Transmucosal administration

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Biopharmaceutics

Transmucosal absorption Mucosal lining:

› Mucous ? Mucin ?› Functions

Epithelia › Thickness› “wear and tear”stratified epithellia› Keratinised-non keratinised epitelium

Physicochemical principles Drug potency consider the site of

administration Delivery form release pattern Drug solubility aqueous solubility – lipid

solubility balance of hydrophilicity and lipophilicity partition and difusion

Mucus- drug interaction Drug stability consider the enzymatic

metabolism Degree of ionization pKa unionized

form absorbed

Physiological consideration

Permeability Blood supply

› High vasculature› Blood flow

Oral cavity delivery Buccal delivery

Sublingual delivery

Oral administration vs oral cavity administration

Oral cavity

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

Category

Buccal delivery Sublingual delivery Oropharyngeal delivery Periodontal delivery

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

Different structure between sublingual and buccal region

Epithelial cell layer and mucous layer thickness

Mucous and saliva mobility

Challenge of delivery

Saliva movement and dilution Enzymatic barrier Thickness of mucosal layer Limited surface area Lipoidal barrier of buccal

Formulation approach Mucoadhesive polymer Enzyme inhibitor Penetration enhancer Chemical modification

Dosage form

Chewing formulation Fast release dosage form Mucoadhesive dosage form

Ophthalmic delivery….in awareness to deliver drugs for

optical pharmacodynamics

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

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

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

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› Precorneal drainage (role of

hydrodynamic)80-90% drug removed

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

(5-10L/drop)› The use of mucoadhesive

carrierprolong the residence time

Factors affecting permeation

Solubility and partition coefficient Molecular weight State of ionisation and pH Protein binding Pigmentation and drug effect

Factors affecting retention time

Proper placement of the dosage form Instillation volume The use of mucoadhesive polymer and

in situ gelling forming viscosity enhancement

Ocular pharmacodynamic

Mydriatics and Cycloplegics Miotics Anti-inflammation Anti bacterial-antifungal Anti-glaucoma Age related macular degeneration Dry eyes artificial tears

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 ingredientanionic-cationic interaction)

Other organic mercurials careful with the side effect of mercury!

Intraocular administration

Intravitreal administration Subconjunctival administration Periocular administration

› Sub Tenon’s capsule administration› Retrobulbar injection

Rectal-vaginal delivery

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

Products: Suppositoria Rectal gel:

Enema

How to use the rectal gel:

Microlax ?

www.drugs.com

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

Why intra vaginal? Local therapy, mostly related to

antibiotics-antifungi Points for systemic delivery:

› Blood supply› Permeability› Hepatic FPE avoidance› Less protease

Consideration for systemic delivery…

Ethic issues Erratic absorption due to epithellium

thickness variation as the consequences of menstrual cycles

Mucus as physical barriers