甲磺酸艾氟替尼片二次处方开发进行了如表3.2.P.2.2-4所示的处方

The development of the second prescription of aftinib mesylate tablets was carried out as shown in Table 3.2.P.2.2-4: prescription and experimental design: <br>pH adjuster or / and surfactant effect on disintegration and dissolution <br>Colloid II The effect of silicon oxide on disintegration and dissolution The <br>specific process of the above prescription development is shown in Appendix 3.2.P.2.2-1 Afatinib mesylate tablet prescription development process. <br>The selection of the final prescription is based on the beagle dog pharmacokinetic study, and there is no significant difference in the pharmacokinetic properties of the formulation and API, as shown in Table 3.2.P.2.2-5. <br>Table 3.2.P.2.2-5 Beagle dog pharmacokinetic test results of eftinib mesylate raw materials and tablets (n = 4) The final prescription specification obtained by optimization of <br>API suspension <br>formulation is Flutinib (C28H31F3N8O2.CH4O3S) is counted as 160mg (equivalent to 140mg of aftinib (C28H31F3N8O2)), and on this basis, optimized and formed prescriptions for supplementary declaration of 120mg and 40mg (according to C28H31F3N8O2) . <br>The summary of the prescription changes of the three specifications is shown in Table 3.2.P.2.2-6. <br>Table 3.2. P.2.2-6 Summary of changes in the composition of the formulation of eftinib mesylate (unit: mg / tablet)

The second prescription development of methamphetamine eflutaintablets has been prescribed and piloted as shown in Table 3.2.P.2.2-2-4:<br>Effects of pH regulators or/and surfactants on disintegrating and dissolving<br>Effect of glued silica on disintegrating and dissolving<br>The specific process of prescription development mentioned above is shown in Annex 3.2.P.2.2-2-1 the prescription development process for the eflonic acid eflutaintablets.<br>The choice of final prescription is based on the study of the pharmacokinetics of beagle dogs, and the results of the trial, as shown in Table 3.2.P.2.2-5, have no significant difference in the pharmacokinetic properties of the preparation and API.<br>Table 3.2.P.2.2-5 Results of the Bigg Canine Pharmacological Experiment synth of the efluotheric acid eflutaphine (n-4)<br>API suspension<br>Prescription optimization gets the final prescription specification sigatorifo (C28H31F3N8O2. CH4O3S) is calculated as 160mg (equivalent to Eflutinib (C28H31F3N8O2) 140mg), on this basis, and optimized to form a prescription for supplementary declaration specifications 120mg and 40mg (in accordance with C28H31F3N8O2).<br>A summary of prescription changes for the three specifications is shown in Table 3.2.P.2.2-6.<br>Table 3.2.P.2.2-6 Summary of Changes in Prescription Composition of Methsuldonic Eflutinib Tablets (in mg/tablets)

The formulation and test design of efetinib mesylate second formulation development are as shown in table 3.2. P.2.2-4:<br>Effects of pH regulators or / and surfactants on disintegration and dissolution<br>Effect of colloidal silica on disintegration and dissolution<br>See Annex 3.2. P.2.2-1 formulation development process of efetinib mesylate tablets for the specific process of formulation development.<br>The final prescription selection is based on the Beagle Dog pharmacokinetic study. There is no significant difference between the pharmacokinetic properties of the preparation and API, as shown in table 3.2. P.2.2-5.<br>Table 3.2. P.2.2-5 pharmacokinetic test results of efetinib mesylate API and tablet in beagle dogs (n = 4)<br>API suspension<br>The final prescription specification obtained from the optimization of the prescription is 160mg (equivalent to 140mg) of efrotinib mesylate (c28h31f3n8o2. Ch4o3s). On this basis, the prescription of 120mg and 40mg (c28h31f3n8o2) for supplementary application is optimized and adjusted.<br>See table 3.2. P.2.2-6 for the change summary of three specifications.<br>Table 3.2. P.2.2-6 summary of changes in prescription composition of efetinib mesylate tablets (unit: mg / tablet)<br>