Taste masked pharmaceutical composition

• US 9,289,390 B2
• Filed: 04/16/2014
• Issued: 03/22/2016
• Est. Priority Date: 08/12/2011
• Status: Active Grant

• Current Assignee: Boehringer Ingelheim Vetmedica GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim Vetmedica GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Folger, Martin, Lehner, Stefan, Grave, Annette, Seidler, Randolph, Poellinger, Norbet
• Primary Examiner(s): AZPURU, CARLOS A
• Application Number:
  US14/254,136
• Publication Number:
  US 20140227351A1
• Time in Patent Office: 706 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/4168 having a nitrogen attached in position 2, e.g. clonidine
• CPC Class Codes: A61K 31/501 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/5415 ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 38/005 Enzyme inhibitors protease inhibitors A61K38/55
• CPC Class Codes: A61K 8/73 Polysaccharides
• 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 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/1676 having a drug-free core with discrete complete coating layer containing drug adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921
• 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 9/2893 Tablet coating processes mechanical aspects A61J3/06
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5047 Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61K 9/5089 Processes
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/10 : Antioedematous agents; Diuretics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure

Abstract

Taste masked multi-layered particles include an inert core, one or more coating layer(s) comprising a pharmaceutically active ingredient and a binder, an intermediate coating layer (seal coating) free from a low molecular weight water-soluble ionic compound and including a water-soluble pharmaceutical film-forming compound selected from (i) HPMC and PEG or (ii) PVP, and an outer coating layer (final or taste masking coating) free from a low molecular weight water-soluble ionic compound and comprising (i) a poly(meth)acrylate or (ii) a mixture including 60-90% (w/w) EC and 10-40% (w/w) HPMC, where the pharmaceutically active ingredient is water-soluble and includes either at least one basic group and/or a bitter taste. Further disclosed are methods for the production of such particles and pharmaceutical compositions including such particles.

Claims

1. A pharmaceutical composition comprising a taste masked multi-layered particle, the multi-layered particle comprising:

a) an inert core,

b) at least one coating layer that comprises a pharmaceutically active ingredient and a binder,

c) an intermediate coating layer (seal coating) free from a low molecular weight water-soluble ionic compound and comprising a water-soluble pharmaceutical film-forming compound, selected from the group consisting of hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG) poly(1-vinylpyrrolidin-2-one) (PVP), and any combination thereof, and

d) an outer coating layer (final or taste masking coating) free from a low molecular weight water-soluble ionic compound and comprising

(i) a poly(meth)acrylate or

(ii) a mixture comprising 60-90% (w/w) ethylcellulose (EC) and 10-40% (w/w) hydroxypropyl methylcellulose (HPMC),

wherein the pharmaceutically active ingredient is water-soluble and comprises either at least one basic group and/or a bitter taste;

wherein the pharmaceutical composition is in solid form with a mass of 20 to 4000 mg per unit.

2. The pharmaceutical composition of claim 1, further comprising the pharmaceutically active ingredient in a final concentration of 0.1 to 1000 mg per unit.

3. The pharmaceutical composition of claim 1 in the form of a tablet with one or more score lines to be split into pieces.

4. The pharmaceutical composition of claim 1 in a liquid form.

5. The pharmaceutical composition of claim 4, wherein the liquid form comprises an oily suspension comprising a viscosity enhancer selected from the group consisting of silicon dioxide, hydrophobic silicon dioxide, EC (cellulose ether), poly(1-vinylpyrrolidin-2-one) (PVP), aluminium stearate, xanthan gum, carrageen, starch derivatives, and one or more combinations thereof.

6. The pharmaceutical composition of claim 5, further comprising a mixture of hydrophilic and hydrophobic colloidal silicium dioxide.

7. The pharmaceutical composition of claim 6 which is an aqueous suspension comprising stabilizers selected from one or more of cellulose ethers, carbopol, xanthan gum, carrageen, microcrystalline cellulose.

8. The pharmaceutical composition of claim 4, further comprising the pharmaceutically active ingredient in a final concentration of 0.1 to 20 mg/ml.

9. A package of an overall liquid, oily pharmaceutical composition according to claim 5 comprising a glass vial and the pharmaceutical composition filled therein.