Solid oral film dosage forms and methods for making same
First Claim
1. An oral film dosage form that maintains a plurality of active ingredient particles in an effective particle size range to maintain reduced structural order, and/or improve solubility and bioavailability of the active, comprising:
- at least one pharmaceutically active ingredient in the form of amorphous particles that are capable of existing in crystalline form;
at least one primary crystallization inhibitor present in an amount that inhibits crystallization, growth and agglomeration of the amorphous particles of the pharmaceutically active ingredient;
propylene glycol caprylate in an amount that further enhances inhibition of crystallization, growth and agglomeration of the amorphous particles of the pharmaceutically active ingredient; and
at least one plasticizer present in an amount that is effective to increase flexibility and elasticity of the film dosage form.
1 Assignment
0 Petitions
Accused Products
Abstract
Improved pharmaceutical solid oral film dosage forms for the buccal and/or sublingual delivery of pharmaceutical, nutraceutical or cosmetic ingredients are endowed with instant hydration potential and complete dissolution potentially enabling the active ingredient to become immediately available for enhanced buccal and/or sublingual absorption and/or reduced absorption through the gastrointestinal route. The improved delivery systems for solubilizing and stabilizing pharmaceutically active ingredients exhibit enhanced stability by the use of a combination of crystallization inhibitors, which together can maintain the active ingredient in a desired plurality of particles in an effective size range within a polymeric film matrix.
-
Citations
30 Claims
-
1. An oral film dosage form that maintains a plurality of active ingredient particles in an effective particle size range to maintain reduced structural order, and/or improve solubility and bioavailability of the active, comprising:
-
at least one pharmaceutically active ingredient in the form of amorphous particles that are capable of existing in crystalline form; at least one primary crystallization inhibitor present in an amount that inhibits crystallization, growth and agglomeration of the amorphous particles of the pharmaceutically active ingredient; propylene glycol caprylate in an amount that further enhances inhibition of crystallization, growth and agglomeration of the amorphous particles of the pharmaceutically active ingredient; and at least one plasticizer present in an amount that is effective to increase flexibility and elasticity of the film dosage form. - View Dependent Claims (25, 26, 27)
-
-
2. An oral film dosage form that maintains a plurality of active ingredient particles in an effective particle size range to maintain reduced structural order, and/or improve solubility and bioavailability of the active, comprising:
-
at least one pharmaceutically active ingredient in the form of amorphous particles having at least two distinct particle size ranges including a first size range of 50-500 nm and a second size range of 100-900 μ
m, the amorphous particles capable of existing in crystalline form;at least one primary crystallization inhibitor present in an amount that inhibits crystallization, growth and agglomeration of the amorphous particles of the pharmaceutically active ingredient; at least one liquid crystallization inhibitor in an amount that further enhances inhibition of crystallization, growth and agglomeration of the amorphous particles of the pharmaceutically active ingredient, the at least one liquid crystallization inhibitor selected from propylene glycol caprylate, glyceryl monooleate, and polyethylene glycol; and at least one plasticizer present in an amount that is effective to increase flexibility and elasticity of the film dosage form, the at least one plasticizer selected from triethyl citrate, tributyl citrate, acetyl tributyl citrate, acetyl triethyl citrate, trioctyl citrate, acetyl trioctyl citrate, trihexyl citrate, dibutyl sebacate, or triacetine, wherein said composition further comprises at least one mucoadhesive polymer. - View Dependent Claims (3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
-
-
13. An oral film dosage form demonstrating a solubilization profile of at least one active ingredient resulting from the combination of two or more distinct, effectively stabilized, particle size ranges, comprising:
-
an active ingredient in the form of amorphous particles having at least two distinct particle size ranges including a first size range of 50-500 nm and a second size range of 100-900 μ
m, the amorphous particles capable of existing in crystalline form;at least one primary crystallization inhibitor present in an amount that inhibits crystallization, growth and agglomeration of the amorphous particles of the pharmaceutically active ingredient; at least one liquid crystallization inhibitor in an amount that further enhances inhibition of crystallization, growth and agglomeration of the amorphous particles of the pharmaceutically active ingredient the at least one liquid crystallization inhibitor selected from propylene glycol caprylate, glyceryl monooleate, and polyethylene glycol; and at least one plasticizer present in an amount that is effective to increase flexibility and elasticity of the film dosage form, the at least one plasticizer selected from triethyl citrate, tributyl citrate, acetyl tributyl citrate, acetyl triethyl citrate, trioctyl citrate, acetyl trioctyl citrate, trihexyl citrate, dibutyl sebacate, or triacetine. - View Dependent Claims (14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24)
-
-
28. An oral film dosage form that maintains a plurality of active ingredient particles in an effective particle size range to maintain reduced structural order, and/or improve solubility and bioavailability of the active, comprising:
-
at least one pharmaceutically active ingredient in the form of amorphous particles having at least two distinct particle size ranges including a first size range of 50-500 nm and a second size range of 100-900 μ
m, the amorphous particles capable of existing in crystalline form;at least one primary crystallization inhibitor present in an amount that inhibits crystallization, growth and agglomeration of the amorphous particles of the pharmaceutically active ingredient; at least one liquid crystallization inhibitor present in an amount effective to further enhance inhibition of crystallization, growth and agglomeration of the amorphous particles of the pharmaceutically active ingredient, the at least one liquid crystallization inhibitor selected from propylene glycol caprylate, glyceryl monooleate and polyethylene glycol; and at least one plasticizer present in an amount that is effective to increase flexibility and elasticity of the film dosage form, the at least one plasticizer selected from triethyl citrate, tributyl citrate, acetyl tributyl citrate, acetyl triethyl citrate, trioctyl citrate, acetyl trioctyl citrate, trihexyl citrate, dibutyl sebacate, or triacetine and in which the liquid crystallization inhibitor comprises from 1% to 19% of the mass of the film dosage form. - View Dependent Claims (29, 30)
-
Specification