Bromhexine Hydrochloride Syrup

MANUFACTURING DIRECTIONS

1. Add 250.0 g of item 10 to a suitable stainlesssteel manufacturing vessel and heat to 65 to70C.

2. Add 20.0 g of item 2 in a separate stainless steelcontainer and mix item 8 using Ekato stirrer,carefully avoiding lump formation.

3. Transfer the slurry to the manufacturing vesselwhile continuing to mix to make a clear muci-lage. Avoid air entrapment.

4. Cool down to 30C while mixing at slow speed.5. Transfer the mucilage to container. Load 100.0

g of item 2 to the manufacturing vessel.6. Add item 6 in a separate stainless steel con-

tainer and dissolve item 3 using stirrer.7. Add 60.0 g of item 2 to the container while

mixing at slow speed.8. Add and dissolve item 1 to the container while

mixing at slow speed. Avoid splashing of thesolution. Check that bromhexine is dissolvedcompletely.

9. Add item 4 to the container and mix well.Transfer the solution to the manufacturing ves-sel while mixing at high speed.

10. Rinse the container with 20.0 g of item 2 andtransfer the rinsing to the manufacturing vesselwhile mixing.

11. Rinse the container with 20.0 g of item 10 andtransfer the rinsing to the manufacturing vesselwhile mixing. Add 15.0 g of item 10 in a sep-arate stainless steel container and dissolve item5 using stirrer and transfer to the manufacturingvessel while mixing.

12. Check clarity of the solution in manufacturingvessel. The solution must be clear without anyundissolved particles of the drug.

13. Add item 7 to the manufacturing vessel whilemixing at high speed.

14. Transfer the cooled mucilage of item 8 to themanufacturing vessel used above while mixingat slow speed.

15. Check and record the pH of the solution (limit3.3 to 3.6).

16. Dissolve item 9 in 5.0 g of cooled item 10(30C) in a separate stainless steel container.

17. Adjust the pH of the syrup in manufacturingvessel using the sodium hydroxide solution.Add sodium hydroxide solution in small por-tions at a time. Mix well and check the pH afterevery addition. Adjust the pH to 3.5 (limit 3.3to 3.6).

18. Make up the volume up to 1.0 L with item 10and, nally, mix for 15 to 20 minutes at highspeed. Check and record the pH (limit 3.3 to3.6). Filter the syrup at 1.5 bar. Recirculate.

Bill of MaterialsScale (mg/5 mL) Item Material Name Quantity/L (g)4.00 1 Bromhexine HCl 0.801000000 2 Glycerin (glycerol) 200.0010.00 3 Benzoic acid 2.001.00 4 All fruits avor 0.345000 5 Tartaric acid 1.00151.50 6 Alcohol (ethanol 95%) 30.312857000 7 Sorbitol (70% solution) 571.4010.00 8 Carboxymethylcellulose sodium (sodium CMC) 2.000.70 9 Sodium hydroxide pellets 0.14q.s. 10 Water, puried, q.s. to 1 L

2004 by CRC Press LLC