Physicochemical characterization of dipeptidyl peptidase-4 inhibitor alogliptin in physical mixtures with excipients

Alogliptin (ALG) is a hypoglycemic drug used in diabetes which inhibits the enzyme dipeptidyl peptidase-4 (DPP-4), preventing the degradation of incretins, stimulating insulin secretion. The physicochemical characteristics of ALG were evaluated by differential scanning calorimetry (DSC), thermogravimetry (TG) and scanning electron microscopy equipped with energy-dispersive X-ray spectrometer (SEM/EDS). The compatibility studies were carried out between ALG and excipients (physical mixtures, 1:1) using DSC, TG, diffuse reflectance Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRPD) and hot-stage microscopy. ALG presented purity near to 99%, melted in the range of 179.4–187.2 °C, followed by decomposition which started in 198.0 °C. SEM/EMS analysis of ALG presented irregular crystals and traces of impurities as copper and lead. DSC investigations obtained by physical mixtures showed minor alterations in the melting ranges of ALG with mannitol, magnesium stearate and commercial tablets. Solubilization of ALG in the fused excipient was observed by hot-stage microscopy between mannitol and ALG, and in tablets. The interaction observed in the mixture with magnesium stearate is due to the melting of the excipient and drug separately, first the excipient and then the drug. FTIR showed additional bands related to the excipients. XRPD proved that ALG has a crystal form and no alterations in the ALG profile were observed after the mixtures. ALG was compatible with all excipients tested. These results were important to understand the characteristics, stability and compatibility of the drug, and proved to be useful in preformulation studies.

     

Thermoanalytical study of fluoxetine hydrochloride

The thermal decomposition of two inclusion compounds Mn(HCOO)₂·1/3C₄H₈O₂ and Mn(HCOO)₂·1/3C₄H₈O was studied in the inert atmosphere. The process of both dioxane, and tetrahydrofurane removal has two steps; the intermediate phase is unstable and kinetically hindered. Manganese formate is stable up to 330°C. Thermogravimetric data (obtained at different rates of linear heating) were processed with computer program (with ‘Model free’ approach). Kinetic parameters were calculated for the first decomposition step, and the process is described by equation of n-order reaction with autocatalysis.     

Bioanalytical method to detect midazolam in plasma

Midazolam (MDZ) is the first choice in palliative sedation, and commonly used in sleep induction in anesthesia, with rapid onset of action. However, monitoring of the level of sedation in patients is not accurate. We developed and validated a bioanalytical method to detect MDZ in plasma using high‐performance liquid chromatography (HPLC) coupled to a photodiode array detector (PDA) for future monitoring of sedation. MDZ was extracted by solid‐phase extraction (SPE). Analyses were performed on a C₁₈ column, using 0.05% triethylamine and acetonitrile as mobile phase, analyzing at 220 nm. Recovery was evaluated by comparing extracted and nonextracted solutions. Precision, accuracy, linearity, limits of detection (LD) and quantification (LQ), specificity and selectivity were determined. The mean recovery obtained by SPE was 101.03%. The method was linear in the range 1.0–50.0 μg/mL. The LD and LQ were, respectively, 0.43 and 1.43 μg/mL. The specificity of the MDZ peak was adequate. The method was able to detect MDZ among other drugs. Plasma anticoagulants showed no interference with the drug detection. The bioanalytical method using HPLC–PDA and SPE was successfully validated and showed linearity, precision, accuracy, specificity and high sensitivity for detection of MDZ in human plasma.     

Development and Validation of Stability Indicating LC Method to Quantify Captopril in Tablets of Controlled Release

An accurate, simple, reproducible, and sensitive liquid chromatographic method was developed and validated for the captopril determination in controlled release tablets. The analyses were performed at room temperature on a reversed-phase Phenomenex Luna C₁₈ column (250 mm × 4.6 mm). The mobile phase was composed of water:methanol (45:55; v/v) pH 2.5, and it was eluted isocratically at a 1.0 mL min⁻¹ flow rate. The method was validated in terms of specificity, linearity, quantification limit, detection limit, accuracy, precision and robustness. The response was linear in the range 0.3–1.5 mg mL⁻¹ (r ² = 0.9983). The relative standard deviation values for inter-and intra-day precision were 0.77% and 0.50%, respectively. Recoveries ranged between 97.7 and 99.1%. The method was successfully applied for the determination of captopril in the developed formulations.

     

Thermal decomposition kinetics and compatibility studies of primaquine under isothermal and non-isothermal conditions

Primaquine (PQ) is the drug of choice for the radical cure of Plasmodium vivax malaria, and currently being administered in solid dosage form. In this study, the compatibility studies were carried out using differential scanning calorimetry (DSC), thermogravimetry (TG), and fourier transformed infrared (FT-IR). Non-isothermal and isothermal methods were employed to investigate kinetic parameters under nitrogen and air atmospheres using TG. The DSC investigations obtained by physical mixtures showed slight alterations in the melting temperatures of PQ with some excipients. The FT-IR confirmed the possible interactions obtained by DSC for the physical mixtures with PQ and lactose, magnesium stearate and mannitol. The results showed that the thermal decomposition followed a zero order kinetic in both atmospheres in non-isothermal method. The activation energy in both methods using nitrogen atmosphere was similar, and in air atmosphere the activation energy decreased.     

Development and Validation of Stability Indicating LC Method to Quantify Captopril in Tablets of Controlled Release

An accurate, simple, reproducible, and sensitive liquid chromatographic method was developed and validated for the captopril determination in controlled release tablets. The analyses were performed at room temperature on a reversed-phase Phenomenex Luna C₁₈ column (250 mm × 4.6 mm). The mobile phase was composed of water:methanol (45:55; v/v) pH 2.5, and it was eluted isocratically at a 1.0 mL min⁻¹ flow rate. The method was validated in terms of specificity, linearity, quantification limit, detection limit, accuracy, precision and robustness. The response was linear in the range 0.3–1.5 mg mL⁻¹ (r ²  = 0.9983). The relative standard deviation values for inter-and intra-day precision were 0.77% and 0.50%, respectively. Recoveries ranged between 97.7 and 99.1%. The method was successfully applied for the determination of captopril in the developed formulations.     

A Multi‐electrochemical Competitive Immunosensor for Sensitive Cocaine Determination in Biological Samples

A multi‐electrochemical competitive immunosensor for the rapid determination of unmetabolized cocaine (COC) in urine, saliva and human serum matrices is reported. Anti‐cocaine polyclonal antibodies were immobilized in an oriented way onto protein‐G functionalized magnetic beads. The immunosensor is based on an array of eight carbon‐based screen‐printed electrodes for simultaneous electrochemical determinations. The treatments of the biological samples were simplified and optimized for avoiding matrix interferences. The immunosensor was sensitive (EC₅₀≈2.92–3.88 ng mL^?1 COC), required a very small volume of sample (200 µL), was reproducible (%RSD was lesser than about 18 %), and accurate (recovery percentages ranged 88–117 %).