COMPLETE SPECIFICATION
ABSTRACT
The present disclosure provides the pharmaceutical formulations comprising a cefpodoxime and azithromycin. The invention further relates to a process for preparing these formulations.
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.
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
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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).
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 Cefpodoxime and Azithromycin which are suitable for the preparation of stable pharmaceutical compositions of Cefpodoxime 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:
• Acute bacterial exacerbations of chronic obstructive pulmonary disease due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae.
• Community-acquired pneumonia of mild severity due to Streptococcus pneumoniae or Haemophilus influenzae
• Streptococcal pharyngitis/tonsillitis due to Streptococcus pyogenes
• Uncomplicated skin and skin structure infections due to Staphylococcus aureus, Streptococcus pyogenes, or Streptococcus agalactiae
• Non-gonococcal urethritis and cervicitis due to Chlamydia trachomatis
• Disseminated Mycobacterium avium complex Disease
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.
Cefpodoxime is highly effective against enterobacteriaceae, H.influenzae, Strep, pyogenes, Streptococcus pneumoniae, and is resistant to various B-lactamases. However, it is not active on 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 Azithromycin and Cefpodoxime and there formulation thereof.
The present invention comprises of the formulation comprising pharmaceutically acceptable salts of Azithromycin and cefpodoxime 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 100mg, more preferably 250 mg to 500mg.
The cefpodoxime 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.
Suitable fillers may be microcrystalline cellulose, powdered cellulose, lactose, starch, pregelatinized starch, or sucrose preferably microcrystalline cellulose and lactose.
Suitable binders are starch, polyvinylpyrrolidone, alginic acid, methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polymethacrylates, and others preferably hydroxypropyl cellulose, hydroxypropyl methylcellulose and polyvinylpyrrolidone.
Suitable disintegrants are starch, pregelatinized starch, sodium starch glycolate, sodium carboxymethylcellulose, cross-linked sodium carboxymethylcellulose, cross-linked polyvinylpyrrolidone, alginic acid, sodium alginate, and others preferably sodium starch
glycolate, cross-linked sodium carboxymethylcellulose and cross-linked polyvinylpyrrolidone.
Suitable glidants are magnesium stearate, calcium stearate, aluminium stearate, stearic acid, palmitic acid, cetanol, stearol, colloidal silicon dioxide, talc, powdered cellulose, starch and others, preferably, colloidal silicon dioxide.
Suitable lubricants are stearic acid, calcium, magnesium, zinc or aluminium stearate, siliconized talc, glycerol monostearate, and others. Preferred lubricants are calcium or magnesium stearate and stearic acid.
The release of cefpodoxime and Azithromycin 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 cefpodoxime and Azithromycin.
The present invention formulated, but not limited to, in the following manner.
Weigh the following ingredients:

(Table Removed)
PART 1
1) Weigh all the materials and pass them according to the following sieve number.
(Table Removed)
2) Take the material of step 1) and Transfer them in RMG. Run the RMG for 10 minutes.
3) Take the composition from RMG and sift them through sieve #18.
PART 2
1) Weigh the following materials and pass them according to
the following sieve number
(Table Removed)
2) Take sifted material of step 1) and transfer them in RMG. Run the RMG for 10 minutes.
3) Binder preparation- i) Take 80 ml of purified water and heat it to boil.
ii) Take 18 gm starch and prepare the slurry by dissolving it in another 50 ml of purified water.
iii) Pour the slurry obtained in step ii) in the boiled water obtained in step iii) so as to get a translucent phase.
iv) Take 4.5 gm of polyvinyl pyrrolidone and dissolve it in 20 ml purified water.
4) Pour the binder of step 3) to the mixed material of step 2). Run the RMG for 10 minutes. Add more solvent to get the dough like consistency. Note the quantity of solvent added. The extra quantity of solvent added is 50 ml.
5) Pass the wet mass of step 4) through sieve # 8. Collect the sifted granules in clean containers.
6) Dry the granules obtained in step 5) in FBD at 50-60° for 90 minutes. Check the LOD of dried granules by I.R. moisture balance at temperature 105° for 5 minutes. If LOD is more than the limit, again dry the granules. LOD found 2.2%.
7) Sift the dry granules of step 6) through sieve # 18. Collect the sifted granules in clean containers.
Part 1 and art 2 are mixed and lubricated together with the help of following lubricants.
Lubricants- Lubricants are sieved through the following sieve numbers-
(Table Removed)
The granules are lubricated for 10 minutes and are compressed to form tablet.
The tablets can optionally be coated with the following coating material-
(Table Removed)
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

We Claim:-
1) A pharmaceutical formulation comprising 50 mg to 500 mg of Cefpodoxime, preferably 100 to 200 mg, and azithromycin 50mg to 1500mg, preferably 200mg to 100mg, more preferably 250 mg to 500mg, 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.