Hot Melt Extrusion of Amorphous Solid Dispersions

Abstract

Hot melt extrusion (HME) is a frontline manufacturing solution for pharmaceutical amorphous solid dispersions. The status of HME technology is validated by the presence of successful commercial solid dispersion products, and is seeing widespread use in early‐stage R&D laboratories that are formulating poorly soluble compounds. This chapter describes a number of important factors that justify HME suitability for solid dispersion applications, ranging from materials performance and quality, equipment performance and versatility, and the proven ability generate to robust finished dosage forms that provide enhanced and controlled solubility behavior leading to improved bioavailability. Solid dispersion development using hot melt extrusion typically includes in vitro and/or in vivo assessment of early formulation prototypes before any process development has occurred. Screening of early prototypes is common because demonstration of a solubility or bioavailability increase will be a critical selection criterion for a solid dispersion.

Development of micro-fibrous solid dispersions of poorly water-soluble drugs in sucrose using temperature-controlled centrifugal spinning

“…It is therefore logical to explore the use of centrifugal spinning processes as a means of producing solid dispersions, given the high surface area generated which may potentially further enhance dissolution advantages. Table 1 compares the technological aspects of the most common methods for the manufacture of solid dispersions with electrospinning and the centrifugal spinning process [25] , [26] , [27] , [29] , [18] , [30] , [31] , [32] , [33] , [34] .…”

Coamorphous Active Pharmaceutical Ingredient–Small Molecule Mixtures: Considerations in the Choice of Coformers for Enhancing Dissolution and Oral Bioavailability

“…Large-scale production could include spray drying, 74,89,90 solvent precipitation methods, 25,91,92 and melt extrusion. 20,93,94 Production specific parameters, such as solubility for spray drying or melting points for extrusion, should be assessed for each system. Characterization and assessment of the larger scale samples will need to be performed to ensure that the materials have the same critical attributes as those produced at small scale.…”

Multiple Linear Regression Modeling To Predict the Stability of Polymer–Drug Solid Dispersions: Comparison of the Effects of Polymers and Manufacturing Methods on Solid Dispersion Stability

“…Choosing an appropriate polymer and processing method is pivotal in producing a successful product as it will greatly affect the stability of the solid dispersions. The most commonly used manufacturing methods are spray-drying and hot melt extrusion (HME) as these are relatively easy to scale up and produce well mixed dispersions 11,12 . The chosen polymer carrier stabilises both the drug in the solid form and in the solid-solution, retarding crystallisation 7,13 .…”

“…Choosing an appropriate polymer and processing method is pivotal in producing a successful product as it will greatly affect the stability of the solid dispersions. The most commonly used manufacturing methods are spray-drying and hot melt extrusion (HME) as these are relatively easy to scale up and produce well mixed dispersions. , The chosen polymer carrier stabilizes the drug both in the solid form and in the solid solution, retarding crystallization. , Solid dispersions have been extensively studied in this context (reviewed by Leuner and Dressman). Solid dispersions have been used successfully to enhance the bioavailability of drugs in several marketed products as summarized in Table .…”

“…The most commonly used manufacturing methods are spray-drying and hot melt extrusion (HME) as these are relatively easy to scale up and produce well mixed dispersions. 11,12 The chosen polymer carrier stabilizes the drug both in the solid form and in the solid solution, retarding crystallization. 7,13 Solid dispersions have been extensively studied in this context (reviewed by Leuner and Dressman 14 ).…”