Abstract: This invention relates to acrystalline form of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-5-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h] [2,5,11]benzoxadiazacyclo-tetradecine-3-carbonitrile (lorlatinib) free base (Form 7). This invention also relates to pharmaceutical compositions comprising Form 7, and to methods of using Form 7 and such compositions in the treatment of abnormal cell growth, such as cancer, in a mammal.

Abstract: The present invention is directed to novel pharmaceutically acceptable polymeric compositions suitable for injection molding of single or multi-component pharmaceutical dosage forms comprising a plurality of drug substance containing sub-units, being capsule compartments and/or solid sub-units comprising a solid matrix of a polymer which contains a drug substance, the sub-units being connected together in the assembled dosage form by a weld between parts of the assembled dosage form.

Abstract: Capsule shells for use in multi-part dosage forms have generally cylindrical shell members with a snap fit component on an interior surface adjacent an open end, for connection to a linker part of the dosage form. The shell member also has a plurality of spaced apart integrally formed thin (relative to circumferentially adjacent shell member portions) panels located adjacent a closed shell member end, for preferential dissolution and release of pharmaceutical compositions from the shell member interior. The ratio of the thickness of the panels to the thickness of the shell member ranges from about 0.2 to about 0.6. The panels can be integrally formed together with the shell member as reliefs or depressions on the inner surface of the shell member by injection molding, and panel thicknesses as thin as about 0.1 mm can be achieved.

Abstract: The present invention is directed to pharmaceutically acceptable polymeric compositions suitable for injection molding of single or multi-component pharmaceutical dosage forms comprising a plurality of drug substance containing sub-units, being capsule compartments and/or solid sub-units comprising a solid matrix of a polymer which contains a drug substance, the sub-units being connected together in the assembled dosage form by a weld between parts of the assembled dosage form.

Abstract: The present invention is directed to pharmaceutically acceptable polymeric compositions suitable for injection molding of single or multi-component pharmaceutical dosage forms comprising a plurality of drug substance containing sub-units, being capsule compartments and/or solid sub-units comprising a solid matrix of a polymer which contains a drug substance, the sub-units being connected together in the assembled dosage form by a weld between parts of the assembled dosage form.

Abstract: A method of manufacturing a linker of the type having an injection molded jacket radially confining a preformed tablet. The method includes grasping the tablet about the outer surface with a plurality of pincers and positioning the grasped tablet and the pincers with respect to a molding apparatus. The method also includes supporting the tablet via the pincers and injecting jacket material to cover the outer tablet surface and the pincers. The method further includes extracting the jacketed tablet from the molding apparatus and removing the pincers from the jacketed tablet. The method may also include supporting and longitudinally positioning the tablet within the mold via a plurality of additional pincers.

Abstract: The present invention is directed to novel pharmaceutically acceptable polymeric compositions suitable for melt extrusion and injection molding of single or multi-component pharmaceutical dosage forms comprising a plurality of drug substance containing sub-units, being capsule compartments and/or solid sub-units comprising a solid matrix of a polymer which contains a drug substance, the sub-units being connected together in the assembled dosage form.

Abstract: The present invention is directed to novel pharmaceutically acceptable polymeric compositions suitable for melt extrusion and injection molding of single or multi-component pharmaceutical dosage forms comprising a plurality of drug substance containing sub-units, being capsule compartments and/or solid sub-units comprising a solid matrix of a polymer which contains a drug substance, the sub-units being connected together in the assembled dosage form.

Abstract: The present invention is directed to pharmaceutically acceptable polymeric compositions suitable for injection molding of single or multi-component pharmaceutical dosage forms comprising a plurality of drug substance containing sub-units, being capsule compartments and/or solid sub-units comprising a solid matrix of a polymer which contains a drug substance, the sub-units being connected together in the assembled dosage form by a weld between parts of the assembled dosage form.

Abstract: The present invention is directed to pharmaceutically acceptable polymeric compositions suitable for injection molding of single or multi-component pharmaceutical dosage forms comprising a plurality of drug substance containing sub-units, being capsule compartments and/or solid sub-units comprising a solid matrix of a polymer which contains a drug substance, the sub-units being connected together in the assembled dosage form by a weld between parts of the assembled dosage form.

Abstract: The present invention is directed to novel pharmaceutically acceptable polymeric compositions suitable for melt extrusion and injection moulding of single or multi-component pharmaceutical dosage forms comprising a plurality of drug substance containing sub-units, being capsule compartments and/or solid sub-units comprising a solid matrix of a polymer which contains a drug substance, the sub-units being connected together in the assembled dosage form.

