Pharmaceutical composition in sustained release unit dose form and process for its preparation

Claim 2

A pharmaceutical composition of a medicament in sustained release unit dosage form for oral administration, comprising a plurality of beads within a closed container of a gastric juice-soluble material, characterized in that each said bead has an inert particulate core having adhered thereto a coating of particles of said medicament, said coating of medicament being surrounded by a sustaining coating comprising at least three admixed polymers, a first said polymer being soluble in gastric juices at all pH values encountered in the gastrointestinal tract, a-second said polymer being substantially insoluble in gastric juices at pH values below 3but soluble therein at pH values of 5 and above and the third said polymer being insoluble in the contents of the gastrointestinal tract at all pH values normally encountered therein, and the three polymers being present in such proportions as to permit a substantially uniform release of the medicament during passage of the beads through the stomach and gastrointestinal tract.

Claim 3

A pharmaceutical composition according to claim 1, characterized in that the weight of the insoluble third polymer in the sustaining coating is greater than the sum of the weights of the other two said polymers.

Claim 4

A pharmaceutical composition according to claim 2, characterized in that the ratio of the weight of the third polymer to the sum of the weights of the other two polymers is from 3:2 to 2:1.

Claim 5

A pharmaceutical composition according to any preceding claim, characterized in that said first polymer constitutes 20 wt.% or less of the polymer mixture forming the sustaining coating.

Claim 6

A pharmaceutical composition according to any preceding claim, characterized in that the medicament is a pyridyl-(lH)-pyridone having the general formula: wherein R is an alkyl group having 1 to 4 carbon atoms, or a solid derivative thereof.

Claim 7

A pharmaceutical composition according to any preceding claim, characterized in that the inert cores of the beads are in the form of nonpareils.

Claim 8

A pharmaceutical composition according to any preceding claim, characterized in that said first polymer is selected from hydroxypropylmethylcellulose and polyvinylpyrrolidone.

Claim 9

A pharmaceutical composition according to any preceding claim, characterized in that said second polymer is hydroxypropylmethylcellulose phthalate.

Claim 10

A pharmaceutical composition according to any preceding claim, characterized in that said third polymer is ethyl cellulose.

Claim 11

A process for producing a pharmaceutical composition of a medicament in sustained release unit dosage form for oral administration, comprising a plurality of beads within a closed container of a gastric juice-soluble material, characterized in that said beads are prepared by: coating inert core particles with particles of said medicament and a binder for adhering said medicament particles to said core particles and applying to said coated core particles a sustaining coating solution comprising at least three admixed polymers, a first said polymer being soluble in gastric juices at all pH values encountered in the gastrointestinal tract, a second said polymer being substantially insoluble in gastric juices at pH values below 3 but soluble therein at pH values of 5 and above and the third said polymer being insoluble in the contents of the gastrointestinal tract at all pH values normally encountered therein, and the three polymers being present in such proportions as to permit a substantially uniform release of the medicament duringpassage of the beads through the stomach and gastrointestinal tract.

Claim 12

A process for producing a pharmaceutical composition of a medicament in sustained release unit dosage form for oral administration, comprising a plurality of beads within a closed container of a gastric juice-soluble material, characterized in that said beads are prepared by: coating inert core particles with particles of said medicament and a binder for adhering said medicament particles to said core particles and applying to said coated core particles a sustaining coating solution comprising at least three admixed polymers, a first said polymer being soluble in gastric juices at all pH values encountered in the gastrointestinal tract, a second said polymer being substantially insoluble in gastric juices at pH values below 3 but soluble therein at pH values of 5 and above and the third said polymer being insoluble in the contents of the gastrointestinal tract at all pH values normally encountered therein, and the three polymers being present in such proportions as to permit a substantially uniform release of the medicament duringpassage of the beads through the stomach and gastrointestinal tract.

Claim 13

A process according to claim 10, characterized in that said sustaining coating is formed by applying to the-medicament-coated core particles a solution of said three polymers in a volatile solvent therefor and evaporating the solvent from the particles thus coated.

