Accessing amorphous solid dispersions for improved Solubility and Bioavailability in paediatric applications

Accessing amorphous solid dispersions for improved Solubility and Bioavailability in paediatric applications

Glatt Pharmaceutical Services - CDMO Unlimited Glatt Pharmaceutical Services - CDMO Unlimited

Glatt Pharmaceutical Services - CDMO Unlimited

The drug product CDMO outsourcing partner for the pharmaceutical industry. OSDs from product idea to commercialisation.

发布日期: 2024年1月30日
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Multiparticulates can be an interesting approach in paediatric drug delivery but what to do when you have BCS class II drug candidate? The pellet solutions shown in this poster by Annette Grave and Bastian Arlt from Glatt Pharmaceutical Services - CDMO Unlimited show some answers we have to the topic.

Introduction

  • BCS class II drugs show a low solubility. Modern paediatric formulations are needed to obtain high acceptance of patients at recommended daily doses
  • Hot-melt extrusion (HME) and Spray Drying (SD) are the standard preparation techniques for ASD formulation attempts [1]
  • Both products are not direct processable to capsules and need further preparation [2,3]

Objectives

  • Investigating two alternative fluid bed systems for the preparation of a free-flowing product for further processing (e.g., filling into capsules)
  • Layering an ASD on beads in a Fluid-Bed-Wurster
  • In-situ SD and agglomeration in a Spouted Bed

Materials

  • 40 % (w/w) Nifedipine as model BCS Class II drug
  • 60 % (w/w) Kollidon VA64, a Vinyl-pyrrolidone/vinyl-acetate copolymer
  • Solvent: Acetone
  • Manufactured in a Glatt Wurster-System and ProCell-Labsystem (Glatt Ingenieurtechnik GmbH, Germany)

Figure 1: Illustration of the manufacturing process for layered ASD pellets produced in the Fluid Bed and for ASD pellets from direct pelletization in the Spouted Bed.

Characterization of the ASD

Table 1: Particle characteristics for Fluid Bed and Spouted Bed particles
Figure 2: SEM images A: ASD layered pellet (Fluid Bed) B: cut trough ASD layered pellet (Fluid Bed) C: ASD pellet from direct pelletization (Spouted Bed) D: cut trough ASD pellet from Spouted Bed
Figure 3: Results of XRPD measurements A)made directly after production B) made after two years of storage under ambient conditions
Figure 4: Dissolution results of the prepared pellets in 750 ml PBS pH 6.5 observed over 3h; Temperature: 37℃ ± 0.5 ℃; Paddle speed: 100 rpm; c(100%) = 80 μg/mL

Conclusion

  • Both techniques proved to be promising tools for the development and manufacturing of ASDs ? Stable over a long time (up to 2 yrs.) ? Good flow properties for further processing to e.g. capsules
  • Good dissolution performance
  • ?Up-scaling to pilot or production scale possible
  • Suitable for batch and continuous process design

See the full poster?on “Accessing amorphous solid dispersions for improved Solubility and Bioavailability in paediatric applications”?here

For more information about the full services and solutions offered by Glatt Pharmaceutical Services - CDMO Unlimited with sites in Germany and USA please contact us via [email protected] or our BD colleagues Dominik Kronauer and Philippe Tschopp for our European operations and Darcy Holding and Steve Radovanovich for our US operations.




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