Modified Release Dosage Forms

Provides a fast onset of action by releasing the drug via first-order kinetics - meaning the rate of elimination is directly proportional to the amount of drug present

Immediate release

Drug action is limited to the time concentrations stay above the _______ _______ _______

Minimum effective concentration

You cannot simply increase the dose of Immediate Release to reduce dosing frequency, as this risks exceeding the _______ _____ _______

Minimum Toxic Concentration

Refers to any release pattern other than immediate release. It is an umbrella term that includes both delayed and extended release formulations

Modified release

Stops drug release until specific regions of the GI tract are reached; it creates a difference in start time, not a prolonged release

Delayed Release

Uses pH-sensitive polymers to protect drugs from low gastric pH degradation and prevent stomach irritation

Delayed Release

Once the coating on a delayed release tablet dissolves, it mimics an _______ ______ profile. It can also be used to deliver proteins and peptides

Immediate release

Provides constant plasma concentrations over time using zero-order kinetics - the rate of release does NOT depend on the remaining drug concentration (input = output); can be delivered orally, transdermally, or vaginally

Controlled release

Maintains drug release over a sustained period to keep drug levels within the therapeutic window for longer than an immediate release formulation would

Sustained release

These systems follow Zero-order kinetics (constant release rate)

Reservoir systems

These systems release is linear as a function of the square root of time

Matrix systems

Directs the drug specifically to a targeted tissue, region or cell type; its goals are to enhance specificity and avoid systemic toxicity

Targeted release

Involves two single doses released back-to-back - for example, a double-layer tablet where one layer releases immediately and the other releases later

Repeat action dosing

Advantages are reduces dosing frequency and cost, improves patient compliance, reduces side effects, maintains constant therapeutic levels, and especially beneficial for narrow therapeutic index drugs

Modified release

Modified release formulations are especially beneficial for _______ ______ ______ drugs

Narrow therapeutic index

Disadvantages are pharmacological effects may take longer to occur, prescriptions usually have fewer refills, and if crushed, there is a major risk of dose dumping - rapid, potentially toxic drug release

Modified release

Modified release systems present the risk of _______ ________ if taken incorrectly

Dose dumping

Best suited for potent drugs requiring relatively small doses used to treat chronic conditions with less flexibility in dose adjustments

Extended release

Drugs using these must have uniform GI absorption, good aqueous solubility, adequate gastric retention, and an absorption/excretion rate that is not too fast or too slow

Extended release

Uses beads, granules (Spansules), or microspheres coated in lipid or cellulosic materials

Pharmaceutical coating

The _________ of the coating determines the release rate

Thickness

Difference thicknesses are often distinguished by _______, and beads of varying thicknesses can be combined in one capsule for tailored release patterns

Color

Hard gelatin capsule containing 8-10 mini-tablets, each 3-4 mm in diameter; allows for higher drug loading and combination of different drugs or release patterns in one dose

PRODAS

Encapsulates drug molecules in biodegradable or non-biodegradable polymers such as gelatin, polyvinyl alcohol, PLGA, ethyl cellulose, polyvinyl chloride

Microencapsulation

Release in microencapsulation is defined by the drug core to polymer wall _______

Ratio

Drugs can be embedded in a slow-eroding or hydrophilic _________ matrix

Cellulosic

In a matrix system, soluble drugs ________ out

Diffuse

In a matrix system, insoluble drugs are released by tablet ________ in gastric fluids

Erosion

Tablet wets, polymer hydrates and gel layer forms; water permeates and gel expands, leading to release of drug from tablet by diffusion or erosion

Matrix system

Granulation with non-biodegradable, non-eroding plastic materials like polyethylene or polyvinyl acetate

Inert plastic systems

Gradumet is an example of an ______ _______ system

Inert plastic

Drug is formulated with cyclodextrins or tannic acid to slowly release the active drug; examples are Brovex and Rynatan

Complex formation

Forms resin-drug complexes dependent on pH and electrolytes; examples are Ionamin and Tussionex

Ion-exchange resin

In stomach, ion exchange occurs with acid (HCl)

Ion-exchange resin

In intestine, ion exchange occurs with electrolytes (NaCl)

Ion-exchange resin

Ionic drug complexed with resin and coated with ethyl cellulose for delayed release

Pennkinetic delivery system

A core tablet covered by a semi-permeable rate-controlling membrane with a laser-drilled delivery orifice; the core contains a polymeric osmotic agent (push layer)

Osmotic pump

In OROS, water is absorbed osmotically which causes the push layer to _________, forcing the drug suspension out of the orifice

Swell

Variants are Push-Pull, L-OROS (for liquid drug formulations), Tri-Layer; example is Procardia XL

OROS

ER/modified release medications should be swallowed ______ - do NOT crush, chew or divide

Whole

Do NOT combine IR forms of the same drug/class with _______ _______ forms without consulting the prescriber

Modified release

For _______, patients may see an empty, inert shell in their stool - this is normal and means the drug was successfully absorbed

OROS