INTRODUCTION:

Oral route is the widely utilized route of administration for the systemic delivery of many drugs¹. The popularity of oral drug administration may be due to ease of administration. Oral drug delivery is limited by many disadvantages. The rate and extent of absorption vary greatly depending on many factors like drug, type of formulation, nature of the food, drug interactions and the pH of gastrointestinal fluids². Extensive hepatic metabolism also reduces the bioavailability of orally administered drugs², metabolites formed due to first-pass metabolism may not be as active or as potent as the parent drug, and thus requirement of the oral dose is much greater than the parenteral dose to cause the same clinical effect³. For some drugs, like isoproterenol and albuterol, first pass breakdown is so high that therapeutic concentrations cannot be achieved with oral administration³.

In contempt of the route of administration, required amount of drug must be absorbed and reach the site of action in order to elicit pharmacological action. Drug distribution can also be non-selective, which leads to appearance of drug residue in tissues like liver and kidney other than the specific tissue/organ and leads to toxicity². As a result, complete therapeutic action of many drugs cannot be achieved by conventional route of administration. In many cases, the use of novel drug delivery systems could overreach these problems, to achieve therapeutic drug concentrations.

The disadvantages of conventional routes of administration have made researchers to search new alternatives for drug administration. Development has been made in recent years in the area of pharmaceutical and biopharmaceutical technology. The systemic delivery of active pharmaceutical ingredients (drugs) through novel methods of administration is one, in which significant changes and improvements have been made.

Conventional routes of drug administration such as oral, intravenous and intramuscular have been supplanted by the advent of new, non peroral routes of administration (novel drug delivery systems) which includes liposomes, nanoparticles, niosomes, TDDS, mucoadhesive drug delivery systems^2,4,5. Advantages of novel drug delivery include sustained/controlled drug delivery leading to less frequent dosing as well as avoidance of marked fluctuations in plasma drug concentration which often is associated with systemic drug administration^6,7. As is the case with the integument, the oral cavity is one of the alternative novel sites for drug delivery. Researchers investigated oral mucosa for local and systemic delivery for many drugs¹. Drug delivery across the oral mucosa is termed transmucosal drug delivery (TMDD). Based on the characteristics of the oral cavity TMDD is divided into

§ Sublingual delivery:

Administration of drugs through the membrane on the ventral surface of the tongue.

§ Buccal delivery:

Administration of drugs through the buccal mucosa of cheeks.

§ Gingival delivery:

Administration of drugs through gingival mucosa⁸.

TMDD via buccal mucosa has proven particularly useful and offers several advantages over other drug delivery systems including: avoidance of first pass metabolism, enzymatic/acid degradation in the gastrointestinal tract, sustains therapeutic drug levels, permits self-administration, non-invasive (no needles or injections), improves patient compliance, reduces side effects and easy termination of delivery by detaching the dosage form. Though buccal mucosa is less permeable than the sublingual area, due to its high vascularization, drugs can be rapidly absorbed into the venous system underneath the oral mucosa resulting faster onset of action^8,
9.

ANATOMY AND NATURE OF ORAL CAVITY:

The oral cavity is divided into two regions¹⁰

· The outer oral vestibule, which is bounded by cheeks, lips, teeth and gingiva.

· The oral cavity, which extends from teeth and gums back to the fauces with the roof comprising of hard and soft palate.

Physical description of oral cavity:

According to function, mucosa that covers the oral cavity is divided into three types¹⁰. A schematic representation of the oral cavity was depicted in Figure 1.

1. Masticatory mucosa

2. Lining mucosa

3. Specialized mucosa

1. Masticatory mucosa:

Mucosa around the teeth and on the hard palate. It’s made up of keratinized epithelium.

2. Lining mucosa:

Mucosa that covers the lips, cheeks, fornix, base of the oral cavity, lower part of tongue, buccal mucosa and the soft palate. These regions are made up of non-keratinized epithelium.

