin

Abstract In this study, the lipophilic drug is solubilized using PF127-Chol micelles and then the solubilized drug was incorporated in to chitosan/HPMC gel in order to use as a wound dressing. Introduction: Simvastatin (Sim) is a HMG-COA reductase inhibitor, and is used conventionally for cholesterol reduction but recent studies demonstrated the potential of this agent for diverse pathologic conditions such as wound healing due to its antioxidant, anti-inflammatory, and antibacterial properties. However, the systemic bioavailability of Sim is very low (approximately 5%). Moreover, the systemic administration of Sim can cause several adverse effects such as myopathy and liver problems. Therefore, topical application of Sim can increase the accessibility of drug in wound area at lower systemic level and decrease the possible incidence of side effects. Methods and Results: Polymeric micelles containing Sim were prepared by the thin film hydration method and optimized using irregular full factorial design. The mean diameter, PDI, and zeta potential of the prepared drug loaded micelles were determined by dynamic laser scattering method using Malvern nanosizer. The gels were prepared using chitosan or/and HPMC at 3% (W/W). Bioadhesion was determined using a tensile strength machine. The in vitro release of Sim from different gel formulations was studied using dialysis method. Statistical analysis showed that solvent type had the most impact on the amount of drug loading and zeta potential. The optimized formulation suggested by desirability of 93.5% was prepared using 1 mg of Sim, 10 mg of copolymer, dichloromethane as the organic solvent, hydration time of 45 min, and hydration temperature of 25 oC. The release of the drug from nanomicelles was found to be biphasic and showed a rapid release in the first stage followed by a sustained release for 96 hrs. The gel-contained nanomicelles exhibited pseudo-plastic flow and more sustained drug release profile compared to nanomicelles. Conclusions: The results indicate the obtained composite gel has great potential for topical applications at the site of wounds

Development and evaluation of wafer loaded with sertaconazole solid dispersion for the treatment of oral candidiasis

Candidiasis is one of the most common fungal infections of oral cavity in humans, causing great oral discomfort, pain and aversion to food. To develop more effective antifungal systems for the treatment of oral candidiasis, an oral mucoadhesive wafer containing sertaconazole solid dispersion (STZ-SD) was developed in this study. Dispersion of STZ in Soluplus® as a solubility enhancement excipient was done by melting, solvent evaporation and freeze drying method at various STZ to Soluplus® ratios. The optimized STZ-SD was then incorporated in the sodium carboxymethyl cellulose (SCMC) gel, xanthan gum gel, or their combination to prepare the lyophilized wafers. The swelling capacity, porosity, and mechanical, release and mucoadhesive properties of the wafers, together with their antifungal activity, were then evaluated. The melting method sample with the ratio of 8:1 showed the best results in terms of saturation solubility and dissolution rate. The STZ-SD-composite wafer exhibited higher hardness and mucoadhesion, as compared to those made of the SCMC polymer. The STZ-SD-wafer also exhibited a greater antifungal effect when compared to the STZ-wafer. The present study, thus, suggested that the STZ-SD-wafer could serve as a novel effective delivery system for oral candidiasis treatment

Effect of different types of surfactants on the physical properties and stability of carvedilol nano-niosomes

Background: Niosomes are non-ionic surfactant vesicles used as drug carriers for encapsulating both hydrophobic and hydrophilic drugs. The aim of this study is to evaluate the effect of different surfactants on the physical properties and stability of carvedilol niosomes designed to improve oral bioavailability. Materials and Methods: Different niosomal formulations were prepared using a film hydration method, with various mixtures of different non-ionic surfactants including Span 20, 40, and 60, and also Tween 20, 40, and 60, along with cholesterol. The physicochemical characteristics of the formulations were evaluated in vitro. Results: The drug encapsulation efficiency was reduced by using lauryl (C12) chain containing surfactants, that is, Span/Tween. Cholesterol content and drug entrapment were the main factors affecting the mean particle size of the niosomes. The drug release profiles from most of the formulations were fitted well with the Baker-Lonsdale model, indicating a diffusion-based drug release mechanism. Niosomes prepared from 50 and 40% of the cholesterol with 25 or 30% of Span/Tween 60 showed the highest stability due to their high transition temperature and solid state feature of these surfactants. Conclusions: From the results obtained, it may be concluded that nanoniosomes are promising stable carriers for the oral delivery of carvedilol

