Acetaminophen compositions containing low doses of chlorpheniramine maleate, method for preparing same and tablets formed therefrom

Claim 1

A spray-dried, direct tabletting, free-flowing, particulate pharmaceutical composition having a substantially high amount of acetaminophen and a substantially low amount of a water-soluble pheniramine maleate, and, when prepared in large quantity, being capable of being directly formed into a multiplicity of dosage-form tablets in high-speed tablet-forming operation of pharmaceutical tabletting presses, the pheniramine maleate being present in the composition in such highly uniform distribution throughout that the tablets have such tablet-to-tablet uniformity of the amount of the pheniramine maleate therein that the percent relative standard deviation of said amount is not more than about 3% as determined for a random sample of 10 tablets, the tablets being substantially free of adherence to the press and having high hardness, short disintegration time, and low friability, the composition comprising as components thereof: (A) acetaminophen in a pharmaceutically effective major amount, (B) a water-soluble pheniramine maleate component in a pharmaceutically effective low amount not exceeding about 5.0% based on the total weight of the acetaminophen, (C) a pharmaceutically acceptable binder-disintegrant agent in an amount effective for imparting said hardness, disintegration time and friability, (D) a pharmaceutically acceptable lubricant in an amount at least sufficient to impart effective mold release properties to said tablets, and (E) water in an amount from about 0.5 to about 1.5% based on the total weight of the composition, the composition being the product of spray drying an aqueous liquid slurry comprising an aqueous liquid medium and said components (A), (B), (C) and (D) dispersed substantially uniformly throughout said medium, the pheniramine maleate being dissolved in said medium.

Claim 16

A method for preparing a direct tabletting, free-flowing, particulate pharmaceutical composition having a substantially high amount of acetaminophen and a substantially low amount of a water-soluble pheniramine maleate, and, when prepared in large quantity, being capable of being directly formed into a multiplicity of dosage-form tablets in high-speed tablet-forming operation of pharmaceutical tabletting presses, the pheniramine maleate being present in the composition in such highly uniform distribution throughout that the tablets have such tablet-to-tablet uniformity of the amount of the pheniramine maleate therein that the percent relative standard deviation of said amount is not more than about 3% as determined for a random sample of 10 tablets, the tablets being substantially free of adherence to the press and hivin high hardness, short disintegration time, and low friability, said method comprises: (1) preparing an aqueous liquid slurry comprising an aqueous liquid medium and components dispersed substantially uniformly throughout said medium, said components comprising: (A) finely divided acetaminophen in a pharmaceutically effective major amount, (B) a water-soluble pheniramine maleate component in a pharmaceutically effective low amount not exceeding about 6 parts per 100 parts of the acetaminophen, (C) a pharmaceutically acceptable binder-disintegrant agent in an amount effective for imparting said hardness, disintegration time and friability, and (D) a pharmaceutically acceptable lubricant in an amount at least sufficient to impart effective mold release properties to said tablets, such properties including the tablets being substantially free of adherence to the press, said medium being a solvent for said pheniramine maleate component and said last-mentioned component being dissolved in said medium, the total amount of the dispersed components being such that the slurry is spray-dryable; and (2) while maintaining said components in substantially uniform dispersion spray drying said slurry under spray drying conditions such that the resulting spray dried particulate composition includes water in an amount from about 0.5 to about 1.5% based on the total weight of the composition, said components being distributed throughout the particles of said composition such that at least a portion of said lubricant is dispersed within said particles and at least a portion of the lubricant is disposed on the outer surfaces of said particles.

Claim 17

A method for preparing a direct tabletting, free-flowing, particulate pharmaceutical composition having a substantially high amount of acetaminophen and a substantially low amount of a water-soluble pheniramine maleate, and, when prepared in large quantity, being capable of being directly formed into a multiplicity of dosage-form tablets in high-speed tablet-forming operation of pharmaceutical tabletting presses, the pheniramine maleate being present in the composition in such highly uniform distribution throughout that the tablets have such tablet-to-tablet uniformity of the amount of the pheniramine maleate therein that the percent relative standard deviation of said amount is not more than about 3% as determined for a random sample of 10 tablets, the tablets being substantially free of adherence to the press and hivin high hardness, short disintegration time, and low friability, said method comprises: (1) preparing an aqueous liquid slurry comprising an aqueous liquid medium and components dispersed substantially uniformly throughout said medium, said components comprising: (A) finely divided acetaminophen in a pharmaceutically effective major amount, (B) a water-soluble pheniramine maleate component in a pharmaceutically effective low amount not exceeding about 6 parts per 100 parts of the acetaminophen, (C) a pharmaceutically acceptable binder-disintegrant agent in an amount effective for imparting said hardness, disintegration time and friability, and (D) a pharmaceutically acceptable lubricant in an amount at least sufficient to impart effective mold release properties to said tablets, such properties including the tablets being substantially free of adherence to the press, said medium being a solvent for said pheniramine maleate component and said last-mentioned component being dissolved in said medium, the total amount of the dispersed components being such that the slurry is spray-dryable; and (2) while maintaining said components in substantially uniform dispersion spray drying said slurry under spray drying conditions such that the resulting spray dried particulate composition includes water in an amount from about 0.5 to about 1.5% based on the total weight of the composition, said components being distributed throughout the particles of said composition such that at least a portion of said lubricant is dispersed within said particles and at least a portion of the lubricant is disposed on the outer surfaces of said particles.