COMPLETE SPECIFICATION
Field of the invention
The present invention relates to a stable effervescent pharmaceutical granule of cephalosporin antibiotic, preferably cefixime for the treatment of bacterial infections.
Summary of the invention
The present invention discloses a stable effervescent formulation comprising cefixime as an active ingredient
In one embodiment, the effervescent composition of the present invention is able to be get suspended in to a liquid. The effervescent composition of the present invention comprised at least of an ingredient which when in contact of moisture capable of producing effervescence.
In another embodiment, a method of scheming the effervescence comprises the steps of providing a composition comprising at least an active ingredient, a ingredient capable of being producing a effervescence when contacted with moisture or liquid and avoiding the effervescence by the composition when the composition is not in contact with the liquid.
In another embodiment, the granules so obtained can be added to with other excipients to form effervescent tablets.
Background of the invention
U.S. Patent No. 6071539 discloses effervescent granules having a controllable rate of effervescence are provided. Such granules comprise an acidic agent, an alkaline agent, a hot-melt extrudable binder capable of forming a eutectic mixture with the acidic agent
and, optionally, a plasticizer. The effervescent granules are made by a hot-melt extrusion process.
U.S. patent No. 6066335 rel ates to a method of producing mechanically stable effervescent tablets with a high dissolving velocity and an according effervescent tablet are described. The effervescent tablets consist of at least one active substance or of a combination of active substances, of at least one binder, of possibly carriers as sweeteners, flavors, colorings, scents, softeners, bleaches, and of sherbets. In producing, propylglycol or glycerin is used as a binder for the effervescent tablets, and the active substances or the combination of active substances and possibly carriers are mixed with the binder. Afterwards, the sherbets are added to this mixture in an air-conditioned room. Then, the mixture including the sherbets is formed into tablets.
U.S. Patent No. 6190697 communicates the effervescent formulation in the form of granules or of a tablet contains, in addition to the effervescent base, at least one water-soluble or at least suspendable plant extract whose particles are coated with at least one oily, fatty or waxy substance. At least one emulsifier and/or at least one antifoam may be present in the coating and/or as a further component of the mixture, in particular applied as a further component of the mixture to a pharmaceutically permissible filler as carrier. The individual phases are prepared by a procedure in which the plant extract or the filler is heated— preferably in a granulator, in particular in a vacuum granulator— and wet or mixed with a melt or solution of the oily, fatty or waxy substance or at least one emulsifier and/or at least one antifoam and then dried—preferably in a vacuum—and sieved to the desired particle size.
U.S. Patent No. 6051254 narrates a pharmaceutical formulation comprising an amoxycillin hydrate and an effervescent couple, for
example citric acid plus sodium bicarbonate or sodium glycine carbonate, or tartaric acid or malic acid plus sodium carbonate. Potassium equivalents of these sodium salts may be used.
U.S. Patent No. 5962002 speaks about a chewable tablet comprises a medicament dispersed in a chewable base, such as mannitol, together with an effervescent couple, such as citric acid-sodium bicarbonate. The combination of effervescence and chewability with optional flavorings improves the taste characteristics of the medicament in oral administration. A disintegrant such as microcrystalline cellulose may be added to give the patient the option of dispersing the tablet in water.
GB-1300998 describes a effervescent compositions comprise a carbonate or bicarbonate of particle size 50 to 500Am, an organic acid (e.g. citric or tartaric) of particle size 200 to 1000 Am and an antibiotic. The weight ratio of carbonate or bicarbonate to acid is in the range 1:1 to 2.0:0.5, that of antibiotic to effervescent couple being from 1:5.5 to 1:15. Specified antibiotics are the sodium and potassium salts of ampicillin, cloxacillin, oxacillin, phenethicillin, phenoxymethyl penicillin, propicillin, novobiocin, fusidinic acid, chloramphenical leucine carbamate and colistin methane sulphonate. The compositions are stated to dissolve with effervescence to give clear, stable solutions, the pH being maintained within the range in which the antibiotic is stable.
GB1287475 discloses a free-flowing readily-wettable aspirin particles comprise a core of aspirin encompassed by a water -soluble pharmaceutically - acceptable coating having a m.p. of at least 105 C which coating comprises amino-acid, a sugar or sugar alcohol. They may be produced by suspending aspirin particles in an aqueous solution of the coating material and spray-drying the suspension. Coating materials specified are mannitol, sorbitol, inositol, sucrose, lactose, an arabino-galactan polymeric sugar,
lycine and methionine. The preparation may also include a wetting agent, a water-soluble filmforming agent, an effervescent couple and/or a sweetener.
EP 0281200 discloses a pharmaceutical tablet is provided containing an amphoteric beta-lactam antibiotic, a cellulose product, being microcrystalline cellulose or microfine cellulose or a mixture of both, and a second disintegrant, being low-substituted hydroxypropylcellu.lose, which fully disintegrates in water within 60 seconds. When swallowed it shows a bioavailability as good as a pharmacy prepared suspension of the antibiotic. The tablet is compressed from a mixture containing a new granulate which is prepared from the antibiotic substance, microcrystalline cellulose and/or microfine cellulose and water only. Such tablets can also be prepared by using other known tablet disintegrants as the second disintegrant.
