Pitt Spiramycin, Roxithromycin And Maleic Acid Fasudil Administered By Injection

OBJECTIVE To investigate the method of lipophilic weak alkaline drugs reactiong to acid to increase their aqueous solubility, bitespiramycin and roxithromycin were selected as typical drugs. By the use of method, injectable powder preparations of the two macrolides drugs were developed respectively, without any organic solvent during the produced process; in addition, injectable preparations of fasudil maleate were prepared.METHOD Under room teperature, two drugs reacted to different acids with mole ratio of 1:1 and produce soluble salts, respectively. After preformulation study, the method was selected to prepare two macrolides drugs concentrated solutions, and the two kinds of injectable powder were obtained finally by freezing -dried. HPLC and microbiological methods were developed to analyze bitesprimycin and HPLC method was set up to analyze roxithromycin during the test of quality and stability. Irritative, anaphylaxis, and haemolyticus tests were performed to evaluate the injectable safety of roxithromycin for injection. Acute toxicity test was performed to determine the LD₅₀ of roxithromycin for injection;After preformulation study, two injectable dosages of fasudil maleate were developed; HPLC method was established to analyze fasudil maleate during the test of quality and stability.RESULT The aqueous solubility of the both lipophilic drugs was highly improved at Various pH by reacting to different acids. By using ways, the concentration of bitespiramycin and roxithromycin could be 100 mg/ml at pH4.5 and 75 mg/ml at pH5.5, respectively. The specifications of the two preparations were 200 mg/bottle (bitespiramycin for injection), and 150 mg/bottle (roxithromycin for injection), respectively. The results of the quality and stability test showed the both macrolides productions met the criterion of Chinese Pharmacopoeia. The safety test proved that roxithromycin for injection was safe to inject. The LD₅₀ and 95% believable margin of roxithromycin was 368.4 (335.2-405.0) mg/kg;The specifications of the two fasudil maleate preparations were 2 ml :37 mg and 37 mg/bottle, respectively. The results of the quality and stability test showed the fasudil maleate injcetion accord with the criterion of Chinese Pharmacopoeia, but fasudil maleate for injection was very unstable under high temperature.CONCLUSION The two macrolides injectable powder preparations and fasudil maleate injection, whose quality could be controlled well, were safe, active and stable; fasudil maleate is unfit to prepare freezing -dried dosage.