Update on compatibility assessment of empagliflozin with the selected pharmaceutical excipients employed in solid dosage forms by thermal, spectroscopic and chromatographic techniques.

Empagliflozin (EGF) received USFDA approval in 2014 for oral use to control the glucose levels in adults with type 2 diabetes mellitus. Albeit, a systematic drug-excipient compatibility study of EGF has not been reported in the open literature. As physical and chemical interactions affect the performance of the formulation, this study intended to unveil the drug and excipients interactions which would later help in development of a robust solid dosage form. Differential scanning calorimetry (DSC) was applied as a screening tool for the assessment of compatibility between EGF and the list of excipients mentioned in the EMEA summary of product characteristics (SmPC)-section 6.1, along with mannitol and polyvinylpyrrolidone. Thermogravimetric analysis (TGA), Fourier Transform Infrared Spectroscopy (FTIR), X-ray Powder Diffraction (PXRD) and Hot Stage Microscopy (HSM) methods were utilized to appraise the interpretation of DSC results adequately. Isothermal stress testing (IST) studies of EGF were performed using the selected excipients to check the presence of interaction products (IPs) and the drug content by HPLC. Additional peaks were observed in the EGF-macrogol mixture than the drug peak in the HPLC analysis after two and half months, and those were separated and identified by the Ultra-High Performance Liquid Chromatography-Quadrupole Time of Flight Mass Spectrometry (UHPLC-QTOF-MS). Overall, EGF had shown compatibility with 13 selected excipients; however, initial observation of DSC and IST studies indicated plausible interaction of the EGF with macrogol.

Comparative evaluation of fish oil and butter oil in modulating delivery of galantamine hydrobromide to brain via intranasal route: pharmacokinetic and oxidative stress studies.

The present study investigates the role of fish oil (FO)- and butter oil (BO)-enriched microemulsion-based system of galantamine hydrobromide (GH), an anti-Alzheimer drug, for its potential role in brain permeation enhancement and neuroprotection against oxidative stress. Microemulsion (ME)-based system of GH was prepared using water phase titration. The prepared ME was characterized by several physicochemical parameters like particle size, polydispersity index, and ex vivo drug permeation. Cell-based oxidative stress assays and pharmacokinetic studies were performed using C6 glial cell lines, and Sprague Dawley rats, respectively. The optimized ME comprised 5.3% v/v of Capmul MCM EP (as oil),15.8% v/v of Tween-80 (as surfactant), 5.3% v/v of Transcutol P (as co-surfactant), and 73.6% v/v of water (as aqueous phase). The addition of FO and BO resulted in a slight increase in the droplet size and decrease in transparency of ME. Cell-based anti-oxidative stress assays (glutathione assay, nitrite assay, and lipid peroxidation assay) showed the efficacy of formulation in the order of ME, BO ME, and FO ME, respectively. A similar trend was also observed in in vivo animal studies, wherein GH FO ME showed a comparatively higher percentage of drug reaching the brain when administered by intranasal route than by IV route. The study concluded the potential benefits of co-administering FO- and BO-enriched microemulsion is not only enhancing the permeation of drugs across BBB but also improving efficacy against lipopolysaccharide-induced oxidative stress. Graphical abstract.