DESCRIPTION
Field of the invention
The present pharmaceutical formulation comprises the pharmaceutical
combination of Gemifloxacin and Roxithromycin. The present invention also
directs to the synergistic pharmaceutical composition which is effective in
treating infections caused by various bacteria which are hard to treat with the
conventional antibiotics.
Background of the invention
US 2005020567 (A1) relates to a method of treating anti-bacterial infections
which method comprises the separate, simultaneous or sequential
administration to a patient in need thereof, of an effective amount of
gemifloxacin or a salt thereof and a carbapenem antibacterial.
The bactericidal effect of gemifloxacin was almost as rapid as that of
ceftriaxone in the rabbit model of meningitis using a penicillin-sensitive S.
pneumoniae Strain. ( Gemifloxacin Is Effective in Experimental Pneumococcal Meningitis A. Smirnov, A. Wellmer, J. Gerber, K. Maier, S. Henne, and R. Nau* Department of Neurology, University of Gottingen, GOttingen, Germany)
Data demonstrate the potential benefit of gemifloxacin in the treatment of Gram-negative urinary tract infection and Gram-positive skin and soft tissue infection.
(Comparative efficacy of gemifloxacin in experimental models of pyelonephritis and wound infection
Roxithromycin is found to be effective in Mycoplasma Pneumonia (Efficacy of
Roxithromycin in the Treatment of Mycoplasma PneumoniaMitsuo Kakua, Shigeru Kohnoa, Hironobu Kogaa, Kazuo Ishidab, Kohei Haraa).
Roxithromycin 300 mg once daily was compared with clarithromycin 250 mg b.i.d. in an open randomized trial in 200 patients with upper respiratory tract infection: sinusitis, pharyngotonsillitis, and otitis media. Average treatment duration was 9 days. Roxithromycin was more effective (p<0.01) particularly in otitis media and pharyngotonsillitis, and better tolerated (only 4% side effects,
p<0.05). (Comparative efficacy and safety of roxithromycin and clarithromycin in upper respiratory tract infections.References and further reading may be available for this article. E. de Campora, A. Camaioni, M. Leonardi, P. Fardella and M. Fiaoni)
Roxithromycin was found to be equally efficacious but well tolerated than amoxyclav for the treatment of lower respiratory tract infections in general
practice. (Roxithromycin 150 mg b.i.d. versus amoxycillin 500 mg/clavulanic acid 125 mg t.i.d. for the treatment of tower respiratory tract infections in general practice N. C. Karalus, J. E. Garrett, S. D. R. Lang, R. A. Leng, G. N. Kostalas, R. T. M. Cursons, B. C. Cooper and C. J. Ryan)
Objectives Of The Invention
The objective of the invention is to provide a combination which is effective
against a large number of microorganisms.
Yet another objective of the invention is to minimize the bacterial resistance
against the antimicrobial agents.
It is an object of the invention to provide particles comprising Gemifloxacin and
Roxithromycin which are suitable for the preparation of stable pharmaceutical
compositions of Gemifloxacin and Roxithromycin.
The present invention also relates to providing the high efficacy formulation to
the general public which will be a cost effective option to treat various bacterial
infections.
Detailed description of the invention
Roxithromycin is a macrolide antibiotic. It is a semi-synthetic 14-mem be red-ring macrolide antibiotic in which the erythronolide A lactone ring has been altered to prevent inactivation in the gastric milieu. Like other macrolides, roxithromycin displays a significant post-antibiotic effect which is dependent on the pathogens under study, the concentration of roxithromycin and the duration of exposure. In vivo, roxithromycin is as effective or more effective than other macrolides in a wide range of infections.
Antibiotics such as roxithromycin can often be prescribed for several different infections, including some STDs, upper and lower respiratory tract infections and asthma, gum infections like gingivitis, and bacterial infections associated with stomach and intestinal ulcers. Roxithromycin is absorbed well into the gastro-intestinal tract, with few side effects, and actively responds to the presence of Cryptosporidium, Pneumocystis carinii (PCP), toxoplasma gondii, and Mycobacterium Avium (MAC). The in-vitro activity of roxithromycin is well documented and similar to that of other macrolide antibiotics. Roxithromycin is active against gram-positive and gram- negative cocci, gram-positive bacilli and some gram-negative bacilli, but has no significant effect on the predominant faecal flora. It also displays good activity against atypical pathogens, such as Mycobacterium avium complex, Helicobacter pylori and Borrelia spp. It penetrates and accumulates within cells, such as macrophages and polymorphonuclear neutrophils (PMNs), where it is distributed between the cytosol and cellular granules. Once inside the cells, it is active against
intracellular pathogens, such as Legionella, Chlamydia, Mycobacterium, Rickettsia and Borrelia spp.
