METHOD AND APPARATUS

Abstract

A method of processing an active pharmaceutical ingredient, the method comprising passing a precursor composition comprising the active pharmaceutical ingredient and a solvent through a twin screw extruder wherein the twin screw extruder is heated at ambient pressure.

Claims

1. A method of processing an active pharmaceutical ingredient, the method comprising passing a precursor composition comprising the active pharmaceutical ingredient and a solvent through a twin screw extruder wherein the twin screw extruder is heated at ambient pressure.

2. A method of preparing a formulated pharmaceutical product, the method comprising: (a) providing an active pharmaceutical ingredient using the method of claim 1; and (b) admixing the treated composition obtained in step (a) with one or more further components.

3. A method according to claim 1 or claim 2 wherein a barrel of the twin screw extruder includes one or more vents along its length.

4. A method according to claim 1 any preceding claim wherein the active pharmaceutical ingredient is selected from paracetamol, ibuprofen, aspirin, felodipine, piracetam, irbesartan, hydrochlorothiazide, caffeine, amoxiciline, griseofulvin, metformin, chlorpheniramine maleate, simvastatin, etoricoxib, eprosartan, levofloxacin and sevelamer.

5. A method according to claim 1 any preceding claim wherein the solvent is selected from water, ethanol, isopropanol, glycerol, ethyl acetate, hexane, cyclohexane, acetone, methanol and propylene glycol.

6. A method according to claim 1 any preceding claim wherein the precursor composition comprises at least 5 wt % solvent.

7. A method according to claim 1 any preceding claim which provides a treated composition comprising less than 1 wt % solvent.

8. Apparatus for processing an active pharmaceutical ingredient, the apparatus comprising: a barrel, two screws located within the barrel, means for inputting material into the barrel, exit means for collected material from the barrel, one or more heating elements arranged to heat material inside the barrel, and one or more vents along a length of the barrel.

9. (canceled)

10. A method according to claim 2, wherein a barrel of the twin screw extruder includes one or more vents along its length.

11. A method according to claim 2, wherein the active pharmaceutical ingredient is selected from paracetamol, ibuprofen, aspirin, felodipine, piracetam, irbesartan, hydrochlorothiazide, caffeine, amoxiciline, griseofulvin, metformin, chlorpheniramine maleate, simvastatin, etoricoxib, eprosartan, levofloxacin and sevelamer.

12. A method according to claim 2, wherein the solvent is selected from water, ethanol, isopropanol, glycerol, ethyl acetate, hexane, cyclohexane, acetone, methanol and propylene glycol.

13. A method according to claim 2, wherein the precursor composition comprises at least 5 wt % solvent.

14. A method according to claim 2, which provides a treated composition comprising less than 1 wt % solvent.

Description

[0082] The invention will now be further described with reference to the following non-limiting examples.

EXAMPLE 1

[0083] A powder mixture of API/excipients blend was continuously fed into a twin screw granulator. After reaching a steady state of powder input/output, a binder feeder was connected to the barrel and the granulation process started. Then, heating elements were fitted to the barrel (with vents to allow vapour to escape) and the temperature of the heated zones was set at 50 degC. The granulated/dried particles were collected and the moisture content and particle size distribution (PSD) measured. The granules produced had a more uniformed PSD and a relatively low moisture content in comparison to the conventional twin screw granulation process.

EXAMPLE 2

[0084] A mixture of paracetamol/ethanol (wet cake), with the solvent content of 28.3 wt % was continuously fed into a twin screw extruder (TSE) at three different flow rates: 28.9 g/h (A), 10.3 g/h (B), and 1.7 g/h (C). In preferred embodiments the extruder barrel is fitted with three to nine longitudinally spaced-apart electric heating elements, each of which is independently controlled with separate thermostats attached to the barrel in the vicinity of the element which it controls. The first heating element is located near the feed inlet of the extruder, and the last near the extrusion orifice. The TSE screw speed was set at 10 rpm and conveying elements were used in screw configuration. Heating elements were fitted to the barrel (with vents to allow vapour to escape) and the temperature of the heated zones was set at 83 C. The granulated/dried particles were collected and the moisture content and particle size distribution (PSD) measured.

[0085] Our results show that at those experimental conditions, the drying efficiency in the twin screw extruder of the model API material (paracetamol/ethanol wet cake (W)) was between 98.8% and 100%, thus the residual moisture was between 0% and 1.2%, depending on the specific conditions. Also, by changing processing conditions (particularly the flow rate) it was possible to tailor the distribution of particle sizes in order to avoid generating both fines and oversized particles.

[0086] FIG. 1 shows the moisture content for flow rates A, B and C compared with the initial wet cake W and includes photographs of the product in each case.