Anti-overingestion dosage forms
Described herein are abuse deterrent oral pharmaceutical compositions, methods for making the same, and methods of treatment using such compositions. In particular, oral pharmaceutical compositions that mitigate the risk of overingestion of one or more active pharmaceutical ingredients are described.
1. An oral pharmaceutical composition comprising an immediately releasing dry admixture of an opioid agonist or a salt thereof and one or more strong cation exchange resins at a mass ratio of about 1:2 to about 1:8 and optionally, one or more pharmaceutically acceptable excipients,
wherein less than about 1% of the opioid agonist is bound to the strong cation exchange resin prior to solvation; and
after solvation of two more doses of the composition simultaneously or successively over about a 4-hour period, the strong cation exchange resin adsorbs about 15% to about 70% by mass of the opioid agonist and impedes its absorption into a subject's systemic circulation, lowering C max for the opioid agonist by about 30% to about 50% as compared to an equivalent dose of the opioid agonist lacking a strong cation exchange resin.
2. The composition of claim 1 , wherein subjects administered the composition exhibit one or more of the following pharmacokinetic parameters:
(a) a delayed T max for the opioid agonist as compared to an equivalent opioid agonist dose lacking a strong cation exchange resin;
(b) a lower plasma AUC for the opioid agonist as compared to an equivalent opioid agonist dose lacking a strong cation exchange resin;
(c) an extended absorption time for the opioid agonist as compared to an equivalent opioid agonist dose lacking a strong cation exchange resin; or
(d) an extended clearance time for the opioid agonist as compared to an equivalent opioid agonist dose lacking a strong cation exchange resin.
3. The composition of claim 1 , wherein the mass ratio of opioid agonist to strong cation exchange resin is about 1:4.
4. The composition of claim 1 , wherein the opioid agonist comprises hydrocodone.
5. The composition of claim 1 , wherein the strong cation exchange resin comprises polystyrene sulfonate or a salt thereof.
6. The composition of claim 1 , wherein the composition comprises:
about 10% to about 30% by mass of hydrocodone; and
about 70% to 90% by mass of a strong cation exchange resin.
7. The composition of claim 1 , wherein the composition comprises:
about 20% by mass of hydrocodone; and
about 80% by mass of a strong cation exchange resin.
8. The composition of claim 1 , wherein the composition comprises:
about 20% by mass of hydrocodone bitartrate; and
about 80% by mass of polystyrene sulfonate or a salt thereof.
9. The composition of claim 1 , wherein the composition comprises a dry powder.
10. The composition of claim 1 , wherein the composition exhibits an in vitro disintegration or dissolution rate comprising about 50% disintegration or dissolution after about 1 minute to about 15 minutes in simulated gastric fluid comprising 34.2 mM NaCl and 0.1 N HCl, pH 1.2 using the USP basket method.
11. The composition of claim 1 , wherein subjects administered the composition exhibit a plasma AUC for the opioid agonist of about 15% lower as compared to an equivalent opioid agonist dose lacking a strong cation exchange resin.
12. The composition of claim 1 , wherein the opioid agonist comprises hydrocodone bitartrate.
13. An oral pharmaceutical composition comprising an immediately releasing dry admixture of hydrocodone or a salt thereof and polystyrene sulfonate or a salt thereof in a mass ratio of about 1:2 to about 1:8, and optionally, one or more pharmaceutically acceptable excipients,
wherein less than about 1% of the hydrocodone is bound to the polystyrene sulfonate prior to solvation, and
after solvation of two more doses of the composition simultaneously or successively over about a 4-hour period, the polystyrene sulfonate adsorbs about 15% to about 70% by mass of the hydrocodone and impedes its absorption into a subject's systemic circulation, lowering C max for the opioid agonist by about 30% to about 50% as compared to an equivalent dose of the opioid agonist lacking polystyrene sulfonate.
14. The composition of claim 13 , wherein subjects administered the composition exhibit one or more of the following pharmacokinetic parameters:
(a) a delayed T max for hydrocodone as compared to an equivalent hydrocodone dose lacking polystyrene sulfonate;
(b) a lower plasma AUC for hydrocodone as compared to equivalent hydrocodone dose lacking polystyrene sulfonate;
(c) an extended absorption time for hydrocodone as compared to an equivalent hydrocodone dose lacking polystyrene sulfonate; or
(d) an extended clearance time for hydrocodone as compared to an equivalent hydrocodone dose lacking polystyrene sulfonate.
15. The composition of claim 13 , wherein the mass ratio of hydrocodone to polystyrene sulfonate is about 1:4.
16. The composition of claim 13 , wherein the composition exhibits an in vitro disintegration or dissolution rate comprising about 50% disintegration or dissolution after about 1 minute to about 15 minutes in simulated gastric fluid comprising 34.2 mM NaCl and 0.1 N HCl, pH 1.2, using the USP basket method.
17. The composition of claim 13 , wherein subjects administered the composition exhibit a plasma AUC for hydrocodone of about 15% lower as compared to an equivalent opioid agonist dose lacking polystyrene sulfonate.
18. The composition of claim 13 , wherein the hydrocodone comprises hydrocodone bitartrate.
19. A dosage form comprising the composition of claim 13 comprising a dry powder.
20. A method for treating pain while mitigating the risk of overingestion, the method comprising administering to a subject in need thereof the composition of claim 13 .