Preparation of powder agglomerates
OwnerTsong-Toh Yanginventor
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Abstract
The invention relates to a method of producing an agglomerate of drug and solid binder. The process involves producing individual agglomerate particles and then converting the convertible amorphous content of same, following agglomeration, by the application of, for example, moisture. Agglomerates capable of conversion as well as the finished agglomerates and oral and nasal dosing systems including same are also contemplated. The process produces agglomerates which are rugged but which will produce an acceptable fine particle fraction during dosing.
Claims63
A process of producing agglomerates comprising the steps of:
- (a) providing particles of at least one first material and particles of at least one solid binder, at least one of said first material and said solid binder having a preselected amount of convertible amorphous content which is capable of being converted to crystalline form upon exposure to a preselected stimulus, said convertible amorphous content being provided in an amount which is sufficient to allow for the formation of agglomerates;
- (b) agglomerating said particles of said first material and said solid binder while maintaining said preselected amount of convertible amorphous content;
- and thereafter (c) exposing said convertible amorphous content within said agglomerates to said preselected stimulus so as to convert said convertible amorphous content to a crystalline form.
A process for producing agglomerates containing a pharmacologically active agent, comprising the steps of:
- (a) providing at least one pharmacologically active agent having an average particle size of below about 10 μm;
- (b) providing at least one solid binder having an average particle size of about 10 μm or below;
- at least one of said pharmacologically active agent and said solid binder having a preselected amount of convertible amorphous content which is sufficient to allow for the formation of agglomerates upon conversion;
- (c) forming a homogeneous mixture of said particles of said pharmacologically active agent and said solid binder while maintaining said preselected amount of convertible amorphous content;
- (d) agglomerating said mixture of said particles of said pharmacologically active agent and said solid binder while maintaining said preselected amount of convertible amorphous content of said solid binder;
- and
- (e) thereafter allowing said convertible amorphous content of said agglomerates to convert to a crystalline form;
- to form
- (f) agglomerates which are free-flowing, have bridges and are characterized by having a strength of between 50 mg and 5000 mg.
A dosage form of a pharmacologically active agent useful for administration by oral inhalation therapy consisting essentially of:
- agglomerates of particles of a pharmacologically active agent and particles of crystalline solid binder, said particles having an average particle size of 10 μm or less and being provided in a weight ratio of between 100:1 to 1:500, said agglomerates having an average size of between 400 and 700 μm, a bulk density of between about 0.2 and about 0.4 g/cm3 and a crush strength of between 200 mg and about 1500 mg.
An intermediate agglomerate useful for producing a free-flowing crystalline agglomerate dosage form of a pharmacologically active agent useful for administration by oral or nasal inhalation therapy, said intermediate agglomerates comprising:
- particles of said pharmacologically active agent and particles of solid binder, said pharmacologically active agent or said solid binder having a preselected amount of convertible amorphous content which is sufficient to allow for the formation of crystalline agglomerates upon exposure to moisture, said particles of said pharmacologically active agent and said particles of said solid binder having an average particle size of 10μm or less, and said particles being provided in a weight ratio of between 1000:1 to 1:1000.
The intermediate agglomerate of claim 63, having a convertible amorphous content of between about 1 and about 50% by weight.
A dosing system comprising:
- (a) an inhaler, said inhaler including a storage reservoir for storing an amount of a pharmacologically active agent in the form of a crystalline agglomerate, sufficient to provide a plurality of individual doses thereof, a metering device for measuring and metering a preselected amount of said pharmacologically active agent from said storage reservoir, and a nozzle for conveying said pharmacologically active agent from said metering device to the mouth or nose of a patient;
- and (b) an amount of a pharmacologically active agent sufficient to provide a plurality of individual doses thereof, said pharmacologically active agent being stored within said storage reservoir, being provided as an agglomerate of particles of said pharmacologically active agent and particles of a crystalline binder, wherein said particles have an average particle size of 10 μm or less and the components thereof are provided in a weight ratio of between 1000:1 to 1:1000, said agglomerates having an average size of between 300 and 1000 μm and a bulk density of between about 0.2 and about 0.4 g/cm3;
- and said agglomerate and said inhaler, when used in combination, being capable of producing a fine particle fraction of at least 10%, at an inhaled air flow rate about 60 L/min.
Dependencies are inferred from the claim text.