Physical–Chemical Characterization of Octreotide Encapsulated in Commercial Glucose-Star PLGA Microspheres

• DOI: 10.1021/acs.molpharmaceut.0c00619
• Publication Date: 2020-09-02T15:49:33Z
• Authors: Avital Beig; Linglin Feng; Jennifer Walker; Rose Ackermann; Justin K. Y. Hong; Tinghui Li; Yan Wang; Bin Qin; Steven P. Schwend...
• Keywords: PLGA; Star (game theory); Characterization

Sandostatin LAR (SLAR) is an injectable long-acting release (LAR) microsphere formulation for octreotide based on a biodegradeable glucose star copolymer of d,l-lactic and glycolic acids (PLGA-glu), which primarily used the treatment patients with acromegaly. There currently no generic SLAR approved in United States despite expiration patent coverage. To understand better this important formulation, was assessed its composition physical–chemical properties. Octreotide kinetics monitored under physiological conditions over 56 days together several bioerosion parameters [mass loss, water uptake, pH media, polymer molecular weight (Mw), confocal microscopy after BODIPY uptake]. A significant increase amount released peptide occurred day 14. After 1 incubation PBST, not extractable completely from during 2 h extraction process, but complete accomplished 24 h, suggested that strong noncovalent PLGA–octreotide interactions beginning initial phase. Leuprolide considered as cationic competitor octreotide–PLGA presence medium resulted more continuous SLAR, linearly correlated mass loss (i.e., indication erosion-controlled release). These data strongly suggest forms salt acid end groups linear PLGA chains are either present impurities in, and/or produced by degradation of, PLGA-Glu. This expected to catalyze acylation extend beyond driven erosion control. The characterization studies physicochemical properties described here could be useful development regulatory evaluation microspheres well new formulations, interacts encapsulated peptides.