A review on Ofloxacin

Ofloxacin is an antibiotic for treating bacterial infections; it is active against gram-positive and gram-negative bacteria.

It is from a second-generation fluoroquinolone class and is considered a broader spectrum analog of norfloxacin and was developed and synthesized by the scientists of Daiichi Seiyaku. As an antibacterial agent, Ofloxacin treats urinary infections, pneumonia, and pelvic inflammatory disease. 

Ofloxacin got approval for medical use in 1985 and was patented in 1980. Ofloxacin got U.S. Food and drug administration (USFDA) approval in 1990. Ofloxacin is on the World Health Organization’s list of Essential Medicines and is available as a generic medication. It was the most prescribed medication in the U.S. in 2017.

Availability of Ofloxacin

Ofloxacin is available in different brand names and as generic drugs in the form of tablets with different strengths, injectable solutions, oral suspension, and ear and eye drops. This drug is a racemic mixture that consists of 50% levofloxacin (active biological component) and 50%, its mirror or enantiomer, dextrofloxacin.

Ofloxacin was first approved in 1985 for marketing in Japan for oral administration and was marketed under the brand name “Tarvid” by Daiichi. FDA got approval in 1990 when Daiichi was working with Johnson & Johnson. Ciprofloxacin and Ofloxacin are fluoroquinolones with differences in their clinical utility, antimicrobial activity, and other profiles.

The structure of Ofloxacin is represented as:

CAS No. 82419-36-1

Molecular formula: C18H20FN3O4

Molecular Weight: 361.37

IUPAC Name: ((±)-9-Fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid)

Ofloxacin and its impurities

In bulk, drug pharmaceuticals and formulations, the detection, identification, structure elucidation, determination of impurities, its impurity profile, and also residual solvents is the key area for the analytical department. United States Food and Drug Administration (USFDA), International Conference on Harmonization (ICH), Canadian Drug and Health Agency (CDHA), and other regulatory agencies have guidelines for the identification of impurities in the drug substance APIs. To develop the final product as per the required pharmacopeia, it is mentioned in different pharmacopeias like Unites States Pharmacopeia, Indian Pharmacopeia, British Pharmacopoeia, and other pharmacopeias. Further, there is also a need to develop analytical methods as per the given new process or the changes in the synthesis and production procedure.

The impurity profile is the most important and crucial to control the impurities like organic and inorganic impurities and their limits during the manufacturing and synthesis of active pharmaceutical ingredient API and the dosage forms.

The process and the impurities are always considered critical as it depends on the manufacturing process and its process parameters. Various analytical techniques are used to control and detect impurities at different stages during the manufacturing process. Further, they can be analyzed and characterized by using mass, IR, NMR spectroscopy, and HPLC column chromatography to get the product purity as per the pharmacopeia and ICH. The specification and the critical intermediates have limits for the specified and unspecified impurities and also the impurity profile for the final active pharmaceutical ingredient (API).

Several impurities of Ofloxacin have been isolated and purified by synthetic chemical methods and analytical techniques, which are reported in the pharmacopeia, and Ofloxacin impurities are also available at Veeprho.

List of Ofloxacin impurities

Ofloxacin EP Impurity A / Ofloxacin Difluoro Carboxylic Acid CAS No: 82419-35-0 Molecular Formula: C13H9F2NO4 Molecular Weight: 281.21 IUPAC Name: 9, 10-Difluoro-2, 3-dihydro-3-methyl-7-oxo-7H-pyrido[1, 2, 3-de]-1, 4-benzoxazine-6-carboxylic Acid

Ofloxacin EP Impurity B / Decarboxyl Ofloxacin CAS No: 123155-82-8 Molecular Formula: C₁₇H₂₀FN₃O₂ Molecular Weight: 317.36 IUPAC Name: 9-Fluoro-2, 3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7H-pyrido[1, 2, 3-de]-1, 4-benzoxazin-7-one

Ofloxacin Impurity B / Ofloxacin Related Compound B CAS No: N/A Molecular Formula: C13H9F2NO4 Molecular Weight: 281.21 IUPAC Name: (9, 10-Difluoro -3-methyl-7-oxo-2, 3-dihydro -7H-pyrido[1, 2, 3- de]- 1, 4- benzoxazine-6-carboxylic Acid)

Ofloxacin EP Impurity C CAS No: 95848-94-5 Molecular Formula: C18H21N3O4 Molecular Weight: 343.38 IUPAC Name: (RS)-2, 3-Dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1, 2, 3-de]-1, 4-benzoxazine-6-carboxylic acid

Ofloxacin EP Impurity D CAS No: 197291-75-1 Molecular Formula: C₁₈H₂₀FN₃O₄ Molecular Weight: 361.37 IUPAC Name: 9-Desfluoro-9-(4-Methyl-piperazino)-10-Des(4-methylpiperazino)-10-Fluoro Ofloxacin

Ofloxacin EP Impurity E / Desmethyl Ofloxacin CAS No.: 82419-52-1 Molecular Formula: C₁₇H₁₈FN₃O₄ Molecular Weight: 347.34 IUPAC Name : 9-Fluoro-2, 3-dihydro-3-methyl-7-oxo-10-(1-piperazinyl)-7H-pyrido[1, 2, 3-de]-1, 4-benzoxazine-6-carboxylic Acid

Ofloxacin EP Impurity F / Ofloxacin N-Oxide CAS No.: 104721-52-0 Molecular Formula: C18H20FN3O5 Molecular Weight: 377.37 IUPAC Name : (RS)-9-Fluoro-2, 3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1, 2, 3-de]-1, 4-benzoxazine-6-carboxylic acid N-oxide

FAQs

References:

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