Hasina Basharat 09-arid-1505 PhD Scholar Of Zoology AN OVERVIEW ON BUCCAL DRUG DELIVERY SYSTEM AND RECENT TRENDS IN ORAL TRANSMUCOSAL DRUG DELIVERY SYSTEMS Hasina Basharat 09-arid-1505 PhD Scholar Of Zoology

CONTENTS Introduction Definition Concepts Structural and functional features of oral mucosa Advantages Disadvantages Categories of drug delivery system Novel buccal dosage forms Novel mucoadhesive polymers Market products Research activity Conclusion Future Aspects

INTRODUCTION Noninvasive systemic administration .Placing a drug or drug delivery system in a particular region of body for extended period of time Local targeting / systemic drug delivery Recent approaches : Bioadhesive polymers Mucoadhesive dosage forms : Wet adhesives Mucoadhesion is defined as the interaction between a mucin surface and a synthetic or natural polymer .

CONCEPT OF BIOADHESION Bioadhesion is the state in which two materials, are held together for an extended period of time by interfacial forces. The term bioadhesion implies attachment of drug- carrier system to specific biological location. If adhesive attachment is to mucous coat then phenomenon is referred to as mucoadhesion.

CONCEPT OF BIOADHESION These drug delivery systems utilize property of bioadhesion of certain water soluble polymers which become adhesive on hydration and hence can be used for targeting particular site. Definition:- Buccal delivery is the administration of the drug via buccal mucosa (lining of the cheek) to the systemic circulation.

STRUCTURAL FEATURES OF ORAL CAVITY Outer oral vestibule, which is bounded by cheeks, lips, teeth and gingiva. Oral cavity is that area of mouth delineated by the lips, cheeks, hard palate, soft palate and floor of mouth. Oral cavity proper, which extends from teeth and gums back to the faces with the roof comprising the hard and soft palate. The tongue projects from the floor of the cavity.

FUNCTIONS OF ORAL CAVITY It helps in chewing, mastication and mixing of food stuff. Helps to lubricate the food material and bolus. To identify the ingested material by taste buds of tongue. To initiate the carbohydrate and fat metabolism. As a portal for intake of food material and water. To aid in speech and breathing process.

VASCULAR SYSTEM OF THE ORAL MUCOSA Table:- Blood flow in the various regions of the oral mucosa Vascular system have been described by Stablein & Meyer (1984) Mucous membrane of buccal cavity is highly vascular Blood supply to mouth : External carotid artery TISSUE BLOOD FLOW Ml/min/100 cm2 Buccal 2.40 Sublingual 3.14 Floor of mouth 0.97 Ventral tongue 1.17 Frenulum 1.00 Gingival 1.47 Palatal 0.89

ADVANTAGES The oral mucosa has a rich blood supply. Buccal administration, the drug gains direct entry into the systemic circulation there by passing the first pass effect. like insulin or other proteins, peptides and steroids. It is good accessibility to the membranes that line the oral cavity, which makes application painless and with comfort. In case of emergencies. Patients can control the period of administration. Increased ease of drug administration

DISADVANTAGES Relatively small absorptive surface area(0,01sq m vs. 100sq m in GIT) Movement affects mucoadhesive system Less permeable than small intestine Salivation and swallowing Taste of the drug

CATEGORIES OF DRUG DELIVERY SYSTEM 1. Sublingual delivery: It is the administration of the drug via the sublingual. 2. Buccal delivery: It is the administration of drug via the buccal mucosa to the systemic circulation. 3. Local delivery: for the treatment of conditions of the oral cavity, ulcers, fungal conditions and periodontal disease .

NOVEL BUCCAL DOSAGE FORMS The novel type buccal dosage forms include: Buccal adhesive patches, Tablets, Films, Semisolids (ointments and gels) Powders.

