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Updated: Oct 19, 2025

Alternating Magnetic Field-Responsive Hybrid Gelatin Microgels for Controlled Drug Release
Published on: February 13, 2016
Experimental design, development and evaluation of extended release subcutaneous thermo-responsive in situ gels for
Divya Sharma1, Faraj Atassi1, Steve Cook1
1Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Boston, MA, USA.
Abstract:
The objective of this work is to develop extended release subcutaneous thermo-responsive in situ gel-forming delivery systems using the following commercially available triblock polymers: poly (lactic-co-glycolic acid)-poly (ethylene glycol)-poly (lactic-co-glycolic acid) (PLGA-PEG-PLGA, copolymer A & B) and poly (lactide-co-caprolactone)-poly (ethylene glycol)-poly (lactide-co-caprolactone) (PLCL-PEG-PLCL, copolymer C). Performance of two optimized formulations containing ketoprofen as a model compound, was assessed by comparing in vitro drug release profiles with in vivo performance following subcutaneous administration in rats. This work employs a Design of Experiment (DoE) approach to explore first, the relationship between copolymer composition, concentration, and gelation temperature (GT), and second, to identify the optimal copolymer composition and drug loading in the thermo-responsive formulation. Furthermore, this work discusses the disconnect observed between in vitro drug release and in vivo pharmacokinetic (PK) profiles. In vitro, both formulations showed extended-release profiles for 5-9 days, while PK parameters and plasma profiles were similar in vivo without extended release observed. In conclusion, a clear disconnection is observed between in vitro ketoprofen drug release and in vivo performance from the two thermogel formulations tested. This finding highlights a remaining challenge for thermogel formulation development, that is, being able to accurately predict in vivo behavior from in vitro results.
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