Simultaneous analysis of the of levamisole with triclabendazole in pharmaceuticals through developing TLC and HPLC-PDA chromatographic techniques and their greenness assessment using GAPI and AGREE methods.

Two simple and rapid chromatographic methods were developed and validated for the analysis of levamisole and triclabendazole simultaneously in pure and pharmaceutical products. The first method is thin-layer chromatography (TLC) with densitometry, and the second method is high-performance liquid chromatography with PDA detection (HPLC-PDA). A Hypersil BDS C18 column with dimensions of 4.6 × 150 mm and a particle size of 5 µm was used in the HPLC-PDA method. An isocratic condition was used to carry out the separation, and the mobile phase was made up of acetonitrile and a 0.03 M potassium dihydrogen phosphate buffer in double-distilled water. The ratio of the mobile phase preparation was 70:30 (v/v), and the flow rate was 1 mL/min. A wavelength of 215 nm was employed for analyte detection. Precoated silica gel 60 F254 aluminium plates were used for the TLC method's separation. Mobile phase was made of ethyl acetate, hexane, methanol, and ammonia (69:15:15:1) for the separation. The detection wavelength selected was 215 nm. According to the International Council for Harmonization (ICH) guidelines, the proposed methods were validated and it was found that the two chromatographic methods are accurate, precise, and linear for both compounds in the range of 3.75-37.5 and 6-60 mg/L for the HPLC method for levamisole and triclabendazole, respectively and in the range of 2-14 µg/spot for the TLC method. The developed methods greenness profile was assessed using AGREE and ComplexGAPI tools.

Determination of linagliptin and empagliflozin by UPLC and HPTLC techniques aided by lean six sigma approach.

Two chromatographic techniques were developed and validated for simultaneous determination of the newly co-formulated antidiabetic combination linagliptin and empagliflozin in their pure form and film-coated tables. The first technique was UPLC; the separation and resolution of both analytes were achieved using a Zorbax eclipse plus C18 column applying an isocratic elution based on phosphate buffer pH 4-acetonitrile (65:35, v/v) as a running mobile phase at flow rate 1.5 ml/min and the effluent was monitored at 220 nm. Augmentation of Lean Six Sigma with UPLC and HPTLC methods had a major impact on the development of robust specifications to ensure that the quality at six sigma level has a high level of statistical confidence and target performance. On the chromatogram, empagliflozin and linagliptin appeared at retention times of 1.417 and 2.453 min, respectively. The second technique was HPTLC; both analytes were fairly well resolved and separated using a developing mobile phase composed of ethyl acetate-chloroform-acetonitrile (55:25:20 by volume). The values of retention factor (RF ) were 0.29 and 0.53 for linagliptin and empagliflozin, respectively. All variables were investigated to adjust the whole conditions.

Second derivative synchronous fluorescence determination of avanafil in the presence of its acid-induced degradation product aided by powerful Lean Six Sigma tools augmented with D-optimal design.

In this work, the quantitative determination of an erectile dysfunctional drug avanafil in the presence of its acid-induced degradation product was achieved via the application of a pre-optimized novel spectrofluorimetric method. The fluorescence emission wavelength was recorded at 370 and 407 nm, after being excited at 268 and 271 nm for avanafil and its acid-induced degradation product, respectively. Direct determination of avanafil based on its native fluorescence is restricted because the emission spectra of both components are heavily overlapped. Therefore, to overcome this constraint, a novel second derivative synchronous fluorescence method was evolved to eliminate this overlapping. The ideal determination wavelength was found to be 377 nm. Augmentation of lean six sigma (LSS) with response surface methodology (RSM) play a significant role in the development of robust specifications to ensure quality at the six sigma level with a high level of statistical confidence and targeted performance. All of the experimental conditions were optimized using D-optimal design as a RSM to select the optimal parameters. In addition, this work includes a graphical representation of the relationships between various variables that can greatly affect the results and the intensity of the synchronous fluorescence.

D-optimal design as a useful tool response surface methodology for the optimization of signals from synchronous fluorescence prior to simultaneous determination of avanafil and tadalafil.

A rapid, smart and sensitive first derivative spectrofluorimetric method has been carried out for the simultaneous estimation of avanafil and tadalafil either in their pure form, tablet dosage form or spiked human plasma. The measurements of normal emission spectra or synchronous fluorescence intensity of both drugs show severe overlap which hindered their determination using normal fluorescence or synchronous intensity. Therefore, a highly sensitive first derivative synchronous fluorescence procedure was used to resolve this overlap. The method is based upon measurement of the amplitude of the first derivative of synchronous fluorescence intensity of both drugs at Δλ = 70 nm and at suitable wavelength of 396 nm and 364 nm for avanafil and tadalafil, respectively. Under the optimum conditions, the linear determination ranges are 50-1800 and 5-400 ng mL-1 with a detection limit of 12.93 and 1.46 ng mL-1 for avanafil and tadalafil, respectively. A response surface methodology was used for optimization using D-optimal design which can be used for determination of the exact optimum parameters specifically designed for this method. In addition; it is a good way to graphically clarify the relationship between various experimental variables and the synchronous fluorescence intensity.

Fabrication of an (α-Mn2O3:Co)-decorated CNT highly sensitive screen printed electrode for the optimization and electrochemical determination of cyclobenzaprine hydrochloride using response surface methodology.

A new chemically optimized screen-printed electrode modified with a cobalt-doped α-Mn2O3 nanostructure on carbon nanotube paste (α-Mn2O3:Co@CNTs) has been constructed for the recognition of cyclobenzaprine hydrochloride. The prepared paste is based on the incorporation of oxide ion conductors, such as the α-Mn2O3 nanostructure with cobalt and ion pairs (tetraphenyl borate coupled with the drug), as electroactive species in the screen-printed electrode to increase the sensor surface area and decrease electrical resistance. The central composite design is a useful methodology for the estimation and modeling of the exact optimum parameters specifically designed for this process. This is a good way to graphically clarify the relationship between various experimental variables and the slope response. The proposed sensor, α-Mn2O3:Co@CNTs, possesses very good sensitivity and the ability to recognize the drug over the concentration range of 1 × 10-6 to 1 × 10-2 mol L-1 at 25 ± °C with a detection limit of 2.84 × 10-7 mol L-1. It exhibits a reproducible potential and stable linear response for six months at a Nernstian slope of 58.96 ± 0.76 mV per decade. The proposed electrode approach has been successfully applied in the direct determination of the drug in its pure and dosage forms.