Spray Drying Supersaturated API Solutions with Acetic Acid
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Solution Overview
Problem
Current methods for preparing spray dried solid dispersions (SDDs) of active pharmaceutical ingredients (APIs) with dispersion polymers face challenges such as limited solubility of APIs in traditional solvents, leading to inadequate concentrations, chemical degradation, and equipment compatibility issues, especially when trying to achieve amorphous solid dispersions.
Innovation Solution
A method involving the creation of a supersaturated solution of the API in a solvent mixture comprising acetic acid and a preferred spray drying solvent like methanol or ethanol, allowing for higher API concentrations and efficient spray drying at modest temperatures, thereby overcoming solubility limitations and equipment compatibility issues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If traditional solvents like methanol or acetone are used for spray drying, then the process is simple and equipment compatibility is good, but the API solubility is limited leading to inadequate concentrations
Solution Approach 1:
The patent introduces acetic acid as an intermediary solvent that mediates between the API and the final spray drying solvent system. Acetic acid first dissolves the API to achieve high concentration, then is mixed with spray drying solvents to create a supersaturated solution that maintains API solubility while being compatible with spray drying equipment.
Solution Approach 2:
The patent changes the solvent composition parameters by introducing acetic acid into the solvent system. This parameter change enables the API to be dissolved at concentrations exceeding traditional solubility limits, creating a supersaturated solution that can be successfully spray dried.
2Quantity of substance
If supersaturated solutions are used to achieve higher API concentrations, then the API solubility limit is exceeded, but this may cause precipitation and loss of amorphous state
Solution Approach 1:
The patent performs preliminary action by first dissolving the API in acetic acid to achieve high concentration, then carefully mixing with spray drying solvents under controlled conditions. This preliminary dissolution step ensures the API is in a stable dissolved state before spray drying, preventing precipitation during the process.
Solution Approach 2:
The patent utilizes phase transition principles by creating a supersaturated solution that remains in the liquid phase during mixing, then rapidly transitions to a solid amorphous dispersion during spray drying. The controlled phase transition prevents crystallization and maintains the desired amorphous state.
3Ease of operation
If conventional spray drying methods are used with limited solubility, then equipment compatibility is maintained, but the resulting particles have lower API content and reduced properties
Solution Approach 1:
Acetic acid serves as an intermediary that enables higher API concentrations in the feed solution without compromising equipment compatibility. The acetic acid-based supersaturated solution can be successfully processed through conventional spray drying equipment while producing particles with enhanced API content and improved properties.
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 enables the production of SDDs with higher API concentrations, enhancing the properties of the resulting particles and improving manufacturing efficiency, while maintaining the API in a completely dissolved state without precipitation, thus achieving amorphous and homogenous mixtures.
Implementation Method 1
spray drying is done with a supersaturated solution of API in a solvent mixture comprising two solvents, one is acetic acid
Implementation Method 2
followed by spray drying
Data Source
AI summary
The invention discloses a method for preparation of spray dried solid dispersions (SDD) comprising an active pharmaceutical ingredient (API) and a dispersion polymer (DISPPOL), wherein the spray drying is done with a supersaturated solution of API in a solvent mixture comprising two solvents, one is acetic acid, this supersaturated solution further comprising DISPPOL.