Routes of Administration: Oral Flashcards
What is absorption?
Movement of drug from site of administration to the
bloodstream
What types of lipids are in biological membranes?
Sphingomyelin
Phosphatidylcholine
Phosphatidylserine
Phosphatidylinositol
Phosphatidylethanolamine
Glycolipid – lipid with a carbohydrate attached
Cholesterol – a type of lipid
What are the two types of cellular transport across membranes?
*transcellular
*paracellular
What are the types of transcellular transport?
- Passive diffusion
- Carrier mediated transport
- Facilitated diffusion
- Active transport
- Vesicular transport (endocytosis)
What is the type of paracellular transport?
- Tight junctions
What structures are involved in the GI tract?
*small intestine
*vilus
*epithelial cells with microvilli
Describe pressure changes during gastric emptying of food
- Stomach pressure remains constant until ~1 L of food ingested
- Relative unchanging pressure results from intrinsic ability of
smooth muscle to exhibit “plasticity”
Describe what happens to chyme (stomach acid) during gastric emptying
Chyme is either:
* Delivered in small amounts (about
3 mL) to the duodenum
* Forced backward into the stomach
for further mixing
What is gastric emptying regulated by?
*neural reflex
* hormonal mechanisms
What is gastric emptying affected by?
*meal volume
*meal composition
*pH content
How does meal composition affect gastric emptying?
- Stomach empties liquids faster than solids
- Carbohydrate-rich chyme quickly moves through duodenum
- Fat-laden chyme is digested more slowly causing food to remain in the stomach
longer
How does pH content affect gastric emptying?
- Acids delays gastric emptying
- pH of chyme in the small intestine of (< 3.5
– 4) will activate reflexes to inhibit stomach
emptying until duodenal chyme can be
neutralised by pancreatic and other
secretions - Careful of antacids (e.g. aluminium
hydroxide gel) that raise the pH of stomach
contents
What is GER?
- Gastric emptying rate (GER) = Speed with which substances leave the
stomach after ingestion
How do the structures of the GI tract do drug gastric emptying?
- The duodenum has the greatest capacity for the absorption of drugs from the GI tract
- Anatomically, a swallowed drug rapidly reaches the stomach
- Eventually, the stomach empties its contents into the small intestine
- Delay in the gastric emptying time will slow the rate and possibly the extent of drug absorption
What type of advice can be given for oral drugs and the disadvantages?
- Take with food
- May irritate the gastric mucosa
during prolonged - Take before food
- Improve absorption as food can
affect absorption
What is the rate limiting step?
Slowest step in the series, which controls the overall
rate and extent of appearance of the intact drug in the systemic
circulation
What are the various rate limiting steps for different drugs?
Rate-limiting step differs from drug to drug:
* Drug release from dosage form – disintegrate
* Gastric emptying
* Dissolution – high log P hardly dissolves
* Permeability – low log P is hardly absorbed
* Metabolism – including metabolism in the liver (first pass effect)
what is the SA of the small intestine epithelium?
- Epithelium brush border
- 3000 microvilli per cell
- 200,000,000 per mm2
How will the epithelium brush SA help?
- With this surface area
even ionised weak acids
will be absorbed in
sufficient quantities
What are the different types of tablets? 6 types + example
*disintegrating tablet (Zantac)
*lozeneges (strepsils)
*chewable tablets (gaviscon)
*effervescent tablets (beroca)
*sublingual tablets (nicorette)
*buccal tablets (buccastem m)
What are the advantages of tablets?
- Ease of administration and patient acceptance
- Swallowing
- Chewable formulations
- Elegance
- Convenient handling/compactness
- Accurate dosage
- Chemical and physical stability
- Different to tamper with
- Low cost of manufacturing, packaging, shipping
What are the types of capsules?
*hard capsules
*soft capsules
What are hard capsules composed of?
- Gelatin
(bovine, porcine, fish) - Alternative polymers
(HPMC
hydroxypropylmethylcellulose,
pullulan)
What are soft capsules composed of?
- Gelatin
- Vegetarian option (Vegecaps)
What are the advantages to capsules? in terms of patient compliance
Patient compliance
* Easier to swallow
* Smooth & slippery
* Tasteless and odourless
* Eliminate all contact between drug
and mouth)
* Can be opened up
* Contents sprinkled on food
* Clear, high-gloss coloured film
* Can be printed on
What are the advantages capsules? in terms of drug delivery
- Fast acting
- Breakdown of capsule shell occurs
readily ≈ disintegration of tablet - Beads/pellets/granules in
addition to dry powder fills - A mixture of beads with different
release rates - Other dosage forms in a capsule
- Mini tablets and liquids
Describe dissolution of capsules containing both hydrophobic and hydrophilic drug particles
*Hard gelatin capsules containing
hydrophobic drug particles and
hydrophilic diluent particles
* the capsules will dissolve in GI liquid leaving a porous mass of drug
*GI fluids can penetrate porous mass
*Effective surface area of
drug and hence dissolution
rate is increased
Describe dissolution of capsules containing only hydrophobic drug particles
*hard capsule containing only hydrophobic drug particles
*the capsule shell will dissolve in GI fluid exposing contents
*Contents remain as capsule-shaped plug.Hydrophobic nature of contents impedes penetration of GI fluids
*Dissolution of drug occurs only from surface of plug-shaped mass. Relatively low rate of dissolution
Why are oral solutions give+ absorption?
- Drugs are commonly given in solution
- in cough/cold remedies
- for the young and elderly
- Absorption from an oral solution is often rapid and complete, greater
bioavailability compared to other oral dosage forms
What is the absorption of oral suspensions like?
- Second to a solution in terms of superior bioavailability
- Absorption may well be dissolution-limited
- Suspension of a finely divided powder will maximize the potential for rapid
dissolution
What are sublingual tablets for?
- Sublingual – application to the
membranes of either the floor of
the mouth or the underside of the
tongue and entry into systemic
circulation following absorption
What are buccal tablets for?
- Buccal – application to the lining
of the cheek – entry into the
systemic circulation following
absorption
What makes up the Floor of the mouth, the soft palate, the lips and the cheek?
Non-keratinised mucosa
What makes up Hard palate, gingiva and tongue?
Keratinised mucosa
What is the epithelium thickness of the sublingual route?
100 – 200 µm on the underside
of the tongue and on the floor of
the mouth
What is the epithelium thickness of the buccal route?
500 – 800 µm in the buccal
cavity
What are some properties of the sublingual route?
- Relatively permeable
- Rapid absorption
- Unsuitable for retentive system
- Ideal for rapid onset of action
- Sprays or fast-dissolving tablets
What are some properties of the buccal route?
- Relatively less permeable
- Not rapid absorption
- Suitable for retentive system
- Ideal for sustained release
- Adhesive tablets or patches
What are the three sublingual oral types?
*chewable tablets
*sprays
*tablet
What are each sublingual oral route made of?
- Sublingual tablets
- Consist of lactose mannitol sucrose for fast dissolution
- Solutions and sprays
- Administration of nitroglycerin (angina prevention)
- Chewing gum
- A gum base of a cellulosic or acrylic polymer
What are some examples of buccal adhesive tablets?
- Buccastem M: prochlorperazine
(antiemetic) - Suscard Buccal: Glyceryl trinitrate
(relieves chest pain) - Buccal sustained release of
flurbiprofen (NSAID)
