Modified release Flashcards
(46 cards)
Advantages for modified release?
Peaks & troughs minimised – steady state therapeutic levels to better manage disease
Improved Compliance- less xxxazsxsdweffrequency doses
Better safety margin- Lower side effects
Efficient use of drug – lower overall amount used
Reduction in healthcare costs- less monitoring, shorter treatment time, less dispensing.
Disadvantages for modified release?
Risk of dose dumping & instability of drug, more costly manufacturing process.
Delayed Release:
The drug is not released immediately following administration but at a later time
e.g. enteric-coated tablets or capsules.
Repeat Action:
An individual dose is released soon after administration. Second or third doses are released at later intervals
Prolonged Release:
The drug is absorbed over a longer period of time than from a conventional dosage form. Implication that onset is delayed because of slower release rate from the dosage form.
Sustained Action:
An initial release of drug sufficient to provide a therapeutic dose soon after administration. Then a gradual release over an extended period.
Extended Release (ER):
Release drug slowly.
Plasma concentrations are maintained for a prolonged period of time (usually between 8 and 12 hours)
Controlled Release (CR):
Controlled Release (CR):
In literature you will find the terms PR and SR are interchangeably used with ER. They terms must not be confused with delayed releaseRepeat-action Versus Sustained-action Drug Therapy?
A repeat-action tablet can be distinguished from sustained-released.
Repeat-action does not release the drug in a slow controlled manner.
Repeat-action tablet usually contains two doses of a drug:
The first is released immediately after administration.
The second dose is delayed. Often by an enteric coat.
Layered tablet – comprises 2 or 3 layers
Tablet within a tablet
MR products are generally designed to provide either:
Prompt achievement of a plasma concentration of drug :
- remaining constant within the therapeutic range of the drug for a prolonged period of time. OR
- declining at such a slow rate that the plasma concentration remains within the therapeutic range for a prolonged period of time.
Suitable drugs for MR?
- Biological t1/2 = 2-8hrs
- High therapeutic window
- Log P = ~2.2-3.3
- uniformly absorbed and not too unstable throughout the - - GIT
- Moderate potency – require small doses
Several physiochemical properties of the active drug can influence the choice of dosage form. The properties include
aqueous solubility and stability; pKa; partition coefficient (or, more appropriately, permeability values) and salt form.
The aqueous solubility and intestinal permeability of drug compounds are of paramount importance.
In practice difficult to achieve ideal drug release rates in mass balance with clearance to achieve constant plasma levels. This is due to many factors, e.g. ;
- Variable physiological conditions of GIT
- Clearance rate can be patient dependent, age, race etc
- Disease status
- Food/diet intake
The Physiology of the Gastrointestinal Tract and Drug Absorption.
It has been reported that:
Solution and pellets (<2mm) leave the stomach rapidly;
Single dose units (>7mm) can stay in the stomach for up to 10 hours if the delivery system is taken with a heavy meal;
The transit time through the small intestine is approximately 3 hours
Choice of Dosage Form:
Single-unit dosage forms include tablets, coated tablets, matrix tablets and some capsules.
A multiple-unit dosage form includes granules, beads, capsules and microcapsules.
Modified-release dosage forms include inert insoluble matrices, hydrophilic matrices, ion-exchange resins, osmotically controlled formulation and reservoir systems.
Ornade Spansule?
Each capsule is so prepared that an initial dose is released promptly and the remaining medication is released gradually over a prolonged period.
Main Classes of Modified-Release Dosage Forms
For convenience of description modified release oral delivery systems can be considered under the following main headings:
Monolithic or matrix systems
Reservoir or membrane-controlled systems
Osmotic pump systems
The two basic mechanisms controlling drug release are:
Dissolution of the active drug component
Diffusion of dissolved or solubilized species
Within the context of the mechanisms controlling drug release there are four processes operating:
Hydrating of the system (swelling of the hydrocolloid or dissolution of the channelling agent)
Diffusion of water into the system
Dissolution of the drug
Diffusion of the dissolved (or solubilized) drug out of the system.
Many formulation techniques are used to ‘build’ the barrier into the peroral dosage form.
for example–>
The use of coatings
Embedding of the drug in a wax or plastic matrix
Microencapsulation
Chemical binding to ion-exchange resin
Incorporation in an osmotic pump
Matrix system?
Drug uniformly distributed in matrix
Can not usually get zero order release
Rate declines with time
How does a wax matrix delivery system work?
Drug contained in hydrophobic matrix which remains intact during release of the drug
In contact with the aqueous media the channeling agent dissolves and leaches out of the compact leaving a porous matrix of tortuous capillaries.
The drug dissolves and diffuses out of the system via the capillaries
The rate of release is governed by both the dissolution and diffusion of the channeling agent and the drug.
Matrix forming agents for wax matrices?
- almost any hydrophobic material that is solid at room temp and doesn’t melt at body temp
Channeling agents for wax delivery system?
Almost any water soluble pharmaceutically acceptable solid material.
