Università di Parma Dipartimento Farmaceutico Viale delle Scienze 27A 43100 Parma Italy Viale delle Scienze 27A 43100 Parma Italy
Università di Milano Istituto Chimico Farmaceutico Viale Abruzzi 42 20132 Milano Italy Viale Abruzzi 42 20132 Milano Italy
Budapest University of Technology and Economics Research Group for Technical Analytical Chemistry of the Hungarian Academy of Sciences & Institute of General and Analytical Chemistry H-1111 Budapest Szent Gellért tér 4 Hungary H-1111 Budapest Szent Gellért tér 4 Hungary
The thermal behavior of binary mixtures of paracetamol and a polymeric excipient (microcrystalline cellulose, hydroxypropylmethylcellulose
and cross-linked poly(vinylpyrrolidone)) was investigated. The physical mixtures, ranging from 50 to 90% by mass of drug,
were submitted to a heating-cooling-heating program in the 35–180C temperature range. Solid-state analysis was performed
by means of differential scanning calorimetry (DSC), hot stage microscopy (HSM), micro-Fourier transformed infrared spectroscopy
(MFTIR), and scanning electron microscopy (SEM).
The polymeric excipients were found to address in a reproducible manner the recrystallization of molten paracetamol within
the binary mixture into Form II or Form III. The degree of crystallinity of paracetamol in the binary mixtures, evaluated
from fusion enthalpies during the first and second heating scans, was influenced by the composition of the mixture, the nature
of the excipient and the thermal history. In particular, DSC on mixtures with cross-linked poly(vinylpyrrolidone) and hydroxypropylmethylcellulose
with drug contents below 65 and75%, respectively, evidenced the presence only of amorphous paracetamol after the cooling phase.
Microcrystalline cellulose was very effective in directing the recrystallization of molten paracetamol as Form II.