Rutin nanosuspension for potential management of osteoporosis: effect of particle size reduction on oral bioavailability, in vitro and in vivo activity.

Clinical significance of Rutin (RUT) is limited by poor dissolution rate and low oral bioavailability. The study was designed to improve the physicochemical and therapeutic potential of the drug by formulating nanosuspension (NS) for osteoporosis. Rutin nanosuspension (RUT-NS) was prepared after screening a range of stabilizers and their combinations at a different concentration by antisolvent precipitation technique. Effect of precipitation on crystallinity (differential scanning calorimetry DSC, X-ray diffraction studies XRD), morphology (scanning electron microscopy, SEM) and chemical interaction (attenuated total reflectance fourier-transform infrared spectroscopy ATR-FTIR) were studied through biophysical techniques. An optimized nanosuspension exhibited a minimum particle size of 122.85 ± 5.02 nm with higher dissolution of RUT-NS (87. 63 ± 2.29%) as compared to pure drug (39.77 ± 2.8 6%). The enhanced intestine absorption and apparent permeability were achieved due to the improved particle size, surface area and dissolution. RUT-NS displayed greater (3 folds) AUC0-24 h than pure drug. In vitro assays with RUT-NS depicted an increased cell proliferation, antioxidant (ROS) activity and osteocalcin production in MG-63 osteoblast cells. The augmented biochemical in vivo biomarkers and bone quality proved the protective effect of RUT-NS. The results supported RUT-NS as a potential therapy for maintaining bone health.

Quantitation of acotiamide in rat plasma by UHPLC-Q-TOF-MS: method development, validation and application to pharmacokinetics.

A novel, sensitive and selective ultra-high-performance liquid chromatography-electrospray ionization mass spectrometry method was developed and validated for the quantification of acotiamide (ACT), a first-in-class drug used in functional dyspepsia, in rat plasma. A simple protein precipitation method with acetonitrile as precipitating solvent was used to extract ACT from rat plasma. ACT and an internal standard (mirabegron, IS) were separated on an Agilent poroshell EC C18 column (50 × 3.0 mm, 2.7 µm) using methanol-10 mM ammonium acetate binary gradient mobile phase at a flow rate of 0.4 mL/min over 4 min run time. Detection was performed using target ions of [M + H](+) at m/z 451.2010 for ACT and m/z 397.1693 for IS in selective ion mode. The method was validated in the calibration range of 1.31-1000 ng/mL. All the validation parameters were well within the limits. The method demonstrated good performances in terms of intra- and inter-day precision (3.27-12.60% CV) and accuracy (87.96-104.94%). Thus the present ultra-high-pressure liquid chromatograhy-high-resolution mass spectrometry method for determination of ACT in rat plasma, is highly sensitive and rapid with a short run-time of 4 min, can be suitable for high sample throughput and for large batches of biological samples in pharmacokinetic studies. This method can be extended to measure plasma concentrations of ACT in humans to understand drug metabolism, drug interaction and adverse effects.

Ethanolic extract of Boswellia ovalifoliolata bark and leaf attenuates doxorubicin-induced cardiotoxicity in mice.

The aim of the study was to investigate the potential protective effect of ethanolic extract of Boswellia ovalifoliolata (BO) bark and leaf against doxorubicin (DOX)-induced cardiotoxicity in mice. Ethanolic extracts of BO bark (400 mg/kg) and leaves (250 mg/kg) were given orally to mice for 9 consecutive days and DOX (15 mg/kg; i.p.) was administered on the seventh day. Extract protected against DOX-induced ECG changes. It significantly inhibited DOX-provoked glutathione depletion and accumulation of malondialdehyde. The decrease in antioxidant enzyme activities of catalase, superoxide dismutase, glutathione peroxidase in cardiac tissue were significantly (p<0.05) mitigated after treatment with BO bark and leaf extracts. Pretreatment with BO significantly (p<0.05) restored the levels of DOX-induced rise of SGPT, SGOT, serum lactate dehydrogenase and creatine kinase-MB levels. These findings suggest that ethanolic extract of BO has protective effects against DOX-induced cardiotoxicity.