PURPOSE: A freeze dried preparation containing flomoxef or the salt thereof pharmaceutically allowed is provided to prolong the expiration date of the final product drastically by rapidly improving long term stability.CONSTITUTION: A manufacturing method of a freeze dried preparation containing flomoxef or the salt thereof pharmaceutically allowed comprises: a step of preparing 7&beta-difluoromethylthio acetamino-7a-methoxy-3 &lsqb1-(2-hydroxy alkyl)-1H-tetrazole-5-yl&rsqb thiomethyl1-dethia-1-oxa-3-cephem-4-carboxylic acid as a starting material a step of adjusting pH by dissolving a weak basic pH adjusting agent in aqueous solvent a step of dissolving the starting material in the above aqueous solvent and a step of quick freezing the liquid from the previous step and adjusting water activity to be 0.020-0.050 while supplying heat of sublimation. The moisture activity of the freeze dried preparation containing flomoxef or the salt thereof pharmaceutically allowed is 0.020-0.050.COPYRIGHT KIPO 2013[Reference numerals] (AA,HH) Initial stage (BB) Example 1 (CC) Example 2 (DD) Example 3 (EE) Example 4 (FF) Example 5 (GG,PP) 3rd week (II) Comparative example 1 (JJ) Comparative example 2 (KK) Comparative example 3 (LL) Comparative example 4 (MM) Comparative example 5 (NN) Comparative example 6 (OO) Comparative example 7플로목세프 또는 이의 약제학적으로 허용되는 염을 포함하는, 안정성이 증가된 동결건조제제를 제조하는 방법으로서, (a) 출발물질로서 7β-디플루오로메틸티오아세트 아미노-7a-메톡시-3[1-(2-히드록시알킬)-1H-테트라졸-5-일]티오메틸-1-데티아-1-옥사-3-세펨-4-카르복실산을 제공하는 단계 (b) 약염기성 pH 조정제를 수성용매에 용해시켜 pH를 조정하는 단계 (c) 상기 (b) 단계의 수성용매에 상기 (a)단계의 출발물질을 용해시키는 단계 및 (d) 상기 (d)단계의 용액을 급속 냉각시키고 승화열을 공급하면서 수분활성도(Aw)를 0.020~0.050로 조정하는 단계를 포함하는 플로목세프 동결건조제제의 제조방법이 제공된다.