3. Specialized mucosa:

Mucosa that covers the dorsum of the tongue and its highly keratinized.

Figure 1: Schematic representation of the oral cavity¹¹

The buccal and sublingual regions are the primary ways for drug delivery via the oral mucosa because they are more permeable than the tissue in other regions of the mouth¹¹. The surface area of the oral mucosa (approx. 200 cm²) is relatively small compared to gastrointestinal tract (approx. 350000 cm²) and skin (approx. 20000 cm²)¹². Advantage of oral mucosal delivery is that the membranes have direct access to systemic circulation (capillaries and venous drainage). So, the drugs that are absorbed through the oral mucosa will directly enter into systemic circulation, bypassing the gastrointestinal tract (GIT) and first-pass metabolism¹³. The regional variation in the composition of oral mucosa pertinent to systemic delivery details were showed in Table 1.

Buccal mucosa:

Buccal mucosa is made up of two components epithelium, underlining connective tissue¹⁴ and the interface between these two layers is formed by the basement membrane¹³. The buccal epithelium is made up of non-keratinized stratified squamous layer of cells¹⁵.

The upper most superficial region is made up of compact layers of flattened differentiated cells (50µm thickness). Epithelial adhesion in the superficial layers is ensured by the composition of lipid and glycolipid contents extruded from the cellular membrane coating granules^14,15, they are oval or spherical organelles found in the prickle-cell layer^2,16, forming the permeability barrier^14,15.

Deeper into the epithelial cells are loosely held desmosomes, less flattened in nature¹⁴. The outermost one-third¹⁶ of the epithelium is the predominant barrier for drug diffusion (about 50µm).

The basement membrane (BM) is a continuous layer composed of extracellular materials and forms a boundary between the basal layer of the epithelium and lamina propria. The basement membrane gives mechanical support to epithelium by providing bond between the epithelium and underlying connective tissues^14,16. The connective tissue is made up of lamina propria and submucosa. The lamina propria is a connective sheet composed of blood capillaries and nerve fibers. Vascular drainage from the oral mucosa is principally by lingual, facial and retro mandibular veins. These veins directly open into the internal jugular vein and thus avoid first-pass metabolism¹⁶.

Secretion of saliva:

The superficial layer of buccal mucosa is constantly washed by about 0.5 to 2 litres of saliva daily which is produced by salivary glands¹⁷; however, exact calculations showed that the total production of saliva is 500-600ml/day; saliva is secreted by a pair of parotid, submaxillary and sublingual glands. Main composition of saliva is 0.6% w/w solutes, which are mainly inorganic salts and glycoprotein. And also comprises inorganic compounds which contain calcium, phosphate and bicarbonate ions. Calcium ions are useful for the proper functioning of some salivary proteins. A decrease in calcium ions will cause an increase in mucosal permeability due to malfunctioning of epithelial desmosomes. The bicarbonate and phosphate ions maintain the pH of saliva, which varies from 5.8 to 7.1.

Mucus layer:

The superficial tissue layer responsible for adhesion with interface is mucus layer. Mucus is a translucent and viscid secretion that forms a thin, continuous gel adherent to the mucosal epithelial surface. Mean thickness of mucus varies from 50 to 450mm in humans. It is secreted by goblet cells lining the epithelia or by special exocrine glands with mucus cells acini. The exact composition of mucus varies depending on species, pathophysiological state and the anatomy of location. The general composition¹⁷ of mucus is water: 95%, glycoprotein, lipids: 0.5-3.0%, mineral salts: 1% and free proteins: 0.5-1%.

Bioadhesion:

The term bioadhesion¹⁸ refers to either adhesion between two biological materials or between a biological material (cells, cellular secretions, mucus and extracellular matrix) or an artificial substrate (metals, ceramics, polymers, etc.). Bioadhesion is classified into three types based on phenomenological observation¹⁹ showed in Table 2.

