Continuous method for preparing pharmaceutical granules

• US 20030224057A1
• Filed: 09/30/2002
• Published: 12/04/2003
• Est. Priority Date: 02/04/2000
• Status: Abandoned Application

• Current Assignee: Rhodia Chimie (Solvac SA)
• Original Assignee: Rhodia Chimie (Solvac SA)
• Inventors: Le Thiesse, Jean-Claude, Martin-Letellier, Stephane
• Application Number:
  US10/182,527
• Publication Number:
  US 20030224057A1
• Time in Patent Office: Days
• US Class Current: 424/489
• CPC Class Codes: A61K 9/1688 resulting in pure drug agglomerate optionally containing up to 5% of excipient
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

The present invention relates to a process for formulating one or more pharmaceutical active principles in the form of granules, characterized in that the various ingredients to be granulated are introduced continuously and this mixture is granulated using a device comprising a chamber and at least one rotary stirring arm, and in the presence of an effective amount of a binder solution, until the said granules are obtained.

Claims

1. Process for formulating one or more pharmaceutical active principles in the form of granules, characterized in that the various ingredients to be granulated are introduced continuously and this mixture is granulated using a single device comprising a chamber and at least one rotary stirring arm, and in the presence of an effective amount of a binder solution, until the said granules are obtained.

2. Process according to claim 1, characterized in that an operation of drying of the said granules can be carried out in continuous mode consecutively to the granulation step.

3. Process according to claim 1 or 2, characterized in that the pharmaceutical materials are introduced into the chamber at a feed rate of between 50 kg/h and 250 kg/h.

4. Process according to one of the preceding claims, characterized in that the rotary stirring arm(s) is(are) subjected to a spin speed of about from 100 rpm to 400 rpm.

5. Process according to one of the preceding claims, characterized in that the chamber is maintained at a temperature of between 20°

C. and 150°

C. during the granulation operation.

6. Process according to one of the preceding claims, characterized in that the binder solution is introduced at ambient temperature or at a temperature above ambient temperature.

7. Process according to one of the preceding claims, characterized in that the binder solution is introduced separately into the chamber.

8. Process according to one of the preceding claims, characterized in that the coefficient of variation of the granules obtained after the calibration step ranges between 30% and 100% and preferably between 40% and 90%.

9. Process according to one of the preceding claims, characterized in that the mean size d₅₀ of the granules obtained after the calibration step is between 300 μ

m and 500 μ

m.

10. Process according to one of the preceding claims, characterized in that the active substances are chosen from non-steroidal anti-rheumatism drugs and anti-inflammatory drugs (ketoprofen, ibuprofen, flurbiprofen, indomethacin, phenylbutazone, allopurinol, nabumetone, etc.), opiate or non-opiate analgesics (paracetamol, phenacetin, aspirin, etc.), antitussive drugs (codeine, codethyline, alimemazine, etc.), psychotropic drugs (trimipramine, amineptine, chlorpromazine, phenothiazine derivatives, diazepam, lorazepam, nitrazepam, meprobamate, zopiclone, and derivatives of the cyclopyrrolone family, etc.), steroids (hydrocortisone, cortisone, progesterone, testosterone, prednisolone, triamcinolone, dexamethazone, betamethazone, paramethazone, fluocinolone, beclomethazone, etc.), barbiturates (barbital, allobarbital, phenobarbital, pentobarbital, amobarbital, etc.), antimicrobial agents (pefloxacin, sparfloxacin, derivatives of the quinolone family, tetracyclines, synergistins, metronidazole, etc.), drugs intended for treating allergies, in particular anti-asthmatic, antispasmodic and antisecretory drugs (omeprazole), cerebral vasodilators (quinacainol, oxprenolol, propranolol, nicergoline, etc.), cerebral protectors, liver protectors, therapeutic agents for gastrointestinal purposes, contraceptive agents, oral vaccines, antihypertensive agents and cardiovascular or cardioprotective agents such as beta-blockers and nitro derivatives.

11. Process according to one of the preceding claims, characterized in that the active material is paracetamol (acetyl-para-aminophenol).

12. Process according to claim 11, characterized in that the starting active material has an overall particle size of between 2 μ

m and 200 μ

m with a d₅₀ size of from 20 μ

m to 70 μ

m and a CV of about from 60% to 150%.

13. Process according to one of the preceding claims, characterized in that the device is in communication with a feed hopper 28 and consists of a cylindrical tank 16 surrounded by a jacket 18 containing a heat-exchange fluid to ensure temperature control of the mixture during granulation, and in which are arranged in parallel and side by side along the axis of the tank and driven by the same motor 24, two counter-rotating stirring shafts 20 equipped with twisted stirring blades 22.

14. Use of a device comprising a cylindrical tank 16, generally made of stainless steel, surrounded by a jacket 18 containing a heat-exchange fluid to ensure temperature control of the mixture during granulation, and in which are arranged in parallel and side by side along the axis of the tank and driven by the same motor 24, two counter-rotating stirring shafts 20 equipped with twisted stirring blades 22, to granulate at least one pharmaceutical active material.