Film coated tablet of paracetamol and domperidone

Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills

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424474, 424482, A61K 932, A61K 936

Patent

active

058143394

DESCRIPTION:

BRIEF SUMMARY
CROSS-REFERENCE TO RELATED APPLICATIONS

This application is based upon PCT Application Ser. No. PCT/EP 95/00719, filed Feb. 27, 1995, which claims priority from European Patent Application Ser. No. 94.200.498.7, filed on Feb. 28, 1994.
The present invention is concerned with a film coated tablet comprising as active ingredients the antipyretic analgesic paracetamol and the antiemetic agent domperidone, and with a process of preparing such tablets.
In Cephalalgia 13 (2), 124-7 (1993) the safety and efficacy of separately administered domperidone in combination with paracetamol in the treatment of migraine, especially acute attacks of migraine is disclosed. Paracetamol is an effective analgesic similar in efficacy to aspirin but less irritant to the stomach. Its normal unit dose is about 500 mg b.i.d., t.i.d. or q.i.d. Domperidone is a peripheral dopamine antagonist effective as an anti-nauseant which is thought not to cross the blood brain barrier, and because of this, not to be likely to cause extrapyramidal side effects. It promotes the gastrointestinal motility and thus could enhance the rate of paracetamol absorption which is sometimes slowed by the mild gastroparesis that may accompany migraine attacks. Its normal unit dose is about 10 mg o.d., b.i.d. or t.i.d.
Up till now, domperidone and paracetamol have been administered as separate dosage forms, but if the two were available as one preparation, as a single tablet for instance, patients would find such an administration form more convenient and would be expected to take the medicine more readily and in the earlier stages of a migraine attack. It is advantageous to start the treatment of a migraine attack at the earliest possible moment as it is then more likely to be effective.
The mere combination of domperidone granules with paracetamol granules such as are used each individually for preparing the art-known single formulations, is conceivably the most simple solution, but fails because it yields large unit dosage forms of about 700 mg which most patients find difficult or impossible to swallow. Indeed, paracetamol crystals are hard, brittle and fracture easily, and consequently can be tabletted only using relatively high amount of excipients. Moreover, for easy oral administration, large tablets should preferably be film coated which yet again increases the tablet size. The present invention therefore seeks to solve the above-mentioned problems by providing an acceptable film coated tablet having the smallest possible size and yet containing the required dose of about 500 mg paracetamol and about 10 mg domperidone per unit dosage form.
In particular the composition of the present invention concerns a tablet comprising ingredients, and a pharmaceutically acceptable carrier, and
Such tablets represent a unit dosage form and comprise about 500 mg paracetamol and about 10 mg domperidone in the core. In the finished film coated tablets according to the present invention, the total tablet weight is about 620-625 mg .+-.5%, 500 mg (ca. 80%) of which is paracetamol and 10 mg (ca. 1.6%) of which is domperidone. Thus the amount of tabletting aids is below 20% (w/w) of the total tablet weight. Tablets for humans having a lower bodyweight may be only half as large and comprise about 250 mg paracetamol and about 5 mg domperidone in the core.
The (1:1) maleate salt of domperidone is preferred as opposed to the base because in the solid dosage form of the present invention better bioavailability is obtained. 10 mg domperidone corresponds to 12.72 mg of domperidone maleate.
The pharmaceutically acceptable carrier comprises one or more solid diluents, disintegrants, tablet binding agents, granulating agents, and optionally other formulating agents known in the art such as, for example, suspending agents, dispersing agents, solvents, flow aids, glidants, anticaking agents, preservatives or lubricants. Carrier compounds may have several functions in the tablets: ingredients used mainly for one particular property may well function also as compounds typical of anoth

REFERENCES:
patent: 5273759 (1993-12-01), Simmons
patent: 5456920 (1995-10-01), Matoba et al.
patent: 5587179 (1996-12-01), Gergley et al.
patent: 5618828 (1997-04-01), Gray et al.
Cephalagia, 13 (2), pp. 124-127, MacGregor et al., "Domperidone plus paracetamol in the treatment of migraine".
S. Afr. J. Sci., 1988, p. 431, Van der Merve et al., "Domperidone reduces the accumulation of paracetamol in saliva".
The Martindale 30th Edition, p. 883.2, "Domperidone".

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