Objective of the Invention
The objective of the present invention is to provide the effervescent granules of highly effective antibiotic and the effervescent tablet thereof.
Yet another objective of the invention is to provide a formulation that is easy to administer.
Another objective of the invention is to provide effervescent tablets of cefixime.
Yet another object of the present invention is to deliver cefixime with fewer side effects.
Detailed Description of the Invention
According to the present invention there is provided a pharmaceutical formulation comprising an antibiotic preferably
cefixime hydrate and an effervescent couple comprising an acid component and an alkaline component, which generates carbon dioxide when contacted with water.
Effervescence is the escape of gas from an aqueous solution and the foaming or fizzing that result from a release of the gas. An everyday example is seen in carbonated beverages such as soft drinks. The visible bubbles are produced by effervescence from the dissolved gas (which itself is not visible in the liquid solution).
In the laboratory, a common example of effervescence is seen if hydrochloric acid is added to a block of limestone. If a few pieces of marble or an antacid tablet are put in hydrochloric acid in a test tube fitted with a cork, effervescence of carbon dioxide can be witnessed.
This process is generally represented by the following reaction, where a pressurized dilute solution of carbonic acid in water releases gaseous carbon dioxide at decompression:
(Formula Removed)
In simple terms, it is the result of the chemical reaction occurring in the liquid which produces a gaseous product.
The choice of ingredients for effervescent granules depends both upon the requirement of the manufacturing process and the necessity of making a preparation which dissolves in water. The required ingredients are at least one acid and at least one base. The base must release carbon dioxide upon reaction with the acid. Examples of such acids include tartaric acid and citric acid. Examples of bases include sodium carbonate, potassium bicarbonate, and sodium bicarbonate.
Effervescent granules are usually prepared from a combination of citric and tartaric acid rather than from a single acid because the use of either acid alone causes difficulties. When tartaric acid is the sole acid, the resulting granules readily crumble and lack mechanical strength. Citric acid alone results in a sticky mixture which is difficult to granulate during the manufacturing process.
Cefixime is prescribed to treat a wide variety of bacterial infections, such as respiratory tract infections, middle ear infections, skin infections, urinary tract infections, tonsillitis, bronchitis, pneumonia, and gonorrhea. This medication is a cephalosporin-type antibiotic, which works by stopping the growth of the bacteria in body.
The cefixime hydrate is preferably cefixime trihydrate. The effervescent couple is preferably based on citric acid and sodium bicarbonate or sodium glycine carbonate, but other solid acid/carbonate couples may be used, for example tartaric or malic acid and sodium carbonate or potassium bicarbonate or mixtures of these acid and alkaline components. The effervescent couple is provided in a sufficient amount to rapidly disperse and assist dissolution of the components of the formulation. The corresponding potassium salts of the alkaline component may be used together with the sodium salts (or as a substitute) to avoid excessive levels of sodium ions.
When the combination is added to water a mixture of the acid and a salt available in the combination undergoes a chemical reaction that liberates carbon dioxide. The acid and salt should be in anhydrous form.
Examples of acids suitable for use in these illustrative embodiments include, but are not limited to, tartaric acid, citric acid, fumaric acid, adipic acid, malic acid, oxalic acid, or sulfamic acid, either alone or in combination. Typically, the effervescent of these embodiments is prepared from citric acid or a combination of citric acid and tartaric acid. Use of citric acid alone may cause difficulties during the manufacturing process. For example, use of citric acid alone may result in a sticky mixture that is difficult to granulate.
Examples of salts suitable for use in illustrative embodiments include, but are not limited to, the alkali metal salts. Sodium carbonate, calcium carbonate, magnesium carbonate, ammonium carbonate, potassium carbonate, sodium bicarbonate, and calcium bicarbonate may all be employed.
In other embodiments, the selection of specific acids and/or salts and their proportions depends, at least in part, upon the requirements for the amount of carbon dioxide release. In some embodiments, the acid may be added in an amount of about 10% to about 60% by weight of the effervescent, while the salt may also be added in an amount of about 10% to 60% by weight of the effervescent.
The effervescent formulation of cefixime can be in the form of granules, tablets, or powder.
The present invention can be formulated, but not limited to, in the following manner:
(Table Removed)

CLAIMS
1) Pharmaceutical effervescent formulation comprising
a) cefixime preferably in the form of cefixime trihydrate
b) at least an acid component
c) at least an alkali salt component
d) pharmaceutically acceptable excipients
2) The pharmaceutical effervescent formulation as claimed in
claim 1 may be in the form of effervescent granules or
effervescent tablets.
3) The acid as claimed in claim 1 is in the range of 25-40%
w/w and may be citric acid, citric acid monohydrate or
tartaric acid or the combination of above.
4) The alkali salt as claimed in claim 1 is in the range of 25-
40% w/w and may be preferably sodium bicarbonate.
5) The pharmaceutically acceptable excipients as claimed in
claim 1 may be lubricants, sweetener and flavoring agent.
6) The lubricant as claimed in claim 5 may be Xanthan Gum,
Colloidal Silicon Dioxide, Sodium Benzoate, Sodium
Bicarbonate, or Sodium Chloride or the combination of
above.
7) The sweetener as claimed in claim 5 may be sugar or
sucralose or the combination of both.
8) A method of preparation of the cefixime effervescent formulation as substantially described in foregoing example and description.