modified release formulation - unfinished Flashcards
what is the pH of the stomach
pH 1-3.5 (fasting) 3-7 (fed)
how is the food digested in the stomach
Digestion of food by acid and enzymatic degradation
what does gastric residence depend on?
Gastric residence time depends on dosage form and amount of food (mins to hours)
how much absorption occurs in the stomach?
Little absorption occurs here - as it is a smaller area
what is the main site of absorption?
small intestine
what does any factor altering gastric emptying also alter?
may alter the rate (and extent) of absorption
what is gastric emptying?
ie the emptying of the contents of the stomach into the intestine
why is it important how quickly the drug arrives in the SI?
rate of movement is constant in SI ( does not matter if it fed or fast state)
Pharmacokinetics of drug release
what is the first order model
In first-order model, drug release is dependent on the amount of drug available for release and therefore the rate of release declines exponentially with time
decreases with drug concentration
extended release dosage forms are governed by which form?
Extended release dosage forms are governed by zero-order kinetics in which the rate of release is independent of amount of drug remaining in the dosage form.
always the same regardless of the drug concentration
what is the advantages of modified release formulation?
Reduced dosing frequency-night dosing
Dose reduction- safety and cost
Improved patient compliance
A constant level of drug concentration in blood plasma
Reduced toxicity due to overdose
Reduces the fluctuation of peak-value
what is the disadvantages of modified release formulation?
Possibility of dose dumping
Reduced potential for dose adjustment
Cost of single unit higher than conventional dosage forms
Increased potential for first-pass metabolism
Decreased systemic availability in comparison to immediate release conventional dosage forms
Poor in vitro and in vivo correlations
what are the factors that affect the release rate?
It is essential that the rate of release is much slower than the rate of absorption.
If we assume the transit time of dosage forms in the absorptive areas of GI tract is about 8-12 hours, the maximum half-life for absorption should be approximately 3-4 hours. Otherwise, the dosage form will pass out of absorptive regions before drug release is complete.
Physicochemical factors affecting extent/rate of drug release
Aqueous solubility: low solubility _ longer time to dissolve
b. Partition coefficient: High Log P_ may diffuse slower from device
c. Drug pKa and ionization at physiological pH_ May affect solubility/ diffusion
d. Drug stability_ hydrolysis, e.g. penicillin
e. Molecular weight and diffusivity: Large MW_ low diffusion
what are the factors which show the drug is a poor candidates for SR?
Drugs with long elimination half-life, i.e., t1/2 >8 hrs
Drugs with narrow therapeutic index
Drugs that require large doses
Drugs showing poor absorption
Drugs with low or slow solubility
A drugs which is extensive metabolised
A drug capable of inducing metabolism, inhibiting metabolism, metabolized at the site of absorption or first-pass effect is poor candidate for SR delivery, as it could be difficult to maintain constant blood level.