1. Patches and Films Patches is consists of: Two laminates, With an aqueous solution of the adhesive polymer being cast onto an impermeable backing sheet, The film which is applied to the oral mucosal can be retained in place for at least 12 hours even when it is challenged with fluids. E.g. buccal film of salbutamol.

Buccal Patches

2. Buccal mucoadhesive tablets Mucoadhesive tablets are : dry dosage forms it is to be moistened prior to placing in contact with buccal mucosa. It is double layer tablet, consisting of adhesive matrix layer of polyacrylic acid and hydroxy propyl, cellulose with an inner core of cocoa butter containing insulin and a penetration enhancer (sodium glycocholate)

Buccal Tablets

3. Semisolid Preparations (Ointments and Gels) Consists of finely ground pectin, gelatin and sodium carboxy methyl cellulose dispersed in a poly (ethylene) and a mineral oil gel base. Which can be maintained at its site of application for 15-150 minutes. Example.chitosan glutamate buccal hydrogel with local anaesthetics activity .

Ointments and Gels

4. Powders Beclomethasone and Hydroxpropyl cellulose in powder form when sprayed onto the oral mucosa of rats. A significant increase in the residence time relative to an oral solution is seen. And 2.5% of beclomethasone is retained on buccal mucosa for over 4 hours (Edsman K et al,2005) .

Buccal Powder

5. BUCCAL SPRAYS. Generex bio technology have been introduced insulin spray. This technology is being used to develop a formulation for buccal delivery of insulin for the treatment of type -1 diabetes. Buccal spray delivers a mist of fine droplets onto mucosal membrane probably on to mucin layer. E.g. Estradiol spray.

Buccal Sprays

Factors Affecting Buccal Absorption Membrane Factors: This involves degree of keratinization. Surface area available for absorption. Mucus layer of salivary pellicle. Intercellular lipids of epithelium. Basement membrane and lamina propria.

Contind….. In addition, the absorptive membrane thickness, blood supply/ lymph drainage, Cell renewal and enzyme content will all contribute to reducing the rate and amount of drug entering the systemic circulation.

2. Environmental Factors Saliva The thickness of salivary film is 0.07 to 0.10 mm. The thickness, composition and movement of this film affect the rate of buccal absorption. It coats throughout the lining of buccal mucosa and is called salivary pellicle or film.

B. Movement of Buccal Tissues Buccal region of oral cavity shows less active movements. The mucoadhesive polymers are to be incorporated to keep dosage form at buccal region for long periods to withstand tissue movements during talking and if possible during eating food or swallowing.

C. Salivary glands It is located in epithelial or deep epithelial region of buccal mucosa. They constantly secrete mucus on surface of buccal mucosa.

Active Ingredients of Drugs Delivered Via Buccal Route Morphine sulphate, Nicotine, Nifedipine, Omeprazole, Oxytocin, Piroxicam, Acitretin, Acyclovir Arecoline, Buprenorpine, Carbamazepine, Chitosan, Chlorpheniramine maleate,

Novel mucoadhesive polymers Capable of forming covalent bonds with the mucus and the underlying cell layers New generation of mucoadhesives, except thiolated polymers, can adhere directly to the cell surface, rather than to mucus. Interact with the cell surface by means of specific receptors or covalent bonding instead of non-specific mechanisms, which are characteristic of the previous polymers

Thiolated mucoadhesive polymers Provide much higher adhesive properties than polymers generally considered to be mucoadhesive Interact with cysteine-rich sub domains of mucus glycoproteins via disulfide exchange reactions or via simple oxidation process. Carbodiimide-mediated thiol bond, exhibit much improved mucoadhesive properties Tensile strength, high cohesive properties, rapid swelling and water uptake behavior

Target-specific mucoadhesive polymers Able to selectively create specific molecular interactions with a particular target, such as a receptor on the cell membrane of a specific tissue, is a very attractive potential for targeted delivery. Specific proteins or glycoproteins, such as lectins, which are able to bind certain sugars on the cell membrane, can increase bioadhesion and potentially improve drug delivery via specific binding and increase the residence time of the dosage Form.

