Purchase this article with an account.
K. W. Burton, P. Markland, G. Winchester, T. Tice; Sustained Release Formulations Administered through Small Bore Needles Useful for Intraocular Applications. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5559.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
This study shows that sustained release formulations using certain compositions of polyesters are readily injectable through small-bore needles (26G) at concentrations and particle sizes suitable for multi-month delivery of therapeutic agents.
Novel compositions of bioerodible polyester particles were manufactured using a emulsion, solvent-extraction process. Particle characteristics such as particle size and distribution and particle appearance (SEM) were determined. The surface of the particles was characterized using Atomic Force Microscopy (AFM). Performance testing was determined using a subjective injectability method and an objective viscosity method.
Standard-size njectable microparticle formulations were prepared having mean particle sizes of 70-90 microns. When prepared using traditional bioerodible polyesters such as poly(lactide-co-glycolide), these formulations were capable of being reproducibly injected through 20G needles (at suspension concentrations upto 50% solids) and through 21G needles using 10-20% solids suspensions. Novel microparticle compositions having similar particle sizes have been identified that can be reproducibly injected through 23G needles from upto 50% solids suspensions and through 25G needles from upto 30% solids suspensions. Injectability was further enhanced using formulations having a smaller mean particle size. Novel microparticle compositions were prepared with a mean particle size of 30-35 microns; these formulations were injectable through 26G needles from 10-50% solids suspensions. A key feature involved in these effects is the addition of a second immiscible polymer into the biodegradable polyester microparticle composition. The composition and concentration level of this second polymer is particularly critical to achieving the beneficial effect on injectability. AFM was used to demonstrate that the immiscible second polymer was indeed present along the surface of the microparticles as distinct phase-separated domains from the remaining polyester composition. Capillary viscometry demonstrated distinct flow characteristics between formulations. Suspensions containing 40% of the traditional polyester microparticles had fall-times of 400 seconds while those of the novel compositions had fall times of 300 seconds demonstrating the enhanced flow properties of these novel microparticle compositions.
Injectable biodegradable polyester microparticle formulations can be administered using small-bore needles to allow multi-month delivery of therapeutic agents.Key Words: Microparticles, drug delivery, intravitreous
This PDF is available to Subscribers Only