Transmucosal administration
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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
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