Influence of Tableting on Enzymatic Activity of Papain along with Determination of Its Percolation Threshold with Microcrystalline Cellulose

The binary mixture tablets of papain and microcrystalline cellulose (MCC), dicalcium phosphate dihydrate (DCP), carrageenan, tragacanth, and agar were prepared by direct compression. Carrageenan, tragacanth, and agar provided maximum protection to enzyme activity compared to MCC and DCP. However, stability studies indicated highest loss of enzyme activity with carrageenan, tragacanth, and agar. Therefore, compression behaviour of different binary mixtures of papain with MCC at different compaction pressures, that is, 40-280 MPa, was studied according to Heckel equation. The compressibility studies of binary mixtures indicated brittle behavior of papain. The application of percolation theory on the relationship between critical density as a function of enzyme activity and mixture composition revealed the presence of percolation threshold for binary mixture. Papain-MCC mixture composition showed significant percolation threshold at 18.48% (w/w) papain loading. Microcrystalline cellulose provided higher protection during stability study. However, higher concentrations of microcrystalline cellulose, probably as dominant particles, do not protect the enzyme with their plastic deformation. Below the percolation threshold, that is, 18.48% (w/w) papain amount in mixture with plastic excipient, activity loss increases strongly because of higher shearing forces during compaction due to system dominance of plastic particles. This mixture range should therefore be avoided to get robust formulation of papain.