CONTROL OF CRYSTAL GROWTH IN DRUG SUSPENSIONS. PART 1:DESIGN OF A CONTROL UNIT AND APPLICATION TO ACETAMINOPHEN SUSPENSIONS

AbstractA monitor system is described for the control of particle growth by crystallization in real pharmaceutical suspensions, based on the measurement of drug concentration in the liquid phase in contact with the drug crystals. The control unit consists of a thermostated vessel containing the drug suspension and a monitoring circuit including a dedector (i.e. refractive index, UV absorption). The concentration of the liquid supernatant is recorded in parallel with the actual temperature. Typical concentration-time curves indicate any dissolution or crystallization if temperature cycling (ΔT ± 10K) is applied on the suspensions.It is demonstrated by acetaminophen crystals that after decreasing the temperature the crystal growth appears significantly impeded even by very small amounts of PVP (3 ppm, mol mass 180,000). The polymer did not influence the rate of dissolution of the crystals at higher temperature.Surfactants reduce the protective action of PVP on crystal growth, in particular anionic surfactan...