Formulation, Design, and Optimization of Taste Masked Effervescent Tablet Containing Methocarbamol: Effervescent Tablet Containing Methocarbamol

Methocarbamol is a skeletal muscle relaxant drug. In this study, we investigated the potential of developing methocarbamol effervescent tablets to facilitate drug administration. Effervescent tablets containing 1000 mg methocarbamol were prepared using the direct compression method. The effect of various formulations parameters such as citric acid, sodium bi-carbonate, PEG 6000, and PVP k30 on different physicochemical properties of tablets was evaluated at two levels. Different formulations with various amounts of mentioned excipients and the constant amount of methocarbamol, sucralose, mannitol, and different flavoring agents were prepared, and their properties included hardness, friability, pH effervescent time, CO2 content, and taste were studied. The optimized formulation was B8, which contained 400 mg of citric acid, 525 mg of sodium bicarbonate, 226.5 mg of PVP k30, 113.2 mg of PEG 6000, 100 mg of mannitol, and 30 mg of sucralose. This formulation had an effervescent time of 112.67± 2.05 seconds, hardness of 71.10± 2.51 N, and pH of 6.01±0.02. Statistical analysis by Design-Expert software showed that the hardness of tablets is mainly affected by the amount of PEG 6000. Volunteers reported that sour cherry had the most pleasant taste to them. In conclusion, current effervescent tablets are shown to be suitable vehicles for methocarbamol with potential for use in patients with swallowing problems and will enhance patient compliance

Development of a Rapid and Precise Reversed-phase High-performance Liquid Chromatography Method for Analysis of Docetaxel in Rat Plasma: Application in Single-dose Pharmacokinetic Studies of Folate-targeted Micelles Containing Docetaxel

Background: A simple and sensitive reversed-phase high-performance liquid chromatography (HPLC) method based on liquid-liquid extraction was established and validated for determination of docetaxel (DTX) in plasma of rat. Materials and Methods: Samples were spiked with paclitaxel as the internal standard and the chromatographic separation was carried out using C18 HPLC column. The mobile phase consisted of a mixture of acetonitrile/water with the ratio of 60/40 v/v. The ultraviolet detector was operated at 230 nm, and the flow rate of mobile phase was 1 ml/min. The method was validated for linearity, precision, accuracy, recovery, and limit of quantification (LOQ). Then the method was applied to quantify DTX in the rat plasma after intravenous (IV) administration of the self-assembled micelles of folate-targeted Synpronic F127/cholesterol (FA-PF127-Chol) loaded with DTX and Taxotere® as the reference marketed solution of DTX. The blood samples were taken from the ophthalmic vein at predetermined time intervals after treatment. Results: Calibration curve was linear between the concentration ranges of 0.1–7.5 μg/ml with the relative standard deviation % and evaluating error % ranged from 2.263 to 15.53 and −12.75 to 12.7 for intra- and inter-day validity, respectively. The mean recovery of the drug after plasma extraction was 95.67 ± 0.99% for the concentration of 1 μg/ml. The LOQ and the limit of detection for DTX in serum were 100 ng/ml and 30 ng/ml, respectively. Conclusions: The results indicated that the developed method could be adopted for pharmacokinetic studies of DTX-loaded FA-PF127-Chol micelles and Taxotere® in rat

Preparation and in vitro evaluation of Vancomycin loaded Montmorillonite-Sodium Alginate topical gel for wound infection

