Polyvinylpyrrolidone affects thermal stability of drugs in solid dispersions
The present study explores the hypothesis that a polymer can affect the thermal stability of a drug in solid polymer-drug dispersions. The hypothesis is tested in a systematic fashion by
combining isoconversional kinetic analysis with thermogravimetric measurements on several solid dispersions. Experimental systems involve three drugs: indomethacin (IMC), felodipine (FD),
and nifedipine (ND) and their solid dispersions with polyvinylpyrrolidone (PVP). It is found that PVP stabilizes IMC but destabilizes FD and ND. Isoconversional kinetic analysis provides
insights into the origin of the observed effects. The enhanced thermal stability of IMC in the PVP matrix is associated with an increase in the activation energy of the respective
degradation process. A detrimental effect of the PVP matrix on the stability of FD and ND has been linked to a decrease in the activation energy and an increase in the preexponential
factor respectively. The molecular underpinnings of the observed effects are discussed. It is concluded that the effects in question are of relevance for drug performance and need to be
taken into account in preformulation studies.