Development and in vitro and in vivo evaluations of a microemulsion formulation for the oral delivery of oxaprozin

Background: Oxaprozin is labeled as a Class II drug in the biopharmaceutical classification system, and its poor solubility in the entire gastrointestinal tract may be the main reason for its poor oral absorption capacity. Objective: The purpose of this study was to develop an oxaprozin formulation to enhance its oral absorption. Method: Oxaprozin-loaded microemulsions were prepared using the titration method and pseudoternary phase diagram. Characterization experiments were performed on microemulsion preparations, including pH, particle size, shape, zeta potential and stability (thermodynamic, dilution, and differential scanning calorimetry). Then, the in vitro release of the microemulsion and in vivo pharmacokinetics in rats were evaluated. Results : Several microemulsion formulations were prepared. The optimal formulation was 15% oleoyl macrogolglycerides, 35% Tween 20/isopropanol (Km=2) and 50% distilled water. Its particle size met the requirements, and it had a spherical shape with a negatively charged surface. This microemulsion-loaded drug was applied to in vitro release and in vivo pharmacokinetic experiments at 7.47 mg/mL. In vitro release of the oxaprozin-loaded microemulsion best fit the first-order model, while the microemulsion preparation had a certain sustained release effect. In vivo pharmacokinetic experiments indicated that the microemulsion formulation significantly delayed the peak time of the blood concentration and simultaneously prolonged the half-life of drug elimination. Conclusions : The obtained data revealed satisfactory results for this novel microemulsion of oxaprozin, which is very meaningful for clinical trials.

DESIGN AND CHARACTERIZATION OF FLUCONAZOLE MICROEMULSION FORMULATED WITH LEMONGRASS OIL

The goal of the current investigation is to formulate Fluconazole loaded microemulsion (ME) with Lemongrass oil for deeper skin penetration and to obtain the dual benefit of drug and oil combination to improve antifungal efficacy of a drug with a reduced dose. We developed a Pseudo ternary phase diagram to identify the microemulsion zone by using the oil (clove oil), surfactant (Tween 20 and Tween 80), and co-surfactant (Propylene glycol) by water titration method. We formulated six different formulations (LM1 – LM6) by changing the oil/surfactant and cosurfactant ratio. The developed microemulsion formulation was characterized for various parameters % Transmittance, viscosity, pH, drug content, surface morphology, zeta potential, and in-vitro drug release study. The optimized microemulsion emulsion formulation is further converted into Microemulgel by dispersing the ME into 2% w/v Carbapol gel (LM-G) and further evaluated for various parameters. The antifungal efficacy was carried out for ME and Microemulgel by diffusion method against Candida albicans (MTCC no: 227) and compared with marketed gel which showed LM and LM-G have a better antifungal effect than marketed product, proved that the synergistic effect could be achieved by both clove oil and fluconazole drug by microemulsion formulation with deeper skin penetration effect.

DEVELOPMENT OF LEVOFLOXACIN LOADED MICROEMULSION FORMULATED WITH MUSTARD OIL

The aim of the current study is to develop Levofloxacin loaded microemulsion formulated with mustard oil for better skin penetration effect and to obtain combined effect of both the oil and the drug to improve the efficacy with a reduced dose. Primarily we developed a pseudo ternary phase diagrams to find out the region of microemulsion formation zone by using oil (mustard oil), surfactant (Tween 20 and Tween 80), and co-surfactant (propylene glycol) by water titration method. We formulated six different formulations (MM1-MM6) by varying the concentrations of the oil water and surfactant and cosurfactant ratio. The developed microemulsion formulation was characterized for various parameters % Transmittance, viscosity, pH, drug content, surface morphology, zeta potential, and in-vitro drug release study. The selected microemulsion formulation is further converted in to microemulgel by dispersing the ME into 2%w/W Carbopol gel (MM-G) and various parameters are evaluated for the gel. The antimicrobial efficacy was carried out for ME and Microemulgel by well diffusion method against Staphylococcus aureus (MTCC: 737) compared with the standard streptomycin which showed that MM3 and MM-G have a better antimicrobial effect than standard proved that the drug levofloxacin and the mustard oil shows the synergistic effect in the Microemulsion formulation with better skin penetration effect.

Design, Development and Optimisation of Carvedilol Microemulsion by Pseudoternary Phase diagram and Central Composite design

Aim of this study is to design and optimise carvedilol loaded microemulsion. Carvedilol microemulsion is prepared and optimised by Phase titration technique. The selections of material attributes for the formulation of microemulsion are chosen by building a pseudo ternary phase diagram with various concentration oils and surfactant. Optimisation of Carvedilol microemulsion formulation technique was carried out by Central composite Design with two centre points by using selected critical material attributes like the different concentration of oils, surfactants and evaluated for its effect on Critical quality attributes like PS nm, ZP mV, EE %, PI, RI,% Drug Content and Self emulsification time (sec). From this optimisation study data, selected Carvedilol Microemulsion is subjected to measure for its in vitro drug release studies. CM9 formulation showed promising result in particle size, poly dispersibility index, entrapment efficiency and drug release studies. All the above data, it has been accomplished that CM9 was selected as an optimised Carvedilol microemulsion formulation.

CYP3A Excipient-Based Microemulsion Prolongs the Effect of Magnolol on Ischemia Stroke Rats

Magnolol, which is a CYP3A substrate, is a well-known agent that can facilitate neuroprotection and reduce ischemic brain damage. However, a well-controlled release formulation is needed for the effective delivery of magnolol due to its poor water solubility. In this study, we have developed a formulation for a CYP3A-excipient microemulsion, which can be administrated intraperitoneally to increase the solubility and bioavailability of magnolol and increase its neuroprotective effect against ischemic brain injury. The results showed a significant improvement in the area under the plotted curve of drug concentration versus time curve (AUC0–t) and mean residence time (MRT) of magnolol in microemulsion compared to when it was dissolved in dimethyl sulfoxide (DMSO). Both magnolol in DMSO and microemulsion, administrated after the onset of ischemia, showed a reduced visual brain infarct size. As such, this demonstrates a therapeutic effect on ischemic brain injury caused by occlusion, however it is important to note that a pharmacological effect cannot be concluded by this study. Ultimately, our study suggests that the excipient inhibitor-based microemulsion formulation could be a promising concept for the substrate drugs of CYP3A.