US5478573A — Delayed, sustained-release propranolol pharmaceut…

Claim 1

Independent Claim 146 words

A delayed, sustained-release pharmaceutical preparation comprising: a) a core containing propranolol hydrochloride drug, and b) a hydratable diffusion barrier surrounding said core and having a thickness of at least 20 microns, said barrier comprising a film-forming polymer which is insoluble under both stomach and intestinal conditions and a sufficient amount of additive to control the hydration rate and permeability of said hydratable diffusion barrier so that less than 5% of said drug dissolves within 2 hours in a U.S.P. basket dissolution at 100 rpm in 1 liter of 0.05M pH 6.8 phosphate buffer but so that said hydratable diffusion barrier is slowly hydrated to become permeable to dissolved drug within 2 to 10 hours after ingestion; whereby said hydratable diffusion barrier delays release of therapeutic levels of said drug for about 2-10 hours after ingestion, and thereafter provides for sustained-release of therapeutic levels of said drug.

Claim 2

Dependent Claim 146 words

A delayed, sustained-release pharmaceutical preparation comprising: a) a core containing propranolol hydrochloride drug, and b) a hydratable diffusion barrier surrounding said core and having a thickness of at least 20 microns, said barrier comprising a film-forming polymer which is insoluble under both stomach and intestinal conditions and a sufficient amount of additive to control the hydration rate and permeability of said hydratable diffusion barrier so that less than 5% of said drug dissolves within 2 hours in a U.S.P. basket dissolution at 100 rpm in 1 liter of 0.05M pH 6.8 phosphate buffer but so that said hydratable diffusion barrier is slowly hydrated to become permeable to dissolved drug within 2 to 10 hours after ingestion; whereby said hydratable diffusion barrier delays release of therapeutic levels of said drug for about 2-10 hours after ingestion, and thereafter provides for sustained-release of therapeutic levels of said drug.

Claim 3

Dependent Claim 22 words

The delayed, sustained-release pharmaceutical preparation of claim 1 wherein said film-forming polymer is a mixture of an acrylic resin and ethyl cellulose.

Claim 4

Dependent Claim 38 words

The delayed, sustained-release pharmaceutical preparation of claim 2 wherein said additive is selected from the group consisting of fully esterified acrylic resins containing quaternary amine side chains, sodium lauryl sulfate, magnesium stearate, citric acid, simethicone, and mixtures thereof.

Claim 5

Dependent Claim 60 words

The delayed, sustained-release pharmaceutical preparation of claim 3 wherein said film forming polymer and said additive are applied to said core drug as aqueous dispersions and wherein said additive dispersion comprises from about 5 to 20% magnesium stearate, from about 0 to 5% citric acid, from about 0 to 1% sodium lauryl sulfate, and from about 80 to 95% water.

Claim 6

Dependent Claim 25 words

The delayed, sustained-release pharmaceutical preparation of claim 4 wherein said additive comprises from about 5 to 40% (solids basis) of the total aqueous dispersion applied.

Claim 7

Dependent Claim 26 words

The delayed, sustained-release pharmaceutical preparation of claim 5 wherein said preparation has been dried at 35°-60° C. for 8-120 hours to form said hydratable diffusion barrier.

Claim 8

Dependent Claim 22 words

The delayed, sustained-release pharmaceutical preparation of claim 1 wherein the thickness of said hydratable diffusion barrier is about 30 to 200 microns.

Claim 9

Dependent Claim 24 words

The delayed, sustained-release pharmaceutical preparation of claim 7 wherein said core drug is in the form of particles from about 500-1500 microns in diameter.

Claim 10

Dependent Claim 182 words

A pharmaceutical preparation comprising a mixture of a delayed, sustained-release component and an immediate release component, i) said delayed, sustained-release component comprising a) a core containing propranolol hydrochloride drug, and b) a hydratable diffusion barrier surrounding said core and having a thickness of at least 20 microns, said barrier comprising a film-forming polymer which is insoluble under both stomach and intestinal conditions and a sufficient amount of additive to control the hydration rate and permeability of said hydratable diffusion barrier so that less than 5% of said drug dissolves within 2 hours in a U.S.P. basket dissolution at 100 rpm in 1 liter of 0.05M pH 6.8 phosphate buffer but so that said hydratable diffusion barrier is slowly hydrated to become permeable to dissolved drug within 2 to 10 hours after ingestion, whereby said hydratable diffusion barrier delays release of therapeutic levels of said drug for about 2-10 hours after ingestion, and thereafter provides for sustained release of therapeutic levels of said drug, ii) said immediate release component comprising free propranolol hydrochloride drug which is immediately released in the stomach after ingestion.

