A novel smartphone HPTLC assaying platform versus traditional densitometric method for simultaneous quantification of alfuzosin and solifenacin in their dosage forms as well as monitoring content uniformity and drug residues on the manufacturing equipment.

The large popularity and rapid technology of smartphones have opened new avenues for their integration into different analytical methodologies and drug quality monitoring as a portable, easily accessible, and user-friendly detector. Herein, a novel and portable smartphone-based high-performance thin layer chromatographic (HPTLC) approach is proposed for the simultaneous analysis of two urological drugs, alfuzosin and solifenacin, which treat benign prostatic hyperplasia accompanied by overactive bladder syndrome. First, chromatographic separation was accomplished using an ecofriendly mobile phase, then the developed plates were visualized using Dragendorff's reagent and photographed via a smartphone's rear-facing camera fixed on a fabricated two-illumination-source chamber. The intensities of the drug spots were quantified using open-source image analysis software ImageJ over the concentration ranges of 2.0 to 30.0 µg per band for both drugs with acceptable results in ICH validation parameters. To improve the method's accuracy and reproducibility, various construction and shooting key parameters were investigated and optimized. Moreover, the study was extended to compare the obtained results with those of a benchtop densitometric method using a Camag TLC Scanner 3 at 215.0 nm; the densitometric method provided an additional assessment tool for peak purity and was capable of assaying lower drug concentrations over a linearity range of 0.2-8.0 µg per band for alfuzosin and 0.1-6.0 µg per band for solifenacin. The fast, simple, reliable, green merits of the proposed HPTLC/smartphone method suggest that it is an excellent platform for assaying marketed combined capsules and assuring their content uniformity. Moreover, the high sensitivity of the densitometric method was used, for the first time, to determine the residual content of the cited drugs on manufacturing equipment surfaces for cleaning validation. Finally, the environmental impact of the developed methods was evaluated based on green analytical chemistry principles.

A sensing platform of molecular imprinted polymer-based polyaniline/carbon paste electrodes for simultaneous potentiometric determination of alfuzosin and solifenacin in binary co-formulation and spiked plasma.

Solid contact ion-selective electrodes (ISEs) have witnessed versatile applications in pharmaceutical and biological analysis however they suffer from some limitations. Besides formation of water layer, the doped ion exchanger in sensing membrane fails to distinguish between two ionic species having relatively similar lipophilicity and carrying same charges. Those shortcomings practically hampered the simultaneous determination of alfuzosin and solifenacin in their combined pharmaceutical combination. Hence, this paper was directed to develop two carbon paste electrodes allowing their simultaneous determination based on molecular imprinted polymers (MIPs). Efforts were firstly directed to stabilize the potential signals through synthesis of polyaniline (PANI) nanoparticles with 26 nm particle size as confirmed by means of UV-spectrophotometry, Zeta-sizer and transmission electron microscope. This was followed by its doping at electrode/ion selective membrane interface leading to diminished potential drift, better Nernstian slopes and lower limit of detections. Secondly, MIPs for each drug were prepared by precipitation polymerization technique and fully characterized by Fourier-transform infrared spectroscopy, field-emission scanning electron microscope, differential scanning calorimetry, surface area analysis and rebinding studies. The prepared MIPs were then incorporated in membrane cocktail and doped over PANI layer. The graved cavities inside MIPs act as synthetic host-tailored receptors that could recognize and bind specifically to each drug. The obtained Nernstian slopes were 57.16 mV/decade for alfuzosin MIP-based sensor and 58.17 mV/decade for solifenacin MIP-based one with respective LOD values of 7.9 × 10-7 M and 8.9 × 10-8 M. Moreover, no interference was ostensibly detected from dosage form excipients, plasma constituents or degradation products/official impurities allowing quantification of alfuzosin and solifenacin in their combined capsule, spiked human plasma and in presence of their degradation products.

Fingerprinting and iso-absorptive resolution techniques for the spectrally overlapping Dutasteride and Silodosin mixture: Content uniformity testing along with greenness profile assessment.

The realm of spectrophotometric analysis has witnessed a remarkable progress in inventing faster and simpler resolution techniques for spectrally overlapping drug mixtures. Eco-friendly and progressive spectrophotometric methods were firstly developed in this work, for the simultaneous determination of Dutasteride (DUT) and Silodosin (SLD) in their newly-marketed dosage form. The proposed methods focused on the unique spectral features of this mixture including spectral extension of SLD over DUT spectrum as well as existence of iso-absorptive points. By such way, the methods were classified into two categories; the first one was "fingerprint resolution techniques" including constant extraction coupled with spectrum subtraction and ratio subtraction coupled with constant multiplication methods. The former represented a new modification to the classical constant extraction method where one divisor and lower steps were manipulated instead. The second category was "iso-absorptive resolution techniques", such as absorptivity centering, absorbance subtraction and amplitude modulation methods. Different solvents were investigated where ethanol was found to be the optimum one regarding drugs solubility, signal sensitivity and environmental, health & safety (EHS) score. Validity of the suggested methods was assessed as per ICH-guidelines and found to be linear over concentration ranges of 5.0-90.0 µg/mL for DUT and 5.0-120.0 µg/mL for SLD. The methods were successfully applied for quantifying the cited drugs in their combined dosage form and evaluating their content uniformity. Moreover, the insignificant statistical difference between the proposed methods and official HPLC ones encourages the utilization of such spectrophotometric methods as greener and faster candidates, especially in modest quality control laboratories. Methods' greenness profile was finally guaranteed through several assessment tools, namely; national environmental methods index (NEMI), analytical eco-scale, green analytical procedure index (GAPI) and analytical greenness (AGREE) metric.

