What is Hot Melt Extrusion (HME) and how does it improve drug bioavailability?

Hot Melt Extrusion (HME) is a pharmaceutical technique that combines drugs with thermoplastic polymers at elevated temperatures, typically between 50°C and 180°C. This process enhances drug bioavailability by transforming poorly soluble drugs into formulations that are more easily absorbed by the body. The controlled parameters of the extruder, such as temperature settings, allow for specialized functions like melting, mixing, and vacuum venting, enabling the creation of formulations with improved solubility and reduced dosing intervals, ultimately leading to better patient outcomes.

How does near-infrared (NIR) spectroscopy optimize the Hot Melt Extrusion (HME) process?

Near-infrared (NIR) spectroscopy optimizes the Hot Melt Extrusion (HME) process by providing real-time monitoring of the formulation. Its non-destructive nature, excellent signal-to-noise ratios, and fiber optic compatibility allow manufacturers to closely monitor and adjust the HME process on the fly. Specifically, the Thermo Scientific™ Antaris™ FT-NIR instrument, when used with an extruder probe, enables continuous spectral acquisition and analysis of the extrudate. This real-time feedback allows for immediate process control, ensuring consistent product quality, reducing the risk of deviations, and potentially creating a more efficient and cost-effective manufacturing process.

What are the advantages of using HME in pharmaceutical manufacturing?

The advantages of using Hot Melt Extrusion (HME) include improved solubility and bioavailability of active pharmaceutical ingredients (APIs), which can reduce patient dosing intervals. HME enables taste masking, provides a continuous and reproducible process, minimizes batch-to-batch variability, and lowers manufacturing costs. Furthermore, it creates thermodynamically stable solid solutions that enhance product temperature and mechanical stability. The process is also amenable to in-line monitoring using techniques like NIR spectroscopy, which aids in process optimization and control.

How was the Thermo Scientific™ Antaris™ FT-NIR instrument used in the study of HME?

In the study, the Thermo Scientific™ Antaris™ FT-NIR instrument, equipped with an extruder probe, was used to monitor the output of the Thermo Scientific™ PRISM Pharmalab 16 HME twin-screw extruder. The probe, placed directly into the output die, collected reflectance measurements of the extrudate in real-time. The instrument was set to a scan range of 4000-10,000cm⁻¹ with 8cm⁻¹ resolution, averaging 32 scans, providing an analysis time of approximately 15 seconds. This setup allowed for the development of a calibration to monitor ibuprofen content in the extrudate and establish a general process algorithm for content uniformity, demonstrating the potential of NIR analysis as a process analytical technology (PAT) tool for both process development and control.

What specific equipment was used to demonstrate the effectiveness of NIR spectroscopy for monitoring Hot Melt Extrusion (HME) and what were the key findings?

The study utilized the Thermo Scientific™ PRISM Pharmalab 16 HME twin-screw extruder and the Thermo Scientific™ Antaris™ FT-NIR instrument. The key finding was the successful application of the Antaris™ FT-NIR analyzer for measuring ibuprofen in the extrudate. A calibration was developed to monitor the output from the Pharmalab extruder in real time. PC scores plots in conjunction with analysis of variance algorithms were used to optimize the process conditions. The results demonstrated that NIR analysis can be used as a process analytical technology (PAT) tool for both process development and control, enabling real-time monitoring and optimization of HME processes.

Pharmaceutical Manufacturing Optimization via NIR Spectroscopy

Melt Away Formulation Challenges: How NIR Spectroscopy Optimizes Hot Melt Extrusion

Nico Varela in Tech & Innovation December 2025 • 5 min read.

"Unlock pharmaceutical formulation secrets with near-infrared spectroscopy, ensuring quality and efficiency in hot melt extrusion processes."