CONTI…… Application of tomato lectin in oral drug delivery for the first time. Lectin-mediated mucoadhesive polymers, as second-generation mucoadhesives, contain an enormous potential for future use in drug delivery which, unfortunately, have not yet been fully explored. The recent idea of developing blectinomimetics Q (lectin-like molecules) based on lectins, and even biotechnologically generated derivatives of such molecules, holds an interesting future for this class of bioadhesion molecules

Bacterial adhesion The adhesive properties of bacterial cells, as a more complicated adhesion system, have recently been investigated. The ability of bacteria to adhere to a specific target is rooted from particular cell-surface components or appendages, known as fimbriae, which facilitate adhesion to other cells or inanimate surfaces. The attractiveness of this approach lies in the potential increase in the residence time of the drug on the mucus and its receptor-specific interaction, similar to those of the plant lectins. As an example, Escherichia coli have been reported to specifically adhere to the lymphoid follicle epithelium of the ileal Peyer’s patch in rabbits. Additionally, different staphylococci possess the ability to adhere to the surface

Biopolymers The use of polymers from natural sources in drug delivery systems has become a very popular field of research; However, the oral transmucosal drug delivery system is most common among all other delivery systems. Recently, more than 50 biopolymers have been identified and isolated For oral transmucosal drug delivery system and most of them are used frequently in various drug delivery systems.

STRIANT Marketed products Manufactured by - Columbia Labs, Uses: it is a testosterone extended-release buccal tablet that delivers testosterone systemically for hormone replacement in hypogonadal men.

Buccal Methyltestosterone Metandren Manufactured by- Ciba Pharmaceuticls Uses- Avoids first-pass hepatic metabolism

Marketed Preparations

RESEARCH ACTIVITY Buccal drug delivery various research activity is going on in the pharmaceutical industries are as follow. Chitosan Based Sustained Release Mucoadhesive Buccal Patches Containing Verapamil Hcl. 2. Formulation and Evalutation of Ropinitrole Buccal patches using Different Mucoadhesive Polymers. 3. Developmement Of Mucoadhesive Buccal Patch Containing Aceclofenac: In Vitro Evaluations 4. Design and evaluation of buccal patches of valsartan 5. Formulation and Evaluation of Mucoadhesive Buccal Patches of Aceclofenac.

CONCLUSION Buccal drug delivery is a promising area for continued research with the aim of systemic delivery of orally inefficient drugs Buccal drug delivery system is having the several advantages for controlled drug delivery for extended periods of time in that mucosa is well supplied with both vascular and lymphatic drainage and first-pass metabolism in the liver and pre-systemic elimination in the gastrointestinal tract are avoided. However, with the developments of new formulations, such as bioadhesive preparations may increases in the future.

Future aspects In mucoadhesive placebo buccal patches we can use any potent drugs which fulfill the criteria for buccal patch as drug delivery system. We can perform the dissolution of medicated mucoadhesive buccal patch for drug release profile studies. We can further perform the in-vivo studies for the prepared mucoadhesive buccal patches. We can perform the stability test for the prepared mucoadhesive buccal patches

REFERENCES D.K. Sanghi and Rakesh Tiwle.2015. An overview on buccal drug delivery system, Inter. J. of Pharmacotherapy ,5(1): 8-16. Nishan N Bobade, Sandeep C Atram, Vikrant P Wankhade, Dr. SD Pande, Dr. KK Tapar.2013. A Review on Buccal Drug Delivery System. International Journal of Pharmacy and Pharmaceutical Science Research, 3(1): 35-40. Recent trends in oral transmucosal drug delivery systems: an emphasis on the soft palatal route Nookala Venkala Satheesh Madhav, Ravindra Semwal†, Deepak Kumar Semwal & Ruchi B Semwal †Dehradun Institute of Technology, Faculty of Pharmacy, Makkawala, Dehradun, Uttarakhand, India