Claim 14

A process according to claim 11, characterized in that said solution is produced by forming a dispersion of the three polymers in a suitable medium, adding a low boiling solvent to the dispersion and sitrring to give a clear solution.

Claim 15

A process according to claim 11 or claim 12, characterized in that the sustaining coating is applied by placing the medicament-coated core particles in a coating column or pan and feeding the polymer solution into the column or pan while passing a current of air through the particles to produce dry coated beads.

Claim 16

A process according to any one of claims 10 to 13, characterized in that the medicament is a pyridyl-(lH)-pyridone having the general formula: wherein R is an alkyl group having 1 to 4 carbon atoms, or a solid derivative thereof.

Claim 17

A process for producing a pharmaceutical composition of a medicament in sustained release unit dosage form for oral administration, comprising a plurality of beads within a closed container of a gastric juice-soluble material, characterised in that said beads are prepared by: coating inert core particles with particles of said medicament and a binder for adhering said medicament particles to said core particles and applying to said coated core particles a sustaining coating solution comprising at least three admixed polymers, a first said polymer being soluble in gastric juices at all pH values encountered in the gastrointestinal tract, a second said polymer being substantially insoluble in gastric juices at pH values below 3 but soluble therein at pH values of 5 and above and the third said polymer being insoluble in the contents of the gastrointestinal tract at all pH values normally encountered therein, and the three polymers being present in such proportions as to permit a substantially uniform release of the medicament during passage of the beads through the stomach and gastrointestinal tract.

Claim 18

A process for producing a pharmaceutical composition of a medicament in sustained release unit dosage form for oral administration, comprising a plurality of beads within a closed container of a gastric juice-soluble material, characterised in that said beads are prepared by: coating inert core particles with particles of said medicament and a binder for adhering said medicament particles to said core particles and applying to said coated core particles a sustaining coating solution comprising at least three admixed polymers, a first said polymer being soluble in gastric juices at all pH values encountered in the gastrointestinal tract, a second said polymer being substantially insoluble in gastric juices at pH values below 3 but soluble therein at pH values of 5 and above and the third said polymer being insoluble in the contents of the gastrointestinal tract at all pH values normally encountered therein, and the three polymers being present in such proportions as to permit a substantially uniform release of the medicament during passage of the beads through the stomach and gastrointestinal tract.

Claim 19

A'process according to claim 1, characterised in that said sustaining coating is formed by applying to the medicament-coated core particles a solution of said three polymers in a volatile solvent therefor and evaporating the solvent from the particles thus coated.

Claim 20

A process according to claim 2, characterised in that said solution is produced by forming a dispersion of the three polymers in a suitable medium, adding a low boiling solvent to the dispersion and stirring to give a clear solution.

Claim 21

A process according to claim 2 or claim 3, characterised in that the sustaining coating is applied by placing the medicament-coated core particles in a coating column or pan and feeding the polymer solution into the column or pan while passing a current of air through the particles to produce dry coated beads.

Claim 22

A process according to any preceding claim characterised in that the medicament is a pyridyl-(lH)-pyridone having the general formula: wherein R is an alkyl group having 1 to 4 carbon atoms, or a solid derivative thereof.

Claim 23

A process according to any preceding claim characterised in that the weight of the insoluble third polymer in the sustaining coating is greater than the sum of the weights of the other two said polymers.

Claim 24

A process according to claim 6, characterised in that the ratio of the weight of the third polymer to the sum of the weights of the other two polymers is from 3:2 to 2:1.

Claim 25

A process according to any preceding claim, characterised in that said first polymer constitutes 20 wt.% or less of the polymer mixture forming the sustaining coating.

Claim 26

A process according to any preceding claim, characterised in that the inert core particles are in the form of nonpareils.

Claim 27

A process according to any preceding claim, characterised in that said first polymer is selected from hydroxypropylmethylcellulose, sodium carboxymethyl cellulose and polyvinylpyrrolidone.

Claim 28

A process according to any preceding claim, characterised in that said second polymer is hydroxypropylmethylcellulose phthalate.

Claim 29

A process according to any preceding claim, characterised in that said third polymer is ethyl cellulose.