Eyal Afergan, Yousef Najajreh, Dikla Gutman, Hila Epstein, Omar Elmalak and Gershon Golomb
Background: A liposomal delivery system requires a complete understanding of the physicochemical characteristics of the drug– liposome system in order to predict their behavior and stability in-vitro and in-vivo .
Objectives: Develop a rapid and simple experimental method to determine the fractions of the drug, alendronate (ALN), encapsulated and as a free form distributed in the liposomal suspension, and the physical state of the encapsulated drug.
Methods: 31 P-NMR measurements utilizing Ga +3 as a shifting reagent in comparison to HPLC determinations, theoretical calculations and differential scanning calorimetry (DSC) studies of various liposomal ALN formulations.
Results: The 31 P-NMR demonstrated that titrating liposomal ALN with increasing amounts of Ga +3 induced a signi fi cant shift in the exterior fraction without changing the interior fraction. Quantitative determination of the encapsulated and non-encapsulated f ractions of ALN has been achieved at Ga +3 concentrations of 3.2-25mM. The DSC study revealed that none of the formulation ingredients is in a solid phase.
Conclusions: 31 P-NMR was found to be sensitive enough to allow accurate differentiation of the distributed fractions of ALN, encapsulated and the non-encapsulated free form. Based on theoretical calculations and DSC analysis it can be concluded that AL N is dissolved in the aqueous core of the liposome.
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