Process for manufacturing chewable dosage forms for drug delivery and products thereof

• US 8,114,455 B2
• Filed: 05/25/2011
• Issued: 02/14/2012
• Est. Priority Date: 12/07/2005
• Status: Active Grant

• Current Assignee: Elanco US Inc. (Elanco Animal Health, Inc.)
• Original Assignee: Bayer BV (Bayer AG)
• Inventors: Paulsen, Neil E., Johnson, Roland, Coffee, Michael
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): Palenik, Jeffrey T
• Application Number:
  US13/115,919
• Publication Number:
  US 20110223234A1
• Time in Patent Office: 265 Days
• Field of Search: None
• US Class Current: 426/514
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• 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 9/0087 Galenical forms not covered by A61K9/02 - A61K9/7023
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 33/10 Anthelmintics
• CPC Class Codes: A61P 33/14 Ectoparasiticides, e.g. scabicides
• CPC Class Codes: A61P 5/14 of the thyroid hormones, e.g. T3, T4

Abstract

A palatable, edible soft chewable medication vehicle for delivery of a pharmaceutically acceptable active ingredient, such as a drug, to an animal or human subject. The edible soft chews contain only food grade or better inactive ingredients, and preferably do not contain ingredients of animal origin. Processes for manufacturing the edible soft chews do not require the use of heat or the addition of water during mixing of active and inactive ingredients, provide stable concentrations of the active ingredient, and produce chews of consistent weight and texture.

Claims

1. A process for manufacturing a palatable soft chewable pharmaceutical product (a “

soft chew”

) having consistent unit-to-unit weight and active content without use of extrusion, comprising;

(a) providing at least one active agent whose stability or potency can be adversely affected by temperatures typically generated during extrusion, an active agent that is not palatable, or both;

(b) blending the active agent with dry inactive ingredients under low shear conditions to produce a edible soft chew mixture having the active agent uniformly blended therein;

(c) adding anon-aqueous fluid to the dry mixture and blending it under low shear conditions to form an edible soft chewable mixture; and

,

(d) forming the edible soft chewable mixture into soft chews without application of compression heat thereto,

wherein the edible soft chew mixture and the ingredients thereof are maintained at room temperature or no more than +1/−

10°

C. thereof during performance of each step of the process; and

,

wherein further the soft chews are more palatable than tablet dosage forms of the active agent.

2. The process according to claim 1, wherein the active is selected from the group of actives consisting of is selected from the group of ingredients consisting of anthelmetics, analgesics, antibiotics, antithyroids, antivirals, anti-inflammatories, endoparasiticides, ectoparasiticides and antifungals.

3. The process according to claim 1, wherein the active is one whose potency or stability is adversely affected at temperatures 10°

C. over or under room temperature.

4. The process according to claim 1, wherein the dry inactive ingredients comprise at least one flavoring and at least one excipient.

5. The process according to claim 3, wherein the excipient comprises starch.

6. The process according to claim 1, wherein the dry active ingredients comprise at least one bulking agent.

7. The process according to claim 6, wherein the bulking agent comprises bran, meal, flour, cereal, fiber, whole grains, vegetables, seeds, gum arabic, pectins, modified starches, alginates, carrageenans, xanthan gums, carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, propylene glycol alginate, polyvinylpyrrolidone, carboxyvinyl polymers, polyethylene oxide polymers, talc, dicalcium phosphate or antacids.

8. The process according to claim 1, wherein the non-aqueous fluid is an oil.

9. The process according to claim 1, further comprising the step of preparing a trituration of the active ingredient with an excipient before the active ingredient is added to the dry inactive ingredients.

10. The process according to claim 1, wherein the active provided is coated.

11. The process according to claim 2, wherein the at least one active is an antibiotic.

12. The process according to claim 11, wherein the active is milbemycin, clindamycin, enrofloxacin, cefpodoxime, ivermectin or amoxicillin.

13. The process according to claim 2, wherein the active is lufenuron.

14. The process according to claim 2, wherein the active is praziquantal.

15. The process according to claim 2, wherein the active is methiamazole.

16. The process according to claim 2, wherein the active is imidacloprid.

17. A finished soft chew produced by the process of claim 1.