Amorphous Solid Dispersions – Part 2

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 8

High Drug-Loading Amorphous Solid Dispersions

Amorphous Solid Dispersions (ASDs) have become a cornerstone technology for enhancing the oral bioavailability of poorly water-soluble drugs (BCS Class II and IV). However, conventional ASDs are often limited by low drug loadings (typically 10–30% w/w), resulting in high excipient burdens and bulky dosage forms that hinder patient compliance. This chapter explores the critical transition from traditional ASDs to High Drug-Loaded (HDL) ASDs, which aim to increase drug fractions beyond 50% w/w. We review the fundamental thermodynamic and kinetic challenges associated with HDL systems, specifically the increased risk of phase separation and recrystallization during storage and dissolution (the “spring-and-parachute” phenomenon). To address these limitations, various innovative formulation and manufacturing strategies are evaluated, including polymer combinations, coprecipitation, chemical and thermal crosslinking, electrospinning, and Atomic Layer Coating (ALC). Additionally, the potential of biomacromolecules, such as whey proteins, as alternative stabilization carriers is discussed. These advanced techniques enable the design of physically stable, high-performance systems that reduce tablet mass while maintaining superior dissolution and therapeutic efficacy. Ultimately, HDL ASDs represent a pivotal advancement in overcoming the practical barriers of oral delivery for challenging new chemical entities.

See the chapter

Kapourani, A., Barmpalexis, P. (2026). High Drug-Loading 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_8

Chapter 9

Downstream Processing of Amorphous Solid Dispersions of Drugs

The superior solubility and absorption of amorphous drugs have fueled massive research on Amorphous Solid Dispersions (ASDs), where “Generally Recognized as Safe” (GRAS) polymers stabilize the drug form. To meet clinical demand, industry has adopted continuous processing methods such as spray drying, hot-melt extrusion, and electrospraying. These technological advances, supported by predictive modeling and rigorous characterization, have enabled so far the development of over 1000 publications and 58 marketed products. Critically, ASDs have allowed high-molecular-weight, highly lipophilic drugs (logP > 5) to be formulated into life-saving therapies. This chapter reviews 25 years of ASD development, beginning with a longitudinal analysis of preparation trends and publication rates. It provides an extensive discussion on downstream processing, comparing the processability and tableting feasibility of ASDs produced via different methods. Key variables are examined, including polymer grade, formulation composition, and the impact of compression pressure, dwell time, and drug load on chemical and physical stability. The chapter concludes with a comprehensive survey of FDA- and EMA-approved ASD products. The increasing number of marketing licenses granted over the last 2.5 decades confirms that ASD-based products will remain a cornerstone of pharmaceutical research and formulation for years to come.

See the chapter

Partheniadis, I., Gkantanidou, M.M., Nikolakakis, I. (2026). Downstream Processing of Amorphous Solid Dispersions of Drugs. 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_9

Chapter 12

Regulatory Aspects and Commercialization of Drug Products Containing Amorphous Solid Dispersions

Amorphous solid dispersions (ASDs) have evolved to a commonly adopted approach for enhancing the bioavailability of poorly water-soluble drugs. This chapter discusses the regulatory framework relevant to the development of products containing ASDs, highlighting key ICH guidelines and their implications for stability, impurity control, specifications, pharmaceutical development, and bioequivalence studies. Differences in the Summary of Product Characteristics (SmPC) between ASD-based and conventional formulations are outlined, including aspects related to food effect, administration requirements, and packaging. A case study of Kalydeco^® tablets and oral granules illustrates how products containing ASDs are developed, assessed, and managed throughout the product lifecycle. Overall, science-based and regulatory-informed pharmaceutical development plays a major role in the quality, safety, and efficacy of medicinal products containing ASDs.

See the chapter

Gkantanidou, M.M., Nikolakakis, I., Partheniadis, I., Malamatari, M. (2026). Regulatory Aspects and Commercialization of Drug Products Containing 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_12

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 1 – coming soon