Histamine and its variousreceptors have been significant drug target for a long time. Histamine isreleased during inflammatory and allergic reactions, anaphylactic shock, andpseudo allergic reactions. The allergenbinds to IgE surfaces where the release of most histamine binds to H1 receptorto induce erythema and itching causing allergic reactions to occur. Histaminereleased has a set of different effects on different target organs for examplein the nervous system, cardiovascular system and bronchiolar smooth muscle.They have been used to treat and relieve symptoms of various types of allergiesincluding airway disorders such as asthma or upper respiratory tract infection,allergic rhinoconjunctivitis, urticaria and also the most severe systemicallergic reaction known to be anaphylaxis.
The precise function receptors ofhistamine in immunomodulation stays vague to this day, while their pathologicalas well as physiological significance and dissemination in variable tissue arebeing recorded.The past studies were done to reveal the role of H1and H2 receptors for immunomodulationand their powerful function on lymphocytes, nevertheless, all these researcheshave studied the concentrations of antibodies acquiring from experimental animalssingle samples of blood at single point in time. Taking into account the pervious discusseddata a conclusion was reached, antihistamine play an important role in immunomodulation.Antihistamines work by the reduction in mediator’s release and expressioncytokine and by also blockage of the predominant receptors on the surface ofcell membrane. However, when using the first-generation antihistamine cautionmust be taken and it must be used properly as it passes BBB causing drowsinessinterfering with daily life activities. Drug ofchoice in this work is KTF which is a relatively noncompetitive H1 antagonistand mast cell stabilizer which can prevent the development of asthmaticconditions and immunomodulate by H1 antagonism, but it is suffering from 50% decreasein bioavailability due to first pass effect. Several trials were made toovercome low bioavailability of ketotifen fumarate through buccal route throughdifferent buccal formulations.Buccal delivery involves the administration of the desired drugthrough the buccal mucosal membrane lining of the oral cavity.
The buccal route is the route ofchoice because it offers distinct advantages which will help in the delivery ofKTF. The lining of the mucosa of oral cavity proposes numerous special advantages.It is richly vascularized and more accessible for the administration andremoval of a dosage form.
Additionally, buccal drug delivery has a high patientacceptability compared to other non-oral routes of drug administration.Avoiding acid hydrolysis in the gastrointestinal (GI) tract and bypassing thefirst-pass effect are some of the advantages of this route of drug delivery.Moreover, rapid cellular recovery and achievement of a localized drug deliverysite on the smooth surface of the buccal mucosa are among the other advantagesof this route of drug delivery. These various advantages especially the bypassingof the first-pass effect offers a solution to the bioavailability problem ofKTF 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 disadvantagesassociated with this route of drug delivery are the low permeability of thebuccal membrane as well as small surface area. The total surface area of themembrane of the oral cavity available for drug absorption is 170 cm2,of which almost 50 cm2 represents non-keratinized tissues. Thecontinuous secretion of saliva (0.
5–2 L/day) leads to subsequent dilution ofthe drug. Swallowing of saliva can also potentially lead to the loss ofdissolved or suspended drug. The disadvantage which might primarily buccoadheseivedisc to be formulated is the low permeability can be solved by permeationenhancers. Permeation enhancers are materials thatease the penetration of the drug through the buccal mucosa. The choice ofenhancer as well as the type of dosages form will aid in the perfect deliveryof the drug the delivery of KTF gracefully.Bothe the enhancerand its efficacy are contingent on a variety of thing including:· Physiochemical propertiesof the drug· Site of administration· Nature of thevehicle· Other excipientsinvolved.From the datawe gathered the preferable formulation of KTF might be the unidirectional releaseformulation because it offers minimal drug loss with the trial of variousenhancers to reach its optimal bioavailability with no to minimal loss.