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.