Method for the manufacture of pharmaceutical cellulose capsules

• US 5,698,155 A
• Filed: 01/24/1995
• Issued: 12/16/1997
• Est. Priority Date: 05/31/1991
• Status: Expired due to Term

• Current Assignee: Catalent Pharma Solutions Incorporated (Catalent, Inc.), Catalent Pharma Solutions Limited (Catalent, Inc.), Catalent USA Packaging LLC (Catalent, Inc.), Catalent USA Paintball, Inc. (Catalent, Inc.), Catalent USA Woodstock, Inc. (Catalent, Inc.)
• Original Assignee: GS Technologies, Inc. (Bain Capital Holdings LP)
• Inventors: Anderson, Jeffory B., Andrew, Clair S., Grosswald, Ralph R.
• Primary Examiner(s): ORTIZ, ANGELA Y
• Application Number:
  US08/377,669
• Time in Patent Office: 1,057 Days
• Field of Search: 425/269, 425/270, 425/272, 425/274, 425/275, 425/804, 425/174, 425/174.4, 425/174.6, 425/547, 425/577, 264/215, 264/299, 264/303, 264/304, 264/310-311, 264/327, 264/DIG. 37, 264/402, 264/405
• US Class Current: 264/402
• CPC Class Codes: A61J 3/077 Manufacturing capsule shells
• CPC Class Codes: B29C 33/06 using radiation , e.g. electro-magnetic waves, induction heating
• CPC Class Codes: B29C 33/30 Mounting, exchanging or centering moulds, mould parts or cores; B29C33/485 takes precedence
• CPC Class Codes: B29C 33/36 continuously movable in one direction, e.g. in a closed circuit B29C49/0021 takes precedence
• CPC Class Codes: B29C 33/44 with means for, or specially constructed to facilitate, the removal of articles, e.g. of undercut articles
• CPC Class Codes: B29C 33/60 Releasing, lubricating or separating agents in general C10M
• CPC Class Codes: B29C 35/0277 Apparatus with continuous transport of the material to be cured B29C35/025, B29C35/06, B29C35/10, B29C35/14 take precedence
• CPC Class Codes: B29C 35/04 using liquids, gas or steam
• CPC Class Codes: B29C 35/045 using gas or flames
• CPC Class Codes: B29C 35/0805 using electromagnetic radiation
• CPC Class Codes: B29C 41/14 Dipping a core B29C41/10 takes precedence
• CPC Class Codes: B29K 2001/00 Use of cellulose, modified cellulose or cellulose derivatives, e.g. viscose, as moulding material
• CPC Class Codes: Y10S 264/37 Processes and molds for making capsules
• CPC Class Codes: Y10S 425/804 Capsule making

Abstract

A method and apparatus for manufacturing pharmaceutical capsules use an aqueous solution of a thermogelling cellulose ether composition and use capsule body pins and capsule cap pins as molds. The method involves heating the pins, dipping the pins into the solution to cause the solution to gelatinize on the surface of the pins, removing the pins and drying the gelatinized solution on the surface of the pins to form capsule bodies and capsule caps. Pins are heated pre-dip and post-dip to facilitate gelating. Counterflow air is applied to provide drying from the inside. Capsule parts are removed by gripping. Capsule parts may have a thick wall and a stiffening ring.

Claims

1. A method of manufacturing pharmaceutical cellulose capsules of a given size number, the capsules suitable for filling by capsule filling machines, each capsule consisting of two parts, a capsule body and a capsule cap, from an aqueous solution of a thermogelling cellulose ether composition, using a capsule machine having capsule body pins and capsule cap pins as molds, comprising the steps of:

heating the pins;

dipping the pins into the solution to cause the solution to gelatinize on the surface of the pins thus forming a gelatinized solution;

drying the gelatinized solution on the surface of the pins to form capsule bodies and capsule caps; and

removing the capsule bodies and capsule caps from the pins;

wherein drying the gelatinized solution includes moving the pins through an enclosure and moving air over the pins within the enclosure, the air moving in a direction opposed to the direction of movement of the pins;

such that, during an early stage of drying, the gelatinized solution on the pins encounters humid air; and

during a later stage of drying encounters drier air.

2. A method of manufacturing pharmaceutical cellulose capsules, the capsules suitable for filling by capsule filling machines, each capsule consisting of two parts, a capsule body and a capsule cap, each part having a dome, from an aqueous solution of a thermogelling cellulose ether composition, using a capsule machine having capsule body pins and capsule cap pins as molds, and using a plurality of pinbars, each pinbar having a bar with a plurality of pins mounted to the bar, comprising the steps of:

heating the pins;

dipping the pins into the solution to cause the solution to gelatinize on the surface of the pins;

further gelatinizing the gelatinized solution, in humid air inside a kiln, on the surface of the pins by applying radiant heat from a dome-setter radiant heater mounted within the kiln and facing the plane of a planar array of domes;

drying the gelatinized solution on the surface of the pins to form capsule bodies and capsule caps; and

removing the capsule bodies and capsule caps from the pins.

3. A method according to claim 2, wherein further gelatinizing the gelatinized solution includes placing a group of pinbars, pins pointing up, below the dome setter radiant heater.

4. A method according to claim 2, wherein further gelatinizing the gelatinized solution includes heating the pins via the bars.

5. A method according to claim 2, wherein further gelatinizing the gelatinized solution includes setting the solution, while spinning the pins within a spinner enclosure, by radiant heat from radiant heaters mounted within the enclosure, and by air blown over the pins.

