Innovative UV Protocols Based on Straightforward Mathematical Filtration for Concurrent Estimation of Two Antidiabetic Drugs in Their Brand-New Combination: A Comparative Study.

BACKGROUND: In 2019, the U.S. Food and Drug Administration approved a brand-new combination of linagliptin and empagliflozin in a formulation called Glyxambi® tablets for managing type 2 diabetes mellitus. Nowadays, spectrophotometric techniques occupy the first place among their peers in terms of ease of application, friendliness to the environment, and low costs. OBJECTIVE: This research discusses the development of two very simple spectrophotometric protocols based on zero-order spectra for the determination of linagliptin and empagliflozin. METHODS: The developed protocols were the induced dual-wavelength and absorption correction protocols. Linagliptin could be determined directly at 305 nm, at which the empagliflozin spectrum was zero-crossing. Empagliflozin was determined using the two developed protocols. The induced dual-wavelength technique was developed by calculating the equality factor of linagliptin to cancel its interference. The absorption correction technique was developed by measuring the correction absorption factor. RESULTS: The concentration ranges of linagliptin and empagliflozin were 1-10 µg/mL and 3-30 µg/mL, respectively. Excellent recovery results were found in bulk, dosage form, and synthetic mixtures. Low LOD and LOQ values were obtained, indicating the high sensitivity of the protocols. The statistical Student's t-test was performed to compare the results of the applied and reported protocols, indicating no difference between them. CONCLUSION: The proposed protocols have the advantages of being straightforward, affordable, and requiring no sophisticated manipulations, just simple mathematical calculations. The proposed protocols are acceptable for routine usage in QC laboratories and in future research applications. HIGHLIGHTS: Two novel univariate methods were developed for quantitative analysis of linagliptin and empagliflozin in their pharmaceutical and laboratory mixtures, and produced satisfactory results.

Earth-friendly micellar UPLC technique for determination of four hypoglycemic drugs in different pharmaceutical dosage forms and spiked human plasma.

A novel, sensitive, and green micellar UPLC method was proposed and validated for the simultaneous determination of four hypoglycemic agents used in type II diabetes mellitus treatment namely, pioglitazone, alogliptin, glimepiride, and vildagliptin. The developed UPLC method was successfully applied for quantitative analysis of these drugs in bulk, in pharmaceutical formulations, and in spiked human plasma. Chromatographic separation was carried out on a Kinetex® 1.7 µm XB-C18 100 Å (50 × 2.1 mm) column, using a degassed and filtered mixture of (0.1 M SDS- 0.3% triethyl amine- 0.1% phosphoric acid (pH 6)) and n-propanol (85:15 v/v), at a flow rate of 0.2 mL/min. The experimental conditions of the suggested method were well investigated and optimized. The newly developed micellar UPLC method is capable of determining different dosage forms at the same time with the same solvents, saving time and effort. The method was found to be efficiently applicable in spiked human plasma and could be extended to study the pharmacokinetics of the cited drugs in real human plasma samples. The greenness of the developed method was evaluated by applying the Eco-scale scoring tool, which verified the excellent greenness of the analytical method.

Eco-friendly-assessed micellar-fluorimetric platform for concurrent analysis of empagliflozin and prucalopride succinate in biological fluids: Docking simulation.

Fluorescence spectroscopy has an important role in the determination of very small quantities of substances, especially in biological fluids. For this reason, most analysts have adopted the use of this technique in their biological studies and research, which helps them in the determination of any substance found in trace amounts. In addition to the high sensitivity of the fluorimetric technique, it has the advantages of simplicity and being green for the environment. All these reasons encourage the use of fluorimetric spectroscopy for quantifying co-administered therapy in biological fluids, which is considered a crucial step for patients, particularly in emergent cases requiring monitoring of administered therapeutic drugs. In this work, a sensitive, simple, economic, and environmentally friendly fluorimetric analytical technique was developed for the simultaneous determination of prucalopride succinate (a novel anti-constipation agent) and empagliflozin (an anti-diabetic agent) in pharmaceutical forms and spiked plasma depending on third-derivative signal processing at 333 and 314 nm, respectively. Conventional fluorescence spectra of both drugs showed a large overlap that hindered their simultaneous determination. So, third-order derivative fluorescence was adopted to overcome this overlap. The third-derivative corresponding to each spectrum was recorded using data points = 17 and a scaling factor of 10. The greenness of the proposed method was evaluated using an eco-scale scoring system, revealing excellent greenness. Analytical method parameters were validated following ICH guidelines. The method showed high sensitivity, covering a concentration range of 50-1100 ng/mL and 4-500 ng/mL for empagliflozin and prucalopride, respectively, allowing the pharmacokinetic study of both drugs in biological fluids. The LOD values were 14.09 and 0.91 ng/mL, while the LOQ values were 42.72 and 2.77 ng/mL for empagliflozin and prucalopride, respectively.

Earth-friendly-assessed silver-nanoparticles spectrophotometric method for rapid and sensitive analysis of Molnupiravir, an FDA-approved candidate for COVID-19: application on pharmaceutical formulation and dissolution test.

