Hot Melt Extrusion (HME) has emerged as a powerful, scalable solution for formulating challenging APIs. In this blog Dr Mihaela Totolici, Head of Formulation Development, and Hiren Moradiya, Senior Formulation Scientist, explore how HME enhances solubility, boosts bioavailability and elevates formulation performance, helping unlock the full potential of even the most complex, poorly soluble APIs.
1. What role do Spray Dried Dispersions and Hot Melt Extrusion each play in improving API solubility?
Spray Dried Dispersions (SDDs) are solid dispersions designed to improve the solubility and bioavailability of poorly water-soluble molecules. The process involves dissolving the active pharmaceutical ingredient (API) in a suitable solvent along with a polymer, then removing the solvent to create an Amorphous Solid Dispersion (ASD).
Hot Melt Extrusion (HME) offers an alternative approach to producing ASDs without the use of solvents. In HME, the API is blended with a polymer and processed above its glass transition temperature, resulting in a uniform amorphous dispersion.
"HME ensures consistent product quality and improved reproducibility, making it a preferred choice for modern pharmaceutical manufacturing. This technique is eco-friendly, solvent-free, and highly scalable."
2. How does Hot Melt Extrusion enhance the solubility and bioavailability of poorly soluble drugs?
HME improves drug performance by converting the API from its crystalline form into an amorphous state using thermal and mechanical energy. The amorphous form has higher free energy than the crystalline form, which makes it more soluble in gastrointestinal fluids.
Polymers used in HME stabilise the amorphous drug, preventing recrystallisation during storage and administration. This combination ensures the drug remains in a more soluble state, leading to faster dissolution and better absorption—critical for improving bioavailability in poorly soluble drug candidates.
3. Beyond improving solubility, what other advantages does Hot Melt Extrusion offer for formulating challenging APIs?
HME brings a range of additional advantages, including the ability to create controlled release formulations, improve taste masking, and avoid the use of solvents—making it a more environmentally friendly option. Its versatility and scalability have positioned HME as a key technology for developing challenging formulations, particularly for Biopharmaceutics Classification System (BCS) Class II and IV APIs where solubility and permeability barriers often limit therapeutic performance.
4. What challenges should formulators be aware of when using Hot Melt Extrusion?
While HME offers many advantages, there are a few practical considerations to be aware of. The process tends to work best when the API has good thermal stability, but even heat sensitive APIs can often be processed successfully with the right combination of polymers, plasticisers and carefully chosen processing conditions—so high temperatures aren’t always required.
There is also an element of process optimisation involved, as fine tuning parameters like temperature profiles, screw design and residence time is key to achieving consistent, reliable performance. The good news is that ongoing advancements in equipment and formulation know how have made this optimisation far more streamlined and robust than ever before.
"Because of this progress, HME has become a highly effective option for developing challenging, poorly soluble drugs—often unlocking improvements in performance that traditional approaches simply can’t deliver."
5. Can Hot Melt Extrusion be used as a scalable process?
One of HME’s greatest strengths is its exceptional scalability. In this continuous process, the API, polymers, and any required plasticisers or surfactants are heated, blended, and pushed through an extruder to form a uniform solid material. Because it operates continuously, HME transitions effortlessly from early-stage development to full commercial manufacture, while minimising variability and ensuring consistent product performance at every scale.
HME equipment ranges from small laboratory extruders for formulation screening to large industrial systems capable of processing hundreds of kilograms per hour. This flexibility allows pharmaceutical companies to start with feasibility studies and scale up predictably. Furthermore, HME aligns with modern manufacturing principles like Quality by Design (QbD) and continuous processing, ensuring efficiency, reproducibility, and regulatory compliance.
6. How does Arcinova apply Hot Melt Extrusion across different development stages, from early formulation work to largescale production?
At Arcinova, we use two advanced HME platforms tailored to different development stages:
- 11 mm Pharma 11 twin screw extruder– Ideal for early-stage formulation work and small-scale trials.
- 16 mm Leistritz twin screw extruder – Designed for large-scale production, ideal for formulations with moderate melt viscosity.
Our process begins with selecting the right polymers and excipients to enhance solubility and stabilise the drug in its amorphous form. We then optimise key extrusion parameters—such as temperature, screw speed, and feed rate—to ensure uniform dispersion. Finally, we perform rigorous analytical testing to confirm stability, homogeneity, and performance, guaranteeing high-quality formulations.