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

This article shows the content of a poster which was presented at the 𝗘𝗨𝗣𝗳𝗜 𝗰𝗼𝗻𝗳𝗲𝗿𝗲𝗻𝗰𝗲 𝗶𝗻 𝗚𝗹𝗮𝘀𝗴𝗼𝘄 2023

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 ASDs

Table 1: Particle characteristics for Fluid Bed and Spouted Bed particles. 1) Characterization after Carr et al.

SEM Images

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

Figure 3: Results of XRPD measurements A)made directly after production B) made after two years of storage under ambient conditions — Figure 3: Results of XRPD measurements
A)made directly after production
B) made after two years of storage under ambient conditions

Conclusion

Both techniques proved to be promising tools for thedevelopment 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

(click the picture to enlarge the poster)

Source: A. Grave; B. Arlt | Glatt Pharmaceutical Services GmbH & Co. KG, Binzen, Germany,
Poster “Accessing amorphous solid dispersions for improved Solubility and Bioavailability in paediatric applications”

excipients formulation