Relationship between encapsulated drug particle size and initial release of recombinant human growth hormone from biodegradable microspheres

Relationship between encapsulated drug particle size and initial release of recombinant human growth hormone from biodegradable microspheres
Published Online: 24 Aug 2004
Received: 6 August 2003; Revised: 30 January 2004; Accepted: 30 January 2004
Journal of Pharmaceutical Sciences
Volume 93, Issue 10 , Pages 2624 - 2634
WileyInterScience
Alkermes, Inc., 88 Sidney Street, Cambridge, Massachusetts 02139

email: Henry R. Costantino (rcostantino@nastech.com)
*Correspondence to Henry R. Costantino, Alkermes, Inc., 88 Sidney Street, Cambridge, Massachusetts 02139. Telephone: 425-908-3686; Fax: 425-908-3655
Keywords
biodegradable polymers ? controlled release/delivery ? initial release ? poly(lactide-co-glycolide) (PLG) microspheres ? particle size ? proteins ? recombinant human growth hormone (rhGH) ? spray-freeze drying
Abstract
Protein microencapsulation in biodegradable polymers is a promising route to provide for sustained release. One important characteristic in this regard is the size of the particles encapsulated within the microspheres. In this investigation, we have employed spray-freeze drying to generate particles for encapsulation, and examined the effect of various atomization conditions. Conditions were identified resulting in minimization of the particle size for the therapeutic protein recombinant human growth hormone (rhGH). The polymer employed was poly(lactide-co-glycolide) (PLG). The greatest friability for the powder, and hence smallest particle size (e.g., sub-micron), was achieved as the mass flow ratio of atomization (air to liquid) was increased. Protein powders over a range of particle sizes were encapsulated in biodegradable microspheres using a cryogenic, non-aqueous process. The initial release (both in vitro and in vivo) from these batches was found to decrease with decreasing encapsulated protein particle size; these findings are consistent with the percolation theory. Hence, judicious selection of process variables to reduce the particle size of rhGH is one strategy that can be used to minimize initial release of the microencapsulated protein. ? 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:2624-2634, 2004
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