Abstract Despite decades of research, wound healing remains a significant public health problem. This study aimed to develop and evaluate a topical sodium alginate gel containing vancomycin (Van) loaded MMT NPs for wound healing applications. Van was loaded in MMT at different conditions (pHs of 6, 7 and temperatures of 40, 50 °C) (Van/MMT NPs). The optimum formulation (with the smallest particle size and a high value of zeta potential; 270.8 ± 77.35 nm and -35.96 ± 2.73, respectively) showed a high drug-loading capacity (entrapment efficacy of 96%) and a sustained release pattern of Van (95%) over 480 min. The optimum Van/MMT NPs were embedded into the sodium alginate (SA) gel (Van/MMT NPs/SA gel). The Van/ MMT NPs/SA gel showed a sustained and slow release pattern of Van (95%) over 50 h. FTIR tests revealed the electrostatic interaction between MMT and Van. The broth macrodilution tube method was used to determine the minimum inhibitory concentration (MIC) of Van, Van/ MMT NPs, and Van/MMT NPs/SA gel against Staphylococcus aureus. The results showed the promising antibacterial activity of Van/MMT NPs/SA gel, thus, this gel can be a promising formulation for the management of infected wounds

Folated Synperonic-Cholesteryl Hemisuccinate Polymeric Micelles for the Targeted Delivery of Docetaxel in Melanoma

The objective of this study was the synthesis of folic acid- (FA-) targeted polymeric micelles of Synperonic PE/F 127-cholesteryl hemisuccinate (PF127-Chol) for specific delivery of docetaxel (DTX). Targeted or nontargeted micelles loaded with DTX were prepared via dialysis method. The effects of processing variables on the physicochemical properties of targeted micelles were evaluated using a full factorial design. After the optimization of the polymer/drug ratio, the organic solvent type used for the preparation of the micelles, and the temperature of dialyzing medium, the in vitro cytotoxicity and cellular uptake of the optimized micelles were studied on B16F10 melanoma cells by flow cytometry and fluorescent microscopy. The anticancer efficacy of DTX-loaded FA-PF127-Chol was evaluated in mice bearing melanoma tumor. Optimized targeted micelles had the particle size of 171.3 nm, zeta potential of −7.8 mV, PDI of 0.325, and a high encapsulation efficiency that released the drug within 144 h. The MTT assay indicated that targeted micelles carrying DTX were significantly more cytotoxic, had higher cellular uptake, and reduced the tumor volume significantly more than the nontargeted micelles and the free drug. FA-PF127-Chol could be, therefore, a promising biomaterial for tumors overexpressing folate receptors

Preparation and in vitro evaluation of Vancomycin loaded Montmorillonite-Sodium Alginate topical gel for wound infection

Despite decades of research, wound healing remains a significant public health problem. This study aimed to develop and evaluate a topical sodium alginate gel containing vancomycin (Van) loaded MMT NPs for wound healing applications. Van was loaded in MMT at different conditions (pHs of 6, 7 and temperatures of 40, 50 °C) (Van/MMT NPs). The optimum formulation (with the smallest particle size and a high value of zeta potential; 270.8 ± 77.35 nm and -35.96 ± 2.73, respectively) showed a high drug-loading capacity (entrapment efficacy of 96%) and a sustained release pattern of Van (95%) over 480 min. The optimum Van/MMT NPs were embedded into the sodium alginate (SA) gel (Van/MMT NPs/SA gel). The Van/ MMT NPs/SA gel showed a sustained and slow release pattern of Van (95%) over 50 h. FTIR tests revealed the electrostatic interaction between MMT and Van. The broth macrodilution tube method was used to determine the minimum inhibitory concentration (MIC) of Van, Van/ MMT NPs, and Van/MMT NPs/SA gel against Staphylococcus aureus. The results showed the promising antibacterial activity of Van/MMT NPs/SA gel, thus, this gel can be a promising formulation for the management of infected wounds