الفهرس 
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Abstract
The peroral route is often considered the preferred route of administration of drugs due to safety considerations and patient compliance. However, peroral administration of drugs has a major disadvantage which is the hepatic first pass metabolism. Transmucosal routes of drug delivery (i.e., the mucosal linings
of the nasal, rectal, vaginal, ocular, and oral cavity) offer distinct advantages over oral administration for
systemic drug delivery. One of these advantages include possible bypass of first pass effect. The oral cavity
is highly acceptable by patients, the mucosa is relatively permeable with a rich blood supply, it is robust
and shows short recovery times after stress or damage and the virtual lack of Langerhans cells makes the
oral mucosa tolerant to potential allergens.
Zolmitriptan and losartan potassium were selected as model drugs for the buccoadhesive tablets. They are
water soluble drugs belong to BCS class III drugs. They suffer from extensive hepatic first pass
metabolism, low absolute oral bioavailability and short half life. Losartan potassium is used for a chronic
disease (hypertension). So, it was a suitable candidate for a sustained release buccoadhesive dosage form.
Buccoadhesive tablets were prepared by direct compression technique then they were evaluated for physicchemical properties, in-vitro and ex-vivo studies and accelerated stability studies. The results showed that
zolmitriptan formula which was containing a combination of carbopol 934LR and chitosan (43% w/w) in
the ratio of 1:3.3 was the optimum one. However, Losartan potassium formula which was containing a
combination of carbopol 934LR and chitosan (40% w/w) in the ratio of 1:2 was the optimum one. The
order of drug release from most formulae of both drugs was zero and the mechanism of drug release from
optimized formula was by diffusion mechanism according to Higuchi’s model for zolmitriptan and by
dissolution mechanism according to Hixson-Crowell model for losartan potassium. Both drugs were
permeated through the sheep buccal mucosa slowly and steady. There was a good correlation between the
drug release and drug permeation process and chitosan played an important role in the study by facilitating
the transport of the drugs by paracellular route due to interaction with tight junctions of the membrane after
getting protonated in the aqueous medium. The drugs were degraded by time and the drug content was not
less than 93%. The degradation followed zero order kinetics and the shelf life for each drug exceeded a
year. The in-vitro drug release profile changed slightly with a minor reduction in the cumulative drug
release. The order of the drug release process was still zero order. There was a significant improvement in
oral bioavailability of zolmitriptan by 1.676 after its administration in the form of buccal mucoadhesive
tablets as compared to oral solution which may be due to the ability of the drug to bypass the extensive
premature metabolism in liver.
It was concluded that buccal route can be an alternative way to deliver both drugs to the systemic
circulation bypassing the extensive pre-systemic metabolism in liver which may increase their absolute oral
bioavailability and patient compliance. Several formulae can be developed with a flexibility in selection of
types of mucoadhesive polymers, the concentration of each polymer and the polymer-polymer ratio within
each formula. The buccoadhesive tablets can be mass produced using direct compression technique with no
need for a granulation process to be carried out prior to compression.