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For a highly hydrophobic and drug, it is difficult to formulate and solidify its nanocrystals with high drug loading and good redispersity. In this study, Allisartan Isoproxil was used as a model drug, and SDS was tested in combination with sugar alcohols to improve the drug loading and redispersity for its spray-dried nanocrystals, simultaneously. These spray-dried nanocrystals had high drug loading of 61.7% and good redispersity, which was mainly attributed to the addition of SDS. In addition, the nanocrystals were characterized by scanning electron microscopy, differential scanning calorimetry, X-ray power diffraction analysis, Fourier transform infrared spectroscopy and Raman spectroscopy. The results showed that Allisartan Isoproxil was unchanged in chemical structure, but was partially amorphous. Regarding the in vitro dissolution, the optimism formulation shown an increased dissolution compared with the bulk drug and aggregated nanocrystals. Importantly, the optimum formulation increased the oral bioavailability of crude ALS-3 for 4.73 times. In conclusion, we developed a method to solidify aqueous nanocrystals with increased drug loading, good redispersity and improved bioavailability for high hydrophobic drugs. [ABSTRACT FROM AUTHOR]

Nisoldipine is a calcium channel blocker mainly used for the treatment of hypertension, but its oral bioavailability is limited because of its low aqueous solubility and extensive metabolism. Solid dispersion and micronized formulations have been tested to improve its oral bioavailability, and we have demonstrated that the two formulations were bioequivalent. In this study, we intended to improve the oral bioavailability by reducing the particle sizes to the nanoscale region. To achieve this, drug crystals with different particle sizes (1227.7 ± 55.1 nm, 472.7 ± 14.5 nm, and 240.3 ± 10.7 nm) were prepared by adjusting the formulation and process parameters using a media milling method. Then, physical characterization (DSC, PXRD, and FT-IR) demonstrated that the crystal state remained unchanged during the preparation, and no interaction between nisoldipine and the excipients was involved in any of the formulations. In vitro dissolution studies showed that the dissolution rates of the nanocrystals were much faster than that of the microcrystals, and pharmacokinetic studies in rats demonstrated that the oral absorption was size-dependent. Above all, this study demonstrated the feasibility of using drug nanocrystal strategy to improve the oral bioavailability of nisoldipine and, in particular, nisoldipine nanocrystals with a size of 240.3 nm showed a superior oral absorption. [ABSTRACT FROM AUTHOR]

Nanocrystal (NC) technology is an effective strategy to enhance the oral bioavailability for poorly water-soluble drugs. Stabilizers are essential and important in NC formulations due to its ability to decrease the system energy. Studies have revealed that stabilizers can affect the particle size and stability of the system. However, whether stabilizers can affect the in vivo behaviors of the NCs is unknown. To investigate the effects of stabilizers on the in vitro and in vivo performances of NCs, four types of spironolactone (SPN) NCs with similar diameters but different stabilizers were prepared. All the NCs were spherical in shape with a size of about 370 nm. In addition, the NCs were also characterized by differential scanning calorimetry, X-ray diffraction, and Raman spectroscopy, the results obtained showed that the SPN in all the formulations was partially amorphous. In fasted state simulated intestinal fluid, all the SPN-NCs showed similar dissolution profiles. However, the dissolution for SPN-NCs/NaDC was suppressed in 0.1 M HCl. Importantly, the AUC (0–48h)total for SPN-NCs/F127, SPN-NCs/F68, SPN-NCs/HPMC-E5, and SPN-NCs/NaDC was 4.96-, 3.91-, 2.88- and 1.72-fold higher than that of the SPN suspension, respectively. These results demonstrated that stabilizers in NCs played an important role for the in vivo pharmacokinetic behaviors. It is highly suggested that the ionic stabilizers are not suitable to stabilize drug nanocrystals alone because it may induce aggregation and agglomeration of drug crystals when transferring through the whole gastrointestinal tract and experiencing the different pH levels. [ABSTRACT FROM AUTHOR]