Uniform films for rapid-dissolve dosage form incorporating anti-tacking compositions

• US 9,855,221 B2
• Filed: 02/21/2017
• Issued: 01/02/2018
• Est. Priority Date: 10/12/2001
• Status: Expired due to Term

• Current Assignee: Aquestive Therapeutics, Inc.
• Original Assignee: Monosol Rx LLC (Kuraray Company Limited)
• Inventors: Myers, Garry L., Sanghvi, Pradeep, Verrall, Andrew Philip, Francis, Vimala, Brooks, Laura
• Primary Examiner(s): PACKARD, BENJAMIN J
• Application Number:
  US15/438,406
• Publication Number:
  US 20170189346A1
• Time in Patent Office: 315 Days
• CPC Class Codes: A23L 33/10 using additives addition of substantially indigestible substances A23L33/21
• CPC Class Codes: A23L 33/105 Plant extracts, their artificial duplicates or their derivatives
• CPC Class Codes: A23L 33/15 Vitamins
• CPC Class Codes: A23L 33/16 Inorganic salts, minerals or trace elements
• CPC Class Codes: A23P 20/20 Making of laminated, multi-layered, stuffed or hollow foodstuffs, e.g. by wrapping in preformed edible dough sheets or in edible food containers
• CPC Class Codes: A23P 30/10 Moulding
• CPC Class Codes: A23V 2002/00 Food compositions, function of food ingredients or processes for food or foodstuffs
• CPC Class Codes: A23V 2200/30 Foods, ingredients or supplements having a functional effect on health
• CPC Class Codes: A23V 2200/324 having an effect on the immune system
• CPC Class Codes: A23V 2250/156 Mineral combination undefined extract A23V2250/1638
• CPC Class Codes: A23V 2250/21 Plant extracts
• CPC Class Codes: A23V 2250/70 Vitamins
• CPC Class Codes: A61K 31/355 Tocopherols, e.g. vitamin E
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• 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 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 9/006 : Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/7007 : Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence

Abstract

The present invention relates to water-soluble films incorporating anti-tacking agents and methods of their preparation. Anti-tacking agents may improve the flow characteristics of the compositions and thereby reduce the problem of film adhering to a user'"'"'s mouth or to other units of film. In particular, the present invention relates to edible water-soluble delivery systems in the form of a film composition including a water-soluble polymer, an active component selected from cosmetic agents, pharmaceutical agents, vitamins, bioactive agents and combinations thereof and at least one anti-tacking agent.

Claims

1. A continuously cast film for delivery of an active in individual self-supporting oral unit doses, said individual self-supporting oral unit doses cut from said continuously cast film containing a desired amount of said active, said continuously cast film comprising:

an ingestible, water-soluble, polymer matrix;

at least one anti-tacking agent selected from the group consisting of stearate;

stearic acid;

vegetable oil;

wax;

a blend of magnesium stearate and sodium lauryl sulfate;

boric acid;

surfactant;

sodium benzoate;

sodium acetate;

sodium chloride;

DL-Leucine;

polyethylene glycol;

sodium oleate;

sodium lauryl sulfate;

magnesium lauryl sulfate;

talc;

corn starch;

amorphous silicon dioxide;

silicon dioxide;

metallic stearate;

Vitamin E;

Vitamin E TPGS;

silica and combinations thereof; and

a substantially uniform distribution of said active substantially locked-in within said polymer matrix, wherein said active is selected from the group consisting of cosmetic agents,

pharmaceutical agents, vitamins, bioactive agents and combinations thereof wherein said active is substantially uniformly distributed in said continuously cast film, whereby said substantially uniform distribution is measured by substantially equally sized individual self supporting oral unit doses cut from said continuously cast film which do not vary by more than 10% of said desired amount of said active.

2. The continuously cast film of claim 1, wherein said anti-tacking agent is present in an amount of about 0.01% to about 20% by weight of said film.

3. The continuously cast film of claim 1, wherein said water-soluble polymer matrix comprises a polymer selected from the group consisting of cellulose, cellulose derivatives, polyethylene oxide (PEO), pullulan, hydroxypropylmethyl cellulose (HPMC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose, polyvinyl pyrrolidone (PVP), carboxymethyl cellulose, polyvinyl alcohol, polysaccharides, sodium alginate, xanthan gum, tragancanth gum, guar gum, acacia gum, arabic gum, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl copolymers, starch, and combinations thereof.

4. The continuously cast film of claim 1, wherein said active is selected from the group consisting of anxiolytics, central nervous system stimulants, ace-inhibitors, antianginal drugs, anti-arrhythmias, anti-asthmatics, anti-cholesterolemics, anesthetics, anti-convulsants, anti-depressants, anti-diabetic agents, anti-diarrhea preparations, antidotes, anti-histamines, anti- hypertensive drugs, anti-inflammatory agents, anti-lipid agents, anti-manics, anti-nauseants, anti-stroke agents, anti-thyroid preparations, anti-tumor drugs, anti-viral agents, acne drugs, alkaloids, amino acid preparations, anti-tussives, anti-uricemic drugs, anti-viral drugs, anabolic preparations, systemic and non-systemic anti-infective agents, anti-neoplastics, anti-parkinsonian agents, anti-rheumatic agents, appetite stimulants, biological response modifiers, blood modifiers, bone metabolism regulators, cardiovascular agents, cholinesterase inhibitors, contraceptives, decongestants, dietary supplements, dopamine receptor agonists, endometriosis management agents, enzymes, erectile dysfunction therapies, fertility agents, gastrointestinal agents, homeopathic remedies, hormones, hypercalcemia and hypocalcemia management agents, immunomodulators, immunosuppressives, migraine preparations, motion sickness treatments, muscle relaxants, obesity management agents, osteoporosis preparations, oxytocics, parasympatholytics, parasympathomimetics, prostaglandins, psychotherapeutic agents, respiratory agents, sedatives, smoking cessation aids, sympatholytics, tremor preparations, urinary tract agents, vasodilators, laxatives, antacids, ion exchange resins, anti-pyretics, appetite suppressants, expectorants, anti-anxiety agents, anti-ulcer agents, anti-inflammatory substances, coronary dilators, cerebral dilators, peripheral vasodilators, psycho-tropics, stimulants, anti-hypertensive drugs, vasoconstrictors, migraine treatments, antibiotics, tranquilizers, anti-psychotics, anti-tumor drugs, anti-coagulants, anti-thrombotic drugs, hypnotics, anti-emetics, anti-nauseants, anti-convulsants, neuromuscular drugs, hyper- and hypo-glycemic agents, thyroid and anti-thyroid preparations, diuretics, anti-spasmodics, uterine relaxants, anti-obesity drugs, erythropoietic drugs, anti-asthmatics, cough suppressants, mucolytics, DNA and genetic modifying drugs, and combinations thereof.

5. The continuously cast film of claim 1, wherein said active is selected from the group consisting of an opiate, an opiate derivative, an analgesic, a biological response modifier, a urinary tract agent, tadalafil, apomorphine, a migraine treatment, a hormone, an anti-convulsant, alprazolam and combinations thereof.

16. The continuously cast film of claim 1, wherein the individual unit doses contain a solvent selected from the group consisting of water, ethanol, isopropanol, acetone, methylene chloride and combinations thereof, present in an amount not greater than 10% by weight.

17. The continuously cast film of claim 1, further comprising polyethylene oxide and an anti-tacking agent.

18. The continuously cast film of claim 1, wherein the individual self-supporting oral unit doses further comprise a layer which is selected from the group consisting of a cast layer, a laminated layer, a coated layer and combinations thereof.

19. The continuously cast film of claim 18, wherein the layer contains an active.

20. The continuously cast film of claim 18, wherein the layer does not contain an active.

6. A continuously cast film for mucosal delivery of an active in individual self-supporting oral unit doses, said individual self-supporting oral unit doses cut from said continuously cast film containing a desired amount of said active, said continuously cast film comprising;

(a) at least one first film layer comprising;

an ingestible, water-soluble polymer matrix; and

(b) at least one additional film layer comprising;

an ingestible, water-soluble polymer matrix; and

wherein the water-soluble polymer matrix of one or more of the first and additional film layers includes a substantially uniform distribution of said active substantially locked-in within said polymer matrix, wherein said active is selected from the group consisting of cosmetic agents, pharmaceutical agents, vitamins, bioactive agents and combinations thereof; and

wherein one or more of the first and additional film layers include at least one anti-tacking agent selected from the group consisting of stearate;

stearic acid;

vegetable oil;

wax;

a blend of magnesium stearate and sodium lauryl sulfate;

boric acid;

surfactant;

sodium benzoate;

sodium acetate;

sodium chloride;

DL-Leucine;

polyethylene glycol;

sodium oleate;

sodium lauryl sulfate;

magnesium lauryl sulfate;

talc;

corn starch;

amorphous silicon dioxide;

silicon dioxide;

metallic stearate;

Vitamin E;

Vitamin E TPGS;

silica and combinations thereof; and

wherein said active is substantially uniformly distributed in said continuously cast film, whereby said substantially uniform distribution is measured by substantially equal sized individual self-supporting oral unit doses cut from said continuously cast film which do not vary by more than 10% of said desired amount of said active.

7. The continuously cast film of claim 6, wherein said active is selected from the group consisting of an opiate, an opiate derivative, an analgesic, a biological response modifier, a urinary tract agent, tadalafil, an anti-convulsant, apomorphine, a migraine treatment, a hormone, alprazolam and combinations thereof.

21. The continuously cast film of claim 6, wherein the individual unit doses contain a solvent selected from the group consisting of water, ethanol, isopropanol, acetone, methylene chloride and combinations thereof, present in an amount not greater than 10% by weight.

22. The continuously cast film of claim 6, wherein the sodium benzoate content is from about 0.01 to about 20% by weight of the cast film.

8. A continuously cast film for delivery of an active in individual self-supporting oral unit doses, said individual self-supporting oral unit doses cut from said continuously cast film containing a desired amount of said active, said continuously cast film comprising:

an ingestible, water-soluble polymer matrix comprising a polymer selected from the group consisting of cellulose, a cellulose derivative, polyethylene oxide (PEO), pullulan, hydroxpopylmethyl cellulose (HPMC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose, polyvinyl pyrrolidone (PVP), carboxymethyl cellulose, polyvinyl alcohol, polys accharide, sodium alginate, xanthan gum, tragancanth gum, guar gum, acacia gum, arabic gum, polyacrylc acid, methylmethacrylate copolymer, carboxyvinyl copolymers, starch, gelatin, and combinations thereof;

at least one anti-tacking agent selected from the group consisting of stearate;

stearic acid;

vegetable oil;

wax;

a blend of magnesium stearate and sodium lauryl sulfate;

boric acid;

surfactant;

sodium benzoate;

sodium acetate;

sodium chloride;

DL-Leucine;

polyethylene glycol;

sodium oleate;

sodium lauryl sulfate;

magnesium lauryl sulfate;

talc;

corn starch;

amorphous silicon dioxide;

silicon dioxide;

metallic stearate;

Vitamin E;

Vitamin E TPGS;

silica and combinations thereof;

a substantially uniform distribution of said active substantially locked-in within said polymer matrix, wherein said active is selected from the group consisting of pharmaceutical agents, bioactive agents and combinations thereof;

wherein said active is substantially uniformly distributed in said continuously cast film, whereby said substantially uniform distribution is measured by substantially equally sized individual self-supporting oral unit doses cut from said continuously cast film which do not vary by more than 10% of said desired amount of said active.

9. The continuously cast film of claim 8, further comprising a component selected from the group consisting of citric acid, propylene glycol, a sweetener, a preservative, a coloring agent, a flavor, a flavor enhancer and combinations thereof.

10. The continuously cast film of claim 8, wherein the film is a multi-layered film.

11. The continuously cast film of claim 8, wherein said active is selected from the group consisting of an opiate, an opiate derivative, an analgesic, a biological response modifier, a urinary tract agent, tadalafil, an anti-convulsant, apomorphine, a migraine treatment, a hormone, alprazolam and combinations thereof.

12. The continuously cast film of claim 9, wherein the flavor is selected from the group of mint oil, citrus flavor and combinations thereof.

13. The continuously cast film of claim 8, further comprising a buffer.

14. The continuously cast film of claim 9, wherein the sweetener is selected form the group consisting of acesulfame K, sodium saccharin, aspartame and combinations thereof.

15. The continuously cast film of claim 8, further comprising an inorganic pigment or filler.

23. The continuously cast film of claim 8, wherein the individual unit doses contain a solvent selected from the group consisting of water, ethanol, isopropanol, acetone, methylene chloride and combinations thereof, present in an amount not greater than 10% by weight.

24. The continuously cast film of claim 8, further comprising polyethylene oxide and an anti-tacking agent.

25. The continuously cast film of claim 24, wherein the anti-tacking agent is selected from the group consisting of silicon dioxide, amorphous silicon dioxide, and combinations thereof.

26. A continuously cast film for delivery of an active in individual self-supporting oral unit doses, said individual self-supporting oral unit doses cut from said continuously cast film containing a desired amount of said active, said continuously cast film comprising:

an ingestible, water-soluble, polymer matrix comprising a polymer selected from the group consisting of hydroxyethylcellulose, hydroxypropylcellulose, carboxymethyl cellulose, polyacrylic acid and combinations thereof;

said active being selected from the group consisting of an opiate, an opiate derivative and combinations thereof;

sodium benzoate;

citric acid;

propylene glycol;

vitamin E acetate;

an inorganic pigment or filler;

a flavor selected from the group consisting of citrus flavor, peppermint oil and combinations thereof;

a sweetener selected from the group consisting of acesulfame K, aspartame, sodium saccharin and combinations thereof;

wherein said active is substantially uniformly distributed in said continuously cast film, whereby said substantially uniform distribution is measured by substantially equally sized individual self-supporting oral unit doses cut from said continuously cast film which do not vary by more than 10% of said desired amount of said active.

27. The continuously cast film of claim 26, wherein the individual unit doses contain a solvent selected from the group consisting of water, ethanol, isopropanol, acetone, methylene chloride and combinations thereof, present in an amount not greater than 10% by weight.

28. The continuously cast film of claim 26, wherein the individual self-supporting oral unit doses further comprise a layer which is selected from the group consisting of a cast layer, a laminated layer, a coated layer and combinations thereof.

29. The continuously cast film of claim 28, wherein the layer contains an active.

30. The continuously cast film of claim 28, wherein the layer does not contain an active.