A method of elevated temperatures coupled with magnetic stirring to predict real time release from long acting progesterone PLGA microspheres

The object of the study was to develop a quick and reproducible accelerated in vitro release method to predict and deduce the function of the real time (37 °C) release for long acting PLGA microspheres. The method could be described in several steps. First, the release of the microspheres were studied using the sample and separate method at 37 °C with normal orbital shaking and elevated temperatures with magnetic stirring to further accelerate the release. Second, the most similar profile at elevated temperatures with the real time release was chosen with the help of the n value in the fitted Korsmeyer-Peppas Function. Third, the Weibull function and conversion ratio were used to deduce the function of real time release according to the chosen profile at elevated temperatures. The key point in this study was to provide a quick and precise method to predict the real time release for long acting progesterone PLGA microspheres. So the elevated temperatures coupled with magnetic stirring were used to accelerate the release further, and when there have many similar release profiles with the real time release at elevated temperatures, releasing time at elevated temperatures and the R2 of the final deduced function will be used to help choosing the most similar release profile with the real time release. Four different types of progesterone PLGA microspheres were used to verify the method, and all the deduced function correlated well with the real time releases, for R2 = 0.9912, 0.9781, 0.9918 and 0.9972, respectively.
Graphical abstract Different types of PLGA were used to make the microspheres with different drug loading rates and particle size distributions. The release profiles at elevated temperatures coupled with magnetic stirring were used to deduce the function of the release at 37 °C with the use of Korsmeyer-Peppas Equation and Weibull Function. Even with different types of microspheres, the deduced functions fitted well with the profiles at 37 °C for R2 = 0.9912, 0.9781, 0.9918 and 0.9972 (from A to D in the figures). Image, graphical abstract