Combination of (M)DSC and Surface Analysis to Study the Phase Behaviour and Drug Distribution of Ternary Solid Dispersions
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Miscibility of the different compounds that make up a solid dispersion based formulation play a crucial role in the drug release profile and physical stability of the solid dispersion as it defines the phase behaviour of the dispersion. The standard technique to obtain information on phase behaviour of a sample is (modulated) differential scanning calorimetry ((M)DSC). However, for ternary mixtures (M)DSC alone is not sufficient to characterize their phase behaviour and to gain insight into the distribution of the active pharmaceutical ingredient (API) in a two-phased polymeric matrix.
MDSC was combined with complementary surface analysis techniques, specifically time-of-flight secondary ion mass spectrometry (ToF-SIMS) and atomic force microscopy (AFM). Three spray-dried model formulations with varying API/PLGA/PVP ratios were analyzed.
MDSC, TOF-SIMS and AFM provided insights into differences in drug distribution via the observed surface coverage for 3 differently composed ternary solid dispersions.
Combining MDSC and surface analysis rendered additional insights in the composition of mixed phases in complex systems, like ternary solid dispersions.
KEY WORDSAFM MDSC Miscibility Solid dispersions ToF-SIMS
Modulated differential scanning calorimetry
Atomic force microscopy
Active pharmaceutical ingredient
Drug delivery system
Human immunodeficiency virus
Glass transition temperature
Time of flight secondary ion mass spectrometry
ACKNOWLEDGMENTS AND DISCLOSURES
Dr. Matthew Piggott (ISAC, Nottingham, United Kingdom) is acknowledged for coordinating the AFM experiments.
- 8.Meeus J, Chen X, Scurr DJ, Ciarnelli V, Amssoms K, Roberts CJ, et al. Nanoscale surface characterization and miscibility study of a spray-dried injectable polymeric matrix consisting of poly(lactic-co-glycolic acid) and polyvinylpyrrolidone. J Pharm Sci. 2012;101(9):3473–85.CrossRefPubMedGoogle Scholar
- 9.Meeus J, Scurr DJ, Amssoms K, Davies MC, Roberts CJ, Van den Mooter G. Surface characteristics of spray-dried microspheres consisting of PLGA and PVP: relating the influence of heat and humidity to the thermal characteristics of these polymers. Mol Pharm. 2013;10(8):3213–24.CrossRefPubMedGoogle Scholar
- 13.Weuts I, Van Dycke F, Voorspoels J, De Cort S, Stokbroekx S, Leemans R, et al. Physicochemical properties of the amorphous drug, cast films, and spray dried powders to predict formulation probability of success for solid dispersions: etravirine. J Pharm Sci. 2011;100(1):260–74.CrossRefPubMedGoogle Scholar
- 22.Tobyn M, Brown J, Dennis AB, Fakes M, Gao Q, Gamble J, et al. Amorphous drug-PVP dispersions: application of theoretical, thermal and spectroscopic analytical techniques to the study of a molecule with intermolecular bonds in both the crystalline and pure amorphous state. J Pharm Sci. 2009;98(9):3456–68.CrossRefPubMedGoogle Scholar
- 23.Janssens S, Nagels S, de Armas HN, D’Autry W, Van Schepdael A, Van den Mooter G. Formulation and characterization of ternary solid dispersions made up of Itraconazole and two excipients, TPGS 1000 and PVPVA 64, that were selected based on a supersaturation screening study. Eur J Pharm Biopharm. 2008;69(1):158–66.CrossRefPubMedGoogle Scholar