Process for manufacturing a resulting pharmaceutical film
The invention relates to the film products and methods of their preparation that demonstrate a non-self-aggregating uniform heterogeneity. Desirably, the films disintegrate in water and may be formed by a controlled drying process, or other process that maintains the required uniformity of the film. The films contain a polymer component, which includes polyethylene oxide optionally blended with hydrophilic cellulosic polymers. Desirably, the films also contain a pharmaceutical and/or cosmetic active agent with no more than a 10% variance of the active agent pharmaceutical and/or cosmetic active agent per unit area of the film.
1. A process for manufacturing a resulting pharmaceutical film suitable for commercialization and regulatory approval said resulting pharmaceutical film having a substantially uniform distribution of a desired amount of a pharmaceutical active in individual doses of the resulting pharmaceutical film, comprising the steps of:
(a) forming a Non-Newtonian visco-elastic polymer matrix, comprising a hydrophilic cellulosic polymer in combination with a polyethylene oxide (PEO) composition comprising PEO or a blend of PEOs, wherein said PEO or said blend of PEOs has a molecular weight range of from about 100,000 to about 900,000, and wherein at least a portion of the PEO composition includes PEO having a molecular weight range of about 100,000 to about 300,000, a solvent selected from the group consisting of water, a polar organic solvent and combinations thereof, and a pharmaceutical active, which polymer matrix is a shear-thinning pseudoplastic fluid when exposed to shear rates of 10-10 5 sec −1 , said polymer matrix having a substantially uniform distribution of said pharmaceutical active;
(b) casting said polymer matrix;
(c) conveying said polymer matrix through a drying apparatus and evaporating at least a portion of said solvent to rapidly form a visco-elastic film having said pharmaceutical active uniformly distributed throughout by rapidly increasing the viscosity of said polymer matrix upon initiation of drying within about the first 4 minutes to maintain said substantially uniform distribution of said pharmaceutical active by locking-in or substantially preventing migration of said pharmaceutical active; wherein the temperature of the polymer matrix is 100° C. or less;
(d) forming the resulting pharmaceutical film from said visco-elastic film, wherein the resulting pharmaceutical film having said substantially uniform distribution of pharmaceutical active by said locking-in or substantially preventing migration of said pharmaceutical active is maintained;
(e) sampling the resulting pharmaceutical film at different locations of the resulting pharmaceutical film, wherein said sampled resulting pharmaceutical film has a water content of 10% or less; and
(f) performing analytical chemical tests for content uniformity of said pharmaceutical active in substantially equal sized individual dosage units of said sampled resulting pharmaceutical film, said tests indicating that uniformity of content in the amount of the pharmaceutical active varies by no more than 10% from the desired amount of the active.
2. The process according to claim 1 , wherein the pharmaceutical active is a pharmaceutical agent which is taste-masked or is a controlled-release agent.
3. The process according to claim 1 , wherein the hydrophilic cellulosic polymer is selected from the group consisting of hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydropropyl cellulose, carboxymethyl cellulose, and combinations thereof.
4. The process according to claim 1 , wherein said pharmaceutical film is cut to form said substantially equal sized individual dosage units.
5. The process according to claim 1 , wherein said casting comprises casting said matrix onto a surface having top and bottom sides.
6. The process according to claim 5 , wherein said drying comprises applying heat to said bottom side of said surface.