Acetic Acid Processing Aid for Spray Drying Basic Drugs
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Solution Overview
Problem
Current methods for preparing spray dried solid dispersions of active pharmaceutical ingredients with limited solubility face challenges such as low API concentrations, chemical degradation, and high viscosity when using volatile solvents, and fail to produce the API in its free base form effectively.
Innovation Solution
A method involving the use of a solvent comprising C1-3 alkanol and acetic acid, where the active agent is dissolved in its free base form with a dispersion polymer, allowing for higher API concentrations and stable spray drying at modest temperatures, resulting in a spray dried solid dispersion with improved particle characteristics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If volatile solvents such as methanol or acetone are used for spray drying, then the API can be dissolved, but the API concentration remains low and chemical degradation occurs
Solution Approach 1:
The patent changes the solvent parameters by using C1-3 alkanols (methanol, ethanol, propanol) instead of highly volatile solvents like acetone. This parameter change allows for higher API concentrations to be dissolved while reducing chemical degradation, as the alkanols have lower volatility and different solvation properties that stabilize the basic drug during the spray drying process
Solution Approach 2:
The patent introduces an intermediary substance (acidic component) that mediates between the basic drug and the solvent system. This intermediary allows the API to be dissolved at higher concentrations in C1-3 alkanols without undergoing chemical degradation, by controlling the chemical environment during dissolution and spray drying
2Productivity
If higher API concentrations are used in the spray solution, then manufacturing throughput increases, but viscosity increases making processing difficult
Solution Approach 1:
The patent changes the solvent parameters by using C1-3 alkanols which have different viscosity characteristics compared to traditional solvents. This allows higher API concentrations to be achieved in the spray solution without proportionally increasing viscosity, as the alkanol-based system maintains better flow properties at elevated concentrations
Solution Approach 2:
The patent creates a composite solvent system using C1-3 alkanols in combination with other components that work synergistically to maintain low viscosity even at high API concentrations. This composite approach allows the solution to achieve both high productivity and ease of processing
3Quantity of substance
If basic drugs are spray dried without acid, then the free base form is obtained, but solubility is insufficient for economical throughput
Solution Approach 1:
The patent introduces an intermediary acidic component that temporarily enhances the solubility of basic drugs in C1-3 alkanol-based spray solutions. This intermediary allows sufficient API to be dissolved for economical throughput, while the specific processing conditions ensure the final product remains in the desired free base form
Solution Approach 2:
The patent changes the chemical parameters of the spray solution by incorporating acidic components that increase API solubility. This parameter change enables higher concentrations to be processed, thereby increasing manufacturing throughput, while controlling other parameters ensures the free base form is recovered in the final product
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 increases API solubility, enabling higher manufacturing throughput and achieving better spray dried particle characteristics by maintaining the API in its free base form, while reducing chemical degradation and viscosity issues.
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 acetic acid
Implementation Method 2
spray drying is done with a solution of AA and of DISPPOL in a solvent comprising C1-3 alkanol and acetic 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 acetic acid, and optionally water.