Predetermination of burst times of elastoplastic osmotic capsules

“Pulsed drug release” for dosing drugs such as vaccines, hormones etc. that require multiple, predetermined release events can be obtained by using capsules that exploit the principle of osmosis to achieve a delayed burst release of their payload. An objective of this study was to precisely determine the lag time before burst which occurs when the hydrostatic pressure developed due to water influx expands the capsule shell to rupture. A novel ‘dip coating’ technique was used to encapsulate osmotic agent solution or solid within biodegradable poly(lactic acid-co-glycolic) (PLGA) spherical capsule shells. As a prelude to determine the hydrostatic pressure to burst, first, elastoplastic and failure characterization of PLGA was conducted by a novel “beach ball inflation” technique. The lag time before burst of various capsule configurations was predetermined by modeling the rate of water uptake by the capsule core as a function of capsule shell thickness, radius of the sphere, core osmotic pressure, and the membrane's hydraulic permeability and tensile properties. In vitro release was studied with capsules of different configurations to determine their actual time to burst. The time to rupture predetermined from the mathematical model corroborated with the in vitro results and was found to increase with increases in capsule radius and shell thickness and decrease in osmotic pressure. Pulsatile drug delivery can be achieved by using a multitude of these osmotic capsules consolidated in a single system, each programmed to release the drug payload after a pre-determined time lag. [Display omitted]