Roxithromycin is active against Gram-positive bacteria like staphylococci, streptococci, listeria, corynebacteria; Gram-negative bacteria such as gonococci, Haemophilus influenzae, Haemophilus ducreyi, Legionella, Campylobacter, and atypical pathogens like Mycoplasma and Chlamydia. Roxithromycin has been found useful in the treatment of upper and lower respiratory, otorhinolaryngological, skin, dental and genital infections. It is well tolerated by adults and children. Beta - Lactam antibiotics are among the safest and the most frequently prescribed agents in India and worldwide. However, emergence of beta-lactam resistance coupled with extended spectrum betalactamase (ESBL) in clinically important pathogens have increasingly limited their use.
The emergence of ESBL producing Enterobacteriaceae, particularly Escherichia Choli and Klebsiella pneumonia, presents significant diagnostic and therapeutic challenges to the management of infection due to these organisms. ESBL bacteria that produce ESBL enzymes and that mediate resistance to extended spectrum cephalosporins. The presence of ESBL producing organism in a clinical infection can result in treatment failure if one of the above classes of the drug is used.
Gemifloxacin mesylate is an oral broad-spectrum quinolone antibacterial agent used in the treatment of acute bacterial exacerbation of chronic bronchitis and mild-to-moderate pneumonia. Gemifloxacin is indicated for the treatment of infections caused by susceptible strains of the designated microorganisms in Acute bacterial exacerbation of chronic bronchitis caused by S. pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, or Moraxella catarrhalis. Community-acquired pneumonia (of mild to moderate severity) caused by S. pneumoniae (including multi-drug resistant strains, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, Chlamydia pneumoniae, or Klebsiella pneumoniae.
Antibiotics were first discovered through a providential experiment by Alexander Fleming in 1928. His work eventually led to the large-scale production of penicillin from the mold Penicillium notatum in the 1940s. As early as the late 1940s resistant strains of bacteria began to appear. Currently, it is estimated
that more than 70% of the bacteria that cause hospital-acquired infections are
resistant to at least one of the antibiotics used to treat them.
Antibiotic resistance continues to expand for a multitude of reasons, including
over-prescription of antibiotics by physicians, non-completion of prescribed
antibiotic treatments by patients, use of antibiotics in animals as growth
enhancers (primarily by the food industry), increased international travel, and
poor hospital hygiene.
The present invention relates to the pharmaceutical comprising the
pharmaceutical^ accepted salts of Roxithromycin and Gemifloxacin and there
formulation thereof.
The present invention comprises of the formulation comprising pharmaceutically
acceptable salts of Roxithromycin and Gemifloxacin and the required excipients
thereof and the process of preparing the formulation.
The Roxithromycin used in the formulation is in the range of 50mg to 1500mg,
preferably 100mg to 400mg, more preferably 150 mg to 300mg.
The Gemifloxacin used in the present formulation is in the range of 100 mg to
400 mg, preferably 150 mg to 350mg, more preferably 200 mg to 300 mg.
The release of Gemifloxacin and roxithromycin from the pharmaceutical
formulations of the present invention can be immediate or modified, controlled,
delayed, sustained, and extended. The release rate for both active drugs can
be the same or different.
The pharmaceutical formulations of the present invention may comprise formed
particles with the same composition or formed particles with different
composition and different release rate of Gemifloxacin and roxithromycin. The
said formulation is manufactured by the method of formulating the fixed dose
formulation as already disclosed in the prior art.

CLAIMS
1) A pharmaceutical formulation comprising 50 mg to 1500 mg of
Roxithromycin, preferably 150 to 300 mg, and Gemifloxacin 100 mg to
400mg, preferably 200mg to 300mg, along with pharmaceutically acceptable
excipients; useful for the treatment of a variety of bacterial infections.
2) The pharmaceutically acceptable excipients are selected from diluents, binding agents, disintegrants, and lubricants.
3) The diluents as claimed in claim 2 can be selected from lactose, sucrose, glucose, mannitol, sorbitol, calcium carbonate, and magnesium stearate.
4) The binding agents as claimed in claim 2 can be selected from polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), xylitol, sorbitol and maltitol which are mixed with the appropriate solvent.
5) The solvent as claimed in claim 4 can be selected from purified water or isopropyl alcohol or the mixture of both.
6) The disintegrants as claimed in claim 2 can be selected from polyvinylpyrrolidone (crospovidone), crosslinked sodium carboxymethyl cellulose (croscarmellose sodium) and sodium starch glycolate.
7) The lubricants as claimed in claim 2 can be selected from talc or silica, and fats, e.g. vegetable stearin, magnesium stearate or stearic acid.
8) The formulation as claimed in claim 1 can be coated with Hydroxypropyl
Methyl Cellulose, along with suitable plasticizer, opacifier, coloring agent and
the solvent.
9) The formulation as claimed in claim 1 can be oral or injectable,
preferably oral.
10)The oral formulation as claimed in claim 9 may be immediate release tablets, capsules, liquid orals, disintegrating tablets, or dry syrups.