title: Encapsulation of immunoglobulin G by solid-in-oil-in-water: effect of process parameters on microsphere properties.
abstract: Antibodies (Abs) are prone to a variety of physical and chemical degradation pathways, which require the development of stable formulations and specific delivery strategies. In this study, injectable biodegradable and biocompatible polymeric particles were employed for controlled-release dosage forms and the encapsulation of antibodies into polylactide-co-glycolide (PLGA) based microspheres was explored. In order to avoid stability issues which are commonly described when water-in-oil (w/o) emulsion is used, a solid-in-oil-in-water (s/o/w) method was developed and optimized. The solid phase was made of IgG microparticles and the s/o/w process was evaluated as an encapsulation method using a model Ab molecule (polyclonal bovine immunoglobulin G (IgG)). The methylene chloride (MC) commonly used for an encapsulation process was replaced by ethyl acetate (EtAc), which was considered as a more suitable organic solvent in terms of both environmental and human safety. The effects of several processes and formulation factors were evaluated on IgG:PLGA microsphere properties such as: particle size distribution, drug loading, IgG stability, and encapsulation efficiency (EE%). Several formulations and processing parameters were also statistically identified as critical to get reproducible process (e.g. the PLGA concentration, the volume of the external phase, the emulsification rate, and the quantity of IgG microparticles). The optimized encapsulation method has shown a drug loading of up to 6% (w/w) and an encapsulation efficiency of up to 60% (w/w) while preserving the integrity of the encapsulated antibody. The produced microspheres were characterized by a d(0.9) lower than 110 μm and showed burst effect lower than 50% (w/w).
authors.affiliation: Laboratory of Pharmaceutics and Biopharmaceutics, Université Libre de Bruxelles (ULB), Brussels, Belgium; Laboratory UCB Pharma S.A., Braine-L'Alleud, Belgium. Electronic address: sarah.marquette@ucb.com.
authors.forename: Sarah
authors.initials: S
authors.lastname: Marquette
authors.affiliation: Laboratory UCB Pharma S.A., Braine-L'Alleud, Belgium.
authors.forename: Claude
authors.initials: C
authors.lastname: Peerboom
authors.affiliation: Laboratory UCB Pharma S.A., Braine-L'Alleud, Belgium.
authors.forename: Andrew
authors.initials: A
authors.lastname: Yates
authors.affiliation: Laboratory UCB Pharma S.A., Braine-L'Alleud, Belgium.
authors.forename: Laurence
authors.initials: L
authors.lastname: Denis
authors.affiliation: Laboratory of Pharmaceutics and Biopharmaceutics, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Goole
authors.affiliation: Laboratory of Pharmaceutics and Biopharmaceutics, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Karim
authors.initials: K
authors.lastname: Amighi
mesh_terms: D000818:Animals; D002417:Cattle; D004339:Drug Compounding / Q000379:methods*; D007074:Immunoglobulin G / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry*; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility
chemical_list: D007074:Immunoglobulin G; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Antibody; Design of experiment; Ethyl acetate; Microspheres; PLGA; Solid-in-oil-in-water