Oral formulation of anhydrous olanzapine form I

Inventors

Diez Martin, Ignacio • Ubeda Perez, Carmen • Pablo Alba, Pablo

Assignees

Neuraxpharm Pharmaceuticals SL

Abstract

The invention relates to a solid formulation for the oral administration of olanzapine that comprises a core of anhydrous olanzapine Form I or a pharmaceutically acceptable salt thereof and, optionally, pharmaceutically acceptable excipients, said core being coated with a functional polymer that acts as filmogenic agent. The method for obtaining it comprises: i) providing anhydrous olanzapine Form I or a salt thereof and, optionally, pharmaceutically acceptable excipients in solid form; ii) providing a functional polymer that acts as filmogenic agent; iii) preparing a dispersion of said functional polymer in an aqueous medium,—and applying the dispersion obtained in step iii) onto the solid form of step i).

Core Innovation

The invention relates to a solid oral formulation of olanzapine in the form of a tablet, where the tablet core comprises anhydrous metastable olanzapine Form I as the active substance. The metastable Form I is defined by a specific X-ray diffraction pattern and is combined with pharmaceutically acceptable excipients. The tablet core is obtained by direct compression or by dry granulation.

The tablet core is coated with an aqueous soluble functional polymer containing PVA, which acts as a filmogenic agent. The underlying problem described is that metastable Form I discoloration occurs, and this is attributed to excipient interactions and moisture/temperature/humidity. The aqueous-soluble filmogenic polymer coating is presented as reducing water vapor uptake while maintaining active release/bioavailability.

The formulation includes coating excipients such as an opacifier/colorant, lubricant, plasticizer, thickening agent, and filler, and includes core excipients such as diluent, disintegrant, and lubricant. The document further states that isolating agents can be used to mitigate negative effects associated with alkaline excipients, and provides examples of filmogenic polymer dispersion preparation using an aqueous polymer dispersion in water with a coating application to the tablet.

Claims Coverage

The independent claim defines one solid oral tablet formulation, with the core defined by anhydrous metastable olanzapine Form I, made by direct compression or dry granulation, and subsequently coated with an aqueous soluble filmogenic PVA-containing polymer. Three inventive features are identified.

Overall, the claim coverage centers on a solid oral tablet where anhydrous metastable olanzapine Form I, specified by X-ray diffraction, is formulated into a tablet core prepared by direct compression or dry granulation and then coated with an aqueous soluble PVA-containing functional polymer filmogenic agent.

Stated Advantages

Documented Applications