Quality Control And Pharmacokinetic Study Of Iodized Lecithin

Iodized lecithin is one of the complex bound drug composed with lecithin and iodine. It is a kind of oculopathy drug developed in Japan. In recent years, we have studied the technology production, and the development of dosage form. The reports of iodized lecithin were main on pharmacology, pharmacodynamic action in past. Up to now, there are none literatures about the bioavailability. This thesis develops the quality specification of iodized lecithin, studies on the clinical pharmacokinetics and approached the excretion in rats, which provide references for manufacture clinical application.1. The development of the quality specificationWe have studied the description, identification, investigation and content determination of iodized lecithin. The product of iodized lecithin was iodine ion by oxygen flask combustion, and it was oxidized to iodine by hydrogen dioxide under acid condition. Iodine was easily dissolved in chloroform, and the absorbance of iodine in chloroform was determined by UV spectrophotometry. The wavelength was set at 512 nm. There was a good linear relationship for iodine within the range of 8.57-23.56μg·mL^-1 (r = 0.9999). The assay results of 3 batches of samples were 7.32 %, 7.06 %, 6.83 %, respectively (n = 3).2. The pharmacokinetics and bioequivalence of iodized lecithin tablets in human volunteersA new method for determination of iodine concentration in human serum has been established. The serum iodine digested in chloric acid (organic iodine was converted to inorganic iodine ion) was determined with kalium hypermanganicum-arsenous acid catalytic spectrophotometry. The SHIMADZU UV-2550 spectrophotometer was used, with the detection wavelength 405 nm and the slit width 2.0 nm. There was a good linear relationship for iodine in human serum within the range of 20-300 ng·mL^-1(r = 0.9984) and the LOQ was 20 ng·mL^-1. There were good intra-day precision and inter-day precision, and the extractive recovery was about 90 %.Oral 4.5 mg dose of iodized lecithin test and reference preparations were given to 18 volunteers in two-cycle crossover design. The peak concentration of serum was achieved in 1-2 h. After a single oral dose, T_max were 1.3±0.4 and 1.2±0.3 h; C_max were 34.5±9.5 and 34.6±12.7 ng·mL^-1; AUC_0-48 were 176.7±34.9 and 171.9±49.4 ng·h·mL^-1; AUC_0-∞, were 188.2±37.6 and 194.4±60.2 ng·h·mL^-1; relative bioavailability was 107.4±23.3 %, respectively. There were no significant differences between preparations and periods of C_max and AUC by ANOVEA, two one-side t-test and (1-2a) confidential interval test, and T_max by Wilcoxon's non-parameter rank-sum test. This showed that the two preparations of iodized lecithin were bioequivalence.3. The excretion of iodized lecithin in ratsA RPIC (Reversed paired ion chromatography) method for determination of iodine in urine and feces has been carried out on a DiamonsilC₁₈ (200 mm×4.6 mm, 5 urn) column with UV detection at 225 nm. The mobile phase was methanol-water (V: V=30: 70) and 3 mmol·L^-1 tetrabutylammonium bromide as the ion-pair reagent. The flow rate was set at 1.0 mL·min^-1 and the column temperature was 25℃. There was a good linear relationship for iodine 0.5-40.0μg·mL^-1 (r = 0.9943) and the LOQ was 0.5μg·mL^-1 in urine. There was good intra-day precision and inter-day precision, and the extractive recovery was about 85 %.After a single ig dose of 15 mg·kg^-1 iodized lecithin in rats, the excretion of iodine in urine was amounted to 80.2 % in 0-24 h, and 10.3 % in 24-48 h. The excretion of iodine in feces was amounted to 6.3 % (n = 6).