Pediatric Solid Dispersion Granules for Accurate Cystic Fibrosis Dosing
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Solution Overview
Problem
Existing pharmaceutical compositions of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide face challenges in administering accurate and stable dosages, particularly in pediatric patients, due to swallowing difficulties and dosing inaccuracies with crushed tablets and powders, leading to therapeutic failures and deviations.
Innovation Solution
A pharmaceutical composition in the form of granules, pellets, or mini-tablets containing a solid dispersion of amorphous Compound 1, with additives like hydroxypropylmethylcellulose acetate succinate, mannitol, lactose, and sucralose, designed for easy administration and accurate dosing, allowing formulation into various solid unit dose forms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If adult tablets are used for pediatric patients, then the pharmaceutical composition can be administered, but dosing inaccuracies and absorption issues occur due to difficulty in crushing and administering the tablets
Solution Approach 1:
The adult tablet is divided into smaller pediatric-sized tablets or granules, allowing accurate dosing for children while maintaining the same active ingredient concentration. This segmentation enables precise measurement of small doses that would be difficult to obtain from crushed adult tablets.
Solution Approach 2:
The physical form and size parameters of the pharmaceutical composition are changed from adult tablet dimensions to pediatric-appropriate smaller tablets or granules. This parameter change allows for accurate dosing in pediatric patients while improving ease of administration.
2Adaptability or versatility
If powdered formulations are used for pediatric patients, then the active ingredient can be administered, but dosing inaccuracies occur due to adherence to container walls and difficulty in complete administration
Solution Approach 1:
The pharmaceutical composition is formulated as a composite material combining the active ingredient with excipients that provide both flow properties and adherence prevention. This composite formulation ensures complete administration of the dose while maintaining flexibility in how it can be given to pediatric patients.
Solution Approach 2:
Excipients serve as intermediaries that facilitate complete administration of the active ingredient by preventing adherence to container walls and ensuring full delivery of the dosed amount to the patient.
3Shape
If crushed tablets are administered to pediatric patients, then the pharmaceutical composition can be given in smaller forms, but absorption problems and therapeutic failure occur
Solution Approach 1:
The pharmaceutical composition is pre-formulated in pediatric-appropriate sizes and forms before administration, eliminating the need for crushing. This preliminary preparation ensures proper dissolution and absorption characteristics are built into the dosage form itself, guaranteeing therapeutic effectiveness.
Solution Approach 2:
The size and physical form parameters are optimized for pediatric patients while maintaining dissolution and absorption properties equivalent to or better than crushed adult tablets, ensuring reliable therapeutic effectiveness.
Data Source
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AI summary
The present invention relates to pharmaceutical compositions containing a solid dispersion of N- [2,4-B is( 1, 1 -dimethy lethyl)-5 -hydroxypheny 1] - 1,4-dihydro-4-oxoquinoline-3 - carboxamide including formulations of the solid dispersions into powders, granules and mini- tablets, methods for manufacturing and processing the powders, granules and mini-tablets, and methods for treating cystic fibrosis employing the pharmaceutical composition.