New potential application of hydroxypropyl-ß-cyclodextrin in solid self-nanoemulsifying drug delivery system and solid dispersion.

The purpose of this study was to use hydroxypropyl-ß-cyclodextrin (HP-ß-CD) as a novel carrier in solid SNEDDS and solid dispersions to enhance the solubility and oral bioavailability of poorly water-soluble dexibuprofen. The novel dexibuprofen-loaded solid SNEDDS was composed of dexibuprofen, corn oil, polysorbate 80, Cremophor® EL, and HP-ß-CD at a weight ratio of 45/35/50/15/100. This solid SNEDDS spontaneously formed a nano-emulsion with a size of approximately 120 nm. Unlike the conventional solid SNEDDS prepared with colloidal silica as a carrier, this dexibuprofen-loaded solid SNEDDS exhibited a spherical structure. Similar to the dexibuprofen-loaded solid dispersion prepared with HP-ß-CD, the transformation of the crystalline drug to an amorphous state with no molecular interactions were observed in the solid SNEDDS. Compared to the solid dispersion and dexibuprofen powder, solid SNEDDS significantly enhanced drug solubility and AUC. Therefore, HP-ß-CD is a novel potential carrier in SNEDDS for improving the oral bioavailability of dexibuprofen.

Self-microemulsifying drug delivery system (SMEDDS) for improved oral delivery and photostability of methotrexate.

Purpose: The objective of this study was to exploit a novel methotrexate (MTX)-loaded solid self-microemulsifying drug delivery system (SMEDDS) with enhanced bioavailability and photostability. Materials and methods: The optimized liquid SMEDDS was composed of castor oil, Tween® 80, and Plurol® diisostearique at a voluminous ratio of 27:63:10. The solid SMEDDS was formulated by spray drying liquid SMEDDS with the solid carrier (calcium silicate). Particle size analyzer, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared (FTIR) spectroscopy experiments characterized the physiochemical properties of the MTX-loaded solid SMEDDS. These properties include a z-average diameter of emulsion around 127 nm and the amorphous form of the solid SMEDDS. Furthermore, their solubility, dissolution, and pharmacokinetics in Sprague-Dawley rats were analyzed in comparison with the MTX powder. Results: The final dissolution rate and required time for complete release of solid SMEDDS were 1.9-fold higher and 10 min shorter, respectively, than those of MTX powder. Pharmacokinetic analysis demonstrated 2.04- and 3.41-fold increments in AUC and Cmax, respectively in comparison to MTX powder. The AUC and Cmax were significantly increased in solid SMEDDS. Finally, the photostability studies revealed the substantially enhanced photostability of the MTX-loaded SMEDDS under the forced degradation and confirmatory conditions. Conclusion: This solid SMEDDS formulation could be an outstanding candidate for improving the oral bioavailability and photostability of MTX.

Do the radiographic findings of symptomatic discoid lateral meniscus in children differ from normal control subjects?

PURPOSE: The aim of this study was to quantitatively compare radiographic findings of symptomatic discoid lateral meniscus in children with those of matched controls. METHODS: Seventy-eight consecutive children (91 knees) who underwent arthroscopic surgery for a symptomatic discoid lateral meniscus (discoid group) were included. Another 91 age- and sex-matched controls with normal medial and lateral menisci on the basis of magnetic resonance imaging findings were included in this study (control group). Each plain radiograph was evaluated from the anteroposterior view for the following variables: height of the lateral tibial spine, lateral joint space distance, height of the fibular head, squaring of the lateral femoral condyle, obliquity of the lateral tibial plateau and cupping of the lateral tibial plateau. Lateral femoral condylar notch was evaluated in lateral view. Statistical analyses were used to determine the differences between the two groups. RESULTS: A significant difference in the mean height of the lateral tibial spine, lateral joint space distance, height of the fibular head, and obliquity of the lateral tibial plateau distinguished the two groups (p < 0.0001). However, there was no statistical difference in the condylar off sign, squaring of the lateral femoral condyle, cupping of the lateral tibial plateau and lateral femoral condylar notch between groups (n.s.). The cut-off values for the height of the lateral tibial spine (6 mm), lateral joint space distance (8 mm), height of the fibular head (14.9 mm) and obliquity of the lateral tibial plateau (17.6°) were determined. With these cut-off values in diagnosing discoid lateral meniscus, the sensitivity and accuracy of height of the fibular head were 78 and 70 %, respectively. CONCLUSIONS: Several plain radiographic findings in symptomatic discoid lateral meniscus in children were significantly different from those in normal control. These findings would be helpful in screening tool of discoid lateral meniscus for children. LEVEL OF EVIDENCE: II.