Buccal, Rectal and Ocular Drug Delivery Flashcards by Nilusha Muraleetharan

When use buccal/ sublingual route? Give an example of each

Can give to treat locally or systematically
Local conditions e.g. candida albicans
Systemic conditions e.g. angina

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What are the advantages of using this route?

Avoids first pass hepatic metabolism
Rapid onset of action
Controlled drug release
Avoid acid/ digestive enzymes in the lower gut therefore you can keep it in the oral cavity and prolong its activity

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Structure + function of oral cavity.

It is the beginning of the alimentary tract
It is bound by the lips, cheeks, tongue and hard palate sublingual mucosa
Functions include: processing food,mastification, lubrication, digestion and taste

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What are the 3 major glands in the oral cavity? What does each one secrete?

Parotid gland (watery saliva, response to food)
Sublingual gland (mucin like saliva)
Submandibular gland (mixed secretions, some contain digestive enzymes + mucin)

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Oral mucosa structure

Squamous stratified epithelium, lamina propria, submucosa

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Give examples of keratinised squamous stratified epithelium

gums, hard palate

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Give examples of non keratinised squamous stratified epithelium

buccal mucosa, sublingual mucosa

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Give examples of specialised mucosa

upper tongue

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Role of and types of saliva

Lubrication, Digestion, Remineralisation of teeth, Antimicrobial
Two types; serous secretions, mucous secretions
Serous secretions are watery but contain salts, proteins and the enzyme amylase. Secreted by paratid gland in response to food
Mucous secretions are viscid and contain salivary mucins. They are secreted by sublingual and minor salivary glands.
Submandibular releases a mix of both

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Typically, humans produce ________ of saliva per day with 80-90|% being ______ saliva

1 litre

serous

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What is the salivary pellicle?

A salivary coating of all internal surfaces of the oral cavity e.g teeth. It is protective and lubricating.

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Microbiology of oral cavity?

Contains 10^7 to 10^8 bacteria/ml.
300 different species
Also some fungi (candida), viruses (herpes simplex), mycoplasmas and protozoa (entamoeba)

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Dental plaque is?

Found on teeth.

A hard, non-shedding surface for microbial colonisation.

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Dental plaque is?

Found on teeth.
A hard, non-shedding surface for microbial colonisation. Multiple habitats found on tooth surface, each supporting different populations of oral bacteria

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The mucosal barrier is formidable but the major barrier is the stratified epithelia. What are the possible routes for drug permeability?

Lipophilic (transcellular)
Hydrophilic (paracellular)
Active transport?

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In terms of absorption, what is the worst and best structure for the drug to go through?

The squamous epithelia is not designed for absorption.
The worst absorption is keratinised epithelia such as gums or hard palate.
The best absorption is through the thinnest areas e.g. buccal and sublingual mucosa.

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What type of drug molecules are absorbed best? Log P between? What type of molecules are poorly absorbed?

Small, lipophilic molecules with a log P between 1.6-3.3.

Therapeutic proteins.

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What are permeation enhancers? How do they act? What are some examples?

They can increase the absorption of proteins from 1-3% to 10% in vitro.
They act by either:
- increasing the fluidity of the cell membrane
- extracting intra/ inter cellular lipids
- altering the cellular proteins
- altering surface mucins
Examples : bile salts, surfactants e.g. sodium dodecyl sulphate, fatty acids

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What are the main problems with oral cavity drug delivery?

Patient acceptance - taste, mouthfeel, odour
Retention i.e. duration of application?
Distribution within the oral cavity? Drugs tend to follow saliva. When released, the pool in the lower part of the oral cavity and are swallowed so not distributed throughout the cavity.

What is mucoadhesion?

adhesion to mucus

For a drug loaded bioadhesive matrix, you can ensure unidirectional drug release into the mucosa by adding an

impermeable backing layer

(BIOADHESIVE SEMISOLIDS)
Slow drug release is seen where particles of a drug and bioadhesive polymer are dispersed in an ______ base. E.g an ________

oily

ointment

(BIOADHESIVE SEMISOLIDS)

Fast drug release is seen where a water soluble drug and polymer are dispersed in an ______ solvent e.g. _____

aqueous

gel

When is rectal route useful?

