Solid Oral MR Dosage Forms - Hydrophilic & Insoluble Polymer Matrix Systems

Immediate release dosage form (IR)

release the active drug promptly upon contact with GI fluids, allowing rapid dissolution and absorption

Key characteristics of IR dosage form

• rapid drug release

• no modification of release or site

• typically produce a quick rise in plasma drug concentration

Common types of IR dosage forms

• conventional tablets/capsules

• oral solutions/syrups/suspensions

• powders for reconstitution

What type of dosage form does the chart show?

immediate release

Modified release dosage form

manipulation of drug release from a dosage form with the specific aim of delivering APIs at:

• desired rate

• predetermined time point

• specific sites in the GI tract

Classifications of modified release dosage forms

1. extended release (ER)

2. delayed release (DR)

Extended-release (ER) dosage forms

maintain therapeutic plasma concentrations over an extended duration

How might an ER formulation dosing differ from IR formulation dosage?

reduced dosing frequency

• once or twice daily

• more stable plasma concentration

Advantages of ER dosage forms

• less fluctuation in drug blood levels

• frequency reduction in dosing

• enhanced convenience and compliance

• reduction in adverse side effects

• reduction in overall health care costs

Hydrophilic matrix system

• also known as swellable soluble matrices

• drug is blended with water-swellable hydrophilic polymer

• blend is compressed into tablets by compression or dry granulation, resulting in a tablet with drug particles are interspersed among polymer particles

Hydrophilic polymers used for hydrophilic matrix system

• HPMC or other polyethylene oxide

• 20% of HPMC results in satisfactory rates of release

Hydrophilic matrix system mechanism of drug release

• upon contact with GI fluid, the polymer hydrates and swells to form a viscous gel layer around the tablet

• water continues to penetrate, gradually thickening gel

• drug is released by diffusion through gel or erosion/dissolution of the gel

Role of gel structure and tortuosity in hydrophilic matrix system

• hydrated hydrophilic polymers form a network of entangled chains

• spaces between chains create continuous aqeous phase, allowing water and dissolved drug to move

• pathways are tortuous, not straight

What factors increase the number of pathways in a hydrophilic matrix system, slowing release?

• high polymer concentration

• higher molecular weight polymer

How can a slow-release profile be achieved in a hydrophilic matrix system?

• high-viscosity or high molecular weight polymers

• increased percentage of polymers

• polymers with greater degree of cross-linking

• adding excipients that strengthen/stabilize gel

How can a faster-release profile be achieved in a hydrophilic matrix system?

• lower-viscosity polymers or lower molecular weight

• lower polymer content

• incorporation of more soluble excipients that loosen gel structure

Insoluble (inert) polymer matrix system

drug is embedded in an inert, water-insoluble polymer often described as a “sponge-like” structure

• tab enters GI tract, water penetrates channels and pores, dissolves drug

• dissolved drug diffuses out water-filled pores

What types of drugs are insoluble polymer matrix systems suitable for?

drugs that are less water soluble

Insoluble polymers used for insoluble polymer matrix systems

• polyethylene

• polyvinyl acetate

• polymethyl methacrylate

What effect does porosity have on controlled release of insoluble polymer matrix systems?

• ↑porosity, faster drug release

• ↑compaction, ↓porosity, slower drug release

• pore-forming agents can be added to facilitate drug release

What effect does tortuosity have on insoluble polymer matrix system release rate?

• increased tortuosity, decreased drug release

Describe the intact nature of insoluble polymer matrix systems

• polymeric matrix does not dissolve/degrade in GI tract

• once drug is released, remaining matrix retains structural integrity

• excreted unchanged in feces; “ghost tablet”

What is an important counseling point when dispensing a drug with an insoluble polymer matrix system?

patients may notice empty shell in stool