Lidocaine is partially soluble in the suppository base, which hinders the exchange with rectal fluid. Lidocaine HCl is preferred because it is less soluble to completely insoluble in the suppository base. However, it is highly soluble in water.

The lidocaine HCl must be finely ground and then sieved. Any material remaining on the sieve should be ground further. This process is necessary to prevent the presence of larger crystals in the suppository, which can cause irritation.