Abstract: The present invention is directed to pharmaceutically acceptable polymeric compositions suitable for injection molding of single or multi-component pharmaceutical dosage forms comprising a plurality of drug substance containing sub-units, being capsule compartments and/or solid sub-units comprising a solid matrix of a polymer which contains a drug substance, the sub-units being connected together in the assembled dosage form by a weld between parts of the assembled dosage form.

Abstract: The present invention is directed to pharmaceutically acceptable polymeric compositions suitable for injection molding of single or multi-component pharmaceutical dosage forms comprising a plurality of drug substance containing sub-units, being capsule compartments and/or solid sub-units comprising a solid matrix of a polymer which contains a drug substance, the sub-units being connected together in the assembled dosage form by a weld between parts of the assembled dosage form.

Abstract: The present invention is directed to novel pharmaceutically acceptable polymeric compositions suitable for melt extrusion and injection moulding of single or multi-component pharmaceutical dosage forms comprising a plurality of drug substance containing sub-units, being capsule compartments and/or solid sub-units comprising a solid matrix of a polymer which contains a drug substance, the sub-units being connected together in the assembled dosage form.

Abstract: A multipart capsule, e.g., a dosage form, is provided which includes a plurality of capsule portions, at least one of which contains a substance to be released into a gastro-intestinal environment and at least one link component interconnecting two adjacent capsule portions. At least one capsule portion is formed from a polymer that is a transitional polymer, for example, a polymer that changes shape, form, or structure within a gastro-intestinal environment, e.g., dispersible, dissolvable, disintegrable, fracturable, breachable, swellable, partially or completely soluble, or otherwise changeable when exposed to stomach pH and/or in intestine pH to thereby release the substance. The capsule portions are connected together in an assembled dosage form. The link component includes at least one aperture in flow communication with interiors of two adjacent capsule portions to control the release of the substance.

Abstract: The present invention is directed to novel pharmaceutically acceptable polymeric compositions suitable for melt extrusion and injection moulding of single or multi-component pharmaceutical dosage forms comprising a plurality of drug substance containing sub-units, being capsule compartments and/or solid sub-units comprising a solid matrix of a polymer which contains a drug substance, the sub-units being connected together in the assembled dosage form.

Abstract: A linker for multicomponent dosage form has a preformed drug substance tablet and an injection molded jacket including one or both axial jacket ends open for dispensing the preformed drug substances. The jacket has snap-fit connection elements on the outer surface adjacent each end for engagement with complementary snap-fit element on capsule-type and cap-type dosage form units. Another multicomponent drug form linker is injection molded with a raised circumferential band and snap-fit elements between the band and respective ends engageable with complementary snap-fit elements on dosage form units to provide compressive abutting contact between ends of the units and the band. The band can have an axially tapered outer surface to accommodate dosage form units of different diameters. Still another multicomponent dosage form linker has separable male and female parts each engageable with, and separately sealing, respective dosage form units to be linked.

Abstract: Capsule shells for use in multi-part dosage forms have generally cylindrical shell members with a snap fit component on an interior surface adjacent an open end, for connection to a linker part of the dosage form. The shell member also has a plurality of spaced apart integrally formed thin (relative to circumferentially adjacent shell member portions) panels located adjacent a closed shell member end, for preferential dissolution and release of pharmaceutical compositions from the shell member interior. The ratio of the thickness of the panels to the thickness of the shell member ranges from about 0.2 to about 0.6. The panels can be integrally formed together with the shell member as reliefs or depressions on the inner surface of the shell member by injection molding, and panel thicknesses as thin as about 0.

Abstract: A method of manufacturing a linker of the type having an injection molded jacket radially confining a preformed tablet. The method includes grasping the tablet about the outer surface with a plurality of pincers and positioning the grasped tablet and the pincers with respect to a molding apparatus. The method also includes supporting the tablet via the pincers and injecting jacket material to cover the outer tablet surface and the pincers. The method further includes extracting the jacketed tablet from the molding apparatus and removing the pincers from the jacketed tablet. The method may also include supporting and longitudinally positioning the tablet within the mold via a plurality of additional pincers.

Abstract: A microcapsule comprising a lipid-based core that is encapsulated in an enteric polymer shell providing enhanced bioavailability of a sparingly water-soluble drug as well as modulated release of the drug, wherein the microcapsule is, in one embodiment, prepared by a centrifugal coextrusion process. The lipid-based core comprises lipidic carriers, either liquid or solid (melting point<1000C), that would provide adequate drug solubilization and is compatible with the enteric shell materials.