الفهرس 
AbstractOnly 14 pages are availabe for public view
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Abstract
Buccal delivery became recently under spotlight in drug delivery research. This is because of the advantages of avoiding the first pass effect on the orally delivered drugs, and the high vascularity of the oral cavity. Buccal mucoadhesive gels are one of the strategies to deliver the actives through the buccal mucosa which utilize the advantage of the presence of the drugs in a solubilized state within the gel matrix. The aim of this research is formulate mucoadhesive buccal gels of two low bioavailable drugs; domperidone and mosapride citrate.
In the first part of the thesis, the possibility of formulating buccal gels of domperidone for pediatric use. After solubility and single solvent permeation studies, transcutol® P was used as cosolvent and penetration enhancer in a 40% mix in water. After characterizing the formulated gels using different tests (rheology, mucoadhesion, release….. etc.), Formula D29 (1% chitosan, 3.5 mg/ml) was used in the comparative pharmacokinetic study against the commercial oral tablet of domperidone (Motilium® 10 mg tablet). The study revealed an enhanced comparative bioavailability of the formulated gels to the oral tablet (202%) with a constant drug plasma level for 5 hours, suggesting a sustained depot of the drug formed in the buccal mucosa.
The second part of the thesis handles the formulation of buccal gels containing mosapride citrate for pediatric use. After solubility and single solvent permeation studies, propylene glycol was used as cosolvent and penetration enhancer in a 40% mix in water. After characterizing the formulated gels using different tests (rheology, mucoadhesion, release….. etc.), Formula M9 (1% xanthan gum, 2.5 mg/ml) was used in the comparative pharmacokinetic study against the commercial oral tablet of domperidone (Fluxpride® 5 mg tablet). The study revealed an enhanced comparative bioavailability of the formulated gels to the oral tablet (160%) with a higher Cmax.
The third part deals with the characterization of the buccal mucosa. This was done through solvent uptake experiment. The study revealed high solvent uptake by the buccal mucosa in case of polar solvents (water, PG, PEG, Glycerol… etc). The second section was dealing with finding a correlation between the porcine buccal mucosa model and the tissue culture model (EpiOral ™). The permeation studies of saturated solutions of domperidone as a model drug, revealed a good correlation between the two models in term of flux, kp and cumulative amount permeated.
The fourth part of the thesis dealt with the effect of cyclodextrins with solubility and permeability of mosapride citrate as model drug. The complex of drug with sulfobutyl-7-beta cyclodextrin prepared by freeze drying achieved the highest solubility of the drug. Permeation studies revealed that complexation of mosapride with cyclodextrins decreased the permeability of the drug through buccal mucosa.
Keywords:
Permeation – buccal – Mucoadhesive – cyclodextrins – permeability – freeze drying.