Drug-carrier interaction in solid dispersions prepared by co-grinding and melt-quenching

In this review, mechanisms of an incipient reaction in drug-SiO2 composites under mechanical stresses are discussed on the basis of changes in the radical species, formation of bridging bonds and short range ordering. Indomethacin (IM), being a sparingly soluble drug, was employed as a representative drug and the effect of the drug-carrier interaction on the physical stability of amorphous IM was studied. The stability of the amorphous IM with SiO2 was found to be higher for those prepared by co-grinding than by melt quenching. Co-grinding the mixture brings about a specific chemical interaction of IM with SiO2. The chemical interaction immobilizes the indomethacin molecules at the interface with the carrier and suppresses the recrystallization. By using a Mg(OH)(2)-SiO2 binary carrier, within which a rapid mechanochemical reaction occurs, the stability of the amorphous IM becomes higher than with SiO2 alone. Computational results agreed well with the experimental study of a ground indomethacin-SiO2 mixture.