buccal and sublingual drug delivery system

05/01/2023 Sagar Kishor Savale

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Buccal and Sublingual Drug Delivery System [BDDS & SDDS]

Mr. Sagar Kishor Savale[Department of Pharmaceutics]

[email protected]

Department of Pharmacy (Pharmaceutics) | Sagar Savale

mailto:[email protected]

05/01/2023 Sagar Kishor Savale 2

Contents Introduction Advantages Disadvantages Ideal Candidates for BDDS

Anatomy of Buccal mucosa

Formulation of buccal dosage form Evaluation of buccal dosage form

References

Conclusion


Introduction

• Administration of a drug via buccal mucosa (lining of cheek) to the systemic circulation is defined as buccal delivery.

• The buccal mucosa lies in inner cheek.

• Placed between upper gingivae.

• To treat locally or systemically


Within the oral mucosal cavity, delivery of drugs is classified into three categories:

a) Subligual deliveryb) Buccal deliveryc) Local delivery a) Sublingual delivery : It is the delivery of drugs or dosage form which is placed below or under the

tongue and allowed to dissolve.


b) Buccal delivery:• Delivery of drug or dosage form to the place between the cheek and the gum.

c) Local delivery:• Which is drug delivery into the oral cavity .• For the treatment of periodontal disease, ulcer, bacterial infection etc.


Advantages of Buccal Drug Delivery

Avoids first pass metabolism.

Avoids acid/Enzyme metabolism.

Permeation is faster with respect to skin & TDDS (4- 4000) Large surface area with respect to sub-lingual mucosa.

Good patient compliance with respect to parenteral.

Easy administration & removal (termination) in case of toxicity. For unconscious or non compatible patients.


Drugs with bitter taste or irritant to mucosa or having noxious smell are poor candidates.

Not for children.

Eating & drinking difficulty.

Salivary erosion & it may enter GIT & choke esophagus.

Less surface area than skin.

Drugs unstable at Buccal pH (6.5 to 7)

Disadvantages


• Mucoadhesion of the device is a key element.

• The term ‘mucoadhesive’ is commonly used for materials that bind to the mucin layer of a biological membrane.

• Achieve systemic delivery of drugs include tablets, patches, tapes, films, semisolids (gels and ointments) and powders. Some times spray and lotions are also used.

BDDS and Mucoadhesivity


Mechanism of Buccal Drug Delivery


1. Molecular size 75-100 Daltons.

2. Dose of drug should be small enough to deliver across the Buccal mucosa.

3. Drug should be hydrophilic/hydrophobic in nature.

4. Drug should be stable in Buccal pH (6.4-7.2)

5. Drug should be free from bitter taste and odorless.

6. Drug which are absorbed only by passive diffusion.

Ideal Candidates For Buccal Drug Delivery System


Anatomy of Buccal Mucosa

Structure of oral mucosa 1) Epithelium - stratum distendum - stratum filamentosum - stratum suprabasale - stratum basale2) Basal lamina3) Connective tissue - lamina propria - submucosa

Fig- Anatomy of buccal mucosa


ANATOMY & PHYSIOLOGY OF ORAL CAVITY


Three different types of oral mucosa are recognized:

• Masticatory mucosa: (25% of the total oral mucosa) 1. Covers gingiva/ hard palate regions 2. keratinized epithelium

• Lining mucosa: (60% of the total oral mucosa ) 1. cover soft palate, floor of mouth, under side of tongue, labial & buccal mucosa. 2. non-keratinized epithelium.

• Specialized mucosa: (15% of the total oral mucosa) 1.The dorsal surface of the tongue 2. Highly keratinised.


Overview of the Oral Mucosaa) STRUCTURE:

fig: structure of oral mucosa .

