Biopharmaceutics Flashcards
IV data
Instant Cmax, leading to gradual elimination of drug
Can determine clearance, volumes of distribution, distribution/elimination half lives
Bioavailability
PO data
Delayed Cmax
Can determine lag time, absorption half life, fraction absorbed
Bioavailability
Biopharmaceutics refers to the relationship that exists between…
The factors that affect the rate and extent of drug delivery to the systemic circulation (bioavailability)Physiology/route of administration
Physicochemical properties of drug
Formulation/dosage form
Why is biopharmaceutics important?
Changes in absorption is a major cause of drug response variability
Counselling of patients to help minister inter and intra patient variability
Appropriateness of dosage from
Physiological factors
Oesophagus: pH 5-6, rapid transit 10-15 seconds
Stomach: pH 1-3, gastric emptying varies from 5 mins to 2 hours
Small intestine: pH 6-7.5, transit fairly constant at 3 hours
Colon: pH 6.5-7.5, transit times vary hugely from 2-48 hours
Effect of food
Food can directly or indirectly influence rate and extent of absorption
Complexation e.g. tetracyclines and calcium
Changes in pH affect drug dissolution
Altered gastric transit times
Stimulation of gastric secretions e.g. pepsin and bile salts
Increased viscosity of GI contents reducing dissolution and diffusion
Changes in pre-systemic metabolism e.g. grapefruit juice
Changes in blood flow causing changes in first pass metabolism
Physicochemical/drug factors
Drug needs to be in dissolution before it can be absorbed Dissolution rate/solubility (pKa) Lipid solubility Chemical stability Complexation potential
Dissolution
Described by Noyes-Whitney equation:
Rate of dissolution of drug particles
Diffusion coefficient
Effective surface area of drug particles
Sat. solubility of drug in diffusion layer- conc. of drug in GI fluid
Thickness of diffusion layer around each drug particle
Physiological factors affecting dissolution
Increased viscosity of GI fluid- decreased diffusion coefficient
Gastric secretions increase wettability of particles- increase effective surface area of drug particles
Contents of stomach- variability in saturated solubility of drug in diffusion layer minus conc. of drug in GI fluid
Gastric motility- changes in thickness of diffusion layer around each drug particle
Drug factors affecting dissolution
Particle size/wettability- changes diffusion coefficient
Drug solubility/pKa/salts- changes in saturated solubility of drug in diffusion layer
Other physicochemical factors
Lipid solubility: influences route of absorption- transcellular vs paracellular
Chemical stability: harsh and varying environment, enteric coated tablets offer protection to drug, prodrugs can delay dissolution until in small intestine
Complexation potential: can reduce or increase absorption; endogenous compounds e.g. mucin and bile salts; excipients e.g. calcium salts, cellulose, surfactants; food/other drugs e.g. adsorbents such as kaolin
Effect of dosage form
Dosage form design is crucial in influencing rate and extent of absorption
Liquid dosage forms: solutions- drug soluble in aqueous solution can eliminate in vivo dissolution; suspensions- fine particles in solution, no delay to dissolution
Solid dosage forms: capsules- liquid vs powder, capsule material delays dissolution; tablets- coated vs uncoated, compression causes huge reduction in surface area
Effect of dosage forms- solutions
Normally eliminates requirement for in vivo dissolution
Poorly soluble drugs in complex formulations may precipitate
Effect of pH on solubility and stability
Viscosity effects
Rate limiting step: gastric emptying
Effect of dosage forms- suspensions
No delay to dissolution cf. powder capsules Particle size/surface area Aggregation/flocculation Viscosity effects Rate limiting step: dissolution
Effect of dosage forms- liquid filled capsules
Soft or hard gelatin
Capsule material delays drug dissolution
Vehicular effects
Rate limiting step: dissolution (capsule and drug)
