Euro-Celtique S.a.

Philip J Neale

Sandra Therese Malkowska

Stewart Thomas Leslie

Ronald Brown Miller

Gordon A Elger

Joanne Heafield

Derek Allan Prater

Trevor John Knott

Joanne Marchant

Stewart I Leslie

A pharmaceutical composition comprising spheroids comprising a water-soluble active ingredient or a pharmaceutically acceptable salt thereof, microcrystalline cellulose and a sugar. Preferably the active ingredient is hydromorphone hydrochloride and the sugar is lactose. Surprisingly the incorporation of a sugar improves the dissolution rate of the spheroid formulation instead of reducing the dissolution rate by competing with the active ingredient for solubilization.

Spheroid formulation

A controlled release, solid, oral dosage form containing a 3-alkylxanthine, preferably theophylline, at least one hydrophilic or hydrophobic polymer, at least one wax having a melting point between 25.degree. and 90.degree. C. and between 3% and 10% (by weight) water. Preferably the dosage form is a tablet and the water content is between 4% and 9% (by weight). The amount of water present in the dosage form determines the rate of release of the 3-alkylxanthine.

Controlled release dosage forms having a defined water content

A controlled release pharmaceutical composition contains a number of spheroids, the spheroids containing a water-insoluble drug dispersed in a controlled release matrix. The matrix contains between 70% and 99.5% (by weight) of microcrystalline cellulose, between 0.5% and 4% (by weight) of a cellulose derivative and, optionally, up to 26% of a sugar or a sugar alcohol. The water insoluble drug must dissolve in water (pH 5) at 20.degree. C. to a concentration of less than 1.0 mg ml-1, preferably less than 0.5 mg ml-1. Preferred drugs are non-steroidal anti-inflammatory agents, especially fenprofen calcium, ibuprofen, ketoprofen, naproxen, diclofenac sodium, fenbufen, flurbiprofen, indomethancin, oxyphenbutazone, phenylbutazone or piroxicam.

Spheroids

A pharmaceutical composition in the form of a multiphase (especially a bilayered, optionally coated) tablet. The tablet has a narcotic analgesic phase containing a therapeutically effective quantity of a narcotic analgesic or an analgesically effective salt thereof (e.g. codeine phosphate) and a non-steroidal anti-inflammatory phase containing a therapeutically effective quantity of a non-steroidal anti-inflammatory carboxylic acid or an anti-inflammatory salt or ester thereof (e.g. ibuprofen). The narcotic analgesic phase is free from a non-steroidal anti-inflammatory carboxylic acid or salt or ester thereof, stearic acid and stearate salt, and the non-steroidal anti-inflammatory phase is free from a narcotic analgesic or salt thereof, stearic acid and a stearate salt. Further, both the narcotic analgesic phase and the non-steroidal anti-inflammatory phase contain a self-lubricating, compression aid, especially a self-lubricating, direct compression aid, such as microcrystalline cellulose.

Pharmaceutical composition comprising analgesic and anti-inflammatory

A controlled release pharmaceutical composition comprising a plurality of film coated spheroids, the film coated spheroids comprising a 3-alkylxanthine, a non-water soluble spheronising agent and between 4% and 9% (by weight) water, wherein the in-vitro dissolution rate of the 3-alkylxanthine from the film coated spheroids, when measured by the USP Paddle Method at 100 rpm in 900 ml aqueous buffer (pH 6.5 at 37.degree. C.) is between 7.5% and 25.0% (by wt) release after 1 hour, between 22.5% and 45.0% (by wt) release after 2 hours, between 40.0% and 60.0% (by wt) release after 3 hours, between 50.0% and 75.0% (by wt) release after 4 hours, between 70.0% and 92.5% (by wt) release after 6 hours, and between 80.0% and 100.0% (by wt) release after 8 hours. Preferably the water content is between 4% and 8%, especially between 4% and 7% (by wt) of the film coated spheroid formulation. The preferred 3-alkylxanthine is theophylline (anhydrous or hydrate), whilst the preferred spheronising agent is microcrystalline cellulose.

A solid, controlled release, pharmaceutical composition comprising an active ingredient incorporated in a matrix comprising a first substance selected from a water soluble polydextrose and a water soluble cyclodextrin and a second substance selected from a C.sub.12 -C.sub.36 fatty alcohol and a polyalkylene glycol.

Controlled release pharmaceutical composition

A solid, controlled release, pharmaceutical composition comprising an active ingredient incorporated in a controlled release matrix comprising a water soluble polydextrose. The controlled release matrix may also contain at least one of a digestibele C.sub.8 --C.sub.50 substituted or unsubstituted hydrocarbon, especially a C.sub.12 --C.sub.36 fatty alcohol, and a polyalkylene glycol, especially polyethylene glycol. Optionally, the matrix may contain a cellulose ether, especially a hydroxyalkylcellulose or a carboxyalkylcellulose.

Growing community of inventors

Cambridge, United Kingdom

Philip J Neale