الفهرس 
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Abstract
Abstract
Vesicular delivery systems for treatment of psoriasis
Rana Abdelgawad Moussa
National Organization for Drug Control and Research
Purpose: The objective of this work was to develop tazarotene containing vesicles capable of overcoming the biological skin barrier of stratum corneum that minimizes drug penetration to desired site of action, with a sufficient reduction in skin inflammatory manifestations accompanying psoriasis. Attempts were made to develop tazarotene vesicles containing ceramide (cerosomes) capable of recompensating the loss of natural ceramide which is responsible of dryness and painful scaly plaques on skin of psoriatic patients.
Methods: Tazarotene vesicles containing ceramide (cerosomes) with or without surfactant addition were prepared by the thin film hydration method by mixing tazarotene, ceramide, surfactant (Tween 80 or Sodium DeoxyCholate) at different ratios in presence of soya phospholipid. Ceramide free tazarotene vesicles were also prepared similarly for comparative purposes. The formed vesicles were then tested for their EE%, viscosity, in-vitro release, followed by characterization of certain formulae by TEM, particle size and zeta potential, DSC, ex-vivo skin deposition, and stability. The clinical effect of 2 chosen formulae was evaluated on certain patients suffering from chronic plaque psoriasis and compared to the commercial gel Acnitaz®. Psoriasis progression was evaluated using PASI score.
Abstract
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Results: All prepared vesicles showed acceptable tazarotene EE%, with higher EE% for ceramide containing vesicles; reflecting ceramide role in improving tazarotene encapsulation in the prepared vesicles. SDC containing vesicles showed higher EE% than their corresponding formulae with Tween 80; owing to the higher solubilizing effect of Tween 80. Ethanol addition was responsible for the decrease in tazarotene EE%; as it increases drug leakage from formed vesicles by its reported ability to increase the permeability of the vesicular membrane.
The edge activator amount was the key factor for determination of vesicular viscosity, with Tween 80 containing vesicles showing higher viscosity than their corresponding SDC containing ones. Ethanol addition contributed to the viscosity of the prepared formulae owing to its ability to form gel like domains in the vesicular phospholipid bilayers.
The in vitro release was quite low for all prepared formulae favoring tazarotene residence in the vesicular lipidic components.
TEM was also performed on cerosomal free formulae showing well identified spherical vesicles. Ethanol containing formulae had unilamellar thinner wall. Cerosomes showed a dramatic change from spherical vesicular to tubulated form owing to ceramide presence which is responsible for the rigidification and flattening of the phospholipid bilayer curvature.
DSC was carried out on free drug, ceramide and some selected formulae, showing tazarotene endothermic peak at 124.6˚C, with no thermal peak for ceramide or thermal changes for the prepared formulae with accompanied disappearance of tazarotene peak revealing successful tazarotene solubilization and presence in phospholipid vesicular bilayer.
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Certain selected formulae were subjected to ex-vivo skin deposition, which showed greater tazarotene deposition over 72 hours than the marketed product, with greater ceramide skin deposition. This was considered of great importance serving our aim to replenish the lack of ceramide in psoriatic patients. Stability study was conducted on selected formulae showing high stability for drug loading after one year storage. Furthermore, the best formula containing ceramide displayed more clinical efficacy manifested by the reduction in PASI scores compared to Acnitaz® marketed product and the reduction of tazarotene topical irritation owing to its encapsulation.
Key words: tazarotene, ceramide, Tween 80, SDC, psoriasis, ethanol