The application of quality by design in the development of the liquid chromatography method to determine empagliflozin in the presence of its organic impurities

Analysis of impurities is an important step in the quality control of pharmaceutical ingredients and final products. From drug synthesis or excipients, even in small concentrations, impurities may affect efficacy and safety. The method was developed following Quality by Design (QbD) for the analysis of the antidiabetic empagliflozin. The concept of QbD is used as a tool for the development of methods and formulations. Through predefined objectives and risk analysis, robust methodologies and reduced solvent consumption are developed. A simple HPLC method was developed and validated for the quantitative determination of empagliflozin and its organic impurities from the synthesis process. The method was carried out in a Shim-pack phenyl column with a mobile phase consisting of an acetonitrile/water mixture (72 : 28), with isocratic elution and the detector wavelength was 230 nm. The validation process, in accordance with international guidelines, shows that the method was linear, precise and accurate for empagliflozin, impurity 1 and impurity 2. Limits of detection (0.01, 0.02 and 0.01 μg mL⁻¹) and quantification (0.10, 0.10 and 0.05 μg mL⁻¹) were determined for EMPA, IMP1 and IMP2, respectively. The HPLC method for impurity determination in empagliflozin was linear, precise, accurate and robust. It can be successfully applied in the quality control of empagliflozin and the synthesis of impurities, being adequate for routine analysis.

Analysis of impurities is an important step in the quality control of pharmaceutical ingredients and final products.     

Comparison of different ultrasonic vibration modes for post removal

This in vitro study compared different ultrasonic vibration modes for intraradicular cast post removal. The crowns of 24 maxillary canines were removed, the roots were embedded in acrylic resin blocks, and the canals were treated endodontically. The post holes were prepared and root canal impressions were taken with self-cured resin acrylic. After casting, the posts were cemented with zinc phosphate cement. The samples were randomly distributed into 3 groups (n=8): G1: no ultrasonic vibration (control); G2: tip of the ultrasonic device positioned perpendicularly to core surface and close to the incisal edge; and G3: tip of the ultrasonic device positioned perpendicularly to core surface at cervical region, close to the line of cementation. An Enac OE-5 ultrasound unit with an ST-09 tip was used. All samples were submitted to the tensile test using an universal testing machine at a crosshead speed of 1 mm/min. Data were subjected to one-way ANOVA and Tukey's post-hoc tests (α=0.05). Mean values of the load to dislodge the posts (MPa) were: G1 = 4.6 (± 1.4) A; G2 = 2.8 (± 0.9) B, and G3= 0.9 (± 0.3) C. Therefore, the ultrasonic vibration applied with the tip of device close to the core's cervical area showed higher ability to reduce the retention of cast post to root canal.     

Orthograde retreatment failure with extruded MTA apical plug in a large periradicular lesion followed by surgical intervention: case report

Absence of periapical healing after orthograde retreatment using an apical plug with mineral trioxide aggregate (MTA) can require surgical intervention. A patient with a root-filled maxillary central incisor with chronic apical periodontitis and sinus tract was referred for endodontic retreatment. Excessive apical enlargement was verified, indicating an MTA apical plug placement; however, an unintentional extrusion of MTA occurred during this step. The root canal was filled with gutta-percha and sealer, and periodic recalls were scheduled. The sinus tract was observed after six months and the lesion remained unaltered, although the extruded MTA had resorbed; therefore, an apicoectomy and retrograde root-end filling with MTA were performed. Absence of sinus tract, normal clinical aspect, and complete repair of the lesion were observed at the two-year follow-up.     

The Correlation Between Obesity-Related Diseases and Non-alcoholic Fatty Liver Disease in Women in the Pre-operative Evaluation for Bariatric Surgery Assessed by Transient Hepatic Elastography

Background

Non-alcoholic fatty liver disease (NAFLD) is a common, severe disease in obese patients. However, NAFLD is usually underestimated by ultrasonography. Liver biopsy is not routinely done in bariatric surgery or during the follow-up. This study therefore examined the correlation between metabolic syndrome and NAFLD in morbidly obese patients based on an assessment using transient hepatic elastography (THE).

Material and Methods

This study involved 50 female patients in the pre-operative phase for bariatric surgery. Before surgery, we collected clinical, laboratory, and anthropometric variables. THE measurements were obtained using a FibroScan® device (Echosens, Paris, France), and steatosis was quantified using Controlled Attenuation Parameter software (CAP). Statistical analyses were done using linear correlation and the Kruskal-Wallis test.

Results

The mean of THE and CAP values were 7.56?±?4.78 kPa and 279.94?±?45.69 dB/m, respectively, and there was a significant linear correlation between the two measurements (r?=?0.651; p?<?0.001). The numbers of metabolic syndrome parameters did not influence the THE (p?=?0.436) or CAP (p?=?0.422) values. HbA1c and HOMA-IR showed a strong linear correlation with CAP (r?=?0.643, p?=?0.013 and r?=?0.668, p?=?0.009, respectively) and a tendency to some linear correlation with THE (r?=?0.500, p?=?0.05 and r?=?0.500, p?=?0.002, respectively).

Conclusion

Morbidly obese women submitted to FibroScan® presented a high prevalence of severe steatosis and advanced fibrosis in our sample. Insulin resistance parameters were correlated with steatosis, but less with fibrosis.

     

Evaluation of root external temperature during the application of ultrasound in removal of intraradicular posts

This study evaluated the temperature rise on external root surfaces by simulating the removal of metallic posts by applying ultrasound, with or without refrigeration and at different times. The crowns of 30 healthy maxillary central incisors were removed and the roots were treated endodontically. The prosthetic spaces were prepared and impressions were taken with self-curing acrylic resin. After casting with a copper-aluminum alloy, the posts were blasted with aluminum oxide and cemented with resin cement. The specimens were randomly assigned to three groups according to the time of ultrasonic vibration (30, 60, or 120 seconds) and were subdivided into two groups, those cooled with and without water refrigeration. A thermocouple connected to a digital thermometer was positioned on the root external surface and the maximum temperature was recorded. Data were submitted to ANOVA and Tukey's test. Analysis of the results revealed statistical difference among groups (p < 0.01). Ultrasound (with and without water spray) increased root temperature significantly, reaching values of more than 50 degrees C. The exception was the group that used 30 seconds of ultrasound with refrigeration; root temperature reached 35.4 degrees C, making it the only tested condition that remained below the critical value (50 degrees C).     

Treatment of a second maxillary molar with six canals

Variations in the dental anatomy are found in all teeth. Knowledge of these variations, particularly concerning the location and treatment of all canals, is very important for the success of the endodontic therapy. The purpose of this study is to present a clinical case of a maxillary second molar with three palatal canals, two mesio-buccal and one disto-buccal canal. This report serves to remind clinicians that such anatomical variations should be taken into account during endodontic treatment of the maxillary molars.