Pharmaceutical formulations of naproxen for soft gel encapsulation and combinations thereof
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing pharmaceutical formulations for naproxen in soft gel capsules face challenges in achieving high concentrations without increasing the capsule size, maintaining pH stability, and avoiding corrosiveness to the shell, while requiring complex neutralization processes.
Innovation Solution
A formulation comprising naproxen, naproxen sodium, polyethylene glycol, propylene glycol, and povidone, with adjustable pH, allows for high concentration and bioavailability without additional neutralization steps, ensuring compatibility with the soft gel shell.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If naproxen is formulated in polyethylene glycol to increase solubility, then the concentration of naproxen improves, but the capsule size becomes too large for comfortable administration
Solution Approach 1:
The patent combines multiple solvents (polyethylene glycol and propylene glycol) with povidone to create a composite fill formulation that achieves higher naproxen solubility (up to 25% w/w) while maintaining capsule size within acceptable limits for patient comfort
Solution Approach 2:
The patent modifies the chemical parameters of the fill system by selecting specific solvent combinations and ratios (polyethylene glycol, propylene glycol, povidone) to optimize naproxen solubility and capsule physical properties simultaneously
2Quantity of substance
If neutralization processes are used to increase naproxen solubility, then bioavailability improves, but the manufacturing process becomes more complex and requires corrosive adjuvants
Solution Approach 1:
The patent eliminates the neutralization step and corrosive adjuvants from the manufacturing process, using only non-corrosive solvents and excipients that directly dissolve naproxen without requiring chemical modification
Solution Approach 2:
The patent uses simple, non-corrosive solvents and excipients that can be easily handled and disposed of without special safety equipment, simplifying manufacturing and reducing operational complexity
3Quantity of substance
If neutralization processes are used to enhance naproxen solubility, then concentration improves, but safety decreases due to corrosive adjuvants
Solution Approach 1:
The patent avoids using corrosive substances entirely, selecting only non-corrosive solvents and excipients that are compatible with soft gelatin capsules, thereby eliminating the harmful effect while achieving the desired naproxen concentration
Solution Approach 2:
The patent uses propylene glycol and povidone as intermediary substances that facilitate naproxen dissolution without exhibiting corrosive properties, mediating between the active ingredient and the capsule shell
Data Source
AI summary
This invention relates to a naproxen formulation suitable for encapsulation into a soft gel dosage unit by increasing the stability, concentration, and bioavailability of naproxen. Fill formulations of the invention may include other active pharmaceutical ingredients and combinations of two or more active pharmaceutical ingredients. This invention also provides for adjusting pH values of fill formulations without additional process steps. A process for increasing the achievable concentration of an active NSAID pharmaceutical ingredient, such as naproxen, relative to fill composition for dosage units is also provided. The highly concentrated formulation of this invention permits a reduction in the fill volume or dosage unit size, or an increase in concentration of the active pharmaceutical ingredient per dosage form. The invention also relates to a formulation of optimal stability suitable for supporting a fill composition compatible with the soft gel dosage unit.