Amorphous Solid Dispersions – Part 1

Amorphous Solid Dispersions

See the new book, edited by Ioannis Nikolakakis, Ioannis Partheniadis. This book is intended for pharmaceutical formulation scientists and researchers, as well as students and academics with interest in the broader area of solid pharmaceutics.

Description: The book provides a comprehensive overview of pharmaceutical amorphous and co-amorphous solid dispersions, covering topics ranging from fundamentals to preparation approaches. It covers principles of ASD formation and the role of molecular interactions, preparation methodology and formulation challenges, characterization methods, physicochemical stability and regulatory aspects. This book is intended for pharmaceutical formulation scientists and researchers, as well as students and academics with interest in the broader area of solid pharmaceutics.

• Offers coverage of all aspects of pharmaceutical amorphous solid dispersions, from fundamentals to future perspectives
• Provides cutting-edge technology and reports the latest research findings, techniques, and advancements in the field
• Presents insights and guidance on various preparation techniques, characterization methods, and regulation

Chapter 3

Polymer Selection for the Successful Preparation of Amorphous Solid Dispersions

The increasing prevalence of poorly water-soluble drug candidates has positioned amorphous solid dispersions (ASDs) as a key enabling technology in modern pharmaceutical development. While the amorphization of active pharmaceutical ingredients is central to this approach, the long-term stability, manufacturability, and biopharmaceutical performance of ASDs are critically governed by the properties of the polymeric carrier. This chapter provides a structured and mechanistic perspective on rational polymer selection for the successful development of ASDs, with a particular focus on antifungal drugs as model compounds.

Key physicochemical principles underlying polymer function: miscibility, intermolecular interactions, glass transition behavior, and steric effects are discussed in relation to their impact on supersaturation generation, crystallization inhibition, and physical stability. Practical decision criteria for polymer selection are outlined, integrating compatibility screening, predictive and data-driven tools, manufacturability constraints, and regulatory considerations. Established, next-generation, and naturally derived polymer classes are reviewed in the context of their advantages and limitations.

Case studies involving azole and non-azole antifungal agents illustrate how polymer chemistry, grade selection, and processing route jointly determine formulation performance and clinical relevance. Finally, emerging early de-risking strategies, including advanced in vitro methodologies and new approach methodologies (NAMs), are highlighted as essential components of future ASD development workflows. Collectively, this chapter emphasizes that polymers are not inert excipients but active design elements whose informed selection is pivotal for translating ASD technologies into robust and clinically reliable drug delivery systems.

See the chapter

Djuris, J., Medarevic, D., Pavic, A., Ibric, S. (2026). Polymer Selection for the Successful Preparation of Amorphous Solid Dispersions. In: Nikolakakis, I., Partheniadis, I. (eds) Amorphous Solid Dispersions . AAPS Introductions in the Pharmaceutical Sciences, vol 5. Springer, Cham. https://doi.org/10.1007/978-3-032-24883-1_3

Chapter 4

Hot Melt Extrusion (HME) as an Innovative Technology for the Design and Development of Amorphous Solid Dispersions

Hot melt extrusion (HME) is increasingly employed as a continuous manufacturing technology for producing amorphous solid dispersions (ASDs) capable of overcoming solubility and bioavailability limitations associated with modern drug candidates. By enabling intimate molecular mixing of drug and polymer under controlled thermal and mechanical conditions, HME transforms crystalline active pharmaceutical ingredients into kinetically stable amorphous systems with enhanced dissolution and supersaturation behaviour. The quality and performance of these extrudates are driven by defined critical quality attributes (CQAs), including glass transition temperature, degree of crystallinity, dissolution kinetics and impurity profiles. These are influenced by critical material attributes (CMAs) such as polymer characteristics, drug loading, particle size, and hygroscopicity, as well as critical process parameters (CPPs), including barrel temperature, screw speed, residence time, and specific mechanical energy. A quality by design (QbD) framework supports rational formulation and process development by linking CQAs, CMAs and CPPs to a justified design space. Contemporary approaches integrating Process Analytical Technology (PAT) and real-time release testing (RTRT) enable continuous monitoring of mixing, amorphization and chemical stability, aligning with the expectations of FDA, EMA and ICH guidelines. Recent case studies demonstrate the versatility of HME beyond solubility enhancement, including taste masked paediatric dosage forms, abuse deterrent designs, fixed dose combinations and gastroretentive systems. Altogether, these advances highlight HME as a scalable, solvent-free and regulatory aligned technology for developing high-performance oral drug products with improved patient outcomes.

See the chapter

Kolipaka, S.S., Douroumis, D. (2026). Hot Melt Extrusion (HME) as an Innovative Technology for the Design and Development of Amorphous Solid Dispersions. In: Nikolakakis, I., Partheniadis, I. (eds) Amorphous Solid Dispersions . AAPS Introductions in the Pharmaceutical Sciences, vol 5. Springer, Cham. https://doi.org/10.1007/978-3-032-24883-1_4

Chapter 7

Evolving Perspectives on Co-amorphous Drug Delivery Systems: From Fundamentals to Recent Advancements (2021–2025)

Co-amorphous drug delivery systems (CAMS) have emerged as a robust alternative to traditional polymer-based amorphous solid dispersions (ASDs) for addressing the poor aqueous solubility and limited bioavailability of Biopharmaceutics Classification System (BCS) Class II and IV drug candidates. While polymer-based systems frequently require high amounts of excipients and have limited drug capacity, CAMS provide a distinct alternative. CAMS are characterized as single-phase amorphous systems containing low-molecular-weight components in either drug-to-drug or drug-to-excipient combinations. They achieve stability through specific intermolecular interactions including hydrogen bonding and ionic forces. This chapter provides a comprehensive review of the CAMS landscape, beginning with an overview of fundamental preparation methods and characterization techniques. It highlights the transition from conventional analytical tools like X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) to sophisticated modern approaches, including solid-state NMR (ssNMR) and computational molecular dynamics (MD) simulations, which offer deeper insights into molecular packing and stability. The discussion centers on the critical quality attributes (CQAs) of CAMS: coformability, physical stability, and dissolution performance. Finally, the chapter analyzes major developments in the field from 2021 to 2025, identifying research gaps and future directions to support the clinical translation of these innovative delivery systems into viable pharmaceutical products.

See the chapter

Partheniadis, I., Martins, I.C.B., Nikolakakis, I., Rades, T. (2026). Evolving Perspectives on Co-amorphous Drug Delivery Systems: From Fundamentals to Recent Advancements (2021–2025). In: Nikolakakis, I., Partheniadis, I. (eds) Amorphous Solid Dispersions . AAPS Introductions in the Pharmaceutical Sciences, vol 5. Springer, Cham. https://doi.org/10.1007/978-3-032-24883-1_7

See the full book here

Amorphous Solid Dispersions, Ioannis Nikolakakis, Ioannis Partheniadis, The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2026, https://doi.org/10.1007/978-3-032-24883-1

There are the additional articles with the remaining book chapter contents:

• See Part 2 – coming soon