The Properties of Solid Dispersions of Indomethacin, Ketoprofen and Flurbiprofen in Phosphatidylcholine

Abstract

Solid dispersions in which the carriers were water-soluble agents have been investigated with the aim of improving the solubilities and dissolution rates of poorly water-soluble drugs. We have now examined the utility of barely soluble, but hydrophilic, phosphatidylcholine (PC) purified from hydrogenated soybean phospholipids as a carrier. As poorly water-soluble drugs, infomethacin (IM), flurbiprofen (FP) and ketoprofen (KP) were used.The X-ray diffraction patterns suggested an a amorphous state of IM when the molar ratio of IM was under 0.75.From the infrared spectra, it was considered that IM and PC had only a weak interaction with the carrier. The phase transition temperature of PC was depressed by IM and the degree of depression became larger with increasing molar ratio of IM. The solubility of IM in pH 7.0 buffer solution became 4.0mg/ml (5 times that of IM powder), when the PC solid dispersion with an IM molar ratio in the range of 0.50-0.75 was used. However, the IM concentration decreased with time and became 2mg/ml after 30h.FP and KP also had a weak interaction with PC and were present in the amorphous state, but this state was stable only when the molar ratio was under 0.50, which was lower that than in the case of IM. The solubilities of FP and KP from the PC solid dispersions were each about 1.5 times that from the powder.PC dissolved in water to the extent of 0.1-0.5mg/ml from the solid dispersions with IM, but the dissolution showed poor reproducibility, and no dissolution of PC was observed from FP and KP solid dispersions. Thus, the increased drug solubilities were considered to be due to the amorphous state of the drugs in the PC solid dispersions.