modified release oral dosage forms Flashcards
clinical needs for modified drug release by oral route
-release of drug in specific sites in GIT, needs to avoid gastric environment, target ileum or colon
-maintenance of drug plasma conc over extended period of time to reduce frequency, reduced side effects, no no dose periods
what is delayed and extended release
delayed release= whole dose released later
extended release= dose release over and extended release
how to achieve delayed release and its advantages
enteric coating
-prevents disintegration of dosage form in stomach so drug gets released in intestines
-core of dosage form coated with polymer insoluble at low pH, polymer dissolves at pH of intestines (>6), core disintegrates and releases drug
advantages= protects stomach from drug, protects drug from stomach environment, maximises drug absorption in intestines
what can delayed release to colon treat
treat colorectal cancer, inflammatory bowel disease, enhances bioavailability of some drugs
-formulation is protected in stomach and small intestine but released in colon, exploitation of colon’s specific conditions (pH 5.5-7)
what 3 things can be controlled to devlier drugs to colon
pH, transit time, microflora
how can controlling pH help deliver drugs to the colon and its issues
-coat with eudragit S, dissolves at pH >7
-issues= no difference in pH between small intestine and colon, drug released in colon mainly due to long transit time, some drug lost in small intestines, polymer doesnt always dissolve
how can controlling transit time help deliver drugs to the colon and example
-pentesa=coating eudragit L and ethyl cellulose (impermeable to water, slows diffusion of drug through pores in coating)
-pulsincap
how can controlling microflora help deliver drugs to the colon
microorganisms excrete non native enzymes, polysaccharides incompletely degraded in upper GIT, polysaccharide coating remains intact in stomach then swells in small intestines then degraded by microflora in colon
what is colon microflora
complex ecosystem of anaerbobic and aerobic bacteria
limitations to colon delivery
small surface area, low fluid volume, primary function is reabsorption of water and electrolytes, phase i and ii enzymes present in colon wall, no avoidance of first pass metabolism, high variability between patients (pH, transit time, microflora), no uptake transporters
requirements of extended release drugs
-sustained blood levels, no short half life, no pharmacologically active metabolites, no toxicity
-release from dosage form must be the rate limiting step, soluble in GI fluid, well absorbed through GI mucosa
-dosage form must contain multiple doses, relatively potent to avoid large tablets
describe drug release from extended release tablets
- hydration of dosage form- leads to swelling or dissolution of components
- diffusion of water into dosage form- controlled by structure and hydrophilicity of system
- dissolution of drug- very soluble drugs not suitable
- diffusion of drug out of dosage form- depends on porosity/tortuosity of system and drug affinity for system
types of extended release formulations
-matrix formulations (modified release ingredients in core)
-membrane controlled formulations (polymer coating)
-gastro retentive formulations (overcome gastric emptying)
name and describe 2 types of matrix formulations
- hydrophobic inert- drug dispersed in insoluble polymer, contains channel that hydrates GIT, drug diffuses out of capillary networks, release rate depends on pore structure and decreases with time
- lipid- drug blended with wax, useful for high water solubility drugs
how is colon delivery achieved
slow dissolution of thick polymeric coating
