ANTI-OVERINGESTION DOSAGE FORMS
Described herein are abuse deterrent oral pharmaceutical compositions, methods for making the same, and methods of treatement 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 immediate release composition comprising:
one or more active pharmaceutical ingredients (API) and one or more strong cation exchange resins capable of interacting with the API at a mass ratio of about 1:2 to about 1:8;
less than 1% of the API 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 API and impedes its absorption into a subject's systemic circulation, lowering C max for the API by about 30% to about 50% as compared to an equivalent dose of the API lacking a strong cation exchange resin.
2 . The composition of claim 1 , wherein the mass ratio of API to strong cation exchange resin is about 1:4.
3 . The composition of claim 1 , wherein the composition comprises a dry powder.
4 . The composition of claim 1 , wherein the composition is non-layered.
5 . The method of claim 1 , wherein the composition is encapsulated in a capsule or formed as a tablet.
6 . The composition of claim 1 , wherein the composition futher comprises one or more pharmaceutically acceptable excipients.
7 . 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 API as compared to an equivalent API dose lacking a strong cation exchange resin;
(b) a lower plasma AUC for the API as compared to an equivalent API dose lacking a strong cation exchange resin;
(c) an extended absorption time for the API as compared to an equivalent API dose lacking a strong cation exchange resin; or
(d) an extended clearance time for the API as compared to an equivalent API dose lacking a strong cation exchange resin.
8 . The composition of claim 1 , wherein the composition comprises:
about 10% to about 30% by mass of API; and
about 70% to 90% by mass of a strong cation exchange resin.
9 . The composition of claim 1 , wherein the composition comprises:
about 20% by mass of API; and
about 80% by mass of a strong cation exchange resin.
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 API of about 15% lower as compared to an equivalent API dose lacking a strong cation exchange resin.
12 . The composition of claim 1 , wherein the strong cation exchange resin comprises polystyrene sulfonate or a salt thereof.
13 . The composition of claim 1 , wherein the API comprises analgesics, anaesthetics, antimigraine drugs, antiepileptics, anticholinergics, antipsychotics, anxiolytics, hypnotics, sedatives, antidepressants, anti-dementia drugs, or combinations thereof.
14 . The composition of claim 1 , wherein the API comprises an opioid agonist.
15 . The composition of claim 1 , wherein the API comprises hydrocodone, oxycodone, oxymorphone, hydromorphone, morphine, codeine, salts thereof, or combinations thereof.
16 . The composition of claim 1 , wherein the API comprises hydrocodone or a salt thereof.
17 . A method for mitigating the risk of overingestion of an active pharmaceutical ingredient (API), the method comprising administering to a subject in need thereof one or more oral immediate release compositions of claim 1 .
18 . A method for regulating the concentration of an active pharmaceutical ingredient in a subject's systemic circulation, the method comprising:
administering to a subject one or more oral immediate release compositions of claim 1 .
19 . The method of claim 15 , further comprising:
(a) acquiring a bodily fluid from the subject;
(b) measuring the concentration of the API in the subject's circulation; and
(c) according to the measured API concentration and a desired optimal API therapeutic concentration, either:
(i) administering one or more doses of the composition comprising the API and the strong cation exchange resin;
(ii) administering an equivalent dose of the API comprising a composition lacking the strong cation exchange resin; or
(iii) administering either one or more doses of the composition comprising the API and the strong cation exchange resin or administering an equivalent dose of the API comprising a composition lacking the strong cation exchange resin after a period of about 30 min to about 12 hours.
20 . The method of claim 19 , where the bodily fluid is blood.