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The case study wants to verify the ability of IMA coating pan to perform a coating process on soft gelatine capsules.

Application of acrylic enteric coating directly on soft gelatine capsules using a GS coating pan.

Introduction

Literature about coating soft gelatine capsules with aqueous, polymeric solutions or dispersions is scarce, and this process poses a tough challenge due to the difficulties in application, formation and adhesion of the film solution to the substratum, particularly in the first phase. High heat efficiency equipment, a correct equilibrium of the process variables and an adequate composition of the polymeric dispersion are the basic requirements to obtain a high quality finished product.

 

Aim of the study

The aim of this study was to verify the following:

  1. the ability of the coating pan to successfully perform a coating process applied to soft gelatine capsules;
  2. the possible application of an isolating sub-coating and an enteric coating.

 

Materials and methods

The soft gelatine capsules, containing a non steroidal anti-inflammatory standard drug, were produced with a capsule filling machine with rotative dies and a product output of 30,000 cps/hour (RP Scherer, Aprilia, LT, I), using oval shaped dies with a diameter of 6 mm. They were subsequently coated in a laboratory coating pan (GS, IMA,) with an initial application of a cellulosic aqueous solution (isolating subcoating, Table 1), followed by an acrylic aqueous dispersion (enteric coating, Table 2).

 

Materials Quantity (g)
Hydroxypropilmetil cellulose (Pharmacoat 606) 238.5
Citric acid 95.4
Glycerol (85%) 23.9
Purified water 2,395.0
Total 2,752.8
Total dry substance 354.3

Table 1: Composition of the sub-coating solution.

 

Materials Quantity (g)
Acrylic aqueous dispersion (Eudragit L 30 D55) 1,000
Triethyl citrate 30
Talc 164
Titanium Dioxide 105
Purified water 1,696
Total 2,995
Total dry substance 599

Table 2: Composition of the enteric dispersion.

 

The execution of the film coating process of the soft gelatine capsules can be summarised as follows:

  1. pre-heating of the coating pan
  2. loading of the cores and relevant gradual heating
  3. application of the coating solution thanks to proper atomization on the heated cores
  4. drying and gradual cooling of the cores.

The Table 3 shows the operating conditions used during the coating process.

 

Parameter Dimension
Batch size (Kg) 7
Inlet air temperature (°C) 45-50
Core temperature (°C) 32-34
Air volume (m3/h) 130-140
Spraying rate (ml/min) 10-16
Pan rotation speed (rpm) 22-24
Diameter of the nozzle (mm) 1.4
Atomization air pressure (bar) 1.6
Process time (hours) 3.5

Table 3: Process parameters.

 

Results and discussions

After the final set-up of the process conditions, mainly focused on core temperature and pan rotation speed, the coating process itself went smoothly: no problems regarding the capsules sticking to one another or to the internal surface of the pan were noticed.
The gelatine cores, if treated at a temperature higher than 34°C, showed little modifications in shape and volume.
From a technological and process feasibility point of view, the application of a sub coating film was not necessary; this film was suitably formulated to favour both the adhesion of the gastro-enteric film to the gelatine sub-coat and to preserve the content from the acid environment.
The yields obtained with the application of the coating material were significantly higher when applied to capsules having a sub-coating (98% vs 82%).
All products, having different characteristics in terms of quantity of acrylic enterosoluble material, with and without isolating film, resulted to be gastro-resistant, passing the disaggregation test according to the USP (Table 4).

 

Parameters Gastroenteric coating
5% 6% 7% 8%
Average weight (mg) 625.5 629.1 632.9 636.5
Standard deviation (mg) 4.6 5.2 4.4 3.2

Disaggregation test (USP), into:

– Simulate gastric juice:
– Simulate enteric juice:

– A
– B
– C

> 1h

 

8
10
13

> 1h

 

6
8
11

>1h

 

9
11
13

>1h

 

8
12
14

A = Disappearance of the enteric coating
B = Opening of the capsules
C = Total Disintegration
Table 4: Technological and physical properties of the capsules without sub-coating, coated with increasing quantities of gastroenteric film (batch 3).

 

The isolating sub-coating caused a slight delay in dissolving the gastro-resistant membrane, thus prolonging the time required for complete disaggregation of the capsules. The elimination of a coating phase undoubtedly makes the process easier and gives economical advantages.
The stability of the gastro-resistant properties will be decisive for the evaluation of the quality of the acrylic coating directly applied to the soft gelatine capsules, without the intermediate film for adhesion and isolation. 

 

Parameters Gastroenteric coating
5% 6% 7% 8%
Average weight (mg) 638.9 643.5 648.0 652.6
Standard deviation (mg) 5.3 5.9 3.9 4.5

Disaggregation test (USP), into:

– Simulate gastric juice
– Simulate enteric juice:

– A (min)
– B (min)
– C (min)

> 1h

 

6
9
11

> 1h

 

9
12
16

> 1h

 

9
12
15

> 1h

 

12
12
19

A = Disappearance of the enteric coating
B = Opening of the capsules
C = Total Disintegration

Table 5: Technological and physical properties of the capsules with a 2% of sub-coating and coated with increasing quantities of gastroenteric film (batch 4).

 

Parameters Gastroenteric coating
5% 6% 7% 8%
Average weight (mg) 656.6 661.1 665.6 670.1
Standard deviation (mg) 4.9 6.7 5.9 5.3

Disaggregation test (USO) into:
– Simulate gastric juice
– Simulate enteric juice: 

– A (min)
– B (min)
– C (min)

>1

 

10
12
17

>1

 

11
16
19

>1

 

14
17
20

>1

 

14
16
19

A = Disappearance of the enteric coating
B = Opening of the capsules
C = Total Disintegration

Table 6: Technological and physical properties of the capsules with a 6% of sub-coating and coated with increasing quantities of gastroenteric film (batch 5).

 

Conclusions

The results obtained in terms of the coating process and the gastro-resistance of the soft gelatine capsules were interesting and satisfactory.
The stability of the technological and gastroenteric properties is crucial to the evaluation of the final quality of the gastrosoluble film coating to be used. The data resulting from this experience demonstrate the ability of the IMA coating and will stand as a basic reference for the development of additional formulating studies on film solutions obtained from aqueous dispersions.

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