Abstract
Thermogravimetry does not give specific information on residual organic solvents in polymeric matrices unless it is hyphenated with the so-called evolved gas analysis. The purpose of this study was to apply, for the first time, derivative thermogravimetry (DTG) to characterize a residual solvent and a drug in poly-d,l-lactide-co-glycolide (PLGA) microspheres. Ethyl formate, an ICH class 3 solvent, was used to encapsulate progesterone into microspheres. DTG provided a distinct peak, displaying the onset and end temperatures at which ethyl formate started to evolve from to where it completely escaped out of the microspheres. DTG also gave the area and height of the solvent peak, as well as the temperature of the highest mass change rate of the microspheres. These derivative parameters allowed for the measurement of the amount of residual ethyl formate in the microspheres. Interestingly, progesterone affected not only the residual solvent amount but also these derivative parameters. Another intriguing finding was that there was a linear relationship between progesterone content and the peak height of ethyl formate. The residual solvent data calculated by DTG were quite comparable to those measured by gas chromatography. In summary, DTG could be an efficient and practical quality control tool to evaluate residual solvents and drugs in various polymeric matrices.
Highlights
Long-acting microspheres are leading dosage forms of injectable poly-d,l-lactide-co-glycolide (PLGA)-based drug delivery systems
To the best of our knowledge, derivative thermogravimetry (DTG) has not been applied to investigating the thermal behavior and quantification of a residual organic solvent and a drug in PLGA microspheres
There are a couple of studies encapsulating progesterone into PLGA microspheres via methylene chloride-based solvent unentrapped hydrophobic drug crystals tend to appear in microsphere suspensions
Summary
Long-acting microspheres are leading dosage forms of injectable poly-d,l-lactide-co-glycolide (PLGA)-based drug delivery systems. Emulsion-based solvent evaporation preparative techniques using methylene chloride or chloroform are commonly applied to prepare PLGA particles [1,2,3]. These solvents have low boiling points and negligible water-immiscibility. To the best of our knowledge, DTG has not been applied to investigating the thermal behavior and quantification of a residual organic solvent and a drug in PLGA microspheres. DTG was applied to assess residual ethyl formate in the microspheres. DTG was used to evaluate the effect of progesterone on the thermal behavior of residual ethyl formate. ICH solvent class Boiling point (◦C) Density (g/cm3) Solubility in water (g/100 mL) Log P (octanol/water)
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