SI9300045A - VERY COOLED NABUMETON AND PROCEDURE FOR ITS MANUFACTURING - Google Patents

Abstract

Nabumetone, which is spray-cooled and formulated into unit dosage forms that have a smaller volume than previously possible, is useful in the manufacture of medications for the treatment of inflammation, sprains, dislocations, cancer pain, fever, osteoporosis, and myofascial pain syndrome.

Description

SmithKline Beecham p.l.c.

Spray-cooled nabumetone and process for its manufacture

The present invention relates to spray-cooled nabumetone and a process for its manufacture.

GB 1,474,377 describes the non-steroidal anti-inflammatory drug 4- (6-methoxy-2-naphthyl) -butan2-one, commonly known as nabumetone. This patent also describes a process for making nabumetone.

Nabumetone is most commonly prescribed in the form of 500 mg or 1000 mg swallow tablets. The resulting tablets containing nabumetone and conventional carriers are considerable in size and may be problematic to swallow for some patients.

Usually isolated and ground nabumetone has a bulk density range of 0.35 to 0.39 gcm ' ³ and a bulk density range of 0.44 to 0.48 gcm' ³ and, when mixed with conventional carriers, produces a 500 mg volume nabumetone tablet with volume 0,485 cm ³ and 1000 mg nabumetone tablet with a volume of 0,970 cm ³ .

Usually isolated and ground nabumetone is formulated into conventional tablets for swallowing by mixing with conventional fillers, surfactants and disintegrants. They found that the maximum amount of drug that can be mixed with the carriers was a special filler

%. Increasing the proportion of the drug further (i.e., reducing the proportion of carriers, especially the fillers) causes the tablet to tend to break during production, storage and transport, which is clearly a disadvantage.

Spray cooling is a technique that has existed for about 30 years and is used in the manufacture of nutrients such as coffee as well as medicines.

Spray cooling is a process that is usually chosen because it produces a product of uniform quality, such as. particle size, moisture content and bulk density.

They use spray cooling in pharmaceutical manufacturing because they can provide products that have improved fluid properties.

We have now found that spray-cooled nabumetone has excellent formulation properties, is less expensive to manufacture and, surprisingly, can be formulated into usable tablets using fewer carriers than previously required. In addition, spray-cooled nabumetone has the unexpected advantage of being denser than the usual isolated and ground nabumetone and can therefore be formulated into smaller tablets that are easier to swallow.

Accordingly, the present invention provides spray-cooled nabumetone.

The present invention further provides spray-cooled nabumetone having a bulk density range of 0.40 to 0.65 gcm ³ .

Of particular note is the bulk density of spray-cooled nabumetone between 0.45 and 0.60 gcm ' ³ or more preferably 0.5 to 0.55 gcm' ³ . Most preferably, the bulk density of spray-cooled nabumetone is about 0.5 gcm ' ³ .

The present invention also provides spray-cooled nabumetone with a density range of 0.50 to 0.65 gcm ³ .

Particularly convenient is the charge density range of spray-cooled numbetone between 0.54 and 0.62 gcm ' ³ or more preferably between 0.58 and 0.62 gcm' ³ . Most preferably, the charged density of spray-cooled nabumetone is about 0.60 gcm ' ³ .

The present invention also provides a pharmaceutical composition comprising spray-cooled nabumetone mixed with a pharmaceutically acceptable carrier.

It should be borne in mind that the term " carrier " used herein means a pharmaceutically acceptable carrier.

In another aspect, the present invention provides spray-cooled nabumetone in a unit dosage form. Suitable unit dosage forms include tablets, sachets, suspensions and suppositories containing nabumetone, which are formulated using conventional techniques known in the art of formulation.

The present invention further provides swallow tablets containing 500 mg of spray-cooled nabumetone mixed with conventional carriers, wherein the tablet has a volume of 0.429 cm ³ . Thus, the present invention provides swallow tablets containing 500 mg of spray-cooled nabumetone with a volume of less than 0.480 cm ³ , preferably less than 0.450 cm ³ and most preferably less than 0.430 cm ³ .

The present invention also provides swallow tablets containing 1000 mg of spray-cooled nabumetone mixed with conventional carriers, wherein the tablet has a volume of 0.858 cm ³ . Thus, the present invention provides swallow tablets containing 1000 mg of spray-cooled nabumetone with a volume of less than 0.960 cm ³ , preferably less than 0.930 cm ^3, and most preferably less than 0.860 cm ³ .

The present invention also provides a uniform dosage formulation of spray-cooled nabumetone prepared using non-conventional or substantially unusual fillers as carriers.

It should be borne in mind that the fillers are those commonly known in the art of formulation, such as e.g. microcrystalline cellulose, hydroxypropylmethyl cellulose, lactose and starch.

The present invention also provides conventional swallow tablets in which the percentage (wt / wt) of spray-cooled nabumetone against the carrier is 82% excess, more preferably 85% excess, more suitable 88% excess and preferably 90% excess .

In another aspect, the present invention provides a process for the preparation of spray-cooled nabumetone, comprising the melting of solid nabumetone, spraying it into the cooling chamber of a spray cooler and collecting the resulting product.

