Supervisors info:
Μαριλένα Βλάχου, Επίκουρη Καθηγήτρια του Τμήματος Φαρμακευτικής του Πανεπιστημίου Αθηνών
Κωνσταντίνος Δεμέτζος, Καθηγητής του Τμήματος Φαρμακευτικής του Πανεπιστημίου Αθηνών
Ευάγγελος Καραλής, Επίκουρος Καθηγητής του Τμήματος Φαρμακευτικής του Πανεπιστημίου Αθηνών
Summary:
In the context of this dissertation, experiments of Differential Scanning Calorimetry (DSC) are carried out in chimeric bilayers (part of the innovative excipient, called “liposome”), composed of hydrogenated soy phosphatidylcholine (HSPC) and poly(n-butylacrylate)-b-poly(acrylic acid) block copolymer with 70% content of PAA (PnBA-b-PAA 30/70), at 6 different molar ratios of 9:0.0, 9:0.1, 9:0,5 9:1.0, 9:2.0 and 9:3.0, in Chimeric liposomes (innovative excipient – advanced Drug Delivery Nanosystem), composed of HSPC:PNBA-b-PAA 30/70:Furosemide, at 3 different molar ratios of 9:0.0:0.0, 9:0.1:0.0 and 9:0.1:1.0, in solid-state pharmaceutical excipients Sodium Alginate, Magnesium Stearate, Lactose Monohydrate, Polyvinylpyrrolidone of 3 different molecular weights (MW: 10.000, MW: 29.000, MW: 55,000), Poly(ethylene oxide) of 2 different molecular weights (MW: 4.000.000, MW: 7.000.000), the bioactive compound Furosemide and mixtures of the solid-state excipients, in the presence and absence of the bioactive furosemide. In chimeric bilayers, increasing the molar ratio PNBA-b-PAA 30/70, both in Citrate Buffer and PBS, broadening of the peaks and appearance of shoulders are observed (solution-like model). Chimeric liposomal systems are characterized as “fluidlike” by their thermograms, which may be potentially translated as an easy way of release of the Furosemide from the advanced delivery system. Concerning the solid-state pharmaceutical excipients and Furosemide, their thermal behavior matches with the literature. Regarding the mixtures of the excipients-Furosemide, their DSC scans are fusion of the thermal behavior of each excipient (the total scan is like putting each scan over the other). This fact indicates that that the formulations, which will contain these mixtures, may retain their stability over time. In conclusion, it is obvious that using the DSC method, combined with other studies, at Preformulation and Development studies, is of great importace. The information which arises about the cooperativity of materials, their thermal stability (which may be extended at the level of kinetic release of the bioactive compound), polymorphism, and the presence of impurities in the mixtures, is very helpful for the research and development of safe and effective pharmaceutical formulations.
Keywords:
Thermal analysis, Differential Scanning Calorimetry, liposome, bilayer, lipid, pH-sensitive polymer, excipient, Furosemide