In the fast-paced world of drug discovery, where high-throughput screening technologies generate a multitude of potential drug candidates, a significant challenge arises: many of these new chemical entities suffer from poor solubility. This issue can severely impact the bioavailability of active pharmaceutical ingredients (APIs), hindering their effectiveness and delaying their journey to market. Overcoming these solubility hurdles is crucial for maintaining a healthy pipeline of new drug substances and ensuring that patients receive the treatments they need.

One innovative solution gaining traction in the pharmaceutical industry is hot melt extrusion (HME). This technique involves combining drugs with thermoplastic polymers at elevated temperatures, typically ranging from 50°C to 180°C. The extruder can be precisely controlled with different temperature settings, allowing for specialized functions such as melting, mixing, sequential addition of formulation constituents, and vacuum venting. By carefully manipulating these parameters, HME can transform poorly soluble drugs into formulations with enhanced bioavailability.

The use of HME is increasing because of its advantages, which include formulation of products with improved solubility and bioavailability, thus reducing dosing intervals for the patient. Formulations allow taste masking of APIs. The continuous technology is reproducible, avoiding batch-to-batch variability. As a continuous process, it allows lower cost manufacturing due to reduced operation steps and smaller volumes of materials in use. It creates thermodynamically stable solid solutions which can deliver improved temperature and mechanical stability of the product. Additionally, HME is amenable to in-line monitoring. Understanding the interactions between formulation characteristics and the extruder mechanisms is important to process efficiency.

NIR Spectroscopy: The Real-Time Monitoring Game Changer

Pharmaceutical Manufacturing Optimization via NIR Spectroscopy

Near-infrared (NIR) spectroscopy has emerged as a powerful tool for analyzing active ingredients in pharmaceutical formulations. Its non-destructive nature, excellent signal-to-noise ratios, and compatibility with fiber optics make it ideally suited for real-time monitoring of processes, aligning perfectly with the principles of Process Analytical Technology (PAT) and Quality by Design (QbD). This technology allows manufacturers to closely monitor and adjust their processes on the fly, ensuring consistent product quality and reducing the risk of deviations.

A study was conducted using a Thermo Scientific™ PRISM Pharmalab 16 HME twin-screw extruder to explore the influence of screw speed and throughput rate on the blend uniformity of an extrudate. The equipment and all the product contact parts of the extruder can be dismantled, allowing for thorough cleaning away from the extruder. Because the barrel is split, every part can be inspected for cleanliness.

Here’s why NIR spectroscopy is becoming the gold standard:

Non-Destructive Analysis: NIR allows for the analysis of samples without altering or damaging them, preserving valuable material and reducing waste.
Excellent Signal-to-Noise Ratios: NIR provides clear and reliable data, even with complex formulations, ensuring accurate monitoring and control.
Fiber Optic Compatibility: NIR can be easily integrated into existing production lines using fiber optics, enabling remote monitoring and real-time adjustments.

During the study, NIR spectra were collected using a Thermo Scientific™ Antaris™ FT-NIR instrument equipped with an extruder probe designed to take reflectance measurements of the extrudate in processes up to 300°C. The probe was fitted directly into the output die of the extruder, enabling real-time monitoring of the product. The analysis conditions included a scan range of 4000-10,000cm⁻¹ using 8cm⁻¹ resolution with 32 scans averaged, giving an analysis time of approximately 15 seconds. The analyzer was run with continuous spectral acquisition to collect repeatability data for each experiment.

Toward Optimized Pharmaceutical Production

The study demonstrated the successful application of the Antaris™ FT-NIR analyzer for measuring ibuprofen in extrudate. A calibration was developed that could be used to monitor the output from the Pharmalab extruder in real time. A general process algorithm was established for the content uniformity of the extrudate as changes were being made to factors in the extruder. PC scores plots in conjunction with analysis of variance algorithms could be used to optimize the process conditions under test. These relationships may be exploited within feed forward or feedback loops for immediate process control. Thus, NIR analysis has the potential for use as a process analytical technology (PAT) tool with extruders for both process development of new processes and control of existing ones.