Kamla Nehru College of Pharmacy Butibori, Nagpur, Maharashtra (India)-441108.
The Buccal drug delivery system includes drug administration through the buccal mucosa, mainly composed of the lining of the cheeks. Buccal drug delivery leads direct access to the systemic circulation through the internal jugular vein bypasses drugs from the hepatic first pass metabolism leading to high bioavailability. Buccal route is an attractive route of administration for systemic drug delivery. basic components of buccal drug delivery system are bioadhesive polymers, Backing membrane, Permeation enhancers. Novel drug dosages forms such as Bio adhesive tablet, films, gel, wafers, etc. and various method used in the preparation of novel buccal drug delivary system. The objective of this article is to review buccal drug delivery by studies on current approaches.
Since traditional dosage forms are typically linked to challenges in getting a prescribed dose to the target place in a timely manner, targeted medicine delivery to specific body parts has emerged as one of the major endeavors of the modern world. This has led to increased demands in recent years for the development and assessment of new medication delivery methods. Actually, there are greater benefits to transmucosal medication delivery routes—such as the nasal, rectal, vaginal, ocular, and oral cavities—than to peroral drug administration. [1]
The buccal mucosa offers a promising alternative to other transmucosal routes and a novel idea for regulated drug administration. When compared to alternative non-oral transmucosal medication administration routes, it offers superior accessibility and high patient satisfaction. Additionally, because the drug avoids the hepatic first pass metabolism and enters the systemic circulation directly, without the need for acid hydrolysis in the GI tract, the buccal mucosa has a higher bioavailability. [1,2] medicine delivery methods that use the bio adhesion of specific water-soluble polymers, which become sticky when hydrated, to target a medicine to a specific area of the body for prolonged periods of time are known as mucoadhesion systems, People Know about the new things, we are discussing novel dosages forms and current approaches of buccal/ Mucoadhesive drug delivery. with some new composition or new technique.[3]
Mucoadhesive Drug administration System in Oral Cavity: There are several categories of drug administration through the oral cavity's membranes, including: (Fig. 1)
1) Sublingual Delivery: medications enter the bloodstream through the mucosal membrane that lines the floor of the mouth.
2) Buccal Delivery: medications are inserted between the cheeks and gums to pass through the mucosal barrier and into the bloodstream.
3) Local Delivery: medication is administered directly into the mouth.[4]
Anatomy of the oral mucosa
The outermost layer of stratified squamous epithelium, the basement membrane, and the connective tissue made up of the lamina propria and submucosa are the three layers that make up the oral mucosa (Fig. 2). The intestinal mucosa has a lower permeability than the buccal mucosa, which is 4–4000 times larger than the skin epidermis.[5] The order of permeability in the oral cavity is sublingual, buccal, and palatal. [6,7]
Fig. 1: Anatomy of the oral cavity
Fig. 2: Buccal mucosa
A. Structure: This oral mucosa is anatomically divided into;
1. Epithelium
2. Connective tissues and the basement membrane
1) Epithelium: The epithelium is made up of roughly 40–50 layers of 500–800 ?m thick stratified squamous epithelial cells. The oral mucosa's epithelium protects tissues and acts as a barrier to keep outside substances out.
2) Connective Tissue and Basement Membrane: The connective tissues and the basal layer of epithelium are separated by the basement membrane (BM), a continuous layer of extracellular materials. Although connective tissue and the basement membrane may restrict the mobility of some macromolecules and complexes, they are not thought to affect the diffusion of the majority of substances of pharmacological significance.
B. Buccal Mucosa Environment: Saliva produced by the salivary glands and mucus secreted by the major and minor salivary glands as part of saliva are characteristics of the oral cavity. [4, 8]
Table 1: Function of saliva and mucus
|
Function of Saliva |
Function of Mucus |
|
• Protective fluid for all tissues of oral cavity. • Continuous mineralization / Demineralization of tooth enamel. • To hydrate oral mucosal dosage forms. |
• Made up of proteins and carbohydrates • Cell-cell adhesion, Lubrication • Bio adhesion of mucoadhesive drug delivery systems Pathways of Drug absorption from buccal mucosa. |
C. Mucus Composition:
The sublingual gland, parotid gland, and other salivary glands are among the glands in the oral cavity that typically secrete oral mucus. Goblet cells or certain exocrine glands that work with mucus cells secrete the mucus, which is a translucent gel.[9]
Table 2: Composition of oral mucus cavity [10]
|
Components |
Percentage |
|
Water |
95% |
|
Glycoproteins and lipids |
0.5-5% |
|
Mineral salts |
61% |
|
Free proteins |
0.5-1% |
Mechanism of buccal absorption:
The non-ionized species passively diffuses the medication into the buccal region. A concentration gradient primarily controls the process of passive diffusion through the epithelium's intercellular gaps. The buccal mucosa is thought of as a lipoidal barrier that prevents drugs from passing through.[11]
Fig. 3: Drug transport across oral epithelium
The enzymes, which include aminopeptidase, carboxypeptidase, and esterase, are usually found on the mucosal surface or inside intracellular compartments. They can act as an extra barrier to medications that penetrate the buccal epithelium. A medicine may or may not interact with all of the enzymes that are present in the mouth cavity, depending on the kind of transport route. However, in contrast to the gastrointestinal tract, the mouth cavity has a less severe enzymatic barrier. The onset of a clinical impact occurs when the drug or drugs diffuse across different biological membrane barriers to reach the target site at the desired concentration. Drugs must either stay at the target site in the buccal area to provide a pharmacological effect or travel through the mucosal epithelial layers to reach systemic circulation after buccal delivery. [12]
Theories of Adhesion: A variety of theories have been put out to explain the mechanism of mucoadhesion, a complex phenomenon. Table 3 provides a summary of these theories, which are helpful in comprehending how mucoadhesive polymers adhere to biological membranes.[13]
Table 3: Theories of mucoadhesion.
