The technology involves using hot melt extrusion (HME) to prepare amorphous drug formulations with reduced decomposition. This method incorporates a pharmaceutically acceptable thermoplastic polymer and an organic solvent to lower processing temperatures and stress, ensuring drug stability.
Background
HME is a widely used technique in the pharmaceutical industry for producing amorphous drug formulations, which are crucial for enhancing the solubility and bioavailability of poorly water-soluble drugs. However, a significant challenge with HME is the thermal and mechanical degradation of the active pharmaceutical ingredients (APIs), due to the high temperatures and shear forces involved in the process. This degradation can compromise the efficacy and safety of the drug.
Traditional methods like spray drying, although useful, have their own drawbacks, including the need for large volumes of solvents, limited processing capacity, and the requirement for expensive equipment. Moreover, spray drying often fails to achieve the desired amorphous state of the drug. Thus, there is a pressing need for improved HME methods that can minimize API degradation while maintaining or enhancing the drug’s amorphous nature, ultimately leading to more effective and stable pharmaceutical formulations.
Technology description
The technology focuses on the preparation of amorphous drug formulations using hot melt extrusion to minimize drug decomposition. This process involves combining a therapeutically active agent, which is sparingly soluble in water, with a pharmaceutically acceptable thermoplastic polymer. An organic solvent, which is volatile and has a boiling point below 100°C, is added to the drug-polymer mixture to reduce thermal and mechanical stress during extrusion. This solvent helps lower the viscosity of the mixture, enabling the use of lower processing temperatures and preserving the amorphous nature of the drug. The solvent is partially evaporated during extrusion, and any remaining solvent is removed in subsequent drying steps. The resulting extrudate can be further processed into pharmaceutical compositions like tablets or capsules. The method also includes specific configurations for the extruder, such as screw design and temperature settings, to optimize the process and ensure the stability of the active pharmaceutical ingredient.
This technology is differentiated by its innovative use of an organic solvent during the hot melt extrusion process, which significantly reduces the thermal and mechanical stress on the drug-polymer mixture. Traditional hot melt extrusion methods often lead to the degradation of the active pharmaceutical ingredient due to high temperatures and mechanical forces. By incorporating a volatile organic solvent, this method maintains the amorphous nature of the drug, which is crucial for its bioavailability and therapeutic effectiveness. Additionally, the solvent's ability to lower the mixture's viscosity allows for lower processing temperatures, further preserving the drug's stability. This approach not only enhances the efficiency of the extrusion process but also expands the range of drugs that can be processed using hot melt extrusion, particularly those that are thermally sensitive or have high melting points.
Benefits
- Uses lower processing temperatures, minimizing drug decomposition
- Reduces thermal and mechanical stress
- Preserves the amorphous nature of the drug
- Improves miscibility between drug and polymer
- Allows for the use of high melting point therapeutically active agents
- Facilitates processing of drugs that degrade at high temperatures
- Decreases viscosity of the mixture
- Enables the use of a variety of organic solvents
- Allows for secondary drying to remove remaining solvent
- Optimizes extruder configurations for stability
- Reduces torque required in the extrusion process
Commercial applications
- Pharmaceutical manufacturing
- Drug formulation
- Solubility enhancement
- Thermal processing
- Amorphous solid dispersions
Patent link
US20210154172A1