The turn over time for the buccal epithelium : 5 - 6 day The epithelium of buccal mucosa – about 40 to 50 cell layer thick The oral mucosal thickness-buccal (500 to 800 μm) sublingual (100 to 200 μm) 14


b) ENVIORNMENT The feature of the environment of the oral cavity is the presence of saliva & mucus. Role of mucus. 1 cell-cell adhesion. 2 Lubrication. 3 Adhesion of mucoadhesive drug delivery systems.

Role of saliva.

1 Protective fluid for all tissues of the oral cavity. 2 Continuous mineralization/demineralization of the tooth enamel. 3 To hydrate oral mucosal dosage forms. c) PERMIABILITY 4-4000 times greater than that of skin.

Permeability of oral mucosa :

sublingual > Buccal > parenteral


The basic components of buccal drug delivery system- Drug substance Bio adhesive polymers Backing membrane Permeation enhancers

Formulation of BDDS – Patch/Film/Adhesive Tape


Ability to attachment of bio adhesive device to mucus membrane

Backing membrane

Inert in nature and impermeable to the drug

Such impermeable membrane prevent dug loss and good patient compliances

Examples – Carbapol, Magnesium sterate, Polycarbapol


IDEAL CHARACTERISTICS: Non toxic, non irritable, free from leachable impurities. Polymer pH should be biocompatible. Quick adherence, and sufficient mechanical strength. Bioadhesive in both dry and liquid state. Acceptable shelf life. Optimum molecular weight.

TYPES: 1 st generation polymers : PAA, NaCMC, HPMC, Carbapol, Chitosan, Xanthan gum, PVA etc. 2 nd generation polymers : Lectins, Multifunctional polymers, Thiolated polymers etc.

Bioadhesive polymer


Sr. no Theory Mechanism of muco/Bioadhesion

1 ElectronicAttractive electrostatic force between glycoprotein mucin network & the Bioadhesive material.

2 AdsorptionSurface force (Covalent bond, hydrogen bond, van der Waals forces) resulting In chemical bonding.

3

Wetting Ability of bioadhesive polymer to spread & develop intimate contact with the mucous membranes.

4 Diffusion Physical entanglement of mucin strands & the flexible polymer chains.

5 Fracture

theory

Analyses the maximum tensile stress developed during detachment of the BDDS from the mucosal surface.

Theories of Muco/Bio-adhesion


FACTOR AFFECTIG MUCOADHESION

a. Polymer related factor :1. Molecular weight 2. Flexibility 3. H-bonding capacity 4. Cross linking density 5. Charge 6. Concentration b. Drug related factor: 1. Molecular weight 2. Lipophilicity

c. Patient related factor: 1. Salivary secretion rate 2. pH of buccal cavity


Substances that help to promote drug permeation through the buccal epithelium are referred to as penetration enhancers, permeation promoters or absorption enhancers.

Most of the compounds used as buccal mucosal penetration enhancers are the ones generally used to compromise barrier function.

Examples - sodium lauryl sulfate, sodiumlaurateBile salts: Sodium glycodeoxycholate, sodium glycocholate, sodium taurodeoxycholate, sodium taurocholate

Permeation Enhancers


Buccal penetration enhancer

• Chemical methods:

Transiently altering the lipid bilayer

membrane.

Increasing cell membrane fluidity.

Extracting structural lipids.

Altering cellular proteins.

Overcoming the enzymatic barrier.22


Physical Methods:

Mechanically by: Removal of the outermost layers of the epithelium to decrease the barrier thickness. Sonophoresis

Electrically by: Iontophoresis, Electro-poration.

Classification & example of penetration enhancer:-

a. Bile salts and there steroidal detergents:- Sodium glycocholate, sodium taurocholate, saponins, etc

b. Surfactants:- 1) Nonionic - Polysorbate 80,sucrose ester, etc.2) Cationic - Cetyltrimethyl ammonium bromide.3) Anionic - SLS,fatty acids.

3) c. Other enhancers:- Azone, chelating agent , sulfoxide.


