6. Factors affecting GI bioavailability Flashcards
GI dosage forms: Oral
Solid:
- Tablets
- Capsules
- Granules
Liquid:
- Solutions
- Suspensions
- Emulsions
GI dosage forms: Rectal
Solid
- Suppositories
Liquid
- Enema
+ Retention
+ Foam
Oral administration
Most common route to administer drugs:
- Safe
- Convenient
- Economic
But has its limitations (compared to other routes)
- Slow onset of action (typically ~30 min)
- Rate & extent of absorption can be variable
Slow onset of action - dissolution (Noyes-Whitney Equation)
- Process of a solid dosage form dissolving
- Rate can be predicted using the Noyes-Whitney equation
- Revise 212 – what does each term mean & how can it be manipulated?
dm/dt = Ds/h (Cs-C)
Disintegration can slow onset of action
- Disintegration of a solid dosage form is often necessary to precede & speed up dissolution
- Disintegration increases surface area of a dosage form
- Remember – for a drug to be absorbed, it must be in solution
- Tablets are deliberately designed to control their disintegration rate
Coatings for oral dosage forms
Adding a coating can: - Aid swallowing - Improve stability - Improve aesthetics - Improve taste - Allow modification of drug release \+ Sustained/controlled release \+ Delayed release
Revise enteric coatings
- Resist acid in the stomach & break down at a higher pH
Diffusion
- Some dosage forms will not disintegrate in the GIT
- Drug release occurs as the drug diffuses through a polymer matrix & enters the surrounding solution
- Movement of drug from a region of high concentration (the dosage form) to an area of low concentration (the body)
Variable absorption - swallowing
- Where does most drug absorption occur, & why?
- What are the consequences of hindering swallowing
- Recommendations for patients
+ Take with a large glass of water
+ Sit upright when taking
Variable absorption - patient factors
- Anatomy (including missing gut)
- Gastric emptying (consider regions where drug is absorbed)
+ Increased when hungry or with mild exercise
+ Also faster for liquids than solids
+ Decreased with large meals, pain, anxiety, surgery - Intestinal motility
+ Effect of drugs (constipation or diarrhoea)
+ Gastroenteritis/diarrhoea
Surface area of the GI tract
OLD data: Oral cavity: ~0.01 m2 Oesophagus: ~0.1 m2 Stomach: ~0.4 m2 Duodenum, jejunum & ileum: ~350 m2 Large intestine (colon): ~0.3 m2 TOTAL: ~350 m2
NEW data: Oral cavity: ~0.02 m2 Oesophagus: ~0.024 m2 Stomach: ~0.05 m2 Duodenum, jejunum & ileum: ~30 m2 Large intestine (colon): ~1.9 m2 TOTAL: ~32 m2
Absorption
Drugs absorbed through transcellular & paracellular mechanisms
Barriers to drug absorption
- Chemical or enzymatic degradation in the lumen
- Adsorption/complexation in the lumen
- Presystemic metabolism in gut wall or liver
P & log P
P = Partition coefficient
Concentration in non-aqueous phase / Concentration in aqueous phase
Calculated by looking at partitioning between octanol & water
- Log P > 0 indicates drug prefers non-aqueous (oily or organic phase)
- Log P < 0 indicates drug prefers water
Systemic absorption
Theoretical understanding of systemic bioavailability
- Dispersible diclofenac tablet is absorbed faster (increased SA)
- Sugar coated diclofenac tablet is absorbed slower (reduced SA)
Suppositories & enemas
Suppositories:
- Solid preparations administered rectally
- Can have local or systemic effect
Enemas:
- Liquid/foam preparations administered rectally
- Can react descending colon
- Typically for local effect
Absorption
- If acting on lower rectum, no first pass
- If acting on upper rectum or higher in GI tract, first pass
Suppositories
- Contain one or more active substances dispersed or dissolved in a suitable base
+ Water soluble base can dissolve in the body
+ Fatty or oily base will melt at body temperature - Drug can be dissolved in the base (if soluble thereby forming a solution) or dispersed in the base (if beyond the solubility limit thereby forming a suspension)
- Drug releases over time, the mechanism of release depends on the contribution of drug & base used
