Pharmaceutical preparation and process for producing the same

Claim 2

A pharmaceutical composition suitable for the treatment of coronary heart disease, comprising nifedipine as the active ingredient, said nifedipine being present as a solution, wherein said solution in addition to the active ingredient comprises: (a) at least a first solvent which is ethanol, which is optionally at least partially replaced by a medium-chain fatty acid triglyceride in a weight ratio of 1:25 to 1:4 (nifedpine:first solvent); (b) at least a co-solvent selected from the group consisting of polyalcohols, alkylphenylethers of polyethylene glycol, polygylcerine fatty acid esters, glycerine-polyethylene glycoloxy fatty acid esters, partial fatty acid esters of sorbitol, partial fatty acid esters of polyhydroxy ethylene sorbitol, polyvinyl alcohols, polyhydroxy ethylene aliphatic acid esters and polyhydroxy ethylene-polyhydroxypropylene condensates; (c) a solubilizing agent selected from the group consisting of acrylic acid-methacrylic acid copolymers, methacrylic acid ester-acrylic acid ester copolymers, methacrylic acid-methacrylic acid methyl ester copolymers, methacrylic acid-acrylic acid ethyl ester copolymers, polyvinylpyrrolidones, alkylenecarbonates and copolyvidone in a weight ratio of 1:2 to 1:25 (nifedipine:co-solvent and solubilizing agent); and (d) a propellant.

Claim 3

A composition according to claim 1, wherein said polyalcohols are selected form the group consisting of polyethylenglycols and polyalkyleneglycols.

Claim 4

A composition according to claim 1, wherein said glycerine polyethyleneglycoloxy fatty acid esters are selected from the group consisting of glycerine-polyethylene glycoloxyoleate and glycerine-polyethyleneglycol stearate.

Claim 5

A liquid pharmaceutical composition suitable for aerosol administration in the treatment of coronary heart disease, comprising nifedipine, ethanol as a solvent therefor and a propellant held within an aerosol-dispensing container, said composition further comprising a co-solvent which is a polyalcohol, at least a part of the ethanol being optionally replaced by a medium-chain fatty acid triglyceride, and one or more solubilizing agents selected from the group consisting of polyalcohols, polyvinylpyrrolidone, alkylene carbonates, copolyvidone and acrylic acid ethyl ester-methacrylic acid copolymers, wherein the weight ratio of nifedipine:ethanol medium-chain fatty acid triglyceride is in the range 1:25 to 1:4 and the weight ratio of nifedipine:co-solvent is in the range 1:2 to 1:25, provided that: (i) when the polyalcohol is polythylene glycol, there is additionally present one or more other polyalcohols and/or a said solubilizing agent and/or at least part of the ethanol is replaced by a medium-chain fatty acid triglyceride; and (ii) when the polyalcohol is glycerine-polyethylene glycoloxystearate, the ratio of propellant:nifedipine is less than 220 and/or at least part of the ethanol is replaced by a medium-chain fatty acid triglyceride.

Claim 6

A liquid pharmaceutical composition suitable for aerosol administration in the treatment of coronary heart disease, comprising nifedipine, ethanol as a solvent therefor and a propellant held within an aerosol-dispensing container, said composition further comprising a co-solvent which is a polyalcohol, at least a part of the ethanol being optionally replaced by a medium-chain fatty acid triglyceride, and one or more solubilizing agents selected from the group consisting of polyalcohols, polyvinylpyrrolidone, alkylene carbonates, copolyvidone and acrylic acid ethyl ester-methacrylic acid copolymers, wherein the weight ratio of nifedipine:ethanol medium-chain fatty acid triglyceride is in the range 1:25 to 1:4 and the weight ratio of nifedipine:co-solvent is in the range 1:2 to 1:25, provided that: (i) when the polyalcohol is polythylene glycol, there is additionally present one or more other polyalcohols and/or a said solubilizing agent and/or at least part of the ethanol is replaced by a medium-chain fatty acid triglyceride; and (ii) when the polyalcohol is glycerine-polyethylene glycoloxystearate, the ratio of propellant:nifedipine is less than 220 and/or at least part of the ethanol is replaced by a medium-chain fatty acid triglyceride.

Claim 7

A composition according to claim 1, wherein the formulation contains a maximum of 7.5 weight % of water relative to the total weight of the solution.

Claim 8

A composition according to claim 1, wherein the solubilizing agent is selected from the group consisting of copolyvidone, PVP, and acrylic acid ethyl ester-methacrylic acid copolymers and is used in an amount of 25-300 weight %, relative to the nifedipine content.

