Lecture 14- Biopharmaceutics I Flashcards
Biopharmaceutics
Pharmacokinetics = investigates the effect of the body on the dosage form (ADME)
Biopharmaceutics= stage prior to this- how the design + formulation of the dosage affects the drug once in the body
^is the relationship between the physical, chemical + biological science applied to drugs, dosage form + route of administration / drug action
Absorption, distribution, metabolism + excretion
Biopharmaceutics + Pharmacokinetics
Slide 5
Drug absorption
Process of movement of unchanged drug from its site of administration to systemic circulation
Effectiveness of a drug can only be assessed by = its concentration + site of action
-difficult to measure
-conc can be measured more accurately in plasma
Correlation between= plasma conc of a drug + therapeutic response
Involved in Biopharmaceutics
Route of administration; oral, injection
Nature of the dosage form; solution + suspension
Physiological parameters; fed, fasted state
Nature of the drug; water solubility, lipophilicity, particle size + stability
Onset of action vs dosage form- slide 9
Route of administration; oral delivery
Given a drug by mouth= most common route of administration- most variable + requires the most complicated pathway to the tissues
Factors affecting GI absorption of a drug from its dosage form
Pharmaceutical factors;
- physiochemical properties of drug substances
- dosage form characteristics and pharmaceutical ingredients
Patient related factors;
Factors relating to the anatomical, physiological + pathological characteristics of the patient
Physiochemical properties of drug substances
Drug solubility + dissolution rate
Particle size + effective surface area
Polymorphism; stable/ metastable
Psueodpolymorphism - L-phenylalanine anhydrous
Salt form of the drug - hydrochloride/ sodium/ sulfate
Lipophilicity of the drug
pKa of the drug + pH
Drug stability
Dosage form characteristics + pharmaceutical ingredients
Disintegration time
Dissolution time
Manufacturing variables; e.g. wet/ dry granulation
Pharmaceutical ingredients
Nature + type of dosage form
Product age + storage conditions
Patient- related factors
Age, gastric emptying time, intestinal transit time, gastrointestinal pH, disease states, blood flow through GIT, gastrointestinal contents and presystemic metabolism
Oral delivery;
Advantages + disadvantages
Advantages;
Convenient, can be self administered, pain free, easy to take, safe, absorption takes place along the whole length of the GI tract, cheap compared to other parenteral routes
Disadvantages;
Some drugs have an unpleasant taste, can’t be given to unconscious pts, effect of first pass metabolism, effect too slow for emergencies, destruction of drugs by gastric acid
First pass effect
Greater the first-pass effect, less drug reaches systemic circulation > reduces bioavailabity when administered via GIT
Drugs subjected to first pass effect;
Lidocaine - anaesthetic
Propranolol- beta blocker
Nitroglycerin- nitrate
Larger oral dose / alternative doseage form = required to achieve required therapeutic effect
Mechanisms of drug absorption
2 mechanisms of drug transport across the GI epithelium;
Transcellular= across the cells and is further divided into;
-lipid diffusion, carrier-mediated transport + facilitated diffusion and endocytosis
Paracellular= between the cells
Principles mechanisms of drug permeation
Passive/aqueous diffusion= Fick’s Law
Lipid diffusion through lipid bilayer
Carrier mechanism
Endocytosis/exocytosis
Passive diffusion
Known as non-ionic diffusion; absorption of 90% of drugs
Fick’s first law of diffusion;
The drug molecule diffuse from a region of higher concentration to one of lower concentration until equilibrium is attained & the rate of diffusion is directly proportional to the concentration gradient across the membrane
Equation- slide 20
Passive diffusion- energy independent but depends more/less on the square root of the molecular size of the drugs
Mol weight of most drugs lie between 100-400 Daltons- can be effectively absorbed passively
