Effect of quick turnaround clean-in-place process with vacuuming and isopropyl alcohol on physicochemical properties of acetylsalicylic acid caplet in continuous manufacturing

Abstract

Cleaning tablet press before operation, and when transiting between formulations, is mandatory, tedious and requires significant personal exposure and downtime. Transiting between batches of same formulation in continuous manufacturing, requires quick turnaround clean-in-place process that does not reduce production quality or efficiency. The effect of cleaning tablet press, using quick turnaround clean-in-place process of vacuuming and isopropyl alcohol, on compression of acetylsalicylic acid was evaluated by assessing the physicochemical properties of the finished caplets. Isopropyl alcohol was chosen as cleaning agent because it dries rapidly without leaving toxic residue. Acetylsalicylic acid was chosen as model API because it is freely soluble in alcohol cleaning solvent. Acetylsalicylic acid granules were prepared using non-aqueous solvent granulation method. For stage ‘A’ operation, single punch tablet press operation was shutdown, disassembled, washed, dried, reassembled, validated, and set at 35 KN pressure to compress 660 mg caplet. For continuous tableting of the granules, the press was used to compress 500 first batch caplets, de-dusted with rubber brush and used to compress second batch caplets, and de-dusted again with rubber brush, and used to compress third batch caplets. Stage ‘B’ operation and continuous tableting was carried out as in stage ‘A’, but in place of the cleaning process of de-dusting with rubber brush, cleaning was done using combination of brushing with rubber brush to de-dust, vacuum cleaning, and wiping cup and barrel to stem chamfer of punches and die-bore and chamfer thoroughly with isopropyl alcohol, and drying, to get three batches of 500 caplets each. Caplets from all six batches were tested for hardness, friability, thickness, and disintegration time. The results were analysed using a one-tailed t-test statistical analysis. The analysis showed significant (p < 0.05) difference in physicochemical properties of acetylsalicylic acid caplets produced after using different press cleaning techniques. Cleaning tableting press with vacuuming and nonaqueous solvent in continuous manufacturing produced better caplets with 1.4 – 3.9 % weight improvement, new-like outlook and sustained physicochemical qualities. The quick turnaround clean-in-place produced quality caplets and achieve regulatory compliance to safety and hygiene, while maintaining machine, machine parts and operation.

Keywords: Continuous manufacturing, non-aqueous solvent granulation, downtime, shutdown time, changeover time, clean-in-place.