COMPLETE SPECIFICATION
Field of the Invention
The present invention relates to an effervescent dosage formulation comprising Aceclofenac and Paracetamol. The effervescent dosage formulation may be either in the form of effervescent granules or in the form of effervescent tablets.
Background of the invention
The first observations about the analgesic and antipyretic properties of paracetamol were made back in the late nineteenth century when alternative compounds were being sought to reduce fever in the treatment of infections.
The antipyretics commonly used at the time consisted of preparations of natural compounds such as cinchona bark, from which quinine is derived, or galenicals based on willow bark, the earliest source of salicylate. Cinchona bark became in short supply and cheaper, synthetic substitutes were needed.
Two alternatives that were developed included acetanilide in 1886 and phenacetin in 1887, both of which had the advantage over quinine of possessing both antipyretic and analgesic properties.
In 1893, another compound, now known as paracetamol, was noted also to have a prompt analgesic and antipyretic action. In 1895, further work on this compound indicated that paracetamol might be present in the urine of patients who had taken phenacetin and in 1889, paracetamol was also shown to be a urinary metabolite of acetanilide.
However, it was not until 1948 that Brodie and Axelrod established that paracetamol was a major metabolite of both phenacetin and acetanilide. This, and other work, led to the belief that the clinical effect of these two drugs was entirely due to rapid conversion in the body to paracetamol. This belief was supported by the observation that the analgesic and antipyretic effects of paracetamol were of the same order as those of its parent compound. Some years later, it was shown that phenacetin had both effects in its own right and that paracetamol formation was not essential for its pharmacological action. However, because a very high proportion is converted to paracetamol during first passage through the liver, phenacetin itself exerts a direct analgesic effect only at very high doses.
United States Patent 7,695,735 concerns an improved multiparticulate tablet disintegrating in the mouth in contact with saliva in less than 40 seconds. The invention is characterized in that it is based on particles of coated active principle, said particles having intrinsic compression properties and a mixture of carriers, the proportion of carrier mixture relative to coated active principle particles being 0.4 to 6 parts by weight, the carrier mixture comprising: a disintegrating agent; a diluting soluble agent with binding properties; a lubricant; a permeabilizing agent; and advantageously lubricants, sweeteners, flavoring and coloring agents, the proportion of disintegrating agent and soluble agent relative to the tablet mass being 1 to 15 wt. % for the former and 30 to 90 wt. % for the latter.
United States Patent 6,319,514 provides a method for eliciting an onset hastened analgesic and anti-inflammatory response and combating nausea in acute migraine attacks. This method comprises administering a pharmaceutical composition comprising more than one active ingredient, wherein said more than one
active ingredient consist essentially of: (i) domperidone or an analogue thereof in an amount sufficient to hasten the onset of the analgesic and anti-inflammatory response and to combat nausea in an acute migraine attack, and (ii) a NSAID, a pharmaceutically acceptable salt thereof or a pure (-) or pure (+) optical isomeric form thereof in an analgesically and antiinflammatory effective amount, wherein said NSAID is selected from the group consisting of proprionic acid derivatives, acetic acid derivatives, fenamic acid derivatives, biphenylcarboxylic acid derivatives and oxicams.
United States Patent 7,510,732 discloses a composition that contains (1) an effective amount of an analgesically and/or antiinflammatory active fraction separated from a mixture of plasma and/or serum, and (2) at least one metal, metal ion or metal salt, in which the mixture has been denatured. Also disclosed are methods of producing the composition for treating a subject afflicted with inflammation and/or pain.
United States Patent 6,929,805 relates to medicinal preparations which can be administered orally and contain a fixed combination of at least one locally acting analgesic with a rapid onset of action and at least one systemically acting analgesic with a sustained action.
GB1328591 (A) describes Pharmaceutical compositions comprising paracetamol (p-hydroxyacetanilide) or a sparingly soluble derivative thereof such as the benzoate or acetanilide, an effervescent couple e.g. NaHCO3 and/or KHCO3 and citric acid and/or monosodium citrate, and vitamin C. A method of preparing such preparations (which may be tableted).