Nabumetone is preferably melted by heating it to a temperature that is 20 ° C above the melting point (80 ° C).

The molten nabumetone is conveniently filled into a cooling chamber at 16-17 kg / h.

The cooling chamber is suitably cooled to 1-4 ° C.

Nabumeton is conveniently filled into a cooling chamber via 2 liquid nozzles, atomized using hot compressed air and the resulting product conveniently collected in a cyclone.

The spray cooler used above is a convenient, usually commercially available cooler.

Nabumeton useful for spray cooling is conveniently prepared according to the procedures described in EP-A-0 003074 (Beecham Group pic) or EP-A-0 288144 (Beecham Group pic), although it must be borne in mind that spray cooling can be used nabumetone prepared by any suitable means.

Nabumetone has previously been described as being useful for the treatment of inflammation, especially those resulting from rheumatoid or osteoarthritis, sprains, outbursts, cancer pain, fever or chills, osteoporosis, and myofacial pain syndrome. The present invention therefore provides a method of treating inflammation, sprains, discharges, cancer pain, fever or chills, osteoporosis and myofacial pain syndrome, comprising administering an effective amount of spray-cooled nabumetone to a patient in need thereof.

The present invention also provides the use of spray-cooled nabumetone in the manufacture of a medicament for the treatment of inflammation, sprains, discharges, cancer pain, fever or chills, osteoporosis and myofacial pain syndrome.

The present invention further provides a pharmaceutical composition useful in the treatment of inflammation, sprains, discharges, cancer pain, fever or chills, the axis of theoporosis and myofacial pain syndrome, comprising spray-cooled nabumetone mixed with pharmaceutically acceptable carriers.

The following examples describe the preparation of spray-cooled nabumetone and the formation of 500 mg / mg swallow tablets. 1000 mg of nabumetone.

Example 1

Preparation of spray-cooled nabumetone

Nabumeton prepared by the process described in EP-A-0 003 074 is melted (80 ° C) and maintained at about 100 ° C. The melt is then filled into the cooling chamber of a conventional spray cooler using a peristaltic pump with a charge rate of 16-17 kg / h via 2 liquid (air atomizing) nozzles, where it is atomized using hot compressed air at 55.16 χ 10 ⁴ Pa. .

The dispersed nabumetone is then cooled because it is dispersed in a cooling chamber maintained at 1-4 ° C and the crystallized product is collected in a cyclone.

The spray cooler used above is commercially available from Drytech Ltd, 46 Morley Road, Tonbridge, Kent, Vel. Britain.

Example 2 (500 mg tablet of spray-cooled nabumetone to swallow)

Mix the following ingredients in the usual way and squeeze to form a pill to swallow.

500 mg spray-cooled nabumetone 25 mg * Explotab 2 mg sodium lauryl sulfate 527 mg

Example 3 (1000 mg tablet of spray-cooled nabumetone for swallowing)

Mix the following ingredients in the usual way and squeeze to form a pill to swallow.

1000 mg of spray-cooled nabumetone mg * Explotab 4 mg sodium lauryl sulfate

1027 mg * Trademark for sodium starch glycolate.

Claims (12)

PATENT APPLICATIONS 1. Spray-cooled nabumetone. 2. Spray-cooled nabumetone having a bulk density range of 0.40 to 0.65 gcm ³ . 3. Spray-cooled nabumetone having a density range of 0.50 to 0.65 gcm ³ . Pharmaceutical composition comprising spray-cooled nabumetone according to any one of claims 1 to 3 mixed with a pharmaceutically acceptable carrier. 5. The spray-cooled nabumetone according to any one of claims 1 to 4 in a unit dosage form. A unit dosage form according to claim 5, characterized in that the swallow tablet contains 500 mg of spray-cooled nabumetone mixed with the carriers, the tablet having a volume of less than 0.480 cm ³ . A unit dosage form according to claim 5, characterized in that the swallow tablet contains 1000 mg of spray-cooled nabumetone mixed with the carriers, wherein the tablet has a volume less than 0.960 cm ³ . A unit dosage form according to any one of claims 5 to 7, characterized in that it does not have or substantially lack fillers as carriers. A swallow tablet according to any one of claims 6 to 8, characterized in that the percentage (wt / wt) of spray-cooled nabumetone against the carrier is 82% excess. 10. A swallow tablet according to claim 9, characterized in that the percentage of spray-cooled nabumetone against the carrier is 90% in excess. Process for the preparation of spray-cooled numbetone, characterized in that the solid numbetone is deposited, sprayed into the spray chamber's cooling chamber and the product collected. Use of spray-cooled nabumetone according to any one of claims 1 to 11 for the manufacture of a medicament for the treatment of inflammation, sprains, discharges, cancer pain, fever or chills, osteoporosis and myofacial pain syndrome. For SmithKlme Bei NUEM1N ft / 2235-I-93-KA SUMMARY Spray-cooled nabumetone and process for its manufacture Nabumetone spray-cooled and formulated into unit dosage forms of a smaller volume than previously possible for use in the manufacture of medicines for the treatment of inflammation, sprains, discharges, cancer pain, fever or chills, osteoporosis and myofacial pain syndrome.