Molnupiravir is the first oral direct-acting antiviral prodrug recently approved for the COVID-19 pandemic. Here and for the first time, we present a novel, sensitive, robust, and simple silver-nanoparticles spectrophotometric technique for molnupiravir analysis in its capsules and dissolution media. This spectrophotometric technique involved silver-nanoparticles synthesis through a redox reaction between the reducing agent (molnupiravir) and the oxidizing agent (silver nitrate) in presence of polyvinylpyrrolidone as a stabilizing agent. The produced silver-nanoparticles have an intense surface plasmon resonance peak at 416 nm where the measured absorbance values were utilized for the quantitative analysis of molnupiravir. The produced silver-nanoparticles were recognized by using the transmission electron microscope. Under optimal conditions, a good linear rapport was accomplished between molnupiravir concentrations and the corresponding absorbance values in a range of (100-2000) ng/mL with a detection limit of 30 ng/mL. Greenness assessment was implemented using eco-scale scoring and GAPI disclosing the excellent greenness of the suggested technique. The suggested silver-nanoparticles technique was authenticated according to recommendations of the ICH and statistically assessed with the reported liquid chromatographic method without significant differences regarding accuracy or precision. Accordingly, the suggested technique is deemed a green and cheap alternative for assaying molnupiravir due to its reliance primarily on water. Furthermore, the suggested technique's high sensitivity can be employed for investigating molnupiravir bioequivalence in future studies.

Innovative Earth-Friendly UV-Spectrophotometric Technique for In Vitro Dissolution Testing of Miconazole Nitrate and Nystatin in Their Vaginal Suppositories: Greenness Assessment.

BACKGROUND: The combined mixture of miconazole nitrate (MIC) and nystatin (NYS) has proven its efficiency as a prodigious remedy to cure women's frequent infections: vaginal mycosis and vaginal candidiasis. OBJECTIVE: A novel green spectrophotometric technique, namely the Fourier self-deconvolution method (FSD), was employed for the quantitative determination of MIC and NYS in their pure and pharmaceutical forms without prior separation. Moreover, the proposed technique was first employed to study the dissolution profile of the cited drugs in their pharmaceutical formulation according to FDA recommendations without excipient interference. METHOD: The FSD method is based on a simple mathematical manipulation of zero-order spectra of the cited drugs, which suffered from severe overlapping, so zero-order spectra of the cited drugs were deconvoluted using the Fourier wavelet function in spectrophotometer software. The deconvoluted amplitudes for MIC and NYS were measured at 255 nm and 320 nm, respectively. RESULTS: Linearity ranges were 70-700 µg/mL for MIC and 1-25 µg/mL for NYS. The greenness of the proposed technique was assessed using two assessment tools, namely eco-scale scoring and green analytical procedure index (GAPI), revealing the excellent greenness of this technique. The proposed technique was validated consistent with ICH guidelines and statistically compared to the reported method with no significant differences between them. CONCLUSIONS: The proposed technique has advantages of being simple, time-saving, and noting need any modification to be suitable for quantitative analysis of MIC and NYS in both pharmaceutical and laboratory mixtures. HIGHLIGHTS: An innovative FSD method was developed for quantitative analysis of MIC and NYS in their synthetic and pharmaceutical mixtures and applied for in vitro dissolution testing of their pharmaceutical mixture, producing satisfactory results.

Simple mathematical data processing method for the determination of sever overlapped spectra of linagliptin and empagliflozin in their pure forms and pharmaceutical formulation: Fourier self deconvulated method.

A new and simple spectrophotometric method was developed for the simultaneous determination of a new antidiabetic mixture of linagliptin and empagliflozin namely fourier self deconvulated method. The developed method based on minimal mathematical data processing on the zero order spectrum for solving sever overlapping spectra of the mentioned drugs in their pure forms and pharmaceutical dosage form. The zero order spectra of linagliptin and empagliflozin were deconvulated using Fourier transforms function. The peak amplitudes at 232 nm were selected for linagliptin and at 239 nm for empagliflozin. The constructed calibration graphs were linear over the range (5-30 µg/mL) and (2-12 µg/mL) for empagliflozin and linagliptin, respectively. The adopted method was simple, accurate, precise and validated according to the ICH guidelines.

Flourimetric study on antidiabetic combined drugs; empagliflozin and linagliptin in their pharmaceutical formulation and human plasma.

Empagliflozin and linagliptin are newly approved FDA combination that used for the treatment of type 2 diabetes mellitus (T2DM) under trade name Glxambi. Two spectroflourimetric methods were developed for simple quantitative determination of empagliflozin and linagliptin in their pharmaceutical formulation and human plasma without need any tedious processing operations. Empagliflozin has a native fluorescence nature, therefore can be directly determined by measuring emission peak at 305 nm after excitation at 234 nm. There is no any interference from linagliptin at this emission wavelength. On the other hand, linagliptin is a very weak florescent compound that needs to react with fluorogenic reagent to be quantitatively determined without any reaction of empagliflozin. So, quantitative analysis of linagliptin was achieved by coupling with NBD-Cl which is an electro active halide reagent (targeting only Linagliptin with no effect on empagliflozin). Dark yellow fluorophore with high fluorescence is a result of this reaction and can be measured at emission wavelength 538 nm after excition at wavelength 469 nm. Experimental conditions of the suggested methods were well checked and optimized. The regression plots were found to be linear over the range of 40-1200 ng/mL and 3-700 ng/mL for empagliflozin and linagliptin, respectively. The obtained results by the suggested methods were statistically compared with those obtained by the reported methods, showing no significant difference with respect to accuracy and precision at p = 0.05.