Foundations of Pharmaceutical Sciences Exam 5

Immediate release oral dosage forms

rapid disintegration

rapid dissolution

• dependent on drug solubility

absorption can take place in entire GI tract but typically takes place in proximal small intestine
dosage forms include tablets, capsules, and suspensions

Sustained release (or prolonged or extended release)

any drug delivery system that achieves a slow release of drug over an extended period of times

Controlled release

• narrower term - usually reserved for zero-order systems (drug is released at a constant rate)

• a drug delivery system in which the system controls the release of the drug in an “intentional” pattern

Advantages of modified release drug products

• enhanced medication adherence and improved quality of life

• decreased fluctuation in peak-and-trough plasma concentrations

• less frequent local and systemic side effects (usually due to lower local and systemic peak concentrations)

• potential to decrease overall health care costs (increased compliance, improved overall therapeutic response)

Disadvantages of modified release drug products

• increased costs (manufacturing and materials)

• additional considerations regarding missed doses

• administration difficulties (large size)

• dangers of mishandling/technology failure (“dose dumping”)

Physiological or chemical characteristics that limit suitability for use in modified release applications

short elimination half-life

• end up with a large dosage form that people couldn’t/wouldn’t swallow

long elimination half-life

narrow therapeutic index

poor solubility

carrier-mediated transport

delayed pharmacodynamic effect

extensive first-pass metabolism

General idea of matrix extended-release system

take the drug dose that we are intending to administer over the dosing interval, incorporate it into the tablet or fill into a capsule

Goal of matrix extended-release system

compressed solid most of the time

Homogenous matrix system

the drug is dissolved and/or dispersed uniformly in the polymer and released by diffusion through the polymer phase

• ex. birth control patches

Inert matrix system

the matrix is insoluble and does not swell or erode. fluid enters the pores and dissolves the drug, which diffuses out through the water-filled channels left behind as the drug particles dissolve.

• ex. making coffee

Hydrophilic (eroding) matrix system

the drug is dispersed in a water-swellable polymer (ex. HPMC). on contact with fluid, the polymer hydrates to form a gel layer. drug is released by diffusion through the gel and by erosion as outer polymer chains disentangle and dissolve

• ex. gummy bears

Release pathway

• original drug has been removed from the depletion zone, and additional drug from the core diffuses through the depletion zone to reach the external surface for release

• drug closer to the surface leaves faster, drug further from the surface takes longer which slows down rate

• as the drug releases from the matrix, the depletion zone’s thickness increases over time

• patient may pass the matrix in their stool, the matrix does not contain drug

Advantages of hydrophilic matrix tablets

• use common, hydratable polymers

• can achieve near, zero-order (constant) release for a portion of the dosing interval due to increased diffusivity through the hydrated gel and eventual reduction in tablet diameter as hydrated gel breaks off/dissolves from surface

• minimal risk of ghost matrix (sometimes gel particles will be observed in stool)

Hydrophilic polymers

hypromellose (HPMC)

General system characteristics of matrix release systems

• matrix may remain intact following drug release (homogenous/inert matrix)

• matrix may dissolve resulting in drug release (erodible matrix)

• drug release is a function of total release surface area of the tablet and the drug concentration at release surface. either of these factors may decrease during the dosing interval resulting in non-constant plasma concentrations

• size and geometry is important for matrix release systems

Gastroretentive matrix technologies

• drug + polymer + effervescent agent

• drug + high density excipient

• drug + swellable polymer

• drug + mucoadhesive polymer

• raft forming

Advantages of gastroretentive matrix technologies

• useful for drugs only absorbed in the upper GI tract

• improve bioavailability of drugs unstable at alkaline pH

• improved targeted delivery for treatments directed to stomach or small intestine

Disadvantages of gastroretentive matrix technologies

• variable residence time in fed and fasted states. longest in fed state

• residence time of floating systems may depend on posture - sitting, standing, supine/prone