Effect Of Storage Time On Crystal Form And Bioavailability Of Pediatric Ibuprofen Suppositories

OBJECTIVESThrough investigating the changing of cystal form of ibuprofen before and after long term-storage and the effect of the changing on in-vitro dissolution and in-vivo bioavailability,so as to offer reference to storage method for suppository and other semi-solid pharmaceutics.METHODS AND RESULTSThe ibuprofen suppository was prepared with partial synthesized fatty glyceride as matrix.The newly-prepared and long-term storaged ibuprofen,which kept for 1.5 year at the temperature of 20±5℃and the relative humidity of 65±5%, were characterized by differential scanning calorimetry and X-ray powder diffraction analysis.In addition, the dissolution principle of ibuprofen suppository in 0.1M NaOH solution after long-term storage was investigated. The results showed DSC curves and X-ray diffraction of ibuprofen suppository after long-term storage changed,suggesting the cystal form of drug and matrix would be transfomed.After storage of 1.5 year, cumulative dissolution in 0.1M NaOH solution decreased from 95.63% to 52.59%.Pharmacokinetic studies of ibuprofen were performed in human, and double preparation and double-cycle crossover experiment were designed for evaluating the bioavailability and bioequiavailability in vivo. The reslults showed that statistically significant difference was found for Tmax,Cmax and AUCo-x, of newly-prepared and long-term storaged ibuprofen (P<0.05),besides the bioavailability obviously decreased after long-term storage.CONCLUSIONSCrystalline would be transformed of Ibuprofen suppository during long-term storage at room temperature, which would lead to the changing of dissolution and bioavailability in-vitro. Especially, storage condition of ibuprofen suppository should be strictly controlled,so as to prevent the poor quality due to crystalline changing of drug and matrix.