Mesalamine Suppository Size Reduction via Tap Density and Melting Point
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Solution Overview
Problem
Current mesalamine suppositories are large and have high melting points, leading to discomfort and potential issues with viscosity, which affects their therapeutic efficacy and ease of use in treating ulcerative colitis.
Innovation Solution
Reducing the size of mesalamine suppositories by increasing the tap density and lowering the melting point of the suppository base, while maintaining therapeutic efficacy, by using a combination of mesalamine and a low melting suppository base such as hard fat, to enhance comfort and dissolution profile.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If the size of mesalamine suppository is reduced, then comfort of use is improved, but the drug load and viscosity may be adversely affected
Solution Approach 1:
The patent applies parameter changes by increasing the tap density of mesalamine from conventional values to at least 0.5 g/mL (preferably 0.55-0.75 g/mL). This parameter change allows more drug to be packed into a smaller suppository volume, reducing size while maintaining therapeutic drug load. The patent also changes the melting point parameter of the suppository base to 30-35°C, optimizing it for rectal administration comfort.
Solution Approach 2:
The patent uses composite materials by combining mesalamine with specific suppository bases (hard fats Witepsol H-12 or H-15, or cocoa butter) in optimized ratios. This composite formulation ensures proper drug distribution, maintains stability, and achieves the desired tap density and melting point characteristics while keeping the suppository size reduced.
2Ease of operation
If the melting point of suppository base is lowered, then comfort of use is improved, but the stability and viscosity control may be adversely affected
Solution Approach 1:
The patent changes the melting point parameter of the suppository base to a specific range of 30-35°C, which is low enough to provide comfort during rectal insertion (avoiding pain from high melting point bases) but high enough to maintain stability during storage. This optimized melting point parameter ensures the suppository remains solid at room temperature but melts appropriately at body temperature.
Solution Approach 2:
The patent applies local quality by selecting different suppository bases with specific properties for different regions of the formulation. Hard fats (Witepsol H-12 or H-15) or cocoa butter are used as the base material, providing the right balance of melting point and stability characteristics locally within the suppository matrix to support the mesalamine drug particles.
3Volume of moving object
If the tap density of mesalamine is increased, then the suppository size is reduced, but the viscosity and ease of manufacture may be adversely affected
Solution Approach 1:
The patent changes the tap density parameter of mesalamine to at least 0.5 g/mL (preferably 0.55-0.75 g/mL), which significantly reduces the volume required to accommodate the therapeutic drug load. This parameter change enables smaller suppository size while maintaining adequate drug quantity. The patent also optimizes the mixing process parameters to handle the higher density material effectively.
Solution Approach 2:
The patent applies preliminary action by pre-processing the mesalamine to achieve the desired tap density before incorporation into the suppository base. This preliminary preparation ensures that the high-density mesalamine can be properly mixed and distributed in the molten base without causing manufacturing difficulties, allowing for smooth production of reduced-size suppositories.
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 smaller, lower melting point mesalamine suppositories provide increased comfort and maintain or improve therapeutic efficacy, with at least 75% of mesalamine dissolving within 2 hours, offering a more reliable and variable dissolution method for treating ulcerative colitis.
Implementation Method 1
lowering the melting point of the suppository base... a low melting suppository base such as hard fat
Implementation Method 2
with at least 75% of mesalamine dissolving within 2 hours, offering a more reliable and variable dissolution method
Data Source
AI summary
The present invention relates to a mesalamine rectal suppository designed to provide improved comfort of use. One embodiment of the invention is a mesalamine rectal suppository containing mesalamine and one or more pharmaceutically acceptable excipients, wherein the drug load of the suppository ranges from 35% to 50%. Another embodiment of the invention is a mesalamine rectal suppository containing from about 850 to about 1150 mg mesalamine and one or more pharmaceutically acceptable excipients, wherein the total weight of the suppository ranges from about 2250 to about 2700 mg. Yet another embodiment of the invention is a mesalamine rectal suppository comprising mesalamine having a tap density ranging from about 600 to about 800 g/L (as measured by USP <616>) and a hard fat having an ascending melting point of 32 to 35.5° C. Methods of preparing and methods of treatment with mesalamine suppositories are also provided. The invention further provides a method of determining a dissolution parameter (such as dissolution rate) of a mesalamine rectal suppository, such as a 1 g mesalamine suppository, by measuring its dissolution with USP Apparatus #2 at 40° C. and a paddle rotation speed of 125 rpm in 0.2 M phosphate buffer at a pH of 7.5.