WK5 - Controlled Release

Why are controlled release formulations needed?

To stop drug-blood level fluctuations, improve patient compliance, and increase therapeutic efficacy

What is dose dumping?

Dangerous failure where the entire drug releases at once due to coating failure

What are the disadvantages of controlled release?

Limited by gut transit time (~12h), costs more, dose dumping risk, affected by pH/enzymes, not all drugs work

What are the 5 requirements for a drug to be a good CR candidate?

Low dose, high therapeutic index, moderate solubility, stable in GIT, no presystemic metabolism, high absorption rate, moderate t1/2 (2-8h)

What is the ideal half-life for a controlled release drug?

2-8 hours

What is extended-release DDS?

Drug delivery system that releases drug over an extended period of time

What is controlled release DDS?

Releases drug at a constant (zero-order) rate

What is sustained release DDS?

Releases drug over time but NOT constant (non-zero-order, fluctuating)

What is zero-order release?

Same amount of drug released per hour (straight line on graph)

What is Type 1 controlled release system?

Polymer membrane diffusion / reservoir system (drug in core, membrane around it)

What law governs Type 1 (reservoir) systems?

Fick's law of diffusion

What is Type 2 controlled release system?

Polymer matrix diffusion / monolithic system (drug dispersed throughout insoluble polymer)

What law governs Type 2 (matrix) systems?

Higuchi diffusion law

What is Type 3 controlled release system?

Polymer matrix dissolution (polymer is water soluble and dissolves away)

What equation governs Type 3 (dissolution) systems?

Noyes-Whitney equation

What is Type 4 controlled release system?

Ion exchange resin systems (drug binds to resin, ions in GIT swap with drug)

What is delayed release?

Drug releases after a lag time (waits, then releases)

What is enteric coating?

A coating that survives stomach acid (pH 1-2) but dissolves in intestine (pH 5.5-7)

Name 4 enteric coating materials.

CAP (cellulose acetate phthalate), polyvinyl acetate phthalate, HPMCAP, Eudragits

What are Eudragits?

A family of methacrylic acid copolymers, each designed to dissolve at a different pH

Why protect a drug from stomach acid?

Drug is acid-labile (e.g., proton pump inhibitors)

Why protect the stomach from a drug?

Drug is irritant (e.g., NSAIDs like ibuprofen)

What are GRDDS?

Gastro-retentive drug delivery systems (keeps drug in stomach longer)

What are the 3 main uses for GRDDS?

Narrow absorption window drugs, local action in stomach, sustaining rapidly absorbed drugs

Name 3 types of GRDDS.

Effervescent (floating), low density (floating), bioadhesive (sticking), swelling (expanding), high density (sinking)

What is gamma scintigraphy?

Imaging method using a radiolabel (e.g., 99m Technetium) and gamma camera to track pill location in body

What radiolabels are used in gamma scintigraphy?

99m Technetium (t1/2 = 6h) and 111 Indium (t1/2 = 2.8 days)

What is HPMC?

Hydroxypropyl methylcellulose (a water-soluble polymer used in Type 3 dissolution systems)

What is the main risk of reservoir systems (Type 1)?

If the membrane breaks, dose dumping can occur

Why are matrix systems (Type 2) safer than reservoir systems?

If the system cracks, drug still has to diffuse through the matrix