31P-NMR and differential scanning calorimetry studies for determining vesicles drug physical state and fraction in alendronate liposomes

Afergan, Eyal
Najajreh, Yousef
Gutman, Dikla
Epstein, Hila
Elmalak, Omar
Golomb, Gershon
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OMICS Publishing Group
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: 31P-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 31P-NMR demonstrated that titrating liposomal ALN with increasing amounts of Ga+3 induced a signifi cant shift in the exterior fraction without changing the interior fraction. Quantitative determination of the encapsulated and non-encapsulated fractions 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: 31P-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 ALN is dissolved in the aqueous core of the liposome.
31P-NMR , Liposomes , Encapsulation , Differential scanning calorimetry (DSC) , Alendronate , Gallium nitrate
Afergan E, Najajreh Y, Gutman D, Epstein H, Elmalak O, et al. (2010) 31P-NMR and Differential Scanning Calorimetry Studies for Determining Vesicle’s Drug Physical State and Fraction in Alendronate Liposomes. J Bioanal Biomed 2: 125-131. doi:10.4172/1948-593X.1000035