Enhanced pharmaceutical co-crystal production via continuous dielectric heating and hot melt extrusion method

CoMIDEx uses microwave heating and extrusion to create drug cocrystals, enhancing their solubility and effectiveness. It’s a continuous, eco-friendly process that improves medicine availability without using solvents.

Background

Pharmaceutical development heavily relies on active pharmaceutical ingredients (APIs) to provide therapeutic benefits. However, a significant number of APIs suffer from poor water solubility, severely limiting their bioavailability and consequently their effectiveness in the body. Enhancing the solubility and bioavailability of these poorly soluble APIs is crucial for improving drug performance and patient outcomes.

As the need for more efficient and effective medications grows, there is an increasing need for innovative technologies that can address these solubility challenges without compromising the quality or scalability of drug production.

Current approaches to improving API solubility often involve methods that are either environmentally unfriendly or inefficient at scale. Traditional techniques frequently rely on the use of organic solvents, which pose environmental hazards and increase manufacturing costs. Additionally, many existing processes are batch-based, limiting their ability to meet the demands of continuous commercial production. These methods also struggle with consistency and reproducibility, making it difficult to ensure uniform quality in the final pharmaceutical products. Moreover, the use of excessive energy and the lack of integration with advanced manufacturing technologies hinder the overall efficiency and sustainability of current solubility enhancement strategies.

Technology description

CoMIDEx integrates dielectric heating, specifically microwave irradiation at 2450 MHz, with hot melt extrusion (HME) to produce pharmaceutical cocrystals that enhance the solubility and bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). The process can operate in either a parallel mode, where the API and co-former mixture are first melted using dielectric heating before extrusion, or a coupled mode, where heating and mixing occur simultaneously within the extruder barrel.

CoMIDEx facilitates continuous, solvent-free manufacturing by optimizing parameters such as microwave power, extruder temperature, screw speed, and feeding rate. It has been successfully applied to a variety of API and co-former combinations, including ibuprofen-nicotinamide and carbamazepine-maleic acid, and employs advanced analytical techniques like polarized light microscopy, X-ray diffraction, and Raman spectroscopy for comprehensive product characterization. This makes CoMIDEx a scalable and environmentally friendly solution for pharmaceutical cocrystal production.

CoMIDEx stands out in the pharmaceutical manufacturing landscape by uniquely combining dielectric heating with HME, effectively addressing the challenge of poor aqueous solubility in APIs. Unlike traditional methods, it eliminates the need for organic solvents, thereby reducing environmental impact and lowering processing costs. The technology offers rapid processing times and is highly scalable, making it suitable for commercial-scale production. Its continuous manufacturing capability enhances production efficiency and allows for higher cocrystal yields compared to conventional techniques. Additionally, CoMIDEx improves powder flowability, facilitating downstream processing steps such as milling, sieving, and tableting.

The versatility of the process is further demonstrated by its compatibility with various API and co-former combinations, and its ability to incorporate additional excipients for tailored properties. These differentiating factors make CoMIDEx a superior and innovative approach for enhancing drug solubility and bioavailability in modern pharmaceutical production.

Benefits

Enhances solubility and bioavailability of poorly water-soluble APIs
Enables continuous, solvent-free manufacturing, reducing environmental impact
Offers rapid processing times, increasing production efficiency
Scalable for commercial pharmaceutical production
Eliminates the use of organic solvents, lowering costs and environmental footprint
Improves powder flowability for efficient downstream processing
Achieves higher cocrystal yields compared to traditional methods
Compatible with continuous manufacturing processes for versatility