Thermal and 31P-NMR studies to elucidate sumatriptan succinate entrapment behavior in phosphatidylcholine/cholesterol liposomes. Comparative 31P-NMR analysis on negatively and positively-charged liposomes.
In this paper, two techniques, differential scanning calorimetry (DSC) and phosphorus nuclear magnetic resonance ((31)P-NMR), have been used to characterize sumatriptan succinate-loaded charged liposomes. To complete the results obtained by DSC a hot stage microscopy (HSM) technique was used. Data concerning the drug entrapment efficiency were published in a previous paper. The differences in data concerning encapsulation into negatively and positively-charged vesicles, indicated an influence of drug in the structural conformation of lipids in the bilayer. Moreover, the inability to formulate chargeless vesicles contributed to the opinion that a physical formulation study might be relevant. Phosphatidylcholine and cholesterol were used as lipid film forming agents, whereas stearylamine (positive) and dicetylphosphate (negative) were added as charge-inducing agents. DSC studies demonstrated that phosphatidylcholine caused the disappearance of the melting peak (Tm) of sumatriptan succinate because a drug dissolution process occurs. In addition, thermograms showed interesting interactions between stearylamine and dicetylphosphate with sumatriptan succinate favoring drug entrapment into the liposomes. In the present work, (31)P-NMR technique demonstrated that the structural conformation of lipids in the membrane affected drug encapsulation into multilamellar (MLVs) and unilamellar (LUVs) vesicles. Bilayer structure in a liquid crystalline phase of the positively-charged REV liposomes membrane has demonstrated a high structural stability and a better encapsulation efficacy for sumatriptan succinate than negatively-charged TLE and REV liposomes. Therefore, phosphatidylcholine interaction with sumatriptan succinate appears to be the cause of the inability to obtain neutral sumatriptan succinate liposomes.
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Seville, Seville, Spain. svillasmil@us.es
Sheila
S
Villasmil-Sánchez
Antonio M
AM
Rabasco
M Luisa
ML
González-Rodríguez
D000588:Amines / Q000494:pharmacology; D002152:Calorimetry, Differential Scanning; D002784:Cholesterol / Q000737:chemistry* / Q000378:metabolism; D008051:Lipid Bilayers / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010755:Organophosphates / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000737:chemistry* / Q000378:metabolism; D018170:Sumatriptan / Q000737:chemistry* / Q000378:metabolism
D000588:Amines; D008051:Lipid Bilayers; D008081:Liposomes; D010755:Organophosphates; D010713:Phosphatidylcholines; C002290:dicetylphosphate; D018170:Sumatriptan; D002784:Cholesterol; C009317:stearylamine