Nimodipine (NM) tablets with high dissolution containing NM solid dispersions prepared by hot-melt extrusion.

Using a mixture of Eudragit EPO and polyvinylpyrrolidone/vinyl acetate copolymer (PVP/VA) (Kollidon VA64) as carriers, a nimodipine solid dispersion (NM-SD) was prepared by hot-melt extrusion (HME) to achieve high dissolution. The dissolution profiles in 900 mL 0.1 mol/L HCl showed that the drug release of NM-SD reached 90% in 1h. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) were used to characterize the state of NM. The results obtained showed that NM was in an amorphous form in the solid dispersion (SD). NM-SD tablets (NM-T-SD) were compressed by wet granulation and direct compression, respectively. The stability of NM-T-SD was examined during a 2-month storage period (40 degrees C, RH 75%). The results showed that the dissolution of NM-T-SD was slightly reduced after 2 months storage (40 degrees C, RH 75%), which implied that aging occurred to some degree. However, no NM crystals could be observed by PXRD after 2 months storage for NM-T-SD (F11) prepared by direct compression.

The inhibition effect of high storage temperature on the recrystallization rate during dissolution of nimodipine-Kollidon VA64 solid dispersions (NM-SD) prepared by hot-melt extrusion.

Nimodipine (NM) solid dispersions (SD) were prepared by hot-melt extrusion with polyvinylpyrrolidone/vinyl acetate copolymer (PVP-VA; Kollidon VA64) as the carrier, then the extrudate was stored at different temperatures (20°C, 40°C, 60°C) after milling. Conventional differential scanning calorimetry and powder X-ray diffraction revealed that the drug was present as an amorphous state in the carrier. The dissolution curves of NM from SD at 37°C in water showed that the rate of recrystallization for NM from SD stored at high temperatures was slower than that from room temperature. The single glass transition temperature (T(g) ) measured by modulated temperature DSC remained constant around 89°C and indicated that the amorphous state of the compound was not altered by heating. However, the C=O vibration of the amide function of Kollidon VA64 increased from 1658 to 1675 cm(-1) was observed in infrared spectra and implied the weakness of H-bonding between the compound and the polymer. The above-mentioned experiments clued to us that suitable postcooking for a short time is good for SD; however, the mechanisms of the changes were still not clear and need further investigation.

A less irritant norcantharidin lipid microspheres: formulation and drug distribution.

Lipid microspheres (LM) have recently been used as intravenous (i.v.) carriers for drugs, which are sufficiently soluble in oil. However, in the case of norcantharidin (NCTD), which is poorly soluble in both the water and oil phases, this approach is not feasible. In this study, NCTD-loaded LM was prepared by transferring the drug to the interfacial surface of the oil and aqueous phases to produce a less irritating i.v. formulation of NCTD. A probe type sonicator was used to disperse NCTD into the oil phase together with lecithin and Tween 80. A high-pressure homogenization process was used to prepare the lipid microspheres and localize the drug at the surfactant layer. The LM loaded with NCTD consisted of 0.02% drug. Characterization of LMs and short-term stability was performed by photon correlation spectroscopy (PCS) and a centrifugation test was also carried out. The results showed that NCTD-loaded LM (2 mg/ml) with over 80% NCTD loaded in the interfacial surface were stable for a period of 2 months, and were suitable for i.v. injection in terms of size and stability, whether be diluted or not. Such formulations produced less pain and irritation in animal studies.