Research On Preparation And Quality Standards Of Cefpodoxime Proxetil Capsules

Cefpodoxime Proxetil is the third-generation cephalosporins, which successfully developed in Japan in1990and listed on production. Cefpodoxime Proxetil Capsules are the prodrug of Cefpodoxime, no antimicrobial activity itself, the intestinal absorption after oral, in the intestinal wall by non-specific esterase hydrolyzed to Cefpodoxime and given play to antibacterial activity. The antibacterial action of Cefpodoxime is inhibiting membrane bound transpeptidase of bacterial cell walls system, which make that the transpeptidation of cross link cannot be performed, the synthesis of mucopeptide of bacterial cell walls is blocked, cell walls is defected and bacterial cell has no protective screening, then make the bacteria swelling, deformation, failure and death. Cefpodoxime Proxetil Capsules have broad spectrum and strong antibacterial effect, have inhibition and killing effect for most gram-positive bacteria and negative bacteria, and high stability for a variety of beta lactamase. Widely used in the respiratory tract, urinary tract, gynecology and obstetrics infectious diseases and the treatment of suppurative otitis media, etc[M].In this paper, first of all, analyzed the reference preparations, and then to reference preparations as a development goal to perform prescription screening, production technology research, quality and stability study of Cefpodoxime Proxetil Capsules.(1) Selection and research of reference preparationSelect Cefpodoxime Proxetil Capsules (Zhejiang Asia-pacific pharmaceutical co., LTD.) approved by CFDA as the reference preparation, and perform the study of dissolution profile of four different dissolution medium (water, O.lmol/L HC1 solution, phosphate buffer of pH4.5and phosphate buffer of pH6.8).(2) Prescription screening and production technology researchPreliminary selected production process based on the physicochemical property of materials, using accessories usually applied by capsule as filling agent, disintegrants, glidants. And accordingly perform the prescription screening test, key indicators for dissolution rate, confirm the feasibility of the prescription process.Finally choose Cefpodoxime Proxetil (in C15H17N5O6S2)100g/1000grains, microcrystalline cellulose60g/1000grains, carboxy methyl starch sodium8.5g/1000grains, micro powder silica gel1.5g/1000grains, mixed filling for capsule preparation. Reference preparation for research and development goals, select prescription by adjusting the ratio of prescription in various accessories and dissolution curve comparison results of similarity factor f2, and perform the process validation.Perform the study of dissolution profile of four different dissolution medium (water,0.1mol/L HC1solution, phosphate buffer of pH4.5and phosphate buffer of pH6.8) between homemade products and reference preparation, the similarity factor f2is in the range of50-100. Homemade products and reference preparation have consistency, select prescription and production process are controlled, reasonable and stable, ensure the stability of product quality.(3) Quality studyAccording to specification of Cefpodoxime Proxetil Capsules required in<Chinese pharmacopoeia>(2010edition Department Ⅱ), we establish the product quality standard and perform the method validation of the dissolution and content, microbial limit test and related substances. The result of this study indicate detection method is specific, auxiliary materials without interference, good repeatability, high recovery rate, and has wide linear range, suitable for the prescription and detection of Cefpodoxime Proxetil Capsules prepared. All the test items of Cefpodoxime Proxetil Capsules prepared conform to the specification of <Chinese pharmacopoeia>(2010edition). (4) Stability test researchAccording to<Chinese pharmacopoeia>(2010edition DepartmentⅡ), Appendix XIX C<Active pharmaceutical ingredients and pharmaceutical preparations stability test guiding principles> we perform the stress test, accelerated test and long-term test.The testing results have no obvious difference and conform to the specifiactions under the illumination condition (45001ux±5001ux). The testing results have no obvious difference except the water content incresed slightly, and all these testing results conform to the specifications in the condition40℃of high temperature. The water content was decreased on the5th day and10th day in the condition of60℃. It is shows that this product is unstable at high temperature. All testing results conform to the specifications in the condition of RH75%, the water content was significant incresed in condition of RH90%, it is shows that this product is unstable at high humidity.The6th month results of accelerated test indicate that the assay was decreased, the water content and related substances increased slightly, but all results conform to the specifications. The24th month results of long-term testing indicate that the assay was decreased slightly, the water content increased, related substances individual impurity and total impurities have an upward tendency, but all testing results meet the requirements.In conclusion, through the prescription of Cefpodoxime Proxetil (in C15H17N5O6S2)100g/1000grains, microcrystalline cellulose60g/1000grains, carboxy methyl starch sodium8.5g/1000grains, micro powder silica gel1.5g/1000grains, the water content of Cefpodoxime Proxetil capsules prepared are obviously changed under high humidity and high temperature environment, but other testing results meet the requirements. This product should be sealed and kept in a cool, dry place. Stability test results showed that the samples have higher stability and conform to the specifications of the<Chinese pharmacopoeia>(2010version).