Formic Acid Processing Aid for Spray Drying Basic Drugs
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Solution Overview
Problem
Existing methods for preparing spray dried solid dispersions of active pharmaceutical ingredients with limited solubility face challenges such as low solubility in conventional solvents, chemical degradation, and high viscosity, especially when using volatile solvents, which can lead to incomplete dissolution and increased costs.
Innovation Solution
A method involving the use of formic acid as a solvent with C1-3 alkanols, such as methanol or ethanol, to create a spray solution that increases the solubility of the active agent, allowing for higher concentrations and stable amorphous solid dispersions at modest temperatures, thereby improving manufacturing throughput and particle characteristics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional volatile solvents (methanol, acetone) are used for spray drying, then the process can be completed at modest temperatures, but the solubility of active agents with limited solubility is insufficient leading to incomplete dissolution
Solution Approach 1:
Formic acid acts as an intermediary substance that mediates between the active agent and the solvent system. It forms a complex with the basic active agent, significantly enhancing solubility in the spray solution while allowing the use of volatile solvents for easy processing. The formic acid-active agent complex serves as the soluble species during spray drying.
Solution Approach 2:
The invention changes the chemical parameters of the solution system by introducing formic acid, which alters the solubility characteristics of the active agent. This parameter change enables the active agent to dissolve at higher concentrations in volatile solvents, resolving the contradiction between solubility and processability.
2Productivity
If higher concentrations of active agent are used in spray solution to improve throughput, then manufacturing efficiency increases, but viscosity increases making spray drying difficult
Solution Approach 1:
Formic acid serves as a mediating agent that enables higher active agent concentrations without proportionally increasing viscosity. The formic acid-active agent complex maintains solution流动性 (fluidity) even at elevated solids content, allowing higher throughput while preserving spray drying capability.
Solution Approach 2:
The introduction of formic acid changes the rheological parameters of the spray solution. It modifies the viscosity-concentration relationship, allowing the solution to maintain acceptable flow properties at higher active agent concentrations, thus enabling improved productivity without compromising processability.
3Reliability
If formic acid is used as the only solvent to increase solubility, then active agent dissolution is improved, but viscosities become too high for spray drying
Solution Approach 1:
The invention segments the solvent system into two components: formic acid (as processing aid/solubilizing agent) and a volatile solvent (methanol, ethanol, or acetone). This segmentation allows formic acid to provide solubility enhancement while the volatile solvent component maintains appropriate viscosity and spray drying characteristics.
Solution Approach 2:
The invention creates a composite solvent system combining formic acid with volatile solvents. This composite approach leverages the solubility-enhancing property of formic acid and the favorable spray drying properties of volatile solvents, achieving both high solubility and processability.
4Quantity of substance
If conventional solvents are used without formic acid, then viscosities remain manageable, but solubility of active agents is limited leading to lower concentrations
Solution Approach 1:
Formic acid acts as a solubilizing intermediary that bridges the gap between the active agent and conventional volatile solvents. It enables the active agent to dissolve at higher concentrations in these solvents by forming soluble complexes, thereby increasing the quantity of active agent that can be processed.
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
This method enhances the solubility of active agents, enabling higher concentration and more stable amorphous solid dispersions, reducing chemical degradation and processing costs, while maintaining the active agent in its free base form for improved stability and bioavailability.
Implementation Method 1
The solubility of the AA is increased, which allows for higher concentration of AA in the spray solution than in absence of formic acid
Implementation Method 2
spray drying is done with a solution of AA and of DISPPOL in a solvent comprising C1-3 alkanol and formic acid
Data Source
AI summary
The invention discloses a method for preparation of spray dried solid dispersions, SDD, comprising an active agent, AA, such as an active pharmaceutical ingredient, API, and a dispersion polymer, DISPPOL, wherein the spray drying is done with a solution of AA and of DISPPOL in a solvent comprising C1-3 alkanol and formic acid, and optionally water.