Advances in transmucosal drug delivery

Recent advances in transmucosal drug delivery system (more focused on buccal area which acts systemicaly and not locally)

1. Evaluatory seminar on Advances in oral trans mucosal drug delivery Presented by : Gasper Fernandes (160603016) MPharm 1 st year Department of Pharmaceutics Under the guidance of : Dr. Shaila Lewis

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

3. Introduction Oral 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

4. Oral cavity

5. Comparison with different part

6. Why Buccal/Sublingual? To avoid first-pass metabolism Protection from pH and digestive enzymes Rapid onset of action Painless administration Rapid and extensive drug absorption Easy termination of therapy

7. Anatomy of oral mucosa

8. Transport routes Passive diffusion Carrier mediated active transport

9. Mucoadhesion Mucoadhesion : 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

10. Theory of Mucoadhesion Diffusion theory : Entanglements of the polymer Electronic theory : Attractive forces Wetting theory : Measure of spread ability of drug delivery system on biological substrate Fracture theory : Force necessary to separate two layers Adsorption Theory : Secondary chemical bonds

11. 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

12. Drug substance Bioadhesive polymers Backing membrane Permeation enhancers Basic components

13. Selection of drug Dose of the drug should be small Half-life between 2-8 hours Exhibit first pass effect or presystemic drug elimination. Absorption should be passive when given orally

14. Bioadhesive polymers Must not decompose on storage Inert and compatible with the environment Polymer 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

15. Backing membrane The 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 .

16. Permeation enhancers Mechanism: Changing mucus rheology Increasing the fluidity of lipid bilayer membrane Acting on the components at tight junctions Increase thermodynamic activity of drug Examples: Capric acid, Citric acid, Aprotinin, Chitosan-cysteine

17. Formulations I. 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.

18. Marketed buccal tablets

19. 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. A dhesive patches are prepared by solvent casting method. Films are laminated patches used for controlled drug release

20. Marketed buccal patches

21. B io E rodible M uco A dhesive

22. 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 :

23. 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.

24. Here the force required to remove the formulation from a model membrane is measured. Texture analyzer :

25. 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 :

26. 3. Degree of swelling of buccal tablet/patches : Where, W 1 is Initial weight of tablet W 2 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 .

27. 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.

28. 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.

29. 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