Stability assessment of tamsulosin and tadalafil co-formulated in capsules by two validated chromatographic methods.

The advent of a new pharmaceutical formulation evokes the need for examining the chemical stability of their constituents and establishing proper stability-indicating methods. Herein, the stability of the newly co-formulated Tamsulosin and Tadalafil were examined under different stress conditions. The acidic degradation of Tamsulosin yielded its sulfonated derivative, while Tadalafil was susceptible to both acidic and basic degradation. Two stability-indicating chromatographic methods, namely; high-performance thin-layer chromatography and high-performance liquid chromatography, have been developed. Significant high-performance thin-layer chromatography-fractionation could be achieved by utilizing a stationary phase of silica gel 60 F254 and a mobile phase composed of ethyl acetate/toluene/methanol/ammonia (4:2:4:0.6, by volumes) with densitometric recording at 280 nm over a concentration range of 0.5-25 µg/band for both drugs. The HPLC-separation could be reached on XBridge® C18 column isocraticaly by using a mobile phase having acetonitrile/phosphate buffer, pH 6.0 (45:55, v/v) pumped at a flow rate of 1.7 mL/min and applying diode array ultraviolet-detection at 210 nm over a linearity range of 3-70 µg/mL for each drug. Specificity of the two methods was additionally assured via peak purity assessment. Moreover, the methods were distinctly exploited for evaluating the drugs' stability in accelerated stability-studied samples of Tamplus® capsules.

A novel HPLC-DAD method for simultaneous determination of alfuzosin and solifenacin along with their official impurities induced via a stress stability study; investigation of their degradation kinetics.

Stability and impurity profiling are in high demand to guarantee the potency, safety and efficacy of new formulations along with their shelf-life. In this study, stability testing of alfuzosin (ALF) and solifenacin (SOL) in their newly co-formulated capsules was conducted under different stress conditions. The obtained degradation products were structurally elucidated and found to be their official impurities, namely; ALF impurity-D and SOL impurities-A, E & I. A selective and reliable stability-indicating HPLC method was developed for assaying the cited drugs along with three of those official impurities. Chromatographic separation was accomplished within 8 minutes using a XBridge® C18 column as the stationary phase and acetonitrile : phosphate buffer (pH 8) : triethylamine (60 : 40 : 0.02, by volume) as the mobile phase at a flow rate of 1.3 mL min-1. Quantification of the analytes was performed at 210 nm using a diode array detector through which peak purity was assessed. The proposed method was validated as per ICH guidelines and it was successfully applied for the determination of the cited drugs in their combined pharmaceutical formulation with percent recoveries of 100.47 and 100.15 for ALF and SOL, respectively. Moreover, the proposed method was exploited for the assessment of the two drugs' stability in Solitral® capsules under accelerated storage conditions. The method was further extended for studying the degradation kinetics of the two drugs.

Novel HPTLC densitometric methods for determination of tamsulosin HCl and tadalafil in their newly formulated dosage form: Comparative study and green profile assessment.

A promising combination of tamsulosin HCl and tadalafil has recently been introduced for treating two prevalent and associated urological disorders: benign prostate hyperplasia and erectile dysfunction. Novel HPTLC methods were designed and validated for assaying the cited drugs in their challenging combined formulation. Separation was achieved using HPTLC silica gel 60 F254 plates as a stationary phase with a densitometric measurement at 280 nm. The proposed methods with two different chromatographic systems were successfully applied: a conventional mixture (method I) of ethyl acetate-toluene-methanol-ammonia (5:3:2:0.5, by volume) and a greener one (method II) with ethyl acetate-ethanol-ammonia (8:2:0.1, by volume). The two methods were evaluated through a comparative study in terms of selectivity, tailing factor, developing time and concentration ranges. The greenness profile for each method was then appraised with several green guides, namely GlaxoSmithKline solvent sustainability guide, Environmental, Health and Safety (EHS) tool, National Environmental Method Index (NEMI) and Eco-scale. Moreover, method specificity and peak homogeneity were evaluated by peak purity assessment using the winCATS® software spectral correlation tool. The methods have potential for being simple, fast, economic and selective, and the greener one could be a good option for sustainable analysis of the drugs.

Smart spectrophotometric assessment of tamsulosin hydrochloride and tadalafil in their new pharmaceutical formulation for treatment of benign prostatic hyperplasia and erectile dysfunction.

A novel combination of tamsulosin hydrochloride and tadalafil is recently available for treatment of benign prostatic hyperplasia and erectile dysfunction. For the first time, four simple, accurate, smart and robust spectrophotometric methods have been suggested for their simultaneous quantification. The methods, namely; first derivative, ratio difference, derivative ratio and mean centering of ratio spectra, successfully resolved the spectral overlap of their challenging binary mixture. Calibration curves were linear at 2.0-40.0 and 2.0-55.0 µg/mL for tamsulosin hydrochloride and tadalafil, respectively. The methods were validated according to ICH guidelines and statistically compared with the official ones, revealing no considerable difference with respect to accuracy and precision. Specificity of the developed methods was assessed by evaluating various laboratory prepared mixtures. Furthermore, the methods were successfully applied for the quantification of the two drugs in their combined dosage form.