Table 2: Bioadhesion types classification

Type	Classification	Examples
Type-I	Bioadhesion occurring between biological objects without involvement of artificial materials.	Cell aggregation²⁰ and cell fusion²¹
Type-II	Bioadhesion of biological materials to artificial substrates like wood, metals and synthetic materials.	Cell adhesion onto culture dishes^{22, 23}
Type-III	Bioadhesion of artificial substances to biological substrates.	Adhesion of polymers to skin or other soft tissues²⁴

MECHANISM OF BIOADHESION:

Step 1: Wetting and swelling of polymer to permit intimate contact with the biological tissue²⁵.

Step 2: Interpenetration of bioadhesive polymer chains and entanglement of polymer and mucin chains²⁵.

Step 3: Formation of chemical bonds between the entangled chains. Chemical bonds can include strong primary bonds (i.e., covalent bonds) as well as weaker secondary forces such as ionic bonds, Van der Waals' interactions and hydrogen bonds²⁵.

Mucoadhesion:

Polymers that adhere to related tissues or the surface coating of the tissues are called as bioadhesive polymers. If the polymer is attached to mucosal tissue i.e., mucin layer, the term “mucoadhesive” can be employed. Mucoadhesive comes into existence when there is a need to localize drug at a specific site in the body. The phenomenon of mucoadhesion satisfies the following features of controlled release systems²⁵

· It permits the localization the drug by forming strong interaction between polymer and mucus of the tissue. (By increasing the contact time)

· It delivers agents locally for the purpose of modulating antigenivity.

· It provides intimate contact between dosage form and absorbing tissue, this results in high drug concentration in a local area and hence high drug flux through the absorbing tissue.

MECHANISMS OF MUCOADHESION:

Electronic Theory:

Electronic theory is based on the principle that both mucoadhesive and biological materials possess opposing electrical charges. Thus, when both the materials come into contact, they transfer electrons leading to the building of a double electronic layer at the interface; where by the attractive forces within this electronic double layer determines the mucoadhesive strength²⁶. Formation of double electronic layer at interface showed in Figure 2.

Figure 2: Formation of double electronic layer at interface

Adsorption theory:

According to the adsorption theory, mucoadhesive device adheres to the mucus by secondary chemical interactions, such as hydrogen bonds, electrostatic attraction or hydrophobic interactions and Vander Waals bonds. For example, hydrogen bonds are the prevalent interfacial forces in polymers containing carboxyl groups. Such forces have been considered the most important in the adhesive interaction phenomenon because, although they are individually weak, a great number of interactions can result in an intense global adhesion²⁶. It is the most widely accepted theory.

Wetting theory:

The ability of at least one of the two materials being bonded, to spread and develop intimate contact with its substrate is an important factor in bond formation. The interfacial tensions are used to predict spreading of the materials and in turn adhesion. The surface energy of both polymer and substrate are studied using surface tension measurements. The wetting theory applies to liquid systems which present affinity to the surface in order to spread over it. This affinity can be found by using measuring techniques such as, contact angle and lower the contact angle greater the affinity. The contact angle should be equal or close to zero to provide adequate spreadability²⁶. Influence of contact angle between device and mucus membrane on mucoadhesion was depicted in Figure 3.

Diffusion theory:

Diffusion theory describes the interpenetration of both polymer and mucin chains to a sufficient depth, to create a semi-permanent adhesive bond. It is believed that the adhesive force increases with the degree of penetration of polymer chains. This penetration rate depends on the diffusion coefficient, flexibility and nature of mucoadhesive chains, mobility and contact time. According to literature²⁶, the depth of interpenetration required to produce an efficient bioadhesive bond lies in the range 0.2-0.5µm. Diffusion of polymer chains of bioadhesive device and mucus was showed in Figure 4.

Fracture theory:

The most useful theory for studying mucoadhesion through tensile experiments is fracture theory, which analyzes the forces required to separate two surfaces after adhesion. The tensile stress produced during detachment is related to the maximum force of detachment divided by the total surface area²⁶. Fracture theory was showed in Figure 5.

