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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]

Multilayer/bilayer tablets have been applied for the formulation of incompatible components for compound preparations, but more often they are used to modify drug release. The objective of this study was to explore the feasibility of developing, using a bilayer tablet strategy, an immediate- and extended-release formulation of amoxicillin. The formulation of each layer was optimized separately and the bilayer tablets were compressed at an immediate/extended layer weight ratio of 3:7. The in vitro release of the bilayer tablets was evaluated and it was found to be very similar to Moxatag®, an immediate- and extended-release formulation approved by FDA. The kinetic mechanism study showed that the release of the bilayer tablets correlated better with the Ritger–Peppas model (correlation coefficient R = 0.9963) and a non-Fickian drug release mechanism, and its release was principally driven by diffusion and secondarily by polymer erosion. The stress testing demonstrated that high temperature and humidity are potential risk factors affecting the quality of the bilayer tablets. In addition, the bilayer tablets showed a similar bioavailability to Moxatag® in beagle dogs. In conclusion, the results of the present study demonstrated for the first time the feasibility of developing an immediate- and extended-release formulation of amoxicillin for once-daily use using a bilayer tablet strategy. [ABSTRACT FROM AUTHOR]

Nisoldipine is widely used clinically as an antihypertensive agent, however, its oral bioavailability and therapeutic effects are hindered by its very low solubility in water. The present study aimed to develop an amorphous solid dispersion (ASD) for nisoldipine, using hot melt extrusion, to increase or equilibrate with the in vitro dissolution and in vivo oral absorption of Nierxin, its commercial tablet formulation. The final preparation was prepared with Kollidon VA64 at a drug polymer weight ratio of 1:10. The amorphous state was confirmed by powder X-ray diffractometry, differential scanning calorimetry, and Fourier-transform infrared spectroscopy. This ASD exhibited a higher dissolution profile than Nierxin and its physical mixtures. It maintained an amorphous state when stored at 60 °C over 10 days, however, the hydrogen bonds between nisoldipine and Kollidon VA64 were disrupted and its dissolution slightly reduced when stored at RH 92.5% for 10 days. The pharmacokinetic study carried out in beagle dogs demonstrated that the ASD was bioequivalent to Nierxin. The results of this study suggest that ASD prepared by hot melt extrusion can be used as a suitable alternative to Nierxin in the future. [ABSTRACT FROM AUTHOR]