Long acting calcium channel blocker composition
AssigneeSyntex (U.S.A.) Inc.
InventorsCalum B. MacFarlane, Alastair B. Selkirk, John R. Langridge, Michael J. Dey
Life of this patent
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Abstract
There is disclosed an improved long acting sustained release pharmaceutical composition for dihydropyridine calcium channel blockers wherein the calcium channel blocker and a pH-dependent binder, which are intimately admixed in essentially spherically shaped non-rugose particles of up to 1.2 mm in diameter, are provided with a coating to obtain slow, sustained release of a safe, therapeutically effective amount of the calcium channel blocker over a period of at least about 24 hours. Thus, the improved pharmaceutical composition for a dihydropyridine calcium channel blockers is suitable for once daily administration.
Claims8
In an improved long acting sustained release pharmaceutical composition for administration of a therapeutically effective amount of a dihydropyridine calcium channel blocking agent, useful in the treatment of disease conditions that may be alleviated by the administration of calcium channel blocking agents, which comprises essentially spherical, non-coated, non-rugose particles having diameters up to 1.2 millimeter, comprising a therapeutically effective amount of calcium channel blocking agent in intimate admixture with at least about 3 weight percent of a pH-dependent binder, which is less soluble below about pH 4.5 and more soluble above about pH 5.5;
- the improvement comprising providing said composition with a single pH-dependent coating applied to said particles containing said calcium channel blocking agent, which is less soluble below about pH 4.5 and more soluble above about pH 5.5, to obtain slow, sustained release of a safe, therapeutically effective amount of the calcium channel blocking agent from said particles over a period of at least about 24 hours.
An improved long acting sustained release pharmaceutical composition for administration of a therapeutically effective amount of dihydropyridine calcium channel blocking agent, useful in the treatment of disease conditions that may be alleviated by the administration of calcium channel blocking agents, comprising:
- essentially spherical, non-coated, non-rugose particles having diameters up to 1.2 millimeter, comprising a therapeutically effective amount of calcium channel blocking agent in intimate admixture with at least about 3 weight percent of a pH-dependent binder, which is less soluble below about pH 4.5 and more soluble above about pH 5.5;
- and
- a pH-dependent, outermost coating, that is less soluble below about pH 4.5 and more soluble above about pH 5.5, to obtain slow, sustained release of a safe, therapeutically effective amount of the calcium channel blocking agent over a period of at least about 24 hours,
- wherein said spherical particles comprise a composition of
- ______________________________________ Ingredient Weight % ______________________________________ Nicardipine HCL 44.4 Microcrystalline cellulose 18.5 Lactose 17.8 Methacrylic 18.5 acid ethylacrylate copolymer Sodium hydroxide 0.4 Polyoxythylene 20 sorbitan 0.4 mono-oleate ______________________________________
- and wherein the coating is applied to the particles as a suspension comprising
- ______________________________________ Ingredient Weight % ______________________________________ Methacrylic 12.5 acid ethylacrylate copolymer Triethylcitrate 1.25 Talc 6.25 Water 80.0 ______________________________________
- the coating suspension being present in an amount sufficient to coat the particles with about 2-20% solids based on the weight of the uncoated particles.
A long acting sustained release pharmaceutical composition for administration of a therapeutically effect amount of dihydropyridine calcium channel blocking agent consisting essentially of:
- (a) non-rugose, spherical particles, up to 1.2 mm in diameter, comprising the calcium channel blocking agent and a pH-dependent binder;
- and
- (b) a pH-dependent, aqueous coating applied to each of said particles, said coating comprising a compound selected from the group consisting of polyvinyl acetate phthalate, methacrylic acid methacrylate ester copolymer, methacrylic acid ethylacrylate copolymer, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate and cellulose acetate trimellitate;
- said pH-dependent binder and said pH-dependent coating being less soluble below about pH 4.5 and more soluble above about pH 5.5.
Dependencies are inferred from the claim text.