Claims
- 1. A process for manufacturing an oral controlled release pharmaceutical preparation in the form of a multiple unit hard gelatin capsule enclosing particles containing a therapeutically effective amount of morphine hydrochloride for administration once daily and consisting of a plurality of particles with a size in the range of 0.2 to 3 mm, each having a core containing morphine hydrochloride coated with a barrier layer containing at least one water insoluble component selected from the group consisting of ethyl cellulose, copolymers of acrylic and methacrylic esters, and natural or synthetic waxes, providing a pH-independent drug release and in that the serum concentration of morphine obtained is at least 50% of the maximum serum concentration during at least 12 hours after the administration of a single dose of said preparation, which comprises the following steps:
- a) mixing morphine hydrochloride together with one or several excipients and a granulating fluid, thereby obtaining a granulated product;
- b) extruding the granulated product of step a);
- c) thereafter spheronizing, drying and size fractionating the granulated product;
- d) spray coating the product from step c) in a fluidized bed with a coating liquid in the form of a solution containing at least one insoluble barrier layer forming component, thereby providing a pH-independent barrier coating on the particles; and
- e) filling the particles into said capsule to formulate a single dosage form.
- 2. The process of claim 1 wherein said capsule is filled with at least 50 morphine containing particles to make up the total single dose of morphine.
- 3. The process of claim 1 wherein said coating barrier layer also contains at least one water soluble component selected from the group consisting of hydroxypropylmethyl cellulose, hydroxypropyl cellulose, copolymers of acrylic and methyacrylic acid esters, and optionally plasticizers or pigments or both.
- 4. The process of claim 3 wherein said capsule is filled with at least 50 morphine containing particles to make up the total single dose of morphine.
- 5. The process of claim 1 which further comprises size fractionating the particles from step d) prior to the filling step e).
- 6. A process for manufacturing an oral controlled release pharmaceutical preparation in the form of a multiple unit hard gelatin capsule enclosing particles containing a therapeutically effective amount of morphine hydrochloride for administration once daily and consisting of a plurality of particles with a size in the range of 0.2 to 3 mm, each having a core containing morphine hydrochloride coated with a barrier layer containing at least one water insoluble component selected from the group consisting of ethyl cellulose, copolymers of acrylic and methacrylic esters, and natural or synthetic waxes, providing a pH-independent drug release and in that the serum concentration of morphine obtained is at least 50% of the maximum serum concentration during at least 12 hours after the administration of a single dose of said preparation, which comprises the following steps:
- a) mixing morphine hydrochloride together with one or several excipients and a granulating fluid, thereby obtaining a granulated product;
- b) extruding the granulated product of step a);
- c) thereafter spheronizing, drying and size fractionating the granulated product;
- d) spray coating the product from step c) in a fluidized bed with a coating liquid in the form of a dispersion, suspension or emulsion, containing at least one insoluble barrier layer forming component, thereby providing a pH-independent barrier coating on the particles; and
- e) filling the particles into said capsule to formulate a single dosage form.
- 7. The process of claim 6 wherein said capsule is filled with at least 50 morphine containing particles to make up the total single dose of morphine.
- 8. The process of claim 6 wherein said coating barrier layer also contains at least one water soluble component selected from the group consisting of hydroxypropylmethyl cellulose, hydroxypropyl cellulose, copolymers of acrylic and methyacrylic acid esters, and optionally plasticizers or pigments or both.
- 9. The process of claim 8 wherein said capsule is filled with at least 50 morphine containing particles to make up the total single dose of morphine.
- 10. The process of claim 6 which further comprises size fractionating the particles from step d) prior to the filling step e).
Parent Case Info
This is a divisional application of Ser. No. 08/213,518 filed on Mar. 16, 1994.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
4557925 |
Lindahl et al. |
Dec 1985 |
|
Foreign Referenced Citations (2)
Number |
Date |
Country |
0097523 |
Jan 1984 |
EPX |
03161 |
Feb 1994 |
WOX |
Non-Patent Literature Citations (2)
Entry |
Olsson et al. (1991). Proc. Int. Symp. Cont. Rel. Biact. Mater., vol. 18, pp. 433-434. |
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Divisions (1)
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Number |
Date |
Country |
Parent |
213518 |
Mar 1994 |
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