1

AN OVERVIEW ON BUCCAL DRUG DELIVERY SYSTEM AND RECENT TRENDS

IN ORAL TRANSMUCOSAL DRUG DELIVERY SYSTEMS

Hasina Basharat09-arid-1505

PhD Scholar Of Zoology

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

2

CONTENTS

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

. 3

INTRODUCTION

4

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.

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.

5

CONCEPT OF BIOADHESION

6

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.

7

8

9

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

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

10

Table:- Blood flow in the various regions of the oral mucosa

11

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

ADVANTAGES

12

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

DISADVANTAGES

13

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 .

CATEGORIES OF DRUG DELIVERY SYSTEM

14

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

NOVEL BUCCAL DOSAGE FORMS

15

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.

16

Buccal Patches

17

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)

18

Buccal Tablets

19

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 .

20

Ointments and Gels

21

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) .

22

Buccal Powder

23

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.

24

Buccal Sprays

25

Factors Affecting Buccal Absorption

1. 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.

26

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.

27

2. Environmental Factors A. SalivaThe 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.

28

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.

29

C. Salivary glands

It is located in epithelial or deep epithelial region of buccal mucosa.

They constantly secrete mucus on surface of buccal mucosa.

30

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

31

Novel mucoadhesive polymersCapable 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

32

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

33

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 areable to bind certain sugars on the cell membrane, can increasebioadhesion and potentially improve drug delivery via specificbinding and increase the residence time of the dosageForm.

34

CONTI……•Application of tomato lectin in oral drug delivery for the firsttime.

• 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

35

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

36

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.

37

Marketed products

STRIANT

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

38

Buccal Methyltestosterone Metandren

Manufactured by- Ciba Pharmaceuticls Uses- Avoids first-pass hepatic metabolism

39

Marketed Preparations

40

RESEARCH ACTIVITY Buccal drug delivery various research activity is going on in the pharmaceutical industries are as follow. 1. 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.

41

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.

42

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

43

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 emphasison 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

44

45