Routes of Administration - Oral Flashcards
List all of the routes of administration;
Sublingual (under tongue)
Buccal
Ocular (eye)
Nasal (nose)
ear
Intrathecal
Intrathymic
Intravcardiac
Inhalation
Intravenous & arterial
Intramuscular
Subcutaneous
Topical (on top of skin)
Vaginal
rectal (intestines)
Oral
Define Absorption
Movement of drug from site of administration to the bloodstream
Biological membranes - phospholipids
Lipid molecules;
Sphingomyelin
Phosphatidylcholine
Phosphatidylserine
Phosphatidylinositol
Phosphatidylethanolamine
What is cholesterol?
A type of lipid
What is Glycolipid?
lipid with a carbohydrate attached
How are molecules arranged in biological membranes?
Arrangement related to solubility of PROTEIN molecules
Phospholipid bilayer
- 2 layers
- mosaic fluid model /cholesterol to helping the bilayer stay fluid in different environmental conditions.
Polar head
Face outwards in contact with aqueous medium(hydrophilic phosphate groups)
Non-polar lipid tails
Face towards the bilayer interior (hydrophobic alkyl chains)
Transport across biological membranes;
1) Trancellular
2) Paracellular
1) Trancellular
Passive diffusion
Carrier mediated transport
Facilitated diffusion
Active transport
Vesicular transport (endocytosis)
2) Paracellular
Tight junctions
Will small charged ions be able to transport through phospholipid bilayer
Yes, small molecule - polar
Gastrointestinal tract
Small intestine
Villus
Epithelial cells with microvilli
Villi > Epithelial cells > Microvilli
Gastric emptying (food)
Most vigorous peristalsis and mixing occurs near the pylorus
Types of transport
1) Transcellular - passive
2) Paracellular - passive
3) Transcelluar - carrier-medicated
5) Endocytosis - specialised (energy required)
*6) Efflux - when membrane will push something back out - cannot be defused in
How long will pressure in stomach remain constant?
Stomach pressure remains constant until ~1 L of food ingested
Relative unchanging pressure results from intrinsic ability of smooth muscle to exhibit “plasticity”
How is Chyme delivered?
Delivered in small amounts (about 3 mL) to the duodenum
Forced backward into the stomach for further mixing
What is chyme in stomach?
Your digestive glands in your stomach lining produce stomach acid and enzymes, which mix with the food to form a murky semifluid mass or paste called chyme
Neural reflex - what mechanism?
Hormonal mechanisms
Gastric emptying is affected by;
Meal volume; exponential function of the volume of a meal
Meal consumption;
- 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
pH of content;
- 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
Gastric emptying rate (GER) =
Speed with which substances leave the stomach after ingestion
Why do we want drug to go into small intenstine;
more abundant - existing in large volume
gastric emptying - process from stomach to small intestine:
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
Take aspirin befor, after or with food?
Take with food
May irritate the gastric mucosa during prolonged
Amoxicillin - take before or after food?
Take before food
Improve absorption as food can affect absorption
Unstable in acid and will decompose if stomach emptying is delayed
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
DELAY absorption
Rate-limiting step differs from drug to drug
because….
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)
Small intestine epithelium - surface area
Epithelium brush border
3000 microvilli per cell
200,000,000 per mm2
With this surface area even ionised weak acids will be absorbed in sufficient quantities
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
Disintegration and dissolution of tablets
- Dinintegration > granules / primary drug particles (deaggration from granules to particles)
- Dissolution
- Drug in solution [in bottom of stomach]
Hard vs Soft capsules:
Hard;
Gelatin (bovine, porcine, fish)
Alternative polymers(HPMC hydroxypropylmethylcellulose, pullulan)
Soft;
Gelatin
Vegetarian option (Vegecaps)
Advantages of capsules - 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
Advantages of capsules - 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
DISSOLUTION from capsule;
Hard gelatin capsules containing only hydrophobic drug particles
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.
In GI fluids, hard gelatin capsule shell dissolves, thereby exposing contents of fluids, and then…
Hard gelatin capsules containing hydrophobic drug particles () and hydrophilic diluent particles ()
Particles of hydrophilic diluent dissolve in GI fluids leaving a porous mass of drug
- GI fluids can penetrate porous mass
- Effective surface area of drug and hence dissolution rate is increased
Liquid oral dosage forms (solution);
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
Injection advantages, consider bioavailability:
great precision and high repeatability, combined with speed, a low cost per part and a huge choice of available plastics
100% bioavailability
What is bioavailability?
the extent a substance or drug becomes completely available to its intended biological destination(s).
Liquid oral dosage forms (suspension)
> 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
Bioavailability (oral dosage forms)
Aqueous solution > precipitation > Suspension of fine particles of drug in Gi fluids > dissolution > solution of drug in GI fluid > absorption > blood
tablet steps - to be absorbed to the blood;
Immediate release solid dosage forms > Disintegration > Aggregate or granules > Degradation > suspension of fine particles of drug in GI fluids > dissolution > solution of drug in GI fluids > absorption > Blood
Which form is quicker liquid of solids + suspensions?
Liquid
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
Buccal
application to the lining of the cheek – entry into the systemic circulation following absorption
Non-keratinised
Keratinised mucosa
Non-keratinised mucosa - Floor of the mouth, the soft palate, the lips and the cheek
Hard palate, gingiva and tongue
Epithelium thickness
Sublingual = 100 – 200 um on the underside of the tongue and on the floor of the mouth
Buccal = 500 – 800 um in the buccal cavity
Sublingual and buccal properties;
S - Relatively permeable
Rapid absorption
Unsuitable for retentive system
Ideal for rapid onset of action
Sprays or fast-dissolving tablets
B - Relatively less permeable
Not rapid absorption
Suitable for retentive system
Ideal for sustained release
Adhesive tablets or patches
Sublingual – tablet, chewing gum & spray
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
Examples of Buccal – adhesive tablets
- Buccastem M: prochlorperazine (antiemetic)
- Suscard Buccal: Glyceryl trinitrate (relieves chest pain)
- Buccal sustained release of flurbiprofen (NSAID)
