DESCRIPTION
FIELD OF THE INVENTION
The present invention relates to the pharmaceutical dosage form comprising a fluoroquinolone and a macrolide, which shows the synergistic effect against the infection caused by a variety of microorganisms.
BACKGROUND OF THE INVENTION
The first macrolide antibiotic, erythromycin, was isolated in 1952 from products produced by Streptomyces erythreus. In 1991, two semisynthetic derivatives of erythromycin, azithromycin and clarithromycin , were brought to market. These new agents possess distinct advantages over erythromycin. Study showed an excellent in vitro activity of azithromycin against Salmonella and Shigella species . Because of its good intracellular activity and relatively low MICs for enteropathogens, this drug may become an important addition to our antimicrobial strategies for the treatment of typhoid fever and also for bacillary dysentery (1).
Another study showed that the single-dose Azithromycin regimen was well tolerated and eradicated the estimated and potential pathogens of nongonococcal urethritis'2'.
In mice and in small clinical trials, the causal prophylactic activity of azithromycin appears to be equal to or somewhat better than that of the clinical agent doxycycline. Drugs of the tetracycline class are contraindicated for young children and women with reproductive potential because of interference with skeletal and tooth development. Thus, an additional advantage of azithromycin is that it can be used in a more general patient population than that which can receive tetracyclines. On the other hand, azithromycin is licensed for short-term use, and side effects in humans because of chronic dosing are as yet unreported. Nevertheless, the activity of azithromycin in comparison with that of doxycycline suggests that azithromycin may have a clinical role in causal prophylaxis against malaria. If causal activity is insufficient, the suppressive prophylactic activity evidenced here and the blood schizonticidal activities demonstrated in other experiments suggest that azithromycin, like the tetracyclines, may have potential as a combined causal and suppressive prophylactic agent(3).

The study regarding the administration of both the drugs is available in the prior art, but has the following shortcomings-
1. These drugs are not available for the use of general public in the convenient dosage formulation.
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 Levofloxacin and Azithromycin which are suitable for the preparation of stable pharmaceutical compositions of Levofloxacin and Azithromycin.
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.
DESCRIPTION OF THE INVENTION
Azithromycin retains the activity of erythromycin against gram-positive organisms but offers increased gram-negative coverage over erythromycin and clarithromycin. It has been demonstrated to be more active than clarithromycin against H. influenzae. However, it has variable activity against the family Enterobacteriaceae. Nonetheless, Salmonella and Shigella species have been shown to be susceptible, as have other diarrheal pathogens such as Yersinia and Campylobacter. Like clarithromycin, azithromycin also has good activity against Legionella and Mycoplasma species. A unique feature of azithromycin is its excellent activity against sexually transmitted pathogens, especially Chlamydia trachomatis.
Azithromycin is indicated for the treatment of mild to moderate infections caused by susceptible strains of the designated microorganisms in the following conditions:
1. Acute bacterial exacerbations of chronic obstructive pulmonary
disease due to Haemophilus influenzae, Moraxella catarrhalis, or
Streptococcus pneumoniae.

2. Community-acquired pneumonia of mild severity due to Streptococcus pneumoniae or Haemophilus influenzae
3. Streptococcal pharyngitis/tonsillitis due to Streptococcus pyogenes
4. Uncomplicated skin and skin structure infections due to Staphylococcus aureus, Streptococcus pyogenes, or Streptococcus agalactiae
5. Non-gonococcal urethritis and cervicitis due to Chlamydia trachomatis
6. Disseminated Mycobacterium avium complex Disease
Levofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone
drug class and is used to treat severe or life-threatening bacterial infections or
bacterial infections that have failed to respond to other antibiotic classes.
The present invention relates to the pharmaceutical comprising the
pharmaceutically accepted salts of Azithromycin and Levofloxacin and there
formulation thereof.
The present invention comprises of the formulation comprising pharmaceutically
acceptable salts of Azithromycin and Levofloxacin and the required excipients
thereof and the process of preparing the formulation.
The azithromycin used in the formulation is in the range of 50mg to 1500mg,
preferably 200mg to 1000mg, more preferably 250 mg to 500mg.
The levofloxacin used in the present formulation is in the range of 50 mg to
1500 mg, preferably 200 mg to 1000mg, more preferably 250 mg to 500mg.
The present formulation is prepared by using the suitable pharmaceutical
excipients, along with the said quantity of Active Pharmaceutical Ingredients.
The excipients used may be selected from the group of diluents, binding
agents, disintegrants, and lubricants.
The diluents can be selected from lactose, sucrose, glucose, mannitol, sorbitol,
calcium, carbonate, and magnesium stearate.
The binding agents can be selected from polyvinylpyrrolidone (PVP),
polyethylene glycol (PEG), xylitol, sorbitol and maltitol which are mixed with the
appropriate solvent.
The solvent can be selected from purified water or isopropyl alcohol or the
mixture of both.

The disintegrants can be selected from polyvinylpyrrolidone (crospovidone),
crosslinked sodium carboxymethyl cellulose (croscarmellose sodium) and
sodium starch glycolate.
The lubricants can be selected from talc or silica, and fats, e.g. vegetable
stearin, magnesium stearate or stearic acid.
The formulation may be coated or uncoated.
The formulation can be coated with Hydroxypropyl Methyl Cellulose, along with
suitable plasticizer, opacifier, coloring agent and the solvent.
The release of Azithromycin and Levofloxacin from the pharmaceutical
formulations of the present invention can be immediate or modified, controlled,
delayed, sustained, or 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 Azithromycin and Levofloxacin.
References:
1) Indian Journal of Medical Microbiology Year: 2009 | Volume : 27 | Issue : 2 | Page : 107-110
2) Clinical efficacy of azithromycin for male nongonococcal urethritis, Journal of Infection and Chemotherapy, Volume 14, Number 6 / December, 2008
3) Antimicrobial agents and chemotherapy, aug. 1994, p. 1862-1863

CLAIMS
1. A pharmaceutical formulation comprising azithromycin in the range of 50mg to 1500mg, preferably 200mg to 1000mg, more preferably 250 mg to 500mg. and levofloxacin in the range of 50 mg to 1500 mg, preferably 200 mg to 1000mg, more preferably 250 mg to 500mg.useful for the treatment of a variety of bacterial infections.
2. The pharmaceutically acceptable excipients claimed in 1 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), Hydroxy propyl cellulose, 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.