TY - JOUR
T1 - Qualification of non-halogenated organic solvents applied to microsphere manufacturing process
AU - Shim, Hyunjin
AU - Sah, Hongkee
N1 - Funding Information:
Funding: This work was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology [NRF-2017R1D1A1A09000891].
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/5
Y1 - 2020/5
N2 - As a non-halogenated dispersed solvent, ethyl acetate has been most commonly used for the manufacturing of poly-D,L-lactide-co-glycolide (PLGA) microspheres. However, ethyl acetate-based microencapsulation processes face several limitations. This study was aimed at proposing ethyl formate as an alternative. Evaluated in this study was the solvent qualification of ethyl formate and ethyl acetate for microencapsulation of a hydrophobic drug into PLGA microspheres. An oil-in-water emulsion solvent extraction technique was developed to load progesterone into PLGA microspheres. Briefly, right after emulsion droplets were temporarily stabilized, they were subject to primary solvent extraction. Appearing semisolid, embryonic microspheres were completely hardened through subsequent secondary solvent extraction. Changes in process parameters of the preparative technique made it possible to manipulate the properties of emulsion droplets, progesterone behavior, and microsphere quality. Despite the two solvents showing comparable Hansen solubility parameter distances toward PLGA, ethyl formate surpassed ethyl acetate in relation to volatility and water miscibility. These features served as advantages in the microsphere manufacturing process, helping produce PLGA microspheres with better quality in terms of drug crystallization, drug encapsulation efficiency, microsphere size homogeneity, and residual solvent content. The present ethyl formate-based preparative technique could be an attractive method of choice for the production of drug-loaded PLGA microspheres.
AB - As a non-halogenated dispersed solvent, ethyl acetate has been most commonly used for the manufacturing of poly-D,L-lactide-co-glycolide (PLGA) microspheres. However, ethyl acetate-based microencapsulation processes face several limitations. This study was aimed at proposing ethyl formate as an alternative. Evaluated in this study was the solvent qualification of ethyl formate and ethyl acetate for microencapsulation of a hydrophobic drug into PLGA microspheres. An oil-in-water emulsion solvent extraction technique was developed to load progesterone into PLGA microspheres. Briefly, right after emulsion droplets were temporarily stabilized, they were subject to primary solvent extraction. Appearing semisolid, embryonic microspheres were completely hardened through subsequent secondary solvent extraction. Changes in process parameters of the preparative technique made it possible to manipulate the properties of emulsion droplets, progesterone behavior, and microsphere quality. Despite the two solvents showing comparable Hansen solubility parameter distances toward PLGA, ethyl formate surpassed ethyl acetate in relation to volatility and water miscibility. These features served as advantages in the microsphere manufacturing process, helping produce PLGA microspheres with better quality in terms of drug crystallization, drug encapsulation efficiency, microsphere size homogeneity, and residual solvent content. The present ethyl formate-based preparative technique could be an attractive method of choice for the production of drug-loaded PLGA microspheres.
KW - L-lactide-co-glycolide
KW - Microencapsulation
KW - Microspheres
KW - Poly-D
KW - Solvent qualification
UR - http://www.scopus.com/inward/record.url?scp=85084354480&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics12050425
DO - 10.3390/pharmaceutics12050425
M3 - Article
AN - SCOPUS:85084354480
SN - 1999-4923
VL - 12
JO - Pharmaceutics
JF - Pharmaceutics
IS - 5
M1 - 425
ER -