Thermo-kinetic mixing for pharmaceutical applications
Inventors
Brough, Chris • McGinity, James W. • Miller, Dave A. • DiNunzio, James C. • Williams, III, Robert O.
Assignees
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Publication Number
US-9339440-B2
Publication Date
2016-05-17
Expiration Date
Abstract
Compositions and methods for making a pharmaceutical dosage form include making a pharmaceutical composition that includes one or more active pharmaceutical ingredients (API) with one or more pharmaceutically acceptable excipients by thermokinetic compounding into a composite. Compositions and methods of preprocessing a composite comprising one or more APIs with one or more excipients include thermokinetic compounding, comprising thermokinetic processing the APIs with the excipients into a composite, wherein the composite can be further processed by conventional methods known in the art, such as hot melt extrusion, melt granulation, compression molding, tablet compression, capsule filling, film-coating, or injection molding.
Core Innovation
The invention relates to thermo-kinetic compounding in pharmaceutical manufacturing. Thermokinetically processing one or more active pharmaceutical ingredients with one or more pharmaceutically acceptable excipients into a composite solid dispersion or composite composition forms a homogenous, heterogeneous, or heterogeneously homogenous composite. At least one of the active pharmaceutical ingredients is thermally labile, and the resulting composite is described as having reduced degradation of the thermally labile active pharmaceutical ingredient.
The thermokinetically processed composite is suitable for subsequent conventional dosage-form processing. The thermokinetic approach is positioned relative to hot-melt extrusion, including shorter processing times and lower thermal exposure during processing. The disclosed composites are solid dispersions or compositions that can be amorphous or single-glass-transition composites, and the release profiles can be immediate, delayed, controlled, extended, or mixed.
The composite can include pharmaceutically acceptable excipients such as polymers, including thermolabile carriers and polymers having high melt viscosity. The document describes composite properties using glass transition temperature behavior and degradation product or potency considerations, including less than about 1.0% degradation products for each thermally labile active pharmaceutical ingredient. The approach is presented as enabling processing of thermally incompatible materials while reducing degradation and enabling tunable release behavior.
Claims Coverage
The partial set includes five independent claims. Across these claims, the inventive focus is thermokinetically processing thermally labile APIs with pharmaceutically acceptable excipients into a composite while controlling degradation and/or defining composite glass transition temperature behavior, including specifying a high melt viscosity polymer excipient and excluding a processing agent in multiple independent claims.
Thermokinetically processed composite with limited API degradation
A pharmaceutical composition comprising one or more active pharmaceutical ingredients with one or more pharmaceutically acceptable excipients thermokinetically processed into a composite, wherein at least one of the APIs is thermally labile, and wherein the composite is a homogenous, heterogeneous, or heterogeneously homogenous composition that has less than about 1.0% degradation products of each thermally labile API.
Thermokinetically processed composite without substantial degradation of API and excipient
A pharmaceutical composition comprising one or more active pharmaceutical ingredients with one or more pharmaceutically acceptable excipients thermokinetically processed into a composite, wherein at least one of the APIs is thermally labile, and wherein the composite is a homogenous, heterogeneous, or heterogeneously homogenous composition that does not have substantial degradation of each thermally labile API and each excipient.
Thermokinetically processed composite limited to API degradation and excludes processing agent
A pharmaceutical composition comprising one or more active pharmaceutical ingredients with one or more pharmaceutically acceptable excipients thermokinetically processed into a composite, wherein at least one of the APIs is thermally labile, and wherein the composite is a homogenous, heterogeneous, or heterogeneously homogenous composition that has less than about 1.0% degradation products of each thermally labile API, does not have substantial degradation of each excipient, and does not comprise a processing agent.
Single glass transition composite with higher Tg than thermally processed comparator
A pharmaceutical composition comprising one or more active pharmaceutical ingredients with one or more pharmaceutically acceptable excipients thermokinetically processed into a composite, wherein the composite is a homogenous, heterogeneous, or heterogeneously homogenous composition that exhibits a single glass transition temperature, does not have substantial degradation of each API, and includes a polymer having a high melt viscosity, while a formulation of identical APIs and pharmaceutically acceptable excipients processed thermally by a process other than thermokinetic compounding exhibits two or more glass transition temperatures.
Glass transition temperature significantly higher than thermal comparator and excludes processing agent
A pharmaceutical composition comprising one or more active pharmaceutical ingredients with one or more pharmaceutically acceptable excipients thermokinetically processed into a composite, wherein the composite is a homogenous, heterogeneous, or heterogeneously homogenous composition in which the glass transition temperature is significantly higher than the glass transition temperature of a formulation of identical APIs and pharmaceutically acceptable excipients processed thermally by a process other than thermokinetic compounding, wherein the formulation comprises a processing agent and the composition does not comprise a processing agent.
Across the independent claims, thermokinetic compounding is claimed for forming composite pharmaceutical compositions from thermally labile APIs and pharmaceutically acceptable excipients, with explicit control of degradation, including less than about 1.0% degradation products and no substantial degradation, and with composite glass transition behavior, including a single glass transition temperature or a glass transition temperature significantly higher than thermally processed comparators. Several independent claims also require a polymer excipient having a high melt viscosity and exclude a processing agent.
Stated Advantages
Less than about 1.0% degradation products of each thermally labile API.
Does not have substantial degradation of each thermally labile API and each excipient.
Exhibits a single glass transition temperature.
Glass transition temperature is significantly higher than glass transition temperature of a thermally processed formulation of identical APIs and excipients.
Composite excludes a processing agent in specified claim formulations.
Documented Applications
Pharmaceutical manufacturing of composite solid dispersions or composite compositions for subsequent conventional dosage-form processing.
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