Transmucosal administration

1. Transmucosal administration Excellent in Quality, Competitiveness and Care Biopharmaceutics

2. Transmucosal absorption Mucosal lining: Mucous ? Mucin ? Functions Epithelia  Thickness “wear and tear”stratified epithellia Keratinised -non keratinised epitelium

3. Physicochemical principles Drug potency  consider the site of administration Delivery form  release pattern Drug solubility  aqueous solubility – lipid solubility  balance of hydrophilicity and lipophilicity  p artition and difusion Mucus- drug interaction Drug stability  consider the enzymatic metabolism Degree of ionization  pKa  unionized form absorbed

4. Physiological consideration Permeability Blood supply  High vasculature Blood flow

5. Oral cavity delivery Buccal delivery Sublingual delivery Oral administration vs oral cavity administration

6. Oral cavity Taken from Florence AT, Attwood D“Physicochemical Principles of Pharmacy” - only for study purpose

7. Category Buccal delivery Sublingual delivery Oropharyngeal delivery Periodontal delivery

8. Why via buccal and sublingual ? Avoidance of GIT hazardous environment Avoidance of First Pass Hepatic Elimination  there are no hepatic portal veins  direct access to the systemic circulation via internal jugular vein Adequate vasculature and blood supply Relatively permeable Rapid onset  sublingual delivery Sustained release  buccal delivery

9. Different structure between sublingual and buccal region Epithelial cell layer and mucous layer thickness Mucous and saliva mobility

10. Challenge of delivery Saliva movement and dilution Enzymatic barrier Thickness of mucosal layer Limited surface area Lipoidal barrier of buccal

11. Formulation approach Mucoadhesive polymer Enzyme inhibitor Penetration enhancer Chemical modification

12. Dosage form Chewing formulation Fast release dosage form Mucoadhesive dosage form

13. Ophthalmic delivery ….in awareness to deliver drugs for optical pharmacodynamics

14. Parts of the eye Eyelid Keep the tear film and lacrimal drainage Cornea Site of drug administration  transcorneal absorption Epithelium- stroma -endothelium Conjunctiva Conjunctiva sac (the inferior one  “ cul de sac ”)  (also) site of drug instillation Drug absorption site Aqueous humor Iris-lens Light entry regulation Vitreous body and vitreous humor Keep the retina pressed against choroid Retina Visual acuity, nerves Configuration of photoreceptor cells Blood retinal barrier  efflux system and tight junction on : Endothelium on retinal vessel Retinal Pigmented Epithellium (RPE) cells

15. Factors to consider the ophthalmic delivery: Ways to across the blood eye barrier and cornea Blood-eye barrier Cornea Localisation the action at the eye Retention time while reducing the frequency of instillation

16. Ophthalmic dosage form Safe and effective Sterile Certain criteria for certain dosage form: Pyrogen -free  parenteral administration Isotonic- Isohydris , free from particles solution ( eyedrop -injection) Free from large particles  suspension-ointment Free from foreign matters Advanced carrier  biodegradable

17. Optical pharmacokinetics Corneal penetration Noncorneal , productive ocular absorption  conjuntival-scleral absorption hydrophilic compounds Conjunctiva and sclera are more permeable than cornea Could be non-productive if penetration through conjunctival blood vessels occurs Noncorneal , non productive absorption, Conjuctival vessels  systemic P recorneal drainage (role of hydrodynamic) 80-90% drug removed

18. Role of hydrodynamic of precorneal tears Force out the matters from the eye and perform nasolacrimal drainage Explain the effect of excessive instillation: Bitter taste after instillation Systemic effect via GI absorption Suggest : the volume of eye drop administration (5-10 L/drop) The use of mucoadhesive carrier prolong the residence time

19. Factors affecting permeation Solubility and partition coefficient Molecular weight State of ionisation and pH Protein binding Pigmentation and drug effect

20. Factors affecting retention time Proper placement of the dosage form Instillation volume The use of mucoadhesive polymer and in situ gelling forming  viscosity enhancement

21. Ocular pharmacodynamic Mydriatics and Cycloplegics Miotics Anti-inflammation Anti bacterial-antifungal Anti-glaucoma Age related macular degeneration Dry eyes  artificial tears

22. Preservatives Most commonly used  benzalkonium chloride (in a concentration of 0,01 %); Role: microbial growth controller, it can also be used as penetration enhancer Limitation : If the concentration exceeded, may cause irritation/corneal damage). incompatible for salt form active ingredientanionic -cationic interaction) Other  organic mercurials careful with the side effect of mercury!

23. Intraocular administration Intravitreal administration Subconjunctival administration Periocular administration Sub Tenon’s capsule administration Retrobulbar injection

24. Rectal-vaginal delivery

25. Background of administration Local therapy, example… Systemic therapy, especially in condition: Unable for oral administration Unconscious Unacceptable taste Unstable against GI hazardous environment Advantages : Non invasive; can be self administered For systemic : High vasculature Permeability anatomy

26. Products: Suppositoria Rectal gel: Enema

27. How to use the rectal gel: Microlax ? www.drugs.com

28. Suppositoria Bases: Fatty base (melted) cocoa butter; adeps solidus; witepsol Water soluble base (dissolved)  osmotic effect hygroscopic Glycero-gelatine base  hygroscopic Consideration: Melting point Solidification rate API- excipient affinity/interaction

29. Why intra vaginal? Local therapy, mostly related to antibiotics- antifungi Points for systemic delivery: Blood supply Permeability Hepatic FPE avoidance Less protease

30. Consideration for systemic delivery… Ethic issues Erratic absorption due to epithellium thickness variation as the consequences of menstrual cycles Mucus as physical barriers