Practically, combination of all these factors leads to bioadhesion/mucoadhesion. The steps of bioadhesion/mucoadhesion are: intimate contact with substrate which is due to good wetting of the bioadhesive surface and the polymer. Penetration of the polymer chains into the crevices of biological tissue surface or interpenetration of the bioadhesive chains with mucus, sometimes with weak chemical bonding²⁷.

FACTORS AFFECTING MUCO/BIOADHESION:

Physicochemical and structural properties of a bioadhesive material influence bioadhesion. High molecular weight, natural or synthetic polymers are generally used for mucoadhesion. Synthetic polymers are prepared by polymerization of monomers in presence or absence of cross-linking agents to give either a cross-linked water insoluble polymers or a linear polymer. Hydrogen bonding which is due to hydrophilic groups such as -OH or -COOH plays a significant role in mucoadhesion²⁴. Strong anionic polyelectrolytes with high charge density of -OH or -COOH functional groups are better candidates for bioadhesion than neutral molecules. The bioadhesive strength of a polymer or combination of polymers is affected by the nature of the polymer and surrounding media.

These factors are mainly divided in three classes:

1) Polymer related factors

2) Environment related factors

3) Physiological variables

1) Polymer related factors:

Molecular weight:

Numerous studies have indicated that, there is certain molecular weight at which bioadhesion is at a maximum. Low molecular weight polymers shows high range of interpenetration and low range of enlargement. High molecular weight polymers show high range of enlargement and low range of interpenetration. Intensity of bioadhesive strength of the polymer depends on optimum molecular weight. The swelling property of polymer in water determines interpenetration of polymer molecules within the mucus. Bioadhesive strength increases with molecular weight of the polymer, upto 10,000 and beyond this level there is no much effect. For polymer chain interpenetration in to mucus, it should have an adequate length. Polymer size and configuration are important factors which plays an important role in mucoadhesion²⁴.

Flexibility of polymer chain:

For the interpenetration and enlargement, flexibility of polymer chain is important. In water soluble polymers the mobility of individual polymer chain decreases due to cross linking.

Spatial conformation:

Spatial conformation of polymer molecule plays an important role in adhesion²⁴. Dextrans though have high molecular weight of 19,500,000, show similar adhesive strength to that of polyethylene glycol having a molecular weight of 200,000.

2) Environment related factors:

Applied strength:

For the application of a solid bioadhesive system, definite strength should be applied. The adhesive strength increases with the applied strength and duration of its application²⁴. The initial pressure applied to the mucoadhesive tissue contact site can alter the depth of interpenetration. Polymer interaction can be increased, for the polymers having less interaction with mucin, by applying high pressure for longer period.

Initial contact time:

Initial contact time is critical for mucoadhesives and is based on the tissue viability. The initial contact time between polymer and the mucus membrane determines the extent of swelling and the interpenetration of polymer chains²⁴. The mucoadhesive strength increases with the increase in initial contact time.

Selection of model substrate surface:

The treatment and handling of biological substrate during testing of mucoadhesives is an important factor because physical and biological changes may occur in the mucus under the experimental conditions²⁴. The viability of biological substrate should be confirmed by examining properties such as permeability and electrophysiology.

Swelling:

Swelling is related to the polymer and its environment. It also depends on concentration of polymer and amount of water. When polymer chains are disintegrated they can easily interpenetrate in to mucosa. When swelling is too high the intensity of bioadhesion will decrease²⁴.

3) Physiological variables:

Mucin turnover:

The residence time of mucoadhesives on the mucus layer depends on the mucin turnover. More is the mucin turnover less will be the residence time. Small amounts of soluble mucin molecules will interact with mucoadhesives before interacting with mucus layer due to mucin turnover²⁵.