|
Theory |
Comments |
|
Diffusion Theory |
? It describes the diffusion of polymer toward the adhesive surface, The diffusion process is governed by its concentration gradient at the applied surface, The penetration of the mucoadhesive polymer depends on the diffusion coefficient |
|
Electronic Theory |
? It describes the transfer of electrons across the applied surface, Adhesion occurs due to differences in electronic distribution and attractive forces result in the formation of an electric double layer at the interface |
|
Adsorption Theory |
? It suggests that forces (van der Waals forces, hydrogen bond, ionic bond, and covalent bond) at the surface are responsible for the adhesive contact developed between a mucoadhesive polymer and the mucosa |
|
Wetting Theory |
?This applies to liquid systems ? It explains the ability of the liquid system to spread on the applied surface |
|
Fracture Theory |
? Describes the force required to separate the two layers after adhesion is completed ? Used to measure the adhesion between rigid or semi-rigid mucoadhesive system |
Basic components of buccal drug delivery system: The basic components of buccal drug delivery system are
Drug substance
Prior to creating mucoadhesive drug delivery systems, it is necessary to determine if a local or systemic effect and quick or extended release are the desired outcomes. Pharmacokinetic characteristics should guide the choice of an appropriate medication for the development of buccoadhesive drug delivery systems.
Characteristics of drug substance:
Bio adhesive polymers
In buccoadhesive medication delivery systems, bioadhesive polymers are essential. Additionally, polymers are employed in matrix devices, which control the length of drug release by embedding the drug in the polymer matrix. The most varied family of polymers are bioadhesive polymers, which offer significant advantages in patient care and treatment. The medicine is delivered into the mucous membrane through a core layer or rate-controlling layer. The oral drug delivery system is greatly enhanced by bioadhesive polymers that stick to the mucin/epithelial surface.
Characteristics of an ideal mucoadhesive polymer
Backing Membrane:
A significant part of the bioadhesive in mucus membranes is the backing membrane. Inert materials that are impermeable to the medication and penetration enhancer should be utilized as backing membranes. This type of impermeable barrier on buccal bioadhesive patches improves patient compliance and stops medication loss. The following compounds are frequently used in backing membranes: polycarbophil, carbopol, magnesium stearate, HPMC, HPC, and CMC.
Permeation Enhancers:
Permeation enhancers are substances that help substances pass through the buccal mucosa. The drug's physicochemical characteristics, the site of administration, the kind of vehicle, and additional excipients all influence the enhancer's choice and effectiveness. [12]
Novel buccal dosage forms: The novel type of buccal drug delivary are show in following chart.
Tablets are not as advantageous as microparticles. Microspheres' physical characteristics allow them to come into close touch with a sizable mucosal surface. The success of these microspheres is restricted by their brief residence duration at the site of absorption, despite the fact that they can also be administered to less accessible locations including the nasal cavity and GI tract and that they produce no local irritation at the site of adhesion.[18]
Nanoparticles: chitosan and dextran sulfate-based mucoadhesive nanoparticles made by the ionic gelation technique. The diameter of the nanoparticles was adjusted between 110 and 360 nm in order to improve their properties and accelerate their commencement of action.
Advantages: Buccal routes of drug delivery offer a large number of advantages over the other route of drug administration.
