Process of manufacturing a lyophilized fast dissolving, multi-phasic dosage form

1. A process of manufacturing a multi-phasic, fast-dissolving dosage form for the delivery of a pharmaceutically active ingredient comprising, in the following order, the steps of:

(a) cooling a formulation comprising 4-10 wt. % non-gelling matrix forming agent, 3-6 wt. % mannitol, and water to a temperature ranging from 2° C. to 15° C. and while maintaining the temperature from 2° C. to 15° C., dosing the formulation comprising the non-gelling matrix forming agent into a preformed mold, wherein the non-gelling matrix forming agent is selected from the group consisting of non-gelling gelatins, modified starches, and combinations thereof;

(b) cooling a formulation comprising 1-4 wt. % gelling matrix forming agent, 3-6 wt. % mannitol, and water to a temperature from 20° C. to 30° C. and while maintaining the temperature from 20° C. to 30° C., dosing the formulation comprising the gelling matrix forming agent into the preformed mold of step (a); and

(c) freeze drying the formulations dosed in steps (a) and (b) to form the multi-phasic, fast-dissolving dosage form;

wherein step (c) comprises the sub-steps of (c1) freezing the formulations dosed in steps (a) and (b) within the preformed mold; and (c2) freeze drying the formulations dosed in steps (a) and (b),

wherein the formulation dosed in step (a) forms a first layer of the dosage form,

wherein the formulation dosed in step (b) forms a second layer of the dosage form distinct from the first layer, and

wherein the first layer and the second layer of the dosage form disintegrate within 1 to 30 seconds.

2. The process according to claim 1 , wherein the at least one non-gelling gelatin is pullulan.

3. The process according to claim 1 , wherein the water is present in an amount ranging from about 50% to about 98% based on weight of the formulation of step (a).

4. The process according to claim 1 , wherein the gelling matrix forming agent is selected from the group consisting of gelling gelatins, gelling polymers having a ratio of bulk viscosity at 5° C. over bulk viscosity at 25° C. of at least 5, and combinations thereof.

5. The process according to claim 1 , wherein the water is present in an amount ranging from about 50% to about 98% based on weight of the formulation of step (b).

6. The process according to claim 1 further comprising repeating step (a) at least once prior to step (b).

7. The process according to claim 1 further comprising repeating step (b) at least once prior to step (c).

8. A process of manufacturing a multi-phasic, fast-dissolving dosage form for the delivery of a pharmaceutically active ingredient comprising, in the following order, the steps of:

(a) dosing a formulation comprising 4-10 wt. % non-gelling matrix forming agent, 3-6 wt. % mannitol, and water into a preformed mold, wherein the non-gelling matrix forming agent is selected from the group consisting of non-gelling gelatins, modified starches, and combinations thereof, and wherein the formulation dosed in step (a) forms a first layer of the fast-dissolving dosage form upon completion of step (c) below;

(b) subsequent to step (a), dosing a formulation comprising 1-4 wt. % gelling matrix forming agent, 3-6 wt. % mannitol, and water into the preformed mold, wherein the formulation dosed in step (b) forms a second layer of the fast-dissolving dosage form upon completion of step (c) below;

(c) freeze-drying the formulations dosed in steps (a) and (b) to form the multi-phasic, fast-dissolving dosage form, wherein the first layer and the second layer of the dosage form disintegrate within 1 to 30 seconds.

9. The process according to claim 8 , wherein the formulation dosed in step (a) is a solution or a suspension.

10. The process according to claim 8 , wherein the formulation dosed in step (b) is a solution or a suspension.

11. The process according to claim 8 , wherein the gelling matrix forming agent is selected from the group consisting of gelling gelatins, gelling polymers having a ratio of bulk viscosity at 5° C. over bulk viscosity at 25° C. of at least 5, and combinations thereof.