Chapter Seven - Moxifloxacin Hydrochloride

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Abstract

A comprehensive profile of moxifloxacin HCl with 198 references is reported. A full description including nomenclature, formulae, elemental analysis, and appearance is included. Methods of preparation for moxifloxacin HCl, its intermediates, and derivatives are fully described. In addition, the physical properties, analytical methods, stability, uses and applications, and pharmacology of moxifloxacin HCl are also discussed.

Section snippets

Systematic chemical names

1-Cyclopropyl-6-fluoro-8-methoxy-7-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid hydrochloride [1].

1-Cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylic monohydrochloride [2].

(4aS-cis)-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[-octahydro-6H-pyrrolo [3,4-b] pyridin-6-yl]-4-oxo-3-quinolinecarboxylic monohydrochloride [2].

1-cyclopropyl-7-[(S,S

Method I [10–12]

l-Cyclopropyl-6,7-difluoro-8-methoxy-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid (I) is condensed with cis [S,S]-2,8-diazabicyclo[4.3.0]nonane (II) under reflux in a mixture of acetonitrile and dimethylformamide in the presence of 1,4-diazabicyclo [2.2.2]octane (DABCO) as a catalyst to get moxifloxacin base. The later compound is dissolved in HCl solution by means of heat, then concentrated, cooled, and precipitated by ethanol to give moxifloxacin HCl (Scheme 7.1). For further purification, it

Ionization constants

Moxifloxacin is an amphoteric compound, which contains a secondary alkyl amine, two tertiary arylamines, and a carboxylic acid (Figure 7.1).

The ionization constants (pKa1 and pKa2) were measured by means of potentiometry and spectrophotometry [27]. The obtained two pKa values were 6.25 and 9.29 for carboxylic acid and secondary amine, respectively. The low acidic character of moxifloxacin was explained by the formation of intramolecular hydrogen bond between the carboxyl and keto groups in the

Moxifloxacin HCl drug substance

Moxifloxacin HCl is a drug substance listed in the European pharmacopeia (Ph. Euro.) [1], United States pharmacopeia-national formulary (USP-NF) [2] and United States pharmacopeia-medicines compendium (USP-MC) [57]. Table 7.15 shows its summary of specifications and methods of analysis.

In addition to the mentioned “Reference Procedure” (Table 7.15), the USP-MC monograph includes the criteria-based procedures necessary to demonstrate that an “Acceptable Procedure” is equivalent to the “Reference

Solid-state stability

Forced degradation of moxifloxacin HCl in solid state was investigated by using densitometric TLC method [104]. It was found that heating moxifloxacin HCl at 100 °C for 8 h leads to a decrease in percentage recovery to 91% with the detection of three degrades.

Stability of moxifloxacin HCl in its tablet dosage form after incubation at 40 °C/75% RH and 50 °C/75% RH for 6 months was investigated using HPLC/UV detection [143]. The stability data for two products (Avelox® and Staxin®) proved that the

Systemic use

Moxifloxacin HCl is a fluoroquinolone antibacterial indicated for treating infections in adults caused by designated, susceptible bacteria. It was initially approved in a tablet form by the EMA in June 1999 [185] and by the USFDA in December 1999 [186].

Moxifloxacin HCl tablets and intravenous are indicated in patients aged 18 years and older for the treatment of the following bacterial infections if they are caused by bacteria susceptible to moxifloxacin:

  • Acute bacterial sinusitis

  • Acute

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