Evaluatory seminar on

Advances in oral trans mucosal drug delivery

Presented by :

Gasper Fernandes (160603016)

MPharm 1st year

Department of Pharmaceutics

Under the guidance of : Dr. Shaila Lewis

Contents Introduction Why Buccal/Sublingual Anatomy of oral mucosa Transport Routes Theories of Mucoadhesion Formulation consideration Basic components Formulation Evaluation Conclusion Reference

IntroductionOral trans-mucosal drug delivery concerned

with the systemic delivery of the drug moiety via mucous membrane of the oral cavity.

Oral trans-mucosal drug delivery can be subdivided into:

Sublingual delivery: floor of the mouth Buccal delivery: lining of the cheek

Oral cavity

Comparison with different part

Why Buccal/Sublingual?

To avoid first-pass metabolism Protection from pH and digestive enzymes Rapid onset of actionPainless administrationRapid and extensive drug absorption Easy termination of therapy

Anatomy of oral mucosa

Transport routesPassive diffusionCarrier mediated active transport

MucoadhesionMucoadhesion: The adhesion between biological

materials or artificial substrate and mucus membrane.

Mucoadhesion is necessary: to maximize the intimacy of contact of the drug

delivery system with the mucosa; to retain the delivery system in the oral cavity

Theory of Mucoadhesion

Diffusion theory: Entanglements of the polymerElectronic theory: Attractive forcesWetting theory: Measure of spread ability of drug

delivery system on biological substrateFracture theory: Force necessary to separate two

layersAdsorption Theory: Secondary chemical bonds

Formulation considerations

Molecular size- small molecules(75-100Da)Degree of ionization- Non-ionized forms of

drug have greater transport. Lipid solubility-More lipid soluble higher its

permeability

Drug substance Bioadhesive polymers Backing membrane Permeation enhancers

Basic components

Selection of drugDose of the drug should be smallHalf-life between 2-8 hours Exhibit first pass effect or presystemic drug

elimination.Absorption should be passive when given

orally

Bioadhesive polymersMust not decompose on storageInert and compatible with the environmentPolymer and its degradation products should be

non-toxic absorbable from the mucous layer. Adhere quickly to moist tissue surface Natural polymers Ex.: Gelatin, sodium alginate. Synthetic and semisynthetic polymers Ex.: PVA, PEG, HPMC, PVP, NA-CMC

Backing membraneThe impermeable backing layer controls the

direction of release and reduces drug loss away from the site of contact.

It also protects the other layers and acts as a mechanical support.

Examples: PVA, Ethyl celulose.

Permeation enhancersMechanism:Changing mucus rheologyIncreasing the fluidity of lipid bilayer membraneActing on the components at tight junctionsIncrease thermodynamic activity of drugExamples: Capric acid, Citric acid, Aprotinin,

Chitosan-cysteine

FormulationsI. Tablets:Buccal tablets are small, flat, and oval, with a

diameter of approximately 5–8 mm.When placed directly onto the mucosal surface

tablets adhere to the buccal mucosa in presence of saliva.

Prepared by direct compression, but wet granulation techniques can also be used.

Marketed buccal tablets

II. Patches & Films:Buccal-adhesive patches may be up to 10-15

sq.cm in size, but are more usually 1-3 sq.cm so as to be convenient and comfortable for the patient.

Adhesive patches are prepared by solvent casting method.

Films are laminated patches used for controlled drug release

Marketed buccal patches

Bio Erodible Muco Adhesive

Buccoadhesive sprays are gaining popularity over other dosage forms because of ◦ flexibility,◦ comfort,◦ availability of drug in

solution form.Drugs generally given by

these routes are fentanyl, buprenorphine. Naloxone etc

III. Buccoadhesive Spray:

Methods for evaluation 1. Tests for measuring mucoadhesive strength:•Measuring the force required to break the binding between the model membrane and the mucoadhesive.•Depending on the direction in which the mucoadhesive is separated from the substrate, is it possible to obtain the detachment, shear, and rupture tensile strengths.

• Here the force required to remove the formulation from a model membrane is measured.

Texture analyzer:

Modified USP dissolution apparatus

Composition: 800-ml pH 6.6 phosphate buffer maintained at 37°C.

The time taken for complete erosion or dislodgment of the tablet/patches from the mucosal surface was noted.

2. Test for measuring ex vivo residence time:

3. Degree of swelling of buccal tablet/patches:

Where,W1 is Initial weight of tabletW2 is weight of swollen tablets

Appropriate swelling property of a buccal adhesive device is required for uniform and prolonged release of drug with proper mucoadhesion.

Other evaluation test:

• In vitro drug release: USP apparatus 2 i.e. rotating paddle method.

• Permeation study of buccal patch: Using Franz diffusion cell.

• Stability of buccal tablets: Performed using human saliva.

• General test for buccal tablet: Weight variation, friability, hardness, content uniformity.

• General test for buccal patch/film: Surface pH studies, content uniformity, folding endurance, thickness & weight variation.

Conclusion

Oral transmucosal drug delivery is a promising area for systemic delivery of orally inefficient drugs as well as an attractive alternative for noninvasive delivery of potent peptide and perhaps protein drug molecules.

References Mathiowitz, Edith. 1999. Encyclopedia Of Controlled Drug Delivery.

Vol.1, New York, John Wiley & Sons, Inc Viralkumar F. Patel a, Fang Liu a, Marc B. Brown, Advances in oral

transmucosal drug delivery, Journal of Controlled Release 153 (2011) 106–116.

Nookala Venkala Satheesh Madhav, Ravindra Semwal,Deepak Kumar Semwal & Ruchi B Semwal, Recent trends in oral transmucosal drug delivery systems: an emphasis on the soft palatal route, Expert Opinion on Drug Delivery · April 2012.

Bandyopadhyay, A. K., 2006. “Buckle bioadhesive drug delivery — A promising option for orally less efficient drugs.” Journal of Controlled Release 114 (2006)15–40.

Smart J. D., 1993. “Drug delivery using buccal-adhesive systems.” Advanced Drug Delivery Reviews, ll (1993) 253-270.

Sudhakar Y., Kuotsu K., et al. (2006). "Buckle bioadhesive drug delivery — A promising option for orally less efficient drugs " Journal of Controlled Release 114: 15-40.

Jain.N.K, editor. New Delhi: CBS Publishers and Distributors PVT. LTD; Advances in Controlled and Novel Drug Delivery). 2001. p. 53-75