Development of composition of infusion medication on basis of moxifloxacin

Abstract

Application of fluoroquinolones covers by experience of treatment more than 800 million patients, and presently they are one of basic classes in the antimicrobial arsenal of practical medicine. Such achievements became possible after the clear under-standing of intercommunication of structure and ac-tivity of molecules of this class of antibiotics. This knowledge became the basis for the synthesis of new derivatives with a wide range, powerful activity and improved pharmacokinetic profile for the best clinical outcome. Moxifloxacin is 8-methoxyfluoroquinolon of wide spectrum which interacts mainly with DNA gyrase of gram-negative and with topoisomerase of IV type of gram-positive bacteria. He has the extended activity against gram-positive cocci, however keeps activity against gram-negative bacteria. Moxifloxacin also has good activity against atypical respiratory pathogens (Legionella of pneumophila, Chlamydia of pneumoniae and Mycoplasma of pneumoniae). Another his feature is high anti-anaerobic activity. Therefore development of domestic medication with Moxifloxacin - a fluoroquinolone 4 generations - is actual. Materials and methods. Research material was a substance of Moxifloxacin hydrochloride, produced by firm «Sansh Biotech Pvt. Ltd.», India, a dosage form on the basis of Moxifloxa-cin - solution for infusion. Qqualitative and quantita-tive control of samples of the drug were conducted on parameters which characterize stability: рН, content of active substance, transparency, colour, related impuri-ties, mechanical inclusions on methods, which are de-scribed in SPhU.  Results and Discussion. Proposed the drug is antibiotic of wide spectrum of action of fluoroquinolone. Moxifloxacin hydrochlo-ride is powder pale yellow with slightly hygroscopic nature. He moderately dissolve in water and methanol, poorly will dissolve in hydrochloric acid and ethanol, and practically will not dissolve in an acetone and tol-uene. рН 0,2 % solution is in a range 3,9 – 4,6 . Active substance enters in comparison drug in the concentra-tion of 1,74 mg/ml or 0,174 %. Thus, solubility of it suffices for the receipt of water solution of necessary concentration without fallouts of precipitation or ap-pearance of suspension and opalescence from insuffi-cient solubility. Also, is not the necessity of addition of auxiliary substances - solubilizers for the increase of solubility. For achievement of necessary level of osmolarity and isotonicity in the complement of prepa-ration was entered sodium chloride which is classic used for these aims. Concentration of sodium of chlo-ride  as well as in medication analogue Avelox IV® is determined 8 mg/ml. By us the optimum pH range was confirmed for solution of preparation «Moxifloxacin 400 mg, solution for infusion in-bottle 250 ml» within the limits of 4,1-4,6. At preparation of solution it is recommended to correct him pH addition of alkaline and acid agents, indicated in composition, is 1М solu-tion of hydrochloric acid and 2 M sodium hydroxide. Conclusions. Rational composition of infusion medication on the basis of Moxifloxacin was theoretically grounded on the basis of study of literary information and physical and chemical and technological properties of sub-stance of Moxifloxacin hydrochloride and experimen-tally confirmed . The optimum the limit of рН  solu-tion was defined for the receipt of stable dosage form of solution for infusion on the basis of  Moxifloxacin. Results of this development are used during compile of registration dossier of preparation, analytical and technological normative documents on his production and control of quality of intermediate products and prepared products. 

Application of fluoroquinolones covers by experience of treatment more than 800 million patients, and presently they are one of basic classes in the antimicrobial arsenal of practical medicine. Such achievements became possible after the clear understanding of intercommunication of structure and activity of molecules of this class of antibiotics. This knowledge became the basis for the synthesis of new derivatives with a wide range, powerful activity and improved pharmacokinetic profile for the best clinical outcome. Moxifloxacin is 8-methoxyfluoroquinolon of wide spectrum which interacts mainly with DNA gyrase of gram-negative and with topoisomerase of IV type of gram-positive bacteria. He has the extended activity against gram-positive cocci, however keeps activity against gram-negative bacteria. Moxifloxacinalso has good activity against atypical respiratory pathogens (Legionella of pneumophila, Chlamydia of pneumoniae and Mycoplasma of pneumoniae). Another his feature is high anti-anaerobic activity. Therefore development of domestic medication with Moxifloxacin - a fluoroquinolone 4 generations - is actual.

Materials and methods

Research material was a substance of Moxifloxacin hydrochloride, produced by firm «Sansh Biotech Pvt. Ltd.», India, a dosage form on the basis of Moxifloxacin - solution for infusion.Qqualitative and quantitative control of samples of the drug were conducted on parameters which characterize stability: рН, content of active substance, transparency, colour, related impurities, mechanical inclusions on methods, which are described in SPhU.

 Results and Discussion

Proposed the drug is antibiotic of wide spectrum of action of fluoroquinolone. Moxifloxacin hydrochloride is powder pale yellow with slightly hygroscopic nature. He moderately dissolve in water and methanol, poorly will dissolve in hydrochloric acid and ethanol, and practically will not dissolve in an acetone and toluene. рН 0,2 % solution is in a range 3,9 – 4,6 . Active substance enters in comparison drug in the concentration of 1,74 mg/ml or 0,174 %.Thus, solubility of it suffices for the receipt of water solution of necessary concentration without fallouts of precipitation or appearance of suspension and opalescence from insufficient solubility. Also, is not the necessity of addition of auxiliary substances - solubilizers for the increase of solubility. For achievement of necessary level of osmolarity and isotonicity in the complement of preparation was entered sodium chloride which is classic used for these aims. Concentration of sodium of chloride  as well as in medication analogue Avelox IV^® is determined 8 mg/ml.By us the optimum pH range was confirmed for solution of preparation «Moxifloxacin 400 mg, solution for infusion in-bottle 250 ml» within the limits of 4,1-4,6. At preparation of solution it is recommended to correct him pH addition of alkaline and acid agents, indicated in composition, is 1М solution of hydrochloric acid and 2 M sodium hydroxide 

Conclusions

Rational composition of infusion medication on the basis of Moxifloxacin was theoretically grounded on the basis of study of literary information and physical and chemical and technological properties of substance of Moxifloxacin hydrochloride and experimentally confirmed .The optimum the limit of рН  solution was defined for the receipt of stable dosage form of solution for infusion on the basis of  Moxifloxacin. Results of this development are used during compile of registration dossier of preparation, analytical and technological normative documents on his production and control of quality of intermediate products and prepared products.