Solubilization of bromhexine hydrochloride in aqueous lecithin dispersions. Physicochemical characterization of interactions between drug and carrier.
In aqueous systems bromhexine hydrochloride (Br-HCl) has a poor solubility (4.54 mg/g) and displays no amphiphilic character e.g. self association. Therefore the drug is molecularly dispersed in water until the solubility product of Br-HCl is exceeded. Solubilization of Br-HCl is linearly increased on addition of lecithin; calculations show that 10 mg Phospholipon 90G (P 90G) enable solubilization of additional 1.25 mg Br-HCl after the solubility product of Br-HCl has been exceeded. This means that four to five phospholipid molecules are needed for the solubilization of one drug molecule. Ternary systems with P 90G concentrations up to 20% have a lamellar microstructure. The systems are multilamellar vesicle dispersions as polarisation microscopy, transmission electron microscopy and small-angle X-ray diffractometry suggest. Furthermore, Br-HCl solubilization leads to a significant reduction of the interlamellar distance d and increases the elastic properties of the systems. 31P NMR data provide evidence that Br-HCl is solubilized within the lipophilic part of the phospholipid bilayer.
Schubert
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Institut für Pharmazeutische Technologie, TU Braunschweig, Germany.
Müller-Goymann
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D001964:Bromhexine / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D003102:Colloids; D004337:Drug Carriers; D004655:Emulsions; D005100:Expectorants / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D017348:Microscopy, Electron, Scanning Transmission; D008859:Microscopy, Polarization; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry*; D017785:Photons; D012212:Rheology; D013500:Surface Tension; D014867:Water; D014961:X-Ray Diffraction
D003102:Colloids; D004337:Drug Carriers; D004655:Emulsions; D005100:Expectorants; D010713:Phosphatidylcholines; C585968:phospholipon 90G; D014867:Water; D001964:Bromhexine