Pharmaceutical composition comprising a triazole antifungal agent and method for preparation thereof
Inventors
Assignees
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Publication Number
US-10328076-B2
Publication Date
2019-06-25
Expiration Date
Abstract
The present invention relates to a stable pharmaceutical formulation of solid dosage forms for oral administration comprising a therapeutically effective amount of a triazole antifungal agent or pharmaceutical acceptable salt thereof, in particular Voriconazole and an effective amount of a solubility enhancing agent. It also relates to a process for the preparation thereof.
Core Innovation
The invention concerns a stable oral solid pharmaceutical composition for oral administration comprising Voriconazole or a pharmaceutically acceptable salt thereof and an effective amount of colloidal silicon dioxide as a solubility enhancing agent. The composition uses an internal phase and an external phase, and colloidal silicon dioxide is incorporated to enhance solubility and thereby support dissolution and disintegration.
In the internal phase, particles have a dimension less than 100 micrometers and each particle of the internal phase comprises the colloidal silicon dioxide intimately mixed and incorporated with the Voriconazole. The external phase is located outside the internal phase and comprises excipients that are not intimately mixed with the Voriconazole, including magnesium stearate.
A process for the preparation of a tablet composition is also described. The process includes dissolving povidone in water, blending Voriconazole with pregelatinized starch, lactose monohydrate, croscarmellose sodium and colloidal silicon dioxide, kneading with the povidone solution, drying the wetted mass, sizing the granules, adding magnesium stearate, compressing the obtained mixture into tablet dosage form, and optionally applying a film-coating on the core. Stability and physicochemical performance are documented, including 6-month stability and test results such as hardness, disintegration time, assay, dissolution, and related substances/impurities.
Claims Coverage
The provided independent claims are directed to two inventive features: a solid oral composition of Voriconazole with colloidal silicon dioxide in an internal phase intimately mixed with particles smaller than 100 micrometers, and a tablet preparation process with specified excipient handling and tablet formation, optionally with film-coating.
Internal and external phases with intimate mixing in internal phase
The solid pharmaceutical composition comprises an internal phase and an external phase, wherein the internal phase particles comprise the colloidal silicon dioxide intimately mixed and incorporated with the Voriconazole, and wherein the external phase is located outside the internal phase and comprises excipients that are not intimately mixed with the Voriconazole.
Sub-100 micrometer internal phase particles
The solid pharmaceutical composition includes an internal phase where each particle has a dimension less than 100 micrometers.
Magnesium stearate in the external phase
The solid pharmaceutical composition has an external phase comprising excipients not intimately mixed with the Voriconazole, wherein one of the excipients in the external phase comprises magnesium stearate.
Tablet preparation with povidone, blending, kneading, drying, sizing, magnesium stearate addition, and compression
A process for preparation of a tablet composition comprising Voriconazole or a pharmaceutically acceptable salt and an effective amount of colloidal silicon dioxide includes dissolving povidone in water; blending Voriconazole with pregelatinized starch, lactose monohydrate, croscarmellose sodium and colloidal silicon dioxide; kneading with povidone solution; drying the wetted mass; sizing the granules; adding magnesium stearate to the mixture; compressing the obtained mixture into tablet dosage form; and optionally applying a film-coating on the core.
Overall, the claims cover a solid oral composition with Voriconazole and colloidal silicon dioxide configured as internal phase particles with intimate mixing and a sub-100 micrometer dimension, an external phase with excipients not intimately mixed with Voriconazole including magnesium stearate, and a corresponding process for preparing the tablet composition including povidone dissolution, blending with specified excipients including colloidal silicon dioxide, kneading, drying, sizing, magnesium stearate addition, compression, and optional film-coating.
Stated Advantages
Improves dissolution and disintegration and overall stability.
Documented Applications
Oral administration in a stable solid pharmaceutical composition as tablet dosage form containing Voriconazole or a pharmaceutically acceptable salt.
Tablet preparation of a tablet composition containing Voriconazole or a pharmaceutically acceptable salt and colloidal silicon dioxide, with optional film-coating.
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