Preparation of products containing nicotinamide with or without a subcoat

Coated pellets containing nicotinamide for the main work were prepared with or without subcoats. Four different subcoats were used i.e. HPMC, EC, and a combination of EC and PVA at two ratios. Sugar spheres were coated first with HPMC to have a thin layer of about 10 µm. Hereafter the thin and homogeneuos layer with primary nicotinamide was coated on the HPMC pellets. Each subcoat was then layered in different thicknesses. If pellets without any subcoats were required then enteric coat was directly applied on the nicotinamide loaded pellets. Figure 2.30 shows the building up of the expected finished products.

1 2 3

1: Sugar sphere 2: HPMC-MO 3: Enteric coat

Figure 2.30: Finished enteric coated pellets containing nicotinamide and different subcoats.

2.4.6.1 The first layer: HPMC

The first layer made from HPMC was used as a mechanical protecting layer of cores.

HPMC coated pellets (Product PP) were prepared from sugar spheres fraction size 800 - 1000 µm. The preparating technique of the solution, formulation R1, was as prescribed in 2.4.4.1. The product was manufactured on an Aeromatic MP-1 with inserted filters and process number X7, Table 2.12.

2.4.6.2 The second layer: Nicotinamide-HPMC

The thin layer containing nicotinamide was prepared by layering the solution containing nicotinamide and HPMC as a binder by using HPMC coated pellets (Product PP) as a loading material. These nicotinamide loaded pellets (Product AA, Aa, aA and aa) were used as a loading material to be coated with different subcoats later on. If no subcoat

1 2 3 4 5

1: Sugar sphere 2: HPMC

3: HPMC-Nicotinamide 4: Subcoat or no subcoat 5: Enteric coat

was needed then these nicotinamide loaded pellets (Nico pellets) were used directly as a loading material for the coating with the dispersion containing CAP and a plasticizer.

2.4.6.2.1 Preparation of a solution containing nicotinamide

As shown in Table 2.15, R3, the 20 % w/w solution of nicotinamide and Pharmacoat 603W as a binder was prepared. Nicotinamide is a well soluble water substance and therefore it was added into water of 2/3 total amount while stirring. The small amount of 3.0 g of Pharmacoat 603W accurately weighed was slowly dispersed into the solution of nicotinamide after nicotinamide was totally dissolved while constantly stirring with a magnetic stirrer {44}.

2.4.6.2.2 Coating process

Coated pellets containing nicotinamide (Nico pellets) were prepared according to the process number X8, Table 2.12. HPMC coated pellets (Product PP, Pp, pP and pp) 500 g were used as cores to prepare four charges of Nico pellets (Product AA, Aa, aA and aa), respectively.

2.4.6.3 The third layer: Different intermediate coats ( subcoats )

A subcoat from four different formulations were prepared by using Nico pellets (Product AA, Aa, aA, aa) as a loading material.

2.4.6.3.1 Subcoat from HPMC

The preparating technique of solution was almost the same as mentioned in 2.4.4.1 on basis of the formulation R4, Table 2.15. The difference was that the orange colour powder (L-orange Z 2010, part 2.1.10.3) was added into heated water. Pharmacoat 603W was added after the colour powder was totally dissolved. The process number X9, Table 2.12 and the Aeromatic MP-1 {20} with inserted filters were used for the manufacture of this product. The resulted product has an orange colour which came from the marker incorporated in the subcoat layer.

2.4.6.3.2 Subcoat from EC

2.4.6.3.2.1 Preparation of a dispersion containing Aquacoat ECD and DBS

All substances i.e., Aquacoat ECD, DBS and red colour powder were exactly weighed using a digital balance {17}. 20.0 g of DBS was added into 333.0 g of Aquacoat ECD-30 while constantly stirring with a magnetic stirrer {43}. After DBS was homogeneuos dispersed i.e. about 15 min, 2 g of red colour powder (L-Rot Z 3020, part 2.1.10.2) was added. Finally the rest amount of water was added into the dispersion to receive the concentration of 20 % w/w. Further mixing for at least one hour followed. The dispersion was filtered through the 100 µm sieve before use as a coating dispersion and the constant stirring {43} of the dispersion during the coating process was performed.

2.4.6.3.2.2 Coating process

The formulation R5, Table 2.15 and the process number X10, Table 2.12 and the Aeromatic MP-1 with inserted filters served for the production. The resulted product has a pink colour.

2.4.6.3.3 Subcoat from E&P

2.4.6.3.3.1 Preparation of a dispersion containing Aquacoat ECD and PVA

All substances i.e., Aquacoat ECD, DBS, Mowiol 4-98 and green colour powder were exactly weighed on a digital balance {16,1}. The first liquid was prepared by adding 2.0 g of green colour powder (L-Grün Z 6130, 2.1.10.4) into 1/3 of total required amount of water which hereafter was heated to 80 °C. 30.0 g of Mowiol 4-98 was slowly added into this heated water while constantly stirring {44}. The second liquid was prepared by adding 20.0 g of DBS into 333.0 g of Aquacoat ECD-30 while constantly stirring with a magnetic stirrer {43}. After DBS was homogeneuosly dispersed i.e. about 15 min, the first liquid containing green colour was added into the white coloured dispersion while constantly stirring. The rest amount of water was added into the dispersion to receive the concentration of 20.0 % w/w. Further mixing for at least one hour followed {43}. The

dispersion was filtered through the 100 µm sieve before coating and the constant stirring {43} of the dispersion during the coating process was performed.

2.4.6.3.3.2 Coating process

This product was manufactured on the basis of the formulation R6, Table 2.15 and the process number X11, Table 2.12 using Aeromatic MP-1 with inserted filters. The resulted product had a green colour.

2.4.6.3.4 Subcoat from P&E

2.4.6.3.4.1 Preparation of a dispersion containing PVA and Aquacoat ECD

All substances i.e., Mowiol 4-98, Aquacoat ECD, DBS and blue colour powder (Indigotin, 2.1.10.1) were exactly weighed on a digital balance {16,1}. The first liquid was prepared by adding 2 g of blue colour powder into 1/3 of total required amount of water which was then heated up to 80 °C. 100.0 g of Mowiol 4-98 were slowly added into this heated water while constantly stirring {44}. The second liquid was prepared by adding 6.0 g of DBS into 100.0 g of Aquacoat ECD-30 while constantly stirring with a magnetic stirrer {43}. After DBS was homogeneuosly dispersed i.e. about 15 min, the first liquid containing blue colour was added into the white coloured dispersion while constantly stirring. The rest amount of water was added into the dispersion to receive the concentration of 7.0 % w/w. Further mixing for at least one hour followed. The dispersion was filtered through the 100 µm sieve before use as a coating dispersion and the constant stirring of the dispersion during the coating process was performed.

2.4.6.3.4.2 Coating process

The product was manufactured according to the formulation R7, Table 2.15 and the process number X12, Table 2.12 using Aeromatic MP-1 with inserted filters. The finished coated product has a blue colour.

2.4.7 Preliminary studies of enteric coating with CAP and different