Claim 9

A composition according to claim 6, wherein said solubilizing agent is used in an amount of 50-200 weight % relative to the nifedipine content.

Claim 10

A composition according to claim 1, wherein propylene carbonate is used as a solubilizing agent.

Claim 11

A composition according to claim 8, wherein, when propylene carbonate is employed, there is no addition of copolyvidone to the formulation.

Claim 12

A composition according to claim 8, wherein, when propylene carbonate is used as a solubilizing agent, 25-40% of propellant are present for the purpose of producing a stable, aerosolisable formulation.

Claim 13

A composition according to claim 10, wherein 30-35 weight % of propellant are present.

Claim 14

A composition according to claim 1, wherein, when propylene carbonate is used as a solubilizing agent, ethanol is at least partly replaced by medium-chain fatty chain triglycerides.

Claim 15

A composition according to claim 8, wherein the ratio of nifedipine:propylene carbonate is in the range 1:6 to 1:10 and the ratio of nifedipine:medium-chain fatty acid triglycerides is in the range 1:6 to 1:10.

Claim 16

A composition according to claim 1, wherein a copolymer of 60% polyvinylpyrrolidone and 40% polyvinyl acetate is used.

Claim 17

A composition according to claim 1, wherein 150 mg of the composition contains 5 mg nifedipine, 40-55 mg glycerine-polyethylene glycoloxystearate, 20-35 mg ethanol, 5-15 mg of a further co-solvent selected from the group consisting of copolyvidone, polyvinylpyrrolidone, polyacrylic acid and mixtures thereof, and 55-70 mg propellant.

Claim 18

A composition according to claim 1, wherein said solution, in addition to nifedipine, comprises ethanol, glycerine-polyethyleneglycoloxystearate, copolyvidone and a propellant.

Claim 19

Process for the manufacture of a dosable sublingually administerable pharmaceutical preparation with nifedipine as the active ingredient, comprising: dissolving the active ingredient in a solution comprising: (a) at least a first solvent which is ethanol, which is optionally at least partially replaced by a medium-chain fatty acid triglyceride in a weight ratio of1:25 to 1:4 (nifedipine:first solvent); (b) at least a co-solvent selected from the group consisting of polyalcohols, alkylphenylethers of poly ethyleneglycol, polyglycerine fatty acid esters, glycerine-polyethyleneglycoloxy fatty acid esters, partial fatty acid esters of sorbitol, partial fatty acid esters of polyhydroxyethylene sorbitol, polyvinylalcohols, polyhydroxy ethylene aliphatic acid esters and polyhydroxyethylene-polyhydroxypropylene condensates; (c) a solubilizing agent selected from the group consisting of acrylic acid-methacrylic acid copolymers, methacrylic acid ester-acrylic acid ester copolymers, methacrylic acid-methacrylic acid methyl ester copolymers, methacrylic acid-acrylic acid ethyl ester copolymers, polyvinylpyrrolidones, alkylenecarbonates and copolyvidone in a weight ratio of 1:2 to 1:25 (nifedipine:co-solvent and solubilizing agent); and (d) a propellant, and introducing the resulting nifedipine-containing solution, together with an inert and pharmaceutically acceptable propellant and an excipient, into a light-protected aerosol can.

Claim 20

Process for the manufacture of a dosable sublingually administerable pharmaceutical preparation with nifedipine as the active ingredient, comprising: dissolving the active ingredient in a solution comprising: (a) at least a first solvent which is ethanol, which is optionally at least partially replaced by a medium-chain fatty acid triglyceride in a weight ratio of1:25 to 1:4 (nifedipine:first solvent); (b) at least a co-solvent selected from the group consisting of polyalcohols, alkylphenylethers of poly ethyleneglycol, polyglycerine fatty acid esters, glycerine-polyethyleneglycoloxy fatty acid esters, partial fatty acid esters of sorbitol, partial fatty acid esters of polyhydroxyethylene sorbitol, polyvinylalcohols, polyhydroxy ethylene aliphatic acid esters and polyhydroxyethylene-polyhydroxypropylene condensates; (c) a solubilizing agent selected from the group consisting of acrylic acid-methacrylic acid copolymers, methacrylic acid ester-acrylic acid ester copolymers, methacrylic acid-methacrylic acid methyl ester copolymers, methacrylic acid-acrylic acid ethyl ester copolymers, polyvinylpyrrolidones, alkylenecarbonates and copolyvidone in a weight ratio of 1:2 to 1:25 (nifedipine:co-solvent and solubilizing agent); and (d) a propellant, and introducing the resulting nifedipine-containing solution, together with an inert and pharmaceutically acceptable propellant and an excipient, into a light-protected aerosol can.