Diseased states:

Physicochemical properties of mucus will change during diseased states like as cystic fibrosis, gastric ulcers, common cold, ulcerative colitis, cystic fibrosis, inflammatory conditions of eye and fungal infections of the female reproductive tract²⁵.

Evaluation of novel buccal drug delivery systems^28-30:

1. Moisture absorption studies for Buccal patches:

The moisture absorption studies for the Buccal patches give an indication about the relative moisture absorption capacities of polymers and an idea whether the Buccal patches maintain their integrity after absorption of moisture. Moisture absorption studies have been performed in 5% w/v agar in distilled water, which while hot was transferred to petri plates and allowed to solidify. Then six Buccal patches from each formulation were selected and weighed. Buccal patches were placed in desiccator overnight prior to the study to remove moisture if any and laminated on one side with water impermeable backing membrane. Placed on the surface of the agar plate and incubated at 37°C for 2 hrs in incubator. The patches were weighed again and the percentage of the absorbed moisture was calculated using the formula²⁸

% Moisture absorbed =

Final weight – Initial weight × 100 Initial weight

2. Swelling and erosion studies for Buccal tablets:

Swelling and erosion studies for Buccal tablets were determined gravimetrically in phosphate buffer, of pH 6.6. The tablets were attached to pre-weighed glass supports using a cyanoacrylate adhesive sealant. The supports with tablets were immersed into the phosphate buffer at 37.0^oC. At pre-determined time intervals, the devices were removed from the media, blotted with tissue paperto remove excess water, and weighed. After determination of the wet weight, the tablets were dried at 40°C until constant mass.

3. Determination of tensile strength²⁹:

Tensile stress is also termed Maximum Stress or Ultimate Tensile Stress. The resistance of a material to a force tending to tear it apart, measured as the maximum tension the material can withstand without tearing. Tensile strength can be defined as the strength of material expressed as the greatest longitudinal stress it can bear without tearing apart. As it is the maximum load applied in breaking a tensile test piece divided by the original cross-sectional area of the test piece, it is measured as Newtons/sq.m.

4. Shear stress method:

The measurement of the shear stress gives an direct correlation to the adhesion strength. In asimple shear stress measurement based method two smooth, polished plexi glass boxes wereselected one block was fixed with adhesive araiditeon a glass plate, which was fixed onleveled table. The level was adjusted with the spirit level. To the upper block, a thread was tied and the thread was passed down through a pulley, the length of the thread from the pulley to the pan was 12cms. At the end of the thread a pan of weight 17gms was attached into which the weights can be added.

5. Permeation studies:

Buccal permeation studies must be conducted to determine the feasibility of this route of administration for the candidate drug. in vitro and/or in vivo both methods are involved to determine the buccal permeation profile and absorption kinetics of the drug³⁰.

In vitro Methods:

For examine drug transport the in vitro studies are carried out with animal buccal tissues. Buccal mucosa with underlying connective tissue is surgically removed from the oral cavity, the connective tissue is then carefully removed and the buccal mucosal membrane is isolated. The membranes are then placed and stored in ice-cold (4°C) buffers (usually Krebs buffer) until mounted between side-byside diffusion cells for the in vitro permeation experiments. Buccal cell cultures have also been suggested as useful in vitro models for buccal drug permeation and metabolism. However, to utilize these culture cells for buccal drug transport, the number of differentiated cell layers and the lipid composition of the barrier layers must be well characterized and controlled³¹.

