Stable Solid Fingolimod Dosage Forms with Rapid Disintegration
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Solution Overview
Problem
Current pharmaceutical formulations of fingolimod lack a stable, rapidly disintegrating solid oral dosage form that is easy to manufacture and exhibits low friability, particularly for patients who cannot swallow tablets, such as infants, children, and elderly individuals.
Innovation Solution
A stable pharmaceutically acceptable solid oral dosage form comprising fingolimod or its pharmaceutically acceptable salt, conjugate, or complex, combined with sugar alcohols and moisture facilitating compounds, which rapidly dissolves in the oral cavity, prepared using methods like wet granulation, dry mixing, and spray drying, ensuring low friability and rapid disintegration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If a solid tablet is used for oral administration, then stability and ease of manufacturing are improved, but rapid disintegration and absorption are worsened
Solution Approach 1:
The patent changes the physical and chemical parameters of the tablet formulation by incorporating specific excipients including sugar alcohols (mannitol, sorbitol, xylitol), disintegrants (crosslinked polyvinylpolypyrrolidone, sodium starch glycolate), and surfactants (polysorbate 80, sodium lauryl sulfate). These parameter changes enable the tablet to maintain stability during storage while achieving rapid disintegration within 2.5 minutes through optimized composition ratios and particle size distributions.
Solution Approach 2:
The patent creates a composite tablet formulation combining fingolimod hydrochloride with multiple excipients serving different functions: sugar alcohols provide structure and rapid dissolution, disintegrants enable quick breakdown, surfactants enhance wetting and dissolution, and lubricants ensure manufacturability. This composite material approach resolves the contradiction by integrating components with complementary properties that simultaneously provide stability and rapid disintegration.
2Ease of manufacture
If a solid tablet is used for oral administration, then manufacturing simplicity is improved, but patient compliance for those who cannot swallow tablets is worsened
Solution Approach 1:
The patent modifies the tablet's physical parameters including reducing tablet size to small dimensions, optimizing hardness to a specific range (5-350 Newtons), and controlling friability to less than 2%. These parameter changes make the tablet easy to manufacture using conventional compression equipment while simultaneously making it suitable for patients who have difficulty swallowing, as the small size and rapid disintegration properties improve ease of administration.
3Ease of operation
If liquid formulations are used to address patient compliance, then ease of administration is improved, but technical complexity and patient compliance difficulties are worsened
Solution Approach 1:
The patent employs a disposable solid tablet formulation that eliminates the need for complex liquid formulation systems. By using a pre-formed solid dosage form with rapid disintegration properties, the patent avoids the technical complexities of liquid formulations including stabilization, packaging, and administration equipment, while maintaining ease of administration for patients who cannot swallow tablets.
4Speed
If rapidly disintegrating techniques are used, then disintegration speed is improved, but friability and stability are worsened
Solution Approach 1:
The patent optimizes multiple formulation parameters including the ratio of binding agents to disintegrants, particle size distribution of excipients, and moisture content control. These parameter changes enable the tablet to achieve rapid disintegration speed while maintaining adequate mechanical strength and low friability through precise control of compression force and formulation composition.
Solution Approach 2:
The patent incorporates pre-formed disintegrant structures and moisture-facilitating compounds that are prepared in advance to enable rapid disintegration. The disintegrants are pre-processed to specific particle sizes and the formulation includes pre-hydrating components that activate upon contact with oral fluids, ensuring rapid breakdown without compromising structural integrity during storage and handling.
Data Source
AI summary
The present invention relates to a solid pharmaceutical dosage forms and methods for preparing the solid pharmaceutical dosage form that contains fingolimod or its pharmaceutically acceptable salts, conjugates or complexes thereof. The solid pharmaceutical dosage forms may rapidly disintegrate in a patient's oral cavity.