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Abstract The fundamental aim of this thesis was to evaluate effect of ethanol and PG concentration in microemulsion formulation on transdermal delivery. Different methods of application (open and occlusive) were also investigated. To achieve this, indomethacin and ketoprofen were selected as model drugs. The proceeding sections summarize the studies performed to achieve this objective. 1- Development of a suitable method for analysis of the drugs. A sensitive HPLC method was developed for analysis of the selected model drugs. The method was validated for the specificity, linearity, precision, accuracy, limit of detection and limit of quantitation. The developed chromatographic methods for indomethacin and ketoprofen were able to quantify the drugs. Indomethacin was eluted at a retention time of 3.5 + 0.1 minutes. With regard to ketoprofen, the drug was eluted at 4 + 0.05 minutes. Both methods were linear in the range of 1–20 g/ml. The validation results indicated both intraday and inter-day precision and accuracy. 2- Construction of pseudo-ternary phase diagrams. Pseudo-ternary phase diagrams were constructed using eugenol oil or oleic acid as the oil phase, water and Tween 40 or 80 as surfactant with ethanol or propylene glycol( PG) being employed as cosurfactant with surfactant/cosurfactant ratio being maintained at 1:1 w/w. These phase diagrams were used to select the composition Abstract Pharmaceutical Technology department, College of Pharmacy, University of Tanta, Tanta, Egypt. 2 of proper microemulsion formulations for transdermal drug delivery investigations. 3- Transdermal delivery of indomethacin from microemulsion. The aim was to optimize eugenol microemulsion for transdermal delivery of indomethacin (model drug). Pseudo-ternary phase diagrams were constructed using Tween 40 (surfactant) in presence and absence of ethanol or PG as co-surfactants. Microemulsion formulations containing eugenol at 10, 20 and 30% w/w with 60% w/w of surfactant or surfactant/co-surfactant were evaluated for indomethacin loading, release and transdermal delivery. Transdermal delivery was assessed using rabbit ear model. The phase diagrams reflected the ability of Tween 40 to form eugenol microemulsion with addition of ethanol or PG increasing the microemulsion zone. Indomethacin loading in microemulsion was increased by increasing eugenol concentration and in presence of co-surfactants. The release rate increased in presence of PG or ethanol. Indomethacin transdermal flux was greater from microemulsions containing high eugenol concentration with PG containing systems being superior. The study introduced eugenol microemulsion formulations for transdermal delivery and highlighted possible synergism with PG. 4- Occlusive versus open application in transdermal delivery of ketoprofen from microemulsion. The study was further extended to investigate occlusive versus open application as a factor affecting transdermal drug delivery from microemulsion. The ability of microemulsion system to fill the microarchitecture of the skin surface was considered as the main Abstract Pharmaceutical Technology department, College of Pharmacy, University of Tanta, Tanta, Egypt. 3 mechanism for enhanced transdermal delivery in addition to the penetration enhancing activity of the components. The first mechanism depends on the fluidity of the formulation. Unfortunately, fluid systems are not widely accepted for topical application. Accordingly, the aim of this work was to compare transdermal delivery of ketoprofen from fluid and non-fluid microemuslion phase transition systems. The tested formulations were fluid ethanol free microemulsion, gel and liquid crystalline (LC) phase systems and ethanol containing microemulsions which thickens after evaporation of ethanol upon open application to skin. All formulations were better than saturated aqueous control. Fluid formulations were superior than gel and LC systems. Open application of ethanol containing systems delivered ketoprofen through the skin at higher rate than the corresponding gel or LC system. The study highlighted the possibility of open application of fluid microemulsion which contains volatile components. This system combines the strong penetration enhancing potential and feasibility of topical application due to thickening after evaporation of the volatile component. The study was extended to cover the effects of PG concentration in microemulsion on drug release and transdermal permeation. Pseudo-ternary phase diagrams were constructed using Tween 80 (surfactant) in presence and absence of PG as co-surfactants. |