Disadvantages
Ideal characteristics of buccal delivary system
METHODS OF PREPARATION
Buccal Tablet: Although alternate methods, such as wet granulation, can sometimes be employed, bioadhesive tablets are typically compressed directly. Tablets intended for buccal administration should dissolve or erode gradually in order to be placed into the buccal pouch. Thus, enough pressure is needed to maintain the tablets' hardness. Additionally, water-impermeable substances like ethylcellulose, hydrogenated castor oil, etc., can be applied to any tablet site—aside from the one that comes into contact with the mucosa—by compression or spray coating.[22]
Buccal Patch: The patches are laminates with three compartments: an impermeable backing layer, a reservoir layer that contains the medicine and allows for regulated release, and a bioadhesive surface for mucosal attachment. Solvent casting and direct milling are the two essential techniques for creating adhesive patches.
Buccal Film: The solvent-casting method, which is typically used to make bioadhesive films, is comparable to laminated patches in terms of both manufacturing process and flexibility. Rolling, solid dispersion extrusion, semisolid casting, solvent casting, and hot-melt extrusion.[23]
The straightforward solvent-casting approach has a few drawbacks, such as a lengthy production time, high cost, and environmental issues because of the solvents used. The hot-melted extrusion technique, which was recently published by Repka and McGinity51, can overcome these obstacles.
Buccal Gel and ointments: Particularly in contrast to tablets and patches, bioadhesive ointments have not been reviewed in the literature as thoroughly as other dosage forms. Gels and ointments are examples of semisolid dose forms that have the advantage of being easily absorbed by the mouth mucosa. Bioadhesive formulations employ a phase transition from a liquid to a semisolid to overcome the inadequate retention of the gels at the application site. The viscosity is improved by this alteration, which leads to a regulated and prolonged release of medications. Another interesting drug delivery method for the buccal region is hydrogels. They are made of polymers that have been hydrated in water, which physically traps drug molecules for later, gradual release through erosion or diffusion. [24]
Nanoparticles: Ionic gelation is used to create mucoadhesive nanoparticles based on chitosan and dextran sulfate.[17]
Method of hot melt extrusion To create a more uniform substance in various forms, such as granules, tablets, or films, a mixture of pharmaceutical ingredients is melted and then forced through an opening in the hot melt extrusion method. Oral disintegrating films, pellets, granules, and controlled release matrix tablets have all been produced via hot melt extrusion. [25, 26]
CURRENT APPROACHES OF BUCCAL DRUG DELIVARY SYSTEM
Some scientists enumerated the following as obstacles to the development and approval of buccal dosage forms: low dose drugs; the complexity of biology and permeability issues; the need for a unique mechanism to improve drug absorption without causing excessive side effects; the drug's taste and patient acceptability; the possibility of difficult dose titration for in vivo studies; and challenges relating to regulations, authorities, and economic circumstances.[27] There are currently investigations on novel buccal drug delivery formulations because of improved factors and new methods. In general, only a small number of novel buccal drug delivery dosage forms have advanced to the clinical development stage. Adding mucoadhesive ingredients or permeability enhancers to traditional dosage formulations has been the primary tactic.[28] As recombinant DNA technology advances, buccal delivery is considered crucial for creating protein and peptide compositions.[29] Numerous studies on the buccal administration of peptides have been carried out in accordance with recent advancements in buccal drug delivery systems, such as lipophilic gel, buccal spray, and phospholipid vesicles. Current research on development methods includes the formulation of a new insulin liquid aerosol and liquid crystal systems. For buccal drug delivery, nanoparticulate systems (Nanocarrier Technique) have been integrated into a number of dosage forms, such as gels, sprays, tablets, films, and patches. Research and innovation have been particularly busy in the last few years in the development of buccal delivery methods. [30, 31]
CONCLUSION:
Buccal dosage forms offer prolonged contact at the site of administration, low enzymatic activity, economy, high patient compliance, and easy administration and withdrawal. Mucoadhesive polymers may provide an important tool to improve the bioavailability of the active agent by improving the residence time at the delivery site and avoiding pre-systemic metabolism in the GIT and hepatic first-pass elimination. However, the need of safe and effective buccal permeation and absorption enhancers is a crucial component for a prospective future in the area of buccal drug delivery. The safety and efficacy of current treatments may be improved if their delivery rates, biodegradation, and site-specific targeting can be predicted, monitored and controlled. Buccal/mucoadhesive systems may play an increasing role in the development of new pharmaceuticals. Currently solid dosage forms, liquids, spray and gels applied to oral cavity are commercially successful. The future direction of buccal adhesive drug delivery lies in vaccine formulations and delivery of small proteins/peptides.
REFERENCES
Neha Naringe*, Dimpal Sarkar, Pankaj Dhapke, Jagdish Baheti, Review On Novel Buccal Drug Delivery System and Their Current Approaches, Int. J. of Pharm. Sci., 2024, Vol 2, Issue 12, 115-123. https://doi.org/10.5281/zenodo.14259094
10.5281/zenodo.14259094