Claim 11

Dependent Claim 182 words

A pharmaceutical preparation comprising a mixture of a delayed, sustained-release component and an immediate release component, i) said delayed, sustained-release component comprising a) a core containing propranolol hydrochloride drug, and b) a hydratable diffusion barrier surrounding said core and having a thickness of at least 20 microns, said barrier comprising a film-forming polymer which is insoluble under both stomach and intestinal conditions and a sufficient amount of additive to control the hydration rate and permeability of said hydratable diffusion barrier so that less than 5% of said drug dissolves within 2 hours in a U.S.P. basket dissolution at 100 rpm in 1 liter of 0.05M pH 6.8 phosphate buffer but so that said hydratable diffusion barrier is slowly hydrated to become permeable to dissolved drug within 2 to 10 hours after ingestion, whereby said hydratable diffusion barrier delays release of therapeutic levels of said drug for about 2-10 hours after ingestion, and thereafter provides for sustained release of therapeutic levels of said drug, ii) said immediate release component comprising free propranolol hydrochloride drug which is immediately released in the stomach after ingestion.

Claim 12

Dependent Claim 19 words

The pharmaceutical preparation of claim 9 wherein said delayed, sustained-release component is in the form of multi-units of microparticles.

Claim 13

Dependent Claim 16 words

The pharmaceutical preparation of claim 10 wherein said free drug is concentrically coated on said microparticles.

Claim 14

Dependent Claim 181 words

A pharmaceutical preparation comprising a mixture of a delayed, sustained-release component and a sustained release component, i) said delayed, sustained-release component comprising a) a core containing propranolol hydrochloride drug, and b) a hydratable diffusion barrier surrounding said core and having a thickness of at least 20 microns, said barrier comprising a film-forming polymer which is insoluble under both stomach and intestinal conditions and a sufficient amount of additive to control the hydration rate and permeability of said hydratable diffusion barrier so that less than 5% of said drug dissolves within 2 hours in a U.S.P. basket dissolution at 100 rpm in 1 liter of 0.05M pH 6.8 phosphate buffer but so that said hydratable diffusion barrier is slowly hydrated to become permeable to dissolved drug within 2 to 10 hours after ingestion, whereby said hydratable diffusion barrier delays release of therapeutic levels of said drug for about 2-10 hours after ingestion, and thereafter provides for sustained release of therapeutic levels of said drug, ii) said sustained-release component comprising a core of said propranolol hydrochloride drug with a diffusion barrier material thereover.

Claim 15

Dependent Claim 181 words

A pharmaceutical preparation comprising a mixture of a delayed, sustained-release component and a sustained release component, i) said delayed, sustained-release component comprising a) a core containing propranolol hydrochloride drug, and b) a hydratable diffusion barrier surrounding said core and having a thickness of at least 20 microns, said barrier comprising a film-forming polymer which is insoluble under both stomach and intestinal conditions and a sufficient amount of additive to control the hydration rate and permeability of said hydratable diffusion barrier so that less than 5% of said drug dissolves within 2 hours in a U.S.P. basket dissolution at 100 rpm in 1 liter of 0.05M pH 6.8 phosphate buffer but so that said hydratable diffusion barrier is slowly hydrated to become permeable to dissolved drug within 2 to 10 hours after ingestion, whereby said hydratable diffusion barrier delays release of therapeutic levels of said drug for about 2-10 hours after ingestion, and thereafter provides for sustained release of therapeutic levels of said drug, ii) said sustained-release component comprising a core of said propranolol hydrochloride drug with a diffusion barrier material thereover.

Claim 16

Dependent Claim 43 words

The pharmaceutical preparation of claim 12 wherein said delayed, sustained-release component is in the form of multi-units of microparticles and said sustained-release component is in the form of said water-soluble drug concentrically coated on said microparticles and then a diffusion barrier coated thereover.

Claim 17

Dependent Claim 24 words

The pharmaceutical preparation of claim 12, said diffusion barrier material is selected from the group consisting of methacrylic acid ester copolymer and ethyl cellulose.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	1998-12-25	1999-06-26	1999-12-26	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	2002-12-25	2003-06-26	2003-12-26	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2006-12-25	2007-06-26	2007-12-26	$7700.00	Window Closed / Lapsed

Delayed, sustained-release propranolol pharmaceutical preparation

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