Preparation Of Nanometer Calcium Carbonate Enteric-coated Bioadhesive Tablets And Its Evaluation Of Removing Lead

OBJECTIVEWe chose nanometer calcium carbonate as model drug used in treatment of lead intoxication, and developed it to a new dosage form: nanometer calcium carbonate enteric-coated bioadhesive tablets (NCaEBT), making sure that the new dosage form had the characteristic of both upper small intestine targeting and bioadhesion. At the same time, we established the new quality assessment, evaluated the removing lead effect of NCaEBT through the removing lead experiment in Dogs(Canis familiaris), moreover, through the comparison of removing lead effect among NCaEBT, CCaDT and CaAEBT, initially investigate the removing lead mechanisms of NCaEBT and CCaDT, which may provide the foundation for developing new drugs in treatment of lead intoxication.METHODS1 Preparation Technology of Nanometer Calcium Carbonate Enteric-coated Bioadhesive TabletsPreparation technology of NCaEBT included two parts:screening formulation of pellet and investigating the coating technology. The pellet of NCaEBT was prepared with two different granules, selecting HPMC and CP as bioadhesive material and selecting MCC and CMS-Na as disintegrating agent. Basing on the results from the single factor experiment, we chose the more influential factors as independent variable, to optimize the formulation of pellet of NCaEBT preparation by central composite design/response surface methodology. In the enteric coating technology, through the effect of three pH5.5 enteric coating materials: Eudragit L100-55, Eudragit L 30D-55 and HPMCP 5.5 on the technology of NCaEBT to determine the best enteric coating materials, and through the effect of coating level on the NCaEBT in simulated gastrointestinal tract environment to determine the best amount of coating materials.2 Study on quality assessment of Nanometer Calcium Carbonate Enteric-coated Bioadhesive TabletsAssessing the quality of NCaEBT included sample identification, tablet weight variation, assaying, release property and bioadhesive force. The release property of NCaEBT was evaluated by ultraviolet spectrophotometry. The content of NCaEBT was determined by acid-base titration. The bioadhesive force of NCaEBT was evaluated by the bioadhesive equipment.3 Study on the effect of Nanometer Calcium Carbonate Enteric-coated Bioadhesive Tablets on the removing lead in Dogs(Canis familiaris)Twenty five dogs(Canis familiaris) were randomLy divided into five groups:blank control group, dying lead control group, CCaDT group, CaAEBT group and NCaEBT group. Dogs in four lead exposed groups were intraperitoneally injected the Pb2+ on alternate days of total 7 times. After cessation of lead exposure, the dogs were administrated the drugs for 30 days of treatment therapy. At 7st,15st,22st,30st day of the experiment during 24h total urine and feces of each 25 dogs were collected, at the same time,2mL of blood of each 25 dogs were obtained through femoral vein bleeding. Through comparing the blood lead, urinary lead and fecal lead levels of all groups to elucidate the removing lead mechanisms of NCaEBT and ordinary calcium tablets.RESULTS1 Preparation Technology of Nanometer Calcium Carbonate Enteric-coated Bioadhesive TabletsPreparation technology of NCaEBT included two parts:screening formulation of pellet and investigating the coating technology. Basing on the results from the single factor experiment, we chose HPMC and CP as independent variable. The results of central composite design/response surface methodology showed that regression coefficients of first order model was higher than second order and third order quadratic models, Optimized formulation of pellet of NCaEBT consisted of HPMC20mg,CP 25mg, MCC 25mg and 2.5% CMS-Na. In enteric coating technology, we found NCaEBT coated with the Eudragit L100-55 were better than Eudragit L 30D-55 and HPMCP 5.5, so we determined the Eudragit L100-55 as enteric coating materials, the coating level of Eudragit L100-55 was about 10%.2 Study on quality assessment of Nanometer Calcium Carbonate Enteric-coated Bioadhesive TabletsThe results of quality assessment were found that appearance of NCaEBT was uniformity and smooth, the identification reaction was reliable, and tablet weight variation met the Chinese pharmacopeia regulation. The determination method of nanometer calcium carbonate in NCaEBT by acid-base titration was reliable and precise. And the determination of sample contents in three batches met the standardization. The determination method of NCaEBT release property by ultraviolet spectrophotometry was stabile and accurate, the determination of sample release property in three batches was ideal. At the same time, the determination method of bioadhesive property of NCaEBT was also accurate, the results of the adhesive forces of NCaEBT was 24.9g·cm-2.3 Study on the effect of Nanometer Calcium Carbonate Enteric-coated Bioadhesive Tablets on the removing lead in Dogs(Canis familiaris)Blood lead levels in four groups after administrating showed that besides the NCaEBT group had the slight effect, there were no significant differences between four groups. Urinary lead levels in four groups after administrating showed that the CaAEBT group had great effect, CCaDT group was second, and the NCaEBT group also had slight effect compared to the control group. Fecal lead levels in four groups after administrating showed that besides the NCaEBT group had the notable and great effect on fecal lead excretion, CCaDT group and CaAEBT group had no significant effect compared to the control group.CONCLUSION1 NCaEBT prepared in our experiment was testified that it had the characteristic of both upper small intestine targeting and bioadhesion in vitro assessment.2 NCaEBT had the removing lead effect through increasing the fecal lead excretive levels by interference with the enterohepatic circulation of praecipitatum displacement reaction, and ordinary calcium carbonate tablets had the removing lead effect mostly by increasing the urinary lead excretive levels.