Formation and isolation of spherical fine protein microparticles through lyophilization of protein-poly(ethylene glycol) aqueous mixture.
OBJECTIVE
Preparation of spherical fine protein microparticles by the lyophilization of a protein-poly(ethylene glycol) (PEG) aqueous mixture was investigated. The main objective was to establish a method for preparing protein microparticles suitable for pharmaceutical production.


METHODS
Aqueous solutions containing bovine serum albumin (BSA) and PEG at various mixing ratios were freeze-dried. The lyophilizates were dispersed in methylene chloride and subjected to particle size analysis. Analogous studies were performed using several model proteins. A phase diagram of the PEG-BSA aqueous system was obtained by the titration method.


RESULTS
The particle size of BSA decreased as the PEG-BSA ratio increased. A bending point was observed in this relationship, at which the PEG-BSA ratio coincided with that of the critical point on the phase diagram of the PEG-BSA system. These results were explained by the freezing-induced condensation, followed by phase separation in the PEG-BSA system.


CONCLUSIONS
Spherical fine protein microparticles were successfully obtained at high yield and without any activity loss under optimum conditions. This new technology could be applicable to proteins with a wide range of molecular weights, and is expected to be developed for dry powder inhalations or long-term sustained release microsphere formulations.
Morita
T
T
DDS Research Department, Tanabe Seiyaku Co. Ltd., Osaka, Japan. t-morita@tanabe.co.jp
Horikiri
Y
Y
Yamahara
H
H
Suzuki
T
T
Yoshino
H
H
D002626:Chemistry, Pharmaceutical; D005079:Excipients / Q000008:administration & dosage / Q000737:chemistry*; D005612:Freeze Drying; D008863:Microspheres; D008970:Molecular Weight; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D011506:Proteins / Q000008:administration & dosage / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000737:chemistry; D012996:Solutions; D014867:Water / Q000737:chemistry
D005079:Excipients; D011506:Proteins; D012996:Solutions; D014867:Water; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols