Abuse deterrent immediate release capsule dosage forms
Capsule dosage forms that provide immediate release of active ingredients and have abuse deterrent properties. In particular, the dosage forms comprise at least one pharmaceutically active ingredient, a combination of hydrophilic gelling polymers, at least one organic acid, and at least one disintegrant.
1. An abuse deterrent capsule dosage form comprising a granular fill encapsulated by a capsule shell, wherein the granular fill comprises at least one active pharmaceutical ingredient (API) susceptible to abuse or a pharmaceutically acceptable salt thereof, a combination of hydrophilic gelling polymers, at least one organic acid, and at least one disintegrant; wherein the combination of hydrophilic gelling polymers comprises at least one natural gum, at least one cellulose ether, and at least one polyalkylene oxide; the granular fill is devoid of a metal carbonate or a metal bicarbonate; the capsule shell has a wall thickness of less than 0.3 mm; the organic acid is present in an amount of about 20% to about 50% by weight of the granular fill; the at least one disintegrant is selected from crospovidone, talc, fumed silica, and combinations thereof, and the at least one disintegrant is present in an amount from about 2% to about 10% (w/w) of the granular fill when fumed silica is present, or the at least one disintegrant is present in an amount from about 40% to about 70% (w/w) of the granular fill when crospovidone and talc are present; and wherein the abuse deterrent capsule dosage form is an immediate-release dosage form.
2. The abuse deterrent capsule dosage form of claim 1 , wherein the at least one natural gum is glucomannan, xanthan gum, guar gum, gum arabic, karaya gum, gellan gum, dextran, welan gum, diutan gum, pullulan, or a combination thereof.
3. The abuse deterrent capsule dosage form of claim 1 , wherein the at least one cellulose ether is hydroxypropylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, hydroxyethylmethylcellulose, methylhydroxyethylcellulose, or a combination thereof.
4. The abuse deterrent capsule dosage form of claim 1 , wherein the at least one polyalkylene oxide is a polyethylene oxide having an average molecular weight of less than 500,000, a polyethylene oxide having an average molecular weight of greater than 1,000,000, or a combination thereof.
5. The abuse deterrent capsule dosage form of claim 1 , wherein the combination of hydrophilic gelling polymers is present in an amount from about 10% to about 70% by weight of the granular fill.
6. The abuse deterrent capsule dosage form of claim 1 , wherein the at least one organic acid is adipic acid, ascorbic acid, benzoic acid, citric acid, fumaric acid, glutaric acid, lactic acid, lauric acid, malic acid, maleic acid, malonic acid, oxalic acid, phthalic acid, sorbic acid, succinic acid, tartaric acid, or a combination thereof.
7. The abuse deterrent capsule dosage form of claim 1 , wherein the at least one API is an opioid or a combination of an opioid and a non-opioid analgesic, and the opioid is oxycodone, oxymorphone, hydrocodone, hydromorphone, codeine, or morphine.
8. The abuse deterrent capsule dosage form of claim 1 , wherein the wall thickness of the capsule shell is less than 0.15 mm.
9. The abuse deterrent capsule dosage form of claim 1 , wherein at least about 50% of the at least one API is released from the capsule dosage form within about 45 minutes when dissolution is measured using an USP-approved in vitro release procedure.
10. The abuse deterrent capsule dosage form of claim 1 , wherein the at least one organic acid deters abuse of the dosage form by causing nasal irritation when the granular fill is inhaled.
11. The abuse deterrent capsule dosage form of claim 1 , wherein the combination of hydrophilic gelling polymers deters abuse of the dosage from by forming a viscous mixture or gel when the granular fill is mixed with about 2 mL to about 10 mL of an aqueous solvent.
12. The abuse deterrent capsule dosage form of claim 1 , wherein the at least one API is oxycodone, oxymorphone, hydrocodone, hydromorphone, codeine, or morphine; the at least one natural gum is glucomannan, xanthan gum, or a combination thereof, the at least one cellulose ether is hydroxypropylmethylcellulose, sodium carboxymethylcellulose, or a combination thereof, the at least one polyalkylene oxide is a first polyethylene oxide having an average molecular weight of about 100,000, a second polyethylene oxide having an average molecular weight of about 4,000,000, or a combination thereof.
13. The abuse deterrent capsule dosage form of claim 12 , wherein the at least one natural gum is present in an amount from about 6% to about 35% (w/w) of the granular fill; the at least one cellulose ether is present in an amount from about 3% to about 25% (w/w) of the granular fill; and the at least one polyalkylene oxide is present in an amount from about 20% to about 40% (w/w) of the granular fill when both the first and the second polyethylene oxide are present, or the at least one polyalkylene oxide is present in an amount from about 0.5% to about 3% (w/w) of the granular fill when only the second polyethylene oxide is present.
14. The abuse deterrent capsule dosage form of claim 13 , further comprising at least one lubricant, at least one preservative, or a combination thereof.
15. The abuse deterrent capsule dosage form of claim 14 , wherein the at least one lubricant is magnesium stearate, polyethylene glycol, stearic acid, or a combination thereof, and the at least one preservative is butylated hydroxytoluene, alpha-tocopherol, ascorbyl palmitate, or a combination thereof.
16. An abuse deterrent capsule dosage form comprising a granular fill encapsulated by a capsule shell, wherein the granular fill comprises:
at least one active pharmaceutical ingredient (API) comprising oxycodone, oxymorphone, hydrocodone, hydromorphone, codeine, or morphine, or pharmaceutically acceptable salts thereof;
a combination of hydrophilic gelling polymers comprising at least one natural gum present in an amount from about 6% to about 35% (w/w) of the granular fill, at least one cellulose ether present in an amount from about 3% to about 25% (w/w) of the granular fill, and at least one polyalkylene oxide comprising first polyethylene oxide having an average molecular weight of about 100,000, a second polyethylene oxide having an average molecular weight of about 4,000,000, wherein the at least one polyalkylene oxide is present in an amount from about 20% to about 40% (w/w) of the granular fill when both the first and the second polyethylene oxide are present, or the at least one polyalkylene oxide is present in an amount from about 0.5% to about 3% (w/w) of the granular fill when only the second polyethylene oxide is present;
at least one organic acid present in an amount of about 20% to about 50% by weight of the granular fill;
at least one disintegrant selected from crospovidone, fumed silica, talc, or a combination thereof, wherein the at least one disintegrant is present in an amount from about 2% to about 10% (w/w) of the granular fill with fumed silica is present, or the at least one disintegrant is present in an amount from about 40% to about 70% (w/w) of the granular fill when crospovidone and talc are present; and
wherein the abuse deterrent capsule dosage form is an immediate-release dosage form, and wherein the capsule shell has a wall thickness that ranges from less than about 0.30 mm.