[TERM2:L1] SOLID ORAL MODIFIED-RELEASE DOSAGE FORMS AND DRUG DELIVERY SYSTEMS Flashcards
MEC
Minimum Effective Concentration
MTC
Maximum Therapeutic Concentration
MTC Advantages
- Less fluctuation in drug blood levels - eliminates peaks
- Frequency reduction in dosing - deliver more than a single dose
- Enhanced convenience and compliance - patient is less apt to neglect a dose
- Reduction in adverse side effects - fewer blood level peaks into toxic range = less adverse effects
- Reduction in overall health care costs - enhanced therapeutic benefit
dosage form with the time course and/or location of the drug release are chosen to accomplish therapeutic or convenience objectives not offered by conventional dosage forms
Modified-release Dosage Form
Types of modified-release products
- Oral
- Transdermal
- Intramuscular (IM)
- Subcutaneous (SC)
Modified-release Products
- extended-release dosage form - the release starts immediately, but is slow - results in at least two-fold reduction in the dosing frequency
- delayed-release dosage form - releases a discrete portion(s) at a later time, although one portion can be released immediately
- targeted-release dosage form - releases drug at or near the intended physiologic site of action
the release starts immediately, but is slow - results in at least two-fold reduction in the dosing frequency
extended-release dosage form
releases a discrete portion(s) at a later time, although one portion can be released immediately
delayed-release dosage form
releases drug at or near the intended physiologic site of action
targeted-release dosage form
allows a reduction in dosing frequency from that necessitated by a conventional dosage form, such as a solution or an immediate-release dosage form.
Extended Release (ER)
Extended Release (ER) Examples
AFDDDI:
Aspirin Extended-release Tablets
Ferrous Fumarate and Docusate Sodium Extended-release Tablets
Diazepam Extended-release Capsules
Diltiazem Extended-release Capsules
Disopyramide Phosphate Extended-release Capsules
Indomethacin Extended-release Capsules
Extended-release Dosage Forms
- prolonged-release dosage form - releases the drug slowly; provides a drug continuous supply over an extended period - oral dosing + all other categories
- sustained-release dosage form - delivers an initial (loading) dose immediately - the loading dose is followed by a slow and constant release
releases the drug slowly; provides a drug continuous supply over an extended period - oral dosing + all other categories
prolonged-release dosage form
delivers an initial (loading) dose immediately - the loading dose is followed by a slow and constant release
sustained-release dosage form
Uses conventional pan coating or air suspension coating.
The solution of the drug substance is placed on small inert nonpareil seeds or beads.
Coated Beads, Granules, and Microspheres
Coated Beads, Granules, and Microspheres Range
- Nonpareil seeds – 425 to 850 mm
- Microcrystalline cellulose spheres – 170 to 600 mm
Small spheroid compressed tablets may be prepared to have varying drug-release characteristics.
They then may be placed in gelatin capsule shells to provide the desired pattern of drug release .
Each capsule may contain 8 to 10 minitablets, some uncoated for immediate release and others coated for extended drug release.
Multitablet System
A process by which solids, liquids, or even gases may be enclosed in microscopic particles by formation of thin coatings of wall material around the substance.
Microencapsulated Drug
Microencapsulated Drug Process
- Dissolving the wall material
- Material is added and the two-phase mixture thoroughly stirred.
- Material is broken up to desired size.
- Second solution is added.
- Added solution concentrates the gelatin (polymer) into tiny liquid droplets.
- Droplets form a film or coat around the particles.
- Dried to ensure the microencapsulation.
Drug substance is combined and made into granules with an excipient material that slowly erodes in body fluids, progressively releasing the drug for absorption.
Embedding Drug in Slowly Eroding or Hydrophilic Matrix System
Drug substances are chemically combined with chemicals to form complexes that may be only slowly soluble in body fluids, depending on the pH of the environment.
Complex Formation
A solution of a cationic drug may be passed through a column containing an ion-exchange resin, forming a complex by the replacement of hydrogen atoms.
Ion-Exchange Resins
The system is composed of a core tablet surrounded by a semipermeable membrane coating having a 0.4-mm-diameter hole produced by laser beam
Osmotic Pump
Sustained-release forms
- Coat beads or granules: (Theo-dur,Key, Sequels)
- Microencapsulation: (Bayer time release Aspirin)
- Matrix tablets: (Gradumet, Lontabs, Dospan, Slow-K)
- Ion-exchange resins: (Ionamin caps)
Delayed Release (DR) Examples
ADEO:
Aspirin Delayed–release Tablets
Doxycycline Hyclate Delayed-release Capsules
Erythromycine Delayed-release Capsules
Oxtriphylline Delayed-release Tablets
Delayed Release (DR) Types
- enteric-coated tablet - the enteric coating is stable in stomach - it will dissolve in the higher pH of small intestine - used for drugs irritating stomach
- repeat-release tablet - the first dose is released immediately - the second dose is released later -saves one administration
the enteric coating is stable in stomach - it will dissolve in the higher pH of small intestine - used for drugs irritating stomach
enteric-coated tablet
the first dose is released immediately - the second dose is released later -saves one administration
repeat-release tablet
the enteric coating is stable in stomach - it will dissolve in the higher pH of small intestine - used for drugs irritating stomach
enteric-coated tablet
Contain two single doses of medication, one for immediate release and the second for delayed release.
Repeat Action
Drug release directed toward isolating or concentrating a drug in a body region, tissue, or site for absorption or for drug action.
Targeted Release
Drug release directed toward isolating or concentrating a drug in a body region, tissue, or site for absorption or for drug action.
Targeted Release
Types of Targeting
first-order targeting - drug is delivered to the capillary bed of the site of action
second-order targeting - drug is delivered to special cell type (e.g. tumor cells)
third-order targeting - drug is delivered to intracellular space of the cells
USP Requirements and FDA Guidance for Modified Release Dosage Forms
Drug Release – USP Chapter <724>
Uniformity of Dosage Units – USP Chapter <905>
In Vitro–In Vivo Correlations (IVIVC)
Labeling
Three categories of IVIVCs
- Level A – A predictive mathematical model for the relationship between the entire in vitro dissolution and release time course and the entire in vivo response time course.
- Level B – A predictive mathematical model of the relationship between summary parameters that characterize the in vitro and in vivo time courses.
- Level C – A predictive mathematical model of the relationship between the amount dissolved in vitro at a particular time and a summary parameter that characterizes the in vivo time course
