Histamine, Antihistamines play a major role in allergic inflammation

Histamine,
a biological amine, that belongs to one of the most important mediators
involved in the regulation of the body’s vital functions plays a great role in
the pathogenesis of different diseases. It stimulates various biological
functions when released from any of the effector cells as a result of either
immunological or non-immunological stimuli. Its reaction is expressed differently
according to the histamine receptors that it affects which are H1, H2, H3 as
well as H4 receptor which are widely distributed in the
body.           Antihistamines are drugs that work by blocking the effects
of histamine. Antihistamines acts as
inverse agonists that combine with and stabilize the inactive conformation of
the H1 receptor, H1 antihistamines including
the first and second generation can be differentiated by their chemical
structure and potential toxicity. Generally, the older generation has more
adverse effects compared to the new generation of antihistamines. Antihistamines
play a major role in allergic inflammation by inhibiting abundant mediators such
as mast cells and basophils in response to the immune system.          Ketotifen Fumarate which
is a relatively noncompetitive H1 antagonist and mast cell suffers from low
bioavailability of 50% due to hepatic first pass metabolism.

     Buccal route delivery
involves the administration of the desired drug through the buccal mucosal
membrane lining of the oral cavity. The buccal mucosa offers some distinct
advantages in delivery of drugs. It is richly vascularized and more accessible
and useful for
systemic transmucosal drug delivery and local
delivery. Additionally, buccal drug delivery
has a high patient acceptability compared to other non-oral routes of drug
administration. To overcome low bioavailability of KTF, the buccal route will
be used to deliver the drug through different buccal formulations mainly
buccoadhesive discs with optimized properties and performance while avoiding
acid hydrolysis in the gastrointestinal (GI) tract and bypassing the first-pass
effect.

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