Tamper-resistant pharmaceutical dosage forms and process for making same
A process for the preparation of an erodible tamper-resistant dosage form that comprises a therapeutic agent-substrate complex embedded in a thermo-formable matrix, such that the complex includes at least one therapeutic agent bound to at least one substrate to form the therapeutic agent-substrate complex. The at least one substrate is being selected from a polyelectrolyte, an organic counter-ion, a pharmacologically inert organic component of a prodrug, an inclusion compound and an inorganic adsorbent; and the thermo-formable matrix includes one or more thermoplastic polymers and optionally at least one pharmaceutical additive. The dosage form provides resistance to intentional or unintentional tampering such as chewing, crushing and grinding, and volatilization.
1. A process of preparing an erodible tamper-resistant dosage form, comprising the steps of:
(1) blending at least one therapeutic agent and at least one substrate in a therapeutic agent-to-substrate ratio from 1:20 to 20:1 by weight;
(2) reacting the at least one therapeutic agent and the at least one substrate to form a therapeutic agent-substrate complex using a twin-screw extruder;
(3) forming a thermo-formable matrix blend with at least one thermoplastic polymer and at least one pharmaceutical additive;
(4) mixing the therapeutic agent-substrate complex and the thermo-formable matrix blend in a ratio from 1:20 to 20:1 by weight;
(5) granulating the therapeutic agent-substrate complex and the thermo-formable matrix blend to form the erodible tamper-resistant dosage form in which the therapeutic agent-substrate complex is embedded in the thermo-formable matrix;
(6) shaping the tamper-resistant dosage form into one of an immediate release or modified release tablet form and an immediate release or modified release multiparticulate form; and
(7) optionally, film-coating one of the tablet form and the multiparticulate form.
2. The process of claim 1 , wherein the reacting step of (2) is carried out by a reactive extrusion process.
3. The process of claim 1 , wherein the granulating step of (5) is carried out by a hot melt extrusion process.
4. The process of claim 1 , wherein the granulating step of (5) is carried out by a wet granulation process.
5. The process of claim 1 , wherein the granulating step of (5) is carried out by a dry granulation process.