Patient is uncooperative/ unconscious/ unable to swallow due to nausea/ trauma/ oesophageal structure
To avoid acid hydrolysis; enzymatic breakdown in liver or gut lumen which may lead to GI side effects

When is rectal route useful?

- Patient is uncooperative/ unconscious/ unable to swallow due to nausea/ trauma/ oesophageal structure - To avoid acid hydrolysis; enzymatic breakdown in liver or gut lumen which may lead to GI side effects - For treatment of rectal conditions e.g haemorrhoids, colitis or laxatives

What are the issues with rectal drug delivery?

- Strong dislike to use - Slow and incomplete absorption - Variation in absorbed dose due to inter-subject (between people) variation

Epithelia of the rectum 1) anal canal 2) Ampulla

- 20% is unkeratinised squamous stratified epithelium. Primarily protective in nature - 80% is simple columnar epithelium. Once cell layer, no villi goblet cells. Primarily absorptive in nature

What are the renal factors affecting drug delivery?

- rectal wall thickness - rectal fluid - motility

State the steps in how drug is released from an oily base (rectal drug delivery). Start with release mechanism..

Melting - Spreading - Sedimentation - Wetting - Dissolution

What are the drug properties that affect absorption?

Solubility, lipid solubility (for partitioning into membrane), surface properties, particle size (50-100um) to prevent not only sedimentation but also prevent agglomeration

What are the drug properties that affect absorption?

Solubility, lipid solubility (for partitioning into membrane), surface properties (wetting of dru in suspension, in base and in rectal fluid), particle size (50-100um) to prevent not only sedimentation but also prevent agglomeration

What are the drug properties that affect absorption?

What are the formulation issues that affect absorption?

viscosity (will affect sedimentation rate of drug particles), melting point - affects drug release (3 degree range is good), compatibility (allows wetting and release)

Once drug is released from formulation and melts/ dissolves, the drug will be in the rectal fluid. It will transport across a cell membrane, transcellularly, via passive diffusion. Once drug is in blood, how does it get to a) Hepatic portal vein to liver and b) to systemic circulation

superior heamorrhoidal vein | middle and inferior haemorrhoidal veins

Why is ocular route used?

To use for local conditions of the external area of the eye - not used for systemic absorption

What are some ocular conditions treated by the topical application of drugs?

- Glaucoma - Conjunctivitis - Dry eye syndrome - Keratitis

What are the three stages that an eye drop goes through in order to elicit its effect.

Precorneal area, anterior chamber and posterior chamber + beyond

What is the desired flow of eye drops once applied?

1. Formulation is placed on ocular surface 2. Drug crosses cornea via passive diffusion 3. Anterior area 4. Posterior area

What is the desired flow of eye drops once applied?

1. Formulation is placed on ocular surface 2. Drug crosses cornea via passive diffusion 3. Anterior chamber 4. Posterior chamber

What are the ways in which drug can be lost once applied to ocular surface?

- Blinking/ tear flow - Local surface action - Drug absorbed into conjunctiva and carried away by vascular system

What are the ways in which drug can be lost once drug crosses cornea by passive diffusion?

Drug diffuses into surrounding tissues

What are the ways in which drug can be lost/reduced once applied to ocular surface?

- Blinking/ tear flow - Local surface action - Drug absorbed into conjunctiva and carried away by vascular system

What are some issues with eye drop therapy?

- Need for frequent dosing - Many patients, especially the very young and the elderly find the eye drops hard to administer - Shelf life (after opening) - Constituents need to be able to withstand sterilisation

What are some ways of enhancing eye drop retention?

- Increase viscosity of vehicle to prolong contact with the cornea, enhancing bioavailability; use high MW hydrophilic molecules OR use polysaccharides (e.g cellulose derivatives)

What are some ways of enhancing eye drop retention?

- Increase viscosity of vehicle to prolong contact with the cornea, enhancing bioavailability; use high MW hydrophilic molecules OR use polysaccharides (e.g cellulose derivatives) - Use mucoadhesive polymers e.g chitosan