In vivo Methods:

In vivo methods were first originated by Beckett and Trigs with the so-called buccal absorption test. Using this method, the kinetics of drug absorption was measured. The methodology involves the swirling of a 25ml sample of the test solution for up to 15 minutes by human volunteers followed by the expulsion of the solution. The amount of drug remaining in the expelled volume is then determined in order to assess the amount of drug absorbed. The drawbacks of this method include salivary dilution of the drug, accidental swallowing of a portion of the sample solution, and the inability to localize the drug solution within a specific site (buccal, sublingual, or gingival) of the oral cavity. However, to utilize these culture cells for buccal drug transport, the number of differentiated cell layers and the lipid composition of the barrier layers must be well characterized and controlled. Other in vivo methods include those carried out using a small perfusion chamber attached to the upper lip of anesthetized dogs. The perfusion chamber is attached to the tissue by cyanoacrylate cement. The drug solution is circulated through the device for a predetermined period of time and sample fractions are then collected from the perfusion chamber (to determine the amount of drug remaining in the chamber) and blood samples are drawn after 0 and 30 minutes (to determine amount of drug absorbed across the mucosa). For study the permeation characteristics of buccal drug delivery systems special attention is require to choice of experimental animal species for such experiments. Many researchers have used small animals including rats and hamsters for permeability studies. However, such choices seriously limit the value of the data obtained since, unlike humans, most laboratory animals have an oral lining that is totally keratinized. The rabbit is the only laboratory rodent that has non-keratinized mucosal lining similar to human tissue but it is hard to isolate the desired non-keratinized region due to sudden transition to keratinized tissue at the mucosal margins. The oral mucosa of larger experimental animals that has been used for permeability and drug delivery studies include monkeys, dogs, and pigs which are having non-keratinized tissue³².

6. Dissolution and drug release test:

Drug release studies for buccal tablets are normally performed using USP apparatus How ever some authors are develop special apparatus or methods for drug release study of buccal tablets.

Ikinci et al. used an alternative method to study the release of nicotine from buccal tablets. They used modified Franz diffusion cells for this purpose. The dissolution medium was 22ml phosphate buffer saline (PBS) (pH 7.4) at 37°C. Uniform mixing of the medium was provided by magnetic stirring at 300 rpm. To provide unidirectional release, each bioadhesive tablet was embedded into paraffin wax which was placed on top of a bovine buccal mucosa as membrane³³.

Table 3: Patents on buccal patches/films

Inventors	Title of the work	Patent number
Garry L Myres, Samuel D Hilbert, Bill J Boone, B. Arlie Borge, Pradeep Sanghvi, Madhusudhan Hariharan³⁵	Sublingual and buccal film compositions	US20110033542A1
Stephen mayer, Greg Slominski, Christopher E F³⁶	Orally administrable films	US20100063110A1
Stephen mayer, Greg Slominski, Christopher E F, Nicole Ouis³⁷	Multi - zone films	US20100266669A1
Meir haber, Throdis Kristmundsdottir, Skuli Skulason³⁸	Orally administrable films and preparation thereof	US8840935B2
Richard T Clark, Maurice E Durschlag³⁹	Oral/Buccal transmucosal delivery methods for electrolyte compositions including xylitol	US20080152695A1
James E Biegajski⁴⁰	Film bandage for mucosal administration of actives	US20070172515A1
Richard C Fuisz⁴¹	Two Phase mucoadhesive composition	US20070298087A1
Joachim Moormann, Klaus Optiz, Hans-Rainer Hoffmann⁴²	Oral formulations of desoxypeganine and thereof	US20070155774A1
Tina Rademacher⁴³	Transmucosal form of administration with reduced mucosal irritation	WO2005000263A1
Kenneth Widder, Warren Hall, Kay Olmstead⁴⁴	Transmucosal delivery of proton pump inhibitors	US20040006111A1
Horst George Zerbe, Jian-Hwa Guo, Anthony Serino⁴⁵	Water soluble film for oral administration with instant wettability	US20020127190A1
Michael A Repka, Staci l Repka, James W Mcginity⁴⁶	Bio adhesive hot-melt extruded film for topical and mucosal adhesion applications and drug delivery and process for preparation and thereof	US6375963B1

