COMPLETE SPECIFICATION
ABSTRACT
The present disclosure provides the pharmaceutical formulations comprising a cefixime and Roxithromycin.
FIELD OF THE INVENTION
The present invention relates to the pharmaceutical dosage form comprising a cephalosporin 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.
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 lower 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)
In a study done on cefixime shows that high efficacy and low incidence of side effects make cefixime a drug of choice for treatment of respiratory tract infections
(Volume 23, Supplement 2 / March, 1995). 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 Cefixime and Roxithromycin which are suitable for the preparation of stable pharmaceutical compositions of Cefixime 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.
DESCRIPTION OF THE INVENTION
Roxithromycin is a macrolide antibiotic. It is a semi-synthetic 14-membered-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 gastrointestinal 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.
Cefixime is highly effective against enterobacteriaceae, H.influenzae, Strep, pyogenes, Streptococcus pneumoniae, and is resistant to various B-lactamases. However, it is not active on Staphhylococcus aureus and Pseudomonas.
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 pharmaceutically accepted salts of Roxithromycin and Cefixime and there formulation thereof.
The present invention comprises of the formulation comprising pharmaceutically

acceptable salts of Roxithromycin and cefixime 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 cefixime used in the present formulation is in the range of 50 mg to 500 mg, preferably 100 mg to 450mg, more preferably 200 mg to 400 mg.
The formed particles, prepared with using the suitable excipients, are suitable for the preparation of multiple unit forms such as capsules or tablets with the primary formed particles wherein a multiple unit form disintegrates to individual primary formed particles from which the active substance is released. The formed particles are also suitable for the preparation of multiple unit forms such as sachets and dozers for multiple unit systems and others. Uncoated and/or coated particles may be used.
The release of cefixime 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 cefixime and roxithromycin.
The present invention also relates to the process for the preparation of the formed particles regular and irregular in shape. They are prepared by the wet granulation with organic solvent. For granulation either a solvent or binder dispersion in an organic solvent may be used.
The formulation can be manufactured by the suitable procedure that are already

been described in the prior art for manufacturing tablets or other suitable dosage forms.

CLAIMS
1) A pharmaceutical formulation comprising 50 mg to 400 mg of Cefixime, preferably 100 to 200 mg, and Roxithromycin 50 mg to 400 mg, preferably 100 to 300 mg, along with pharmaceutically acceptable excipients; 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.