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  • Effect of water on exenatide acylation in poly(lactide-co-glycolide) microspheres.

Effect of water on exenatide acylation in poly(lactide-co-glycolide) microspheres.

International journal of pharmaceutics (2013-07-23)
Rongcai Liang, Xiang Li, Yanan Shi, Aiping Wang, Kaoxiang Sun, Wanhui Liu, Youxin Li
PMID23872225
ABSTRACT

Peptide or protein degradation often occurs when water flows into the dosage form. The aim of this study was to investigate the effect of water on exenatide acylation in poly(lactide-co-glycolide) (PLGA) microspheres. Exenatide-loaded PLGA microspheres were incubated at different relative humidities (RH) as well as in solutions of different pH for 20 days. The stability of exenatide was monitored using HPLC and HPLC-MS analysis. The alteration of exenatide conformation caused by water was investigated by FT-IR spectroscopy. Exenatide and glycolide were incubated in DMSO-water solutions to verify the effect of exenatide conformation state on the peptide acylation. Exenatide was relatively stable in microspheres at lower RH, and the absorbed water could act as a plasticizer and thus promote the peptide acylation by PLGA. However, when the microspheres were incubated at 100% RH, the excessively absorbed water could cause conformation recovery of exenatide and play an inhibitory effect on acylation. The formation of acylated exenatide incubated in acetate buffer saline of pH 6.0 was more than that of pH 4.5 and 3.0. Stability studies of exenatide in glycolide solutions showed that exenatide in nonnative monomer state was easier to be acylated by eletrophiles than that in aggregation state.

MATERIALS
Product Number
Brand
Product Description
719900
Sigma-Aldrich
Resomer® RG 504 H, Poly(D,L-lactide-co-glycolide), acid terminated, lactide:glycolide 50:50, Mw 38,000-54,000
739960
Sigma-Aldrich
Resomer® RG 505, Poly(D,L-lactide-co-glycolide), ester terminated, Mw 54,000-69,000
430471
Sigma-Aldrich
Poly(D,L-lactide-co-glycolide), ester terminated, Mw 50,000-75,000
P2191
Sigma-Aldrich
Poly(D,L-lactide-co-glycolide), lactide:glycolide (50:50), mol wt 30,000-60,000
P2066
Sigma-Aldrich
Poly(D,L-lactide-co-glycolide), lactide:glycolide 65:35, Mw 40,000-75,000
P1941
Sigma-Aldrich
Poly(D,L-lactide-co-glycolide), lactide:glycolide (75:25), mol wt 66,000-107,000
739979
Sigma-Aldrich
Resomer® RG 858 S, Poly(D,L-lactide-co-glycolide), ester terminated, lactide:glycolide 85:15, Mw 190,000-240,000
739952
Sigma-Aldrich
Resomer® RG 503, Poly(D,L-lactide-co-glycolide), lactide:glycolide 50:50, ester terminated, Mw 24,000-38,000
739944
Sigma-Aldrich
Resomer® RG 504, Poly(D,L-lactide-co-glycolide), lactide:glycolide 50:50, ester terminated, Mw 38,000-54,000
719897
Sigma-Aldrich
Resomer® RG 502 H, Poly(D,L-lactide-co-glycolide), acid terminated, viscosity 0.16-0.24 dL/g 
719870
Sigma-Aldrich
Resomer® RG 503 H, Poly(D,L-lactide-co-glycolide), acid terminated, lactide:glycolide 50:50, Mw 24,000-38,000
719862
Sigma-Aldrich
Resomer® RG 653 H, Poly(D,L-lactide-co-glycolide), acid terminated, Mw 24,000-38,000
719889
Sigma-Aldrich
Resomer® RG 502, Poly(D,L-Lactide-co-Glycolide), lactide:glycolide 50:50, ester terminated, Mw 7,000-17,000
719919
Sigma-Aldrich
Resomer® RG 752 H, Poly(D,L-lactide-co-glycolide), acid terminated, lactide:glycolide 75:25, Mw 4,000-15,000
719927
Sigma-Aldrich
Resomer® RG 756 S, Poly(D,L-lactide-co-glycolide), ester terminated, lactide:glycolide 75:25, Mw 76,000-115,000