الفهرس 
Chemical penetration enhancersOnly 14 pages are availabe for public view
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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.