Study of a low-dose capsule filling process by dynamic and static tests for advanced process understanding

Area of Science:

• Pharmaceutical Technology
• Powder Engineering
• Drug Delivery Systems

Background:

• Accurate mg-range capsule filling is crucial for effective drug delivery.
• Understanding powder flow and filling dynamics is essential for process optimization.
• Dosator capsule filling machines require precise control for low-dose accuracy.

Purpose of the Study:

• To investigate the process steps influencing capsule filling accuracy.
• To evaluate the performance of a novel static filling system compared to a dynamic system.
• To assess the impact of powder properties and instrumental settings on fill weight and variability.

Main Methods:

• Dynamic tests using a laboratory dosator filling machine.
• Static tests using a novel, stand-alone filling system.
• Experiments with three lactose grades, varying capsule size, nozzle diameter, powder bed height, and filling speed.

Main Results:

• Fill weight was sensitive to the gap at the powder container bottom, particularly for cohesive Lactohale 220.
• The static test tool successfully filled Lactohale 220 (5-20 mg) without pre-compression, achieving acceptable relative standard deviations (RSDs).
• Vibration during static sampling significantly reduced fill weight variability, though no direct correlation was found with dynamic mode vibration effects.

Conclusions:

• Fine-tuning instrumental settings enables precise filling of challenging powders with dosator capsule filling machines.
• The static mode setup is suitable for studying fill weight and variability, especially for cohesive powders.
• This research contributes to the scientific qualification of dosator nozzles for low-fill weight applications (1-45 mg).