Process analytical techniques for hot-melt extrusion and their application to amorphous solid dispersions.
Newly developed active pharmaceutical ingredients (APIs) are often poorly soluble in water. As a result the bioavailability of the API in the human body is reduced. One approach to overcome this restriction is the formulation of amorphous solid dispersions (ASDs), e.g., by hot-melt extrusion (HME). Thus, the poorly soluble crystalline form of the API is transferred into a more soluble amorphous form. To reach this aim in HME, the APIs are embedded in a polymer matrix. The resulting amorphous solid dispersions may contain small amounts of residual crystallinity and have the tendency to recrystallize. For the controlled release of the API in the final drug product the amount of crystallinity has to be known. This review assesses the available analytical methods that have been recently used for the characterization of ASDs and the quantification of crystalline API content. Well-established techniques like near- and mid-infrared spectroscopy (NIR and MIR, respectively), Raman spectroscopy, and emerging ones like UV/VIS, terahertz, and ultrasonic spectroscopy are considered in detail. Furthermore, their advantages and limitations are discussed with regard to general practical applicability as process analytical technology (PAT) tools in industrial manufacturing. The review focuses on spectroscopic methods which have been proven as most suitable for in-line and on-line process analytics. Further aspects are spectroscopic techniques that have been or could be integrated into an extruder.
Process Analysis and Technology (PA&T), Faculty Applied Chemistry, Reutlingen University, Alteburgstr. 150, 72762, Reutlingen, Germany.
Patrick
P
Hitzer
Process Analysis and Technology (PA&T), Faculty Applied Chemistry, Reutlingen University, Alteburgstr. 150, 72762, Reutlingen, Germany.
Tim
T
Bäuerle
Process Analysis and Technology (PA&T), Faculty Applied Chemistry, Reutlingen University, Alteburgstr. 150, 72762, Reutlingen, Germany.
Tobias
T
Drieschner
Process Analysis and Technology (PA&T), Faculty Applied Chemistry, Reutlingen University, Alteburgstr. 150, 72762, Reutlingen, Germany.
Edwin
E
Ostertag
AbbVie Deutschland GmbH & Co.KG, Knollstr. 50, 67061, Ludwigshafen, Germany.
Katharina
K
Paulsen
AbbVie Deutschland GmbH & Co.KG, Knollstr. 50, 67061, Ludwigshafen, Germany.
Holger
H
van Lishaut
Process Analysis and Technology (PA&T), Faculty Applied Chemistry, Reutlingen University, Alteburgstr. 150, 72762, Reutlingen, Germany.
Günter
G
Lorenz
Process Analysis and Technology (PA&T), Faculty Applied Chemistry, Reutlingen University, Alteburgstr. 150, 72762, Reutlingen, Germany. karsten.rebner@reutlingen-university.de.
Karsten
K
Rebner
D002626:Chemistry, Pharmaceutical; D004304:Dosage Forms; D004339:Drug Compounding; D004867:Equipment Design; D006358:Hot Temperature; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000379:methods*
D004304:Dosage Forms
Amorphous solid dispersions; Hot-melt extrusion; Pharmaceutical manufacturing; Process analytical technology; UV/VIS spectroscopy; Vibrational spectroscopy