Method of manufacturing modified release dosage forms

• US 7,972,624 B2
• Filed: 02/24/2009
• Issued: 07/05/2011
• Est. Priority Date: 09/28/2001
• Status: Expired due to Fees

• Current Assignee: Johnson & Johnson Consumer Inc. (Johnson & Johnson)
• Original Assignee: David Wynn, Der-Yang Lee, Harry S. Sowden, Shun-Por Li, Thomas Martin
• Inventors: Wynn, David, Sowden, Harry S., Lee, Der-Yang, Li, Shun-Por, Thomas, Martin
• Primary Examiner(s): Wax; Robert A
• Assistant Examiner(s): PALENIK, JEFFREY T
• Application Number:
  US12/391,475
• Publication Number:
  US 20090155372A1
• Time in Patent Office: 861 Days
• Field of Search: None
• US Class Current: 424/468
• CPC Class Codes: A23G 1/54 Composite products, e.g. layered laminated, coated, filled
• CPC Class Codes: A23G 3/0029 Moulding processes for hollow products, e.g. opened shell
• CPC Class Codes: A23G 3/04 Sugar-cookers
• CPC Class Codes: A23G 3/368 containing vitamins, antibiotics
• CPC Class Codes: A23G 3/54 Composite products, e.g. layered, coated, filled
• CPC Class Codes: A23L 29/30 containing carbohydrate syrups; containing sugars; containing sugar alcohols, e.g. xylitol; containing starch hydrolysates, e.g. dextrin products from apiculture A23L21/20; artificial sweetening agents A23L27/30
• CPC Class Codes: A61J 3/005 Coating of tablets or the like coating of sweetmeats or confectionery A23G3/20; coating of granules in general B01J2/006
• CPC Class Codes: A61J 3/06 into the form of pills, lozenges or dragees
• CPC Class Codes: A61J 3/10 into the form of compressed tablets tablet presses B30B11/00
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2068 Compounds of unknown constitution, e.g. material from plants or animals oils, fats, waxes, shellac A61K9/2013
• CPC Class Codes: A61K 9/2072 characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms A61K9/0004, A61K9/0056, A61K9/0065 take precedence
• CPC Class Codes: A61K 9/2081 with microcapsules or coated microparticles according to A61K9/50
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/2095 : Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61K 9/282 : Organic compounds, e.g. fats
• CPC Class Codes: A61K 9/2826 : Sugars or sugar alcohols, e.g. sucrose; Derivatives thereof
• CPC Class Codes: A61K 9/284 : obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/286 : Polysaccharides, e.g. gums; Cyclodextrin
• CPC Class Codes: A61K 9/2873 : Proteins, e.g. gelatin
• CPC Class Codes: A61K 9/2886 : having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer of the type active core-drug layer-inactive layer A61K9/209
• CPC Class Codes: A61K 9/2893 : Tablet coating processes mechanical aspects A61J3/06
• CPC Class Codes: A61K 9/5084 : Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077
• CPC Class Codes: A61P 11/00 : Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: B30B 11/08 : co-operating with moulds carried by a turntable
• CPC Class Codes: B30B 11/34 : for coating articles, e.g. tablets
• CPC Class Codes: B30B 15/302 : Feeding material in particulate or plastic state to moulding presses
• CPC Class Codes: Y10T 428/1352 : Polymer or resin containing [i.e., natural or synthetic]

Abstract

In one embodiment a dosage form comprises at least one active ingredient and a molded matrix which comprises 10-100% of a material having a melting point of less than about 100 degrees C. selected from the stamp consisting of thermoplastic polyalkylene oxides, low melting hydrophobic materials, thermoplastic polymers, thermoplastic starches and combinations thereof, and the matrix is capable of providing modified release of the active ingredient upon contacting of the dosage form with a liquid medium. The dosage form may additionally comprise uncoated particles which may contain at least one active ingredient. In another embodiment, a dosage form comprises at least one active ingredient, a plurality of particles and a molded matrix, wherein at least a portion of the particles are coated. The coated particles, the matrix or both may comprise at least one active ingredient, and the coated particles or the matrix or a combination thereof is capable of providing modified release of the active ingredient upon contacting of the dosage form with a liquid medium.

