Formic Acid Supersaturation for API Spray Drying
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Solution Overview
Problem
Current methods for preparing spray dried solid dispersions of active pharmaceutical ingredients (APIs) with dispersion polymers face challenges such as limited solubility of APIs in traditional solvents, leading to inefficient processes, chemical degradation, and incomplete dissolution, which can result in unstable products and equipment issues like nozzle clogging.
Innovation Solution
A method involving the Solvent-Shift route, where the API is dissolved in formic acid to create a supersaturated solution, then diluted with a low-viscosity solvent like methanol or ethanol containing the dispersion polymer, allowing for higher API concentrations and efficient spray drying without solid API presence, thereby achieving a metastable supersaturated solution with enhanced viscosity control and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If API is dissolved in traditional solvents like methanol or acetone, then spray drying can be performed, but API solubility is limited leading to low concentrations and inefficient throughput
Solution Approach 1:
The invention changes the solvent parameter from traditional solvents (methanol, acetone) to formic acid, which enables significantly higher API solubility and concentration in the spray drying solution, thereby improving manufacturing throughput
Solution Approach 2:
Formic acid acts as an intermediary solvent that facilitates high-concentration API dissolution. The process uses formic acid to dissolve API at high concentrations, then mixes with dispersion polymer solution to create the final spray drying formulation
2Productivity
If API concentration is increased in traditional solvents, then throughput improves, but chemical degradation and instability occur
Solution Approach 1:
Changing the solvent parameter to formic acid allows high API concentrations to be achieved without chemical degradation or instability, enabling both high throughput and product reliability
3Ease of manufacture
If suspension is used for spray drying, then process simplification occurs, but nozzle clogging happens
Solution Approach 1:
The invention changes the physical state parameter of the API from suspended solid particles to dissolved molecular state in formic acid, eliminating nozzle clogging while maintaining process simplicity
4Manufacturing precision
If API and dispersion polymer are both dissolved in spray drying solvent, then homogeneous amorphous solid dispersion is achieved, but solubility limitations prevent sufficient API concentration
Solution Approach 1:
The invention changes the solvent parameter to formic acid, which enables both homogeneous amorphous solid dispersion formation and high API concentration to be achieved simultaneously, overcoming the solubility limitations of traditional solvents
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 approach enables higher API concentrations, improved manufacturing throughput, and enhanced properties of spray-dried particles, including larger particle sizes beneficial for dosage forms, while maintaining stability and avoiding chemical degradation.
Implementation Method 1
dissolving the API to a high concentration in formic acid, thereby providing a solution of the API in formic acid having a relatively high viscosity, then diluting this API solution with a preferred spray drying solvent... that result in a metastable supersaturated solution of API in a solvent mixture
Implementation Method 2
dissolving the API and the dispersion polymer in a volatile solvent, such as methanol or acetone, or in a mixture of solvents
Implementation Method 3
by the dilution of the solution of the API in formic acid with the preferred spray drying solvent, the viscosity of the resulting metastable supersaturated solution can be chosen to be noticeably lower than the viscosity of a solution of the API in formic acid
Implementation Method 4
spray drying... 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, this supersaturated solution further comprising DISPPOL.