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• Propranalol• Nitrites and nitrates• Nefidipine• Fenoterol• Estradiol• Oxytocin• Metoprolol• Metoclopromide• Insulin• Nitro glycerine• Codeine• Morphine• Diltiazem• Chlorpheniramine maleate

Drugs administered as buccal tablets


Mechanism of Drug Absorption or Transport Routes

Mostly drugs are absorbed by passive diffusion mechanism. Nutrients are absorbed by carrier mediated mechanism.


BUCCAL ROUTE OF DRUG ABSORPTION

• There are two permeation pathways for passive drug transport across the oral mucosa:

1.Transcellular route : Route for lipophilic compounds. 2. Paracellular route : Route for hydrophilic drug.

Fig : Transportation route of drug molecule

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BUCCAL DOSAGE FORM

1. TabletTablets is small, flat, generally oval shape with 5-8mm diameter. Monolithic and two-layered matrix tablets have been designed for

buccal delivery of drugs. Monolithic tablets is consist of a mixture of drug with a swelling

bioadhesive/sustained release polymer. They can be coated on the outer or on all sides but one face with water

impermeable hydrophobic substances to allow an unidirectional drug release for systemic delivery.

Two-layered tablets comprise an inner layer based on a bioadhesive polymer and an outer non-bioadhesive layer containing the drug for a bi-directional release but mainly for local action.

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Limitation of adhesion of tablet:1. Small mucosal surface for contact.2. Extent & frequency of contact might causes irritation.

2.Patches

• They are long ,flat, thin & transparant with high surface area.

• Patches are laminated and generally consist of an impermeable backing layer and a drug-containing layer that has mucoadhesive properties and from which the drug is released in a controlled manner.

They can be prepared by two method : 1. Solvent casting method 2. Direct milling method Example: Melatonin (cydot)


3. Chewing Gum :

Advantage:

Ability to retain in the oral cavity for long periods for prolong drug delivery.

Gum base consist of Resin, fats, emulsifier, filler & antioxidant .

4. Gels & ointment:

They typically contain bioadhesive polymer (HEC, carbomer, etc)&Drug plus any required excipients dissolved or suspended as finePowder in aqueous or non- aqueous base.

Example-Metronidazole (zidovel).

5. Buccal Spray : - The drugs may be administered by a buccal spray especially to children.


In vitro Swelling rate and bio adhesion studies Surface pH studies Drug release studies Permeation studies Mucoadhesion strength Residence time

Evaluation test


Ex vivo studies

Animals are sacrificed.

Buccal mucosa with underlying connective tissue is surgically removed, and then isolated.

Placed and stored in ice-cold (4°C) buffers. (usually Krebs buffer) .

Generally dogs, monkeys and pigs are used.


In vivo Drug release studiesStability studies in human salivaEx vivo Mucoadhesion timeMucoadhesion force Transmucosal permeation studied.


In vivo method

First originated by Beckett & Triggs .

The methodology involves the swirling of a 25 ml 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 determined in order to assess the amount of drug absorbed.

Drawback:1 . Salivary dilution of the drug.2. Accidental swallowing of a portion of the sample solution.


Applications

1. Smoking cessation therapy.

2. Hormone replacement therapy .

3. Hypertention.

4. Angina pectoris.

5. Cancer.

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References1.Shojaei Amir H., Buccal Mucosa As A Route For Systemic Drug Delivery: A Review, University of Alberta, Faculty of Pharmacy and Pharmaceutical Sciences, Edmonton, Alberta, Canada, J Pharm Pharmaceut Sci 1 (1):15-30, 1998

2.Hans E. Junginger , Janet A. Hoogstraate, J. Coos Verhoef, Recent advances in buccal drug delivery and absorption — in vitro and in vivo studies, Journal of Controlled Release 62 (1999) 149–159

3.N.Chidambaram and A.K.Srivatsava, buccal drug delivery systems, Drug development and industrial pharmacy, 21(9), 1009-1036 (1995)

buccal and sublingual drug delivery system

Health & Medicine