Voriconazole Solid Dosage Formulation for Enhanced Bioavailability
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Solution Overview
Problem
Current pharmaceutical formulations of Voriconazole for oral administration face challenges with low water solubility, stability, and bioavailability, requiring improved dissolution profiles and physical characteristics.
Innovation Solution
A stable solid dosage form of Voriconazole is developed using a specific particle size (D90 < 100µm) and incorporating colloidal silicon dioxide in the internal phase, along with other excipients like povidone, pregelatinized starch, and croscarmellose sodium, to enhance solubility and bioavailability, and optionally film-coated for improved stability and release.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If Voriconazole is formulated for oral administration, then bioavailability is improved, but water solubility remains low
Solution Approach 1:
The patent changes the physical parameters of Voriconazole by reducing particle size (D90 < 100µm) to enhance dissolution rate and bioavailability while addressing the inherent low water solubility issue
Solution Approach 2:
The patent introduces colloidal silicon dioxide as an intermediary excipient that facilitates wetting and dissolution of Voriconazole particles, acting as a mediator between the poorly soluble drug and aqueous environment
2Stability of the object's composition
If Voriconazole is formulated as a solid dosage form, then stability is improved, but dissolution rate decreases
Solution Approach 1:
The patent modifies the physical parameter of particle size (D90 < 100µm) to increase surface area and dissolution rate while maintaining the solid dosage form stability through appropriate excipient selection and formulation design
3Reliability
If particle size is reduced to enhance dissolution, then bioavailability is improved, but manufacturing complexity increases
Solution Approach 1:
The patent specifies a target particle size parameter (D90 < 100µm) that can be achieved through standard milling techniques, balancing improved bioavailability with manufacturability using conventional equipment and processes
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The formulation achieves enhanced bioavailability, predictable drug release, and improved stability, with increased solubility and dissolution rates, ensuring effective treatment while maintaining cost-effectiveness and ease of manufacturing.
Implementation Method 1
incorporating colloidal silicon dioxide in the internal phase, along with other excipients like povidone, pregelatinized starch, and croscarmellose sodium, to enhance solubility and bioavailability
Implementation Method 2
incorporating colloidal silicon dioxide in the internal phase... to enhance solubility and bioavailability
Implementation Method 3
Dissolving povidone in water; Blending the active ingredient with the rest of the excipients of internal phase; Kneading with povidone solution
Implementation Method 4
optionally applying a film-coating on the core
Data Source
AI summary
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.