To Determine the Dosing Disk and Encapsulation Speed for Encapsulation of a Drug
Product Using Automated Encapsulator
Bhavesh Barot, Lalji Kathiria, Milan Babubhavesh.barot@thermofisher.com | lalji.kathiria@thermofisher.com | milan.babu@thermofisher.com

Thermo Fisher Scientific

PURPOSERESULT(S)The purpose of this research work was:

Physical properties of the blend:

1) to determine the dosing disk for automatedencapsulator in order to obtain the target fill
weight during the encapsulation
2) to optimize the encapsulation speed for theencapsulation processOBJECTIVE(S)The overall objective of the research work was todetermine the optimal equipment setting for an
encapsulation process using automatedencapsulator

METHOD(S)••••Placebo Direct blend was prepared followed byencapsulation using automatic encapsulator (Bosch1700). The placebo formulation was selected forthis trial as drug load is very low (maximum 1%)
and it is representative of the active formulation.
One common blend was manufactured at a scale of
80 kg comprising diluent, Super Disintegrant,lubricant. The blending was performed using 325 L
tote using Gallay tote blender.
The common blend was split into three batches,
where Batch A, Batch B and Batch C wereencapsulated with 12 mm, 11.5 mm and 10 mm
Size 4 dosing disk respectively using similar fillweight. Each batch was encapsulated at threedifferent encapsulation speeds i.e. 800 (low), 900(medium) and 1000 (high) caps / min.
The capsules were polished, and metal checked inline using Combo Capsule Polisher/ Metal detector;
and further check-weighed using Bosch checkweigher fitted with Size 4 change parts. The trials
were assessed for filling the capsules with target fill
weight with minimal weight variation.

• The physical properties of the final blend (PSD,Bulk/tap density and flow) resulted in acceptablecharacteristics. The PSD data shows that 70% of theparticles were beyond 140 mesh (higher fines) screen.
The formulation consists of Microcrystalline cellulose
and is a major contributor towards the fines in theblend. Although the flow was characterized as beingpoor, there were no flow issues encountered during
encapsulation.

Table 1: Physical test results of the direct blendTestParticle Size
Distribution(% Retained)

Encapsulation:• No technical issues were encountered during theencapsulation of Batch A and B, however for Batch C,
the fill weight could not be achieved. Hence, nofurther evaluation was performed on Batch C.
• For Batch A and B, the encapsulation process wasstable and consistent (≈ 2 hr. 15 minutes in duration)at three different encapsulation speeds producing aminimal number of rejects. The results show that no
significant differences between both batches atdifferent encapsulation speeds. The RSD was less than
2% indicating that the weights were well controlledthroughout the encapsulation process. Both Batch A
and B batch showed lower % rejects at higher speed(1000 caps/ min) compared to 900 and 800 caps/ min.
• The filled capsules showed no visual defects based onlevel II AQL criteria for appearance. Overall, the results
pertaining to the filled capsules indicate a stableencapsulation process. However, from the % rejects
the Batch A showed better weight controls over Batch
B. Therefore, based on these results, it is suggested touse 12 mm dosing disc and a target speed of 900
capsules / minute ( with ± 100 caps/minute range) for
future trials.

CONCLUSION(S)Bulk/Tapped Density

Data / Process Stage

Encapsulation

Mesh Size

Final Blend#40 Mesh (425 µm)

0.4#60 Mesh (250 µm)

0.5#80 Mesh (180 µm)

9.8#100 Mesh (149 µm)

8.9#140 Mesh (150 µm)

44.3#270 Mesh (90 µm)

5.7

Pan

30.4

Bulk density (g/ml)

0.383 / 0.383

Tapped density (g/ml)

0.521 / 0.521

Hausner ratio

1.363 /1.350

Compressibility Index(%)

FlowDirect Blend for26.61 / 25.93

Flow Character

Poor

Flow Angle

36.6°

Flow Index0.45

Flow Quality

Poor• The evaluation of the quality of the manufacturing
process and product was based on weight control
during encapsulation at different speed using different
dosing discs.
• Properties of blend and capsules that were ofparticular interest includes bulk / tapped density,
particle size distribution, capsule appearance, closed
length and weight variation and hence they are
considered as critical quality attributes of theencapsulated drug product.
• In conclusion, the encapsulation trials conducted atthree different speeds using 12 mm and 11.5 mm
dosing disc had no technical concerns except for 10.5mm dosing disc. The 10.5 mm dosing disc failed toachieve the target fill weight and may not be suitable
for this product. Based on the results, 12 mm dosing
disc and 900 ± 100 capsules/minute encapsulation
speed is recommended for all future trials.

Figure 1: Tamping pin adjustment for obtaining target weightusing automated encapsulator

REFERENCES:
1. Wagner, B., Brinz, T., Otterbach, S. and Khinast, J.,
2018. Rapid automated process development of acontinuous capsule-filling process. International
journal of pharmaceutics, 546(1-2), pp.154-165.