6. A method of manufacturing pharmaceutical cellulose capsules, the capsules suitable for filling by capsule filling machines, each capsule consisting of a capsule body and a capsule cap, from an aqueous solution of a thermogelling cellulose ether composition, using capsule body pins and capsule cap pins as molds, and using a plurality of pinbars, each pinbar having a bar with a plurality of pins mounted to the bar, comprising the steps of:

a) dipping hot pins into the solution such that heat from a pin causes solution to gelatinize on the surface of the pin;

b) drying gelatinized solution on the surface of the pins of a drying group of pinbars to form capsule bodies and capsule caps;

c) differentially heating the pins of the drying group of pinbars in accordance with the expected differential heat loss between differentially heating and dipping;

d) removing the capsule bodies and capsule caps from the pins;

e) greasing the pins; and

f) moving the pins in a closed loop so as to repeat steps a) through e);

further comprising the step of providing supplemental heat to the pins, after removing capsule bodies and capsule caps from the pins and before dipping the pins, by non-contact heating such that the pins have a predetermined dip temperature at dipping.

7. A method according to claim 6, wherein providing supplemental heat to the pins includes heating the pins by thermal convection.

8. A method according to claim 6, wherein providing supplemental heat to the pins includes heating the pins by radiant energy.

9. A method according to claim 6, wherein providing supplemental heat to the pins includes heating a group of pins conductively via a bar after greasing the pins.

10. A method according to claim 6, wherein providing supplemental heat to the pins includes heating a group of pins conductively via a bar before greasing the pins.

11. A method according to claim 6, wherein the step of providing supplemental heat occurs before greasing.

12. A method according to claim 6, wherein the step of providing supplemental heat occurs during greasing.

13. A method according to claim 6, wherein the step of providing supplemental heat occurs after greasing.

14. A method according to claim 6, having a predetermined body pin dip temperature of approximately 152°

F. (66.7°

C.).

15. A method according to claim 6, having a predetermined body pin dip temperature in the range 144°

F.-156°

F. (62.2°

C.-68.9°

C.).

16. A method according to claim 6, wherein differentially heating the pins includes exposing the pins to a predetermined temperature profile having temperatures greater than the predetermined pin dip temperature.

17. A method of manufacturing pharmaceutical cellulose capsules, the capsules suitable for filling by capsule filling machines, each capsule consisting of a capsule body and a capsule cap, from an aqueous solution of a thermogelling cellulose ether composition, using capsule body pins and capsule cap pins as molds, and using a plurality of pinbars, each pinbar having a bar with a plurality of pins mounted to the bar, comprising the steps of:

a) greasing the pins;

b) dipping hot pins into the solution such that heat from a pin causes solution to gelatinize on the surface of the pin;

c) drying gelatinized solution on the surface of the pins of a drying group of pinbars to form capsule bodies and capsule caps;

d) differentially heating the pins of the drying group of pinbars in accordance with the expected differential heat loss between differentially heating and dipping, such that pins have predetermined dip temperature at dipping;

e) removing the capsule bodies and capsule caps from the pins; and

f) moving the pins in a closed loop so as to repeat steps a) through e).

18. A method according to claim 17,

wherein body pins have a predetermined dip temperature approximately 152°

F. (66.7°

C.) and cap pins have a predetermined dip temperature of approximately 151°

F. (66.1°

C.).

19. A method according to claim 17,

wherein body pins have a predetermined dip temperature in the range 144°

F.-156°

F. (62.2°

C.-68.9°

C.) and cap pins have a predetermined dip temperature in the range 149°

F.-156°

F. (65.0°

C.-68.9°

C.).

20. A method according to claim 17, wherein step d) includes differentially heating on a split deck having a predetermined temperature profile.

21. A method according to claim 20, wherein the predetermined temperature profile is shaped to compensate for differential cooling of pins resulting from different pinbars having different wait times between heating and dipping.

22. A method according to claim 20, wherein the predetermined temperature profile is shaped to compensate for different pins, within a group of pins mounted to a bar, having different cooling rates according to position on the bar.

23. A method according to claim 17, further including the step of:

heating the pins of the dipping group, as a group, by non-contact heating between greasing the pins and dipping the pins.

24. A method of manufacturing pharmaceutical cellulose capsules, the capsules suitable for filling by capsule filling machines, each capsule consisting of a capsule body and a capsule cap, from an aqueous solution of a thermogelling cellulose ether composition, in a capsule machine using capsule body pins and capsule cap pins as molds, and using a plurality of pinbars, each pinbar having a bar with a plurality of pins mounted to the bar, comprising the steps of:

a) greasing the pins to form a layer of grease on a pin;

b) heating the pins of a dipping group of pinbars, as a group, to a predetermined dip temperature, by non-contact heating after greasing so the layer of grease on a pin is non-disturbed;

c) dipping the hot pins of the dipping group of pinbars, as a group, into the solution so that heat from a pin causes solution to gelatinize on the surface of the pin;

d) drying the gelatinized solution on the surface of the pins to form capsule bodies and capsule caps;

e) removing the capsule bodies and capsule caps from the pins; and

f) moving the pins in a closed loop so as to repeat steps a) through e);

such as to minimize cellulose capsule wall thickness variation caused by pin temperature differences at dipping and by disturbance to a layer of grease on a pin.

25. A method according to claim 24, wherein non-contact heating includes heating by thermal conduction via a bar.

26. A method according to claim 24,

wherein the step of heating the pins occurs in an extended dipper section prior to dipping.