**3.1 Oral route**

The oral route has traditionally been chosen over other existing administrative methods due to its ease of administration, patient compliance, and possible formulation flexibility. The buccal area (buccal mucosa) of the oral cavity provides an appealing channel for medication delivery for both local and systemic activities. Buccal mucosa possesses morphological and physiological properties that make it a good drug delivery route, including the presence of smooth muscles with high vascular perfusion, high accessibility, minimal enzymatic activity, and escape of hepatic first-pass metabolism. However, the formulation's transit duration at an application location is limited by the constant salivary flush in the mouth cavity. More study into the use of bioadhesive polymers to prolong the residence time (RT) of formulations in living tissue has resulted as a result of this [16]. Drug delivery through to the buccal mucosa has been accomplished with tablets, lozenges, chewing gums, sprays, films, patches, hydrogels, pastes, ointments, solutions, microspheres, and other dosage forms, but buccal films have been reported to be the most favourable and successful strategy for delivering through the epithelium with greater patient compliance [17].

The microenvironment of the mucosa controls medication disintegration (release) and penetration through the mucosa. The environment of the mucosa can be modified or transformed with the help of well-designed mucoadhesive drug delivery devices [17]. These systems are designed and formulated with mucoadhesive polymers, which are generally of high molecular weight and high viscosity grades with improved flexibility and optimal chain length. A variety of mucoadhesive polymers have also been used to study buccal drug delivery. Buccal films are superior to oral gels and buccal tablets among mucoadhesive drug delivery systems due to their long residence time, more flexibility in covering the buccal mucosa, and improved comfort [18]. The major goal of this study was to create a buccal mucoadhesive patch that would maintain a stable miconazole level in the mouth for lengthy periods. The created patch's performance will be compared to that of a commercial oral gel. In addition, the effect of ageing on the produced patches' mucoadhesive function will be examined.

The oral route, which includes buccal mucosa, is the most suitable for both local and systemic drug delivery among the different locations accessible for mucoadhesive drug delivery. The created buccal mucosal membrane by Jacob S et al., 2021 presents an appealing drug-delivery channel to boost both systemic and local therapy. The advantages and disadvantages of buccal drug delivery, anatomical and physiological

characteristics of the oral mucosa and several in vitro techniques often employed for assessing buccal drug-delivery systems are all discussed in this paper. The importance of mucoadhesive polymers, penetration enhancers, and enzyme inhibitors in overcoming formulation problems, including the salivary refurbishment cycle, masticatory effect, and limited absorption area, is discussed. Because of their flexibility, convenience, lightness, acceptability, ability to endure mechanical stress, and specific size, biocompatible mucoadhesive films and patches are preferred dosage forms for buccal administration. The methods of preparation, the scaling-up process, and the manufacturing of buccal films are discussed [19].

Furthermore, Semalty et al. develop mucoadhesive buccal films of enalapril maleate to increase therapeutic efficacy, patient compliance, and bioavailability. Using the solvent casting technique, five formulations of mucoadhesive drug delivery systems of enalapril maleate were created as buccal films in this study. Mucoadhesive polymers employed were sodium carboxymethylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, and polyvinyl pyrrolidone K-90. In permeation tests, films showed controlled release for more than 10 hours. The films containing 20 mg of enalapril maleate in sodium carboxymethylcellulose 2% w/v and hydroxyethylcellulose 2% w/v showed good swelling, a convenient residence time, and promising controlled drug release, and thus can be chosen for the development of buccal films for effective therapeutic uses [17].
