Histamine and its various
receptors have been significant drug target for a long time. Histamine is
released during inflammatory and allergic reactions, anaphylactic shock, and
pseudo allergic reactions. The allergen
binds to IgE surfaces where the release of most histamine binds to H1 receptor
to induce erythema and itching causing allergic reactions to occur. Histamine
released has a set of different effects on different target organs for example
in the nervous system, cardiovascular system and bronchiolar smooth muscle.
They have been used to treat and relieve symptoms of various types of allergies
including airway disorders such as asthma or upper respiratory tract infection,
allergic rhinoconjunctivitis, urticaria and also the most severe systemic
allergic reaction known to be anaphylaxis.
The precise function receptors of
histamine in immunomodulation stays vague to this day, while their pathological
as well as physiological significance and dissemination in variable tissue are
The past studies were done to reveal the role of H1and H2 receptors for immunomodulation
and their powerful function on lymphocytes, nevertheless, all these researches
have studied the concentrations of antibodies acquiring from experimental animals
single samples of blood at single point in time.
Taking into account the pervious discussed
data a conclusion was reached, antihistamine play an important role in immunomodulation.
Antihistamines work by the reduction in mediator’s release and expression
cytokine and by also blockage of the predominant receptors on the surface of
cell membrane. However, when using the first-generation antihistamine caution
must be taken and it must be used properly as it passes BBB causing drowsiness
interfering with daily life activities.
choice in this work is KTF which is a relatively noncompetitive H1 antagonist
and mast cell stabilizer which can prevent the development of asthmatic
conditions and immunomodulate by H1 antagonism, but it is suffering from 50% decrease
in bioavailability due to first pass effect. Several trials were made to
overcome low bioavailability of ketotifen fumarate through buccal route through
different buccal formulations.
Buccal delivery involves the administration of the desired drug
through the buccal mucosal membrane lining of the oral cavity.
The buccal route is the route of
choice because it offers distinct advantages which will help in the delivery of
KTF. The lining of the mucosa of oral cavity proposes numerous special advantages.
It is richly vascularized and more accessible for the administration and
removal of a dosage form. Additionally, buccal drug delivery has a high patient
acceptability compared to other non-oral routes of drug administration.
Avoiding acid hydrolysis in the gastrointestinal (GI) tract and bypassing the
first-pass effect are some of the advantages of this route of drug delivery.
Moreover, rapid cellular recovery and achievement of a localized drug delivery
site on the smooth surface of the buccal mucosa are among the other advantages
of this route of drug delivery. These various advantages especially the bypassing
of the first-pass effect offers a solution to the bioavailability problem of
KTF increasing its bioavailability and decreasing the dose required.
Like any other route, the buccal route has disadvantages; nevertheless,
they will not be as hindering to the KTF buccal formulation. The disadvantages
associated with this route of drug delivery are the low permeability of the
buccal membrane as well as small surface area. The total surface area of the
membrane of the oral cavity available for drug absorption is 170 cm2,
of which almost 50 cm2 represents non-keratinized tissues. The
continuous secretion of saliva (0.5–2 L/day) leads to subsequent dilution of
the drug. Swallowing of saliva can also potentially lead to the loss of
dissolved or suspended drug. The disadvantage which might primarily buccoadheseive
disc to be formulated is the low permeability can be solved by permeation
Permeation enhancers are materials that
ease the penetration of the drug through the buccal mucosa. The choice of
enhancer as well as the type of dosages form will aid in the perfect delivery
of the drug the delivery of KTF gracefully.
Bothe the enhancer
and its efficacy are contingent on a variety of thing including:
· Physiochemical properties
of the drug
· Site of administration
· Nature of the
· Other excipients
From the data
we gathered the preferable formulation of KTF might be the unidirectional release
formulation because it offers minimal drug loss with the trial of various
enhancers to reach its optimal bioavailability with no to minimal loss.