Solid oral film dosage forms and methods for making same

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.

Description

CROSS REFERENCE TO RELATED APPLICATION[0001]This application claims benefit under 35 U.S.C. Section 119(e) of provisional application Ser. No. 61 / 267,626, filed Dec. 8, 2009, entitled SOLID ORAL FILM DOSAGE FORMS AND METHODS FOR MAKING SAME, the entire contents of which are incorporated herein in their entirety.FIELD OF THE INVENTION[0002]This invention relates to solid oral pharmaceutical film dosage forms and more particularly to buccal and / or sublingual oral dosage forms comprised of at least one pharmaceutically active ingredient present as a stabilized plurality of particles.BACKGROUND OF THE INVENTION[0003]An oral film is a solid oral dosage form containing at least one water soluble polymer in combination with other acceptable ingredients and can provide therapeutic, nutritional and / or cosmetic effects. The polymeric matrix carrying the pharmaceutical, nutritional and / or cosmetic ingredient(s) is molded in a thin layer of variable area and shape. In contrast to conventional o...

AI Technical Summary

Benefits of technology

[0012]The solid dosage form described is an oral film for delivery of pharmaceutical, nutraceutical or cosmetic ingredients, with buccal delivery preferred. The film possesses an instant hydration potential, rapid dissolution and a stabilized increased water solubility of the active ingredient, thereby delivering the active ingredient available for immediate enhanced local absorption and consequently limiting loss or absorption later in the gastrointestinal route. The invention provides, among other things, improved delivery systems for solubilizing and stabilizing a plurality of pharmaceutically active ingredient particles in an effective particle size range that exhibit enhanced chemical stability, pharmaceutical formulations exhibiting improved bioavailability and / or absorption of pharmaceutically active ingredients when administered, and / or dosage forms for administration of pharmaceutically active ingredients achieved by the use of a combination of crystallization inhibitors, which together can maintain the active ingredient in a molecular dispersion within the polymeric film matrix. A description of the oral film manufacture is also disclosed.

Problems solved by technology

There are many major difficulties and challenges associated with the manufacture of oral film dosage forms ranging from brittleness, tackiness, the hygroscopic nature and potential lack of homogeneity within the dosage form.

Attaining ideal conditions for one characteristic usually comes at the expense of other, often equally important, properties, resulting in a necessary compromise in various properties to achieve a working film dosage form.

Therefore, the main challenges and obstacles encountered when using oral film technology as a pharmaceutical delivery vehicle are due to the very properties upon which oral film technology is based.

For example, challenges are encountered when attempting to provide an oral dosage as a film exhibiting a high content of liquid ingredients (0-35% wt / wt), and high drug loading in a matrix which is formulated as a very thin (under 80 micron) and continuous, yet flexible film layer.

However these approaches can often be inadequate or inappropriate due to potential stability concerns.

The increase in surface area results in a significant increase in surface energy leading to greater solubilization.

However the increase in surface energy is thermodynamically unfavorable and reagglomeration or crystallization / recrystallization of the particles is thermodynamically preferred resulting in a loss in the solubility of the material due to particle growth, and leading to decreased bioavailability.

This approach is often inadequate and leads to agglomeration and / or crystallization / recrystallization over time.

However, these techniques are not suitable for the production of oral films characterized by a physical continuity of the matrix and a high level of liquid ingredients necessary to impart flexibility and tensile strength to the film.

Reducing the amount of ingredients that impart flexibility to the oral film is undesirable, as it would result in a rigid matrix with reduced tensile strength and that is difficult to manufacture on a large scale.

It is well known that within the buccal cavity the amount of biological fluids (saliva) available for the solubilization of a drug is very limited as compared with the gastrointestinal fluids.

Another characteristic in determining the resistance of the drug to reagglomeration within films is the extremely thin physical continuity of the matrix which provides minimal physical resistance to particle migration, and makes it difficult to prevent reagglomeration of the pharmaceutically active ingredient.

Further concern arising from conventional techniques is the increase in the susceptibility of the active to degradation due to the increase in available surface area.

The prior art does not fully address the difficulty associated with preparing a pharmaceutical oral film capable of delivering a film dosage form with stabilized increased solubility and enhanced bioavailability while maintaining essential film characteristics.