Table 4: Commercially available oral mucosal drug delivery systems⁴⁷

Drug	Mucosal site	Dosage form	Product name	Manufacturer
Fentanyl citrate	Buccal	Lozenge	Actiq	Cephalon
Fentanyl citrate	Buccal	Tablet	Fentora	Cephalon
Buprenorphine hydrochloride	Buccal	Tablet	Subtex	ReckittBenckiser
Buprenorphine hydrochloride naloxane HCl	Buccal	Tablet	Suboxane	ReckittBenckiser
Proclorperazine	Buccal	Tablet	Buccastem	ReckittBenckiser
Triamcinalone	Buccal	Tablet	Aphtac	Teijin Ltd
Testosterone	Buccal	Tablet	Striant SR	Columbia Pharmaceuticals
Nitroglycerine	Sublingual, Buccal	Tablet, Spray	Nitrostat	W Lambert-P Davis-Pfi zer Pharmaceuticals
Glyceryl trinitrate	Buccal	Spray	Nitromist	NovaDel
Glyceryl trinitrate	Buccal	Tablet	Suscard	Forest laboratories
Nicotine	Buccal	Chewing gum	Nicorette	GSK consumer health
Nicotine	Buccal	Lozenge	Nicotinelle	Novartis consumer health
Micanazole	Buccal	Tablet	Loramyc	Bio Alliance Pharma SA
Cannabis-derived	Buccal	Spray	Sativex	GW Pharmaceuticals, PLC
Fentyl	Buccal	Film	Onsolis	Meda Pharmaceuticals
Rizatriptan	Buccal	Films wafers	Maxalt Wafers	Merck and Co
Ondansetron	Buccal	Film	Zuplenz	Strativa Pharmaceuticals

Mumtaz and Ch’ng introduced another method for studying the dissolution of buccal tablets. The device that they introduced is based on the circulation of pre-warmed dissolution medium through a cell as shown in Fig- II. Here the buccal tablet was attached on chicken pouches. Samples were removed at different time intervals for drug content analysis. They stated “the results obtained by using this apparatus for the release of drug from bioadhesive tablets concurred with the predicted patterns”³⁴.

Patents and commercial products approved for oral transmucosal administration:

Several dosage forms like tablets, lozenges, gels, patches, films and microspheres has been developed by various research works in the progress of improving transmucosal delivery. Commercially marketed products are mostly tablets and lozenges. Few companies succeeded in development of patches and films for rapid drug release and clinical response. Table 3 shows the list of patents and Table 4 shows the list of commercial products approved for oral transmucosal administration.

CONCLUSION:

Now a days the Buccal mucoadhesive drug delivery system getting more popularity. The most important objective of using bioadhesive systems orally would be achieved by obtaining a substantial enhance in residence time of the drug for local drug effect and to permit once daily dosing. Buccal adhesive systems offer innumerable advantages in terms of accessibility, administration and withdrawal, retentivity, low enzymatic activity, economy and high patient compliance. The natural mucoadhesive polymer as a carrier for Buccal drug delivery can be used to get better health of all living things and to reduce the unwanted effect of synthetic polymers. Pharma researchers who are working on natural polymers should introduce new natural natural polymers in Bucco mucoadhesive drug delivery. The future direction of buccal adhesive drug delivery lies in vaccine formulations and delivery of small proteins/ peptides.

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Received on 29.08.2019 Modified on 12.10.2019

Research J. Pharm. and Tech 2020; 13(6): 2954-2962.

DOI: 10.5958/0974-360X.2020.00523.5

Tissue	Structure	Epithelial thickness (µm)	Turnover time (days)	Surface area (cm²±SD)	Permeability	Blood flow^*	Residence time
Buccal	Non-keratinized	500-600	5-7	50±2.9	Intermediate	20.3	Intermediate
Sublingual	Non-keratinized	100-200	20	26.5±4.2	Very good	12.2	Poor
Gingival	Keratinized	200	---	---	Poor	19.5	Intermediate
Palatal	Keratinized	250	24	20.1±1.9	Poor	7.0	Very good