CN 101411699 (A) discloses an aceclofenac paracetamol tablet, which uses aceclofenac and paracetamol as basic medicines,
starch as a filling agent, hyprolose as a disintegrant, 20 percent polyvinyl pyrrolidone anhydrous ethyl alcohol solution as an adhesive, and magnesium stearate as a lubricant, and is prepared through pelletizing, drying, finishing granule, tabletting and lagging cover.
Objective of the Invention
The objective of the invention is to provide a pharmaceutical composition containing Aceclofenac and Paracetamol.
Another objective of the invention is to provide a combination which is having a quick onset of action.
Yet another objective of the invention is to provide a composition which improves the patient compliance.
Yet another objective of the invention is to provide a
pharmaceutical dosage formulation which can be taken easily through the oral route.
Detailed Description of the Invention
Aceclofenac is an orally administered phenyl acetic acid derivatives with effects on a variety of inflammatory mediators.
Structure Activity Relationship
Structure-activity relationship in this series, have not been extensively studied. It does appear that the function of the two o-chloro groups is to force the anilino-phenyl ring out of the plane of the phenylacetic acid portion, this twisting effect being important in the binding of NSAIDs to the active site of the cyclooxygenase enzyme.
Pharmacology
The mode of action of aceclofenac is largely based on the inhibition of prostaglandin synthesis. Aceclofenac is a potent inhibitor of the enzyme cyclooxygenase, which is involved in the production of prostaglandins.
The Drugs inhibits synthesis of the inflammatory cytokines interleukin (IL)-l and tumor necrosis factor and prostaglandin E2 (PGE2) production. Effects on cell adhesion molecular from neurophils have also been noted. In vitro data indicate inhibition of cyclooxygenase (Cox)-l and 2 by aceclofenac in whole blood assays, with selectivity for Cox-2 being evident.
Aceclofenac has shown stimulatory effects on cartilage matrix synthesis that may be linked to the ability of the drug to inhibit IL-1 activity. In vitro data indicate stimulation by the drug of synthesis of glycosaminoglycan in osteoarthritic cartilage. There is also evidence that aceclofenac stimulates the synthesis of IL-1 receptor antagonist in human articular chondrocytes subjected to inflammatory stimuli and that 4'-hydroxyacelofenac has chondroprotective properties attributable to suppression of IL-1 mediated promatrix metalloproteinase production and proteoglycan release.
In patients with osteoarthritis of the knee, aceclofenac decrease pain reduces disease severity and improves the functional capacity of the knee. It reduces joint inflammation, pain intensity and the duration of morning stiffness in patients with rheumatoid arthritis. The duration of morning stiffness and pain intensity are reduced and spinal mobility improved, by aceclofenac in patients with ankylosing spondylitis.
Particular features of Paracetamol include:
• Its analgesic (pain relief) and antipyretic (fever relief) effects are comparable to those of aspirin.
• There are virtually no groups of people who should not take it.
• Interactions with other treatments are not a problem.
• At the recommended dosage there are virtually no side-effects.
• It is suitable for small children and the elderly.
• It can be taken by those sensitive to aspirin.
• It is well tolerated by patients with peptic ulcers.
The combination of Aceclofenac and Paracetamol has antipyretic, anti-inflammatory and analgesic efficacies, is suitable for the treatment of pain and inflammation symptoms caused by osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, lumbago, toothache and the like, and for the treatment of gynecological inflammation, and ear, nose and throat inflammations, and can be widely applied to the clinic.
The present invention discloses a novel dosage formulation for the two known antipyretic and analgesic drugs used.
According to the present invention there is provided a pharmaceutical formulation comprising Aceclofenac and Paracetamol 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 feast 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.
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 one embodiment, the effervescent granules of Aceclofenac and paracetamol are prepared and can be further formulated in to tablets.
The present invention can be formulated, but not limited to, in the following manner-
WEIGHMENT SHEET
(Table Removed)

CLAIMS
We Claim:-
1) Pharmaceutical effervescent formulation comprising
a) Aceclofenac and Paracetamol
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 said effervescent formulation as substantially described in foregoing example and description.