Claims

1. A dosage form comprising:

a molded matrix; and

at least one active ingredient dispersed in the molded matrix,

wherein the matrix comprises 10-100% of a thermal reversible carrier having a melting point of less than about 100 degrees C. selected from (a) polyethylene glycols having molecular weight from about 100 to about 20,000 Daltons; and

(b) a release-modifying excipient comprising a combination of croscarmellose sodium and shellac, and

wherein the matrix is capable of providing modified release of the active ingredient upon contacting the dosage form with a liquid medium.

2. A method for manufacturing a dosage form comprising a molded matrix and at least one active ingredient dispersed in the molded matrix comprising:

injecting a matrix in flowable form into a molding chamber to form said dosage form,

wherein the matrix comprises 10-100% of a thermal reversible carrier having a melting point of less than about 100 degrees C. selected from (a) polyethylene glycols having molecular weight from about 100 to about 20,000 Daltons; and

(b) a release-modifying excipient selected from the group consisting of croscarmellose sodium, shellac and combinations thereof, and

wherein the matrix is capable of providing modified release of the active ingredient upon contacting of the dosage form with a liquid medium.

4. A method of claim 2, wherein said matrix comprises a plurality of particles, and at least a portion of the particles comprise at least one active ingredient.

6. A method of claim 4, wherein at least a portion of the particles are coated with a coating capable of providing modified release of the active ingredient contained therein upon contacting of the dosage form with a liquid medium.

8. A method of claim 2, wherein the dosage form releases the active ingredient at a substantially constant rate.

9. A method of claim 2, wherein upon contacting of the dosage form with a liquid medium, a time delay occurs prior to release of at least a portion of the active ingredient.

10. A method of claim 9, wherein the portion of the active ingredient released after the time delay is released in a sustained manner.

11. A method of claim 2, wherein the dosage form additionally comprises a plurality of particles, the matrix comprises a first dose of active ingredient and at least a portion of the particles comprise a second dose of active ingredient which may be the same or different than the first active ingredient, and upon contacting of the dosage form with a liquid medium, immediate release of the first dose of active ingredient occurs followed by a lag time, followed by delayed release of the second dose of active ingredient.

13. A method of claim 2, wherein the thermal reversible carrier is from about 30 to about 70 weight percent of the matrix.

3. A method for manufacturing a dosage form comprising a molded matrix and at least one active ingredient dispersed in the molded matrix at a level of more than about 20 weight percent comprising:

injecting a matrix in flowable form into a molding chamber to form said dosage form,

wherein the matrix comprises 10-100% of a material having a melting point of less than about 100 degrees C. selected from (a) polyethylene glycols having molecular weight from about 100 to about 20,000 Daltons; and

(b) a release-modifying excipient comprising a combination of croscarmellose sodium and shellac, and

wherein the matrix is capable of providing modified release of the active ingredient upon contacting of the dosage form with a liquid medium.

5. A method of claim 3, wherein said matrix comprises a plurality of particles, and at least a portion of the particles comprise at least one active ingredient.

7. A method of claim 5, wherein at least a portion of the particles are coated with a coating capable of providing modified release of the active ingredient contained therein upon contacting of the dosage form with a liquid medium.

12. A method of claim 3, wherein the dosage form additionally comprises a plurality of particles, the matrix comprises a first dose of active ingredient and at least a portion of the particles comprise a second dose of active ingredient which may be the same or different than the first active ingredient, and upon contacting of the dosage form with a liquid medium, immediate release of the first dose of active ingredient occurs followed by a lag time, followed by delayed release of the second dose of active ingredient.

14. A method of claim 3, wherein the thermal reversible carrier is from about 30 to about 70 weight percent of the matrix.