Green micellar liquid chromatographic analysis of alfuzosin hydrochloride and sildenafil citrate in a binary mixture compared to classical RPLC with stability indicating studies.

Two simple and validated chromatographic studies were performed for simultaneous estimation of sildenafil citrate (SIL) and alfuzosin hydrochloride (ALF) in bulk, pharmaceuticals, and in the presence of their main degradation products. Two systems of mobile phase were applied isocratically for their first chromatographic separation using conventional and micellar mobile phases. Methanol, acetonitrile, and 0.02 M potassium dihydrogen phosphate (43:14:43 v/v; pH 4.66) were pumped at 1.3 mL/min in method I. Meanwhile, method II was based on less hazardous micellar mobile phase of nonionic surfactant (0.005 M Brij-35 in water; pH 2.5 adjusted with 0.1% orthophosphoric acid) with a flow rate of 1 mL/min. Both methods were carried on C18 column and coupled with UV detection at 225 nm at ambient temperature. The first method was rectilinear over the concentration range of 5-62.5 µg/mL for both drugs, while the second method showed higher linearity ranges of 0.5-40, 2.5-62.5 µg/mL for ALF and (SIL), respectively. The developed methods successfully enabled the quantification of the studied binary mixture in their tablets dosage form and evaluation their stabilities. Validation of the proposed methods according to ICH guidelines and system suitability were ascertained. Moreover, the applied methods were evaluated and compared from the perspective of green analytical chemistry, employing the National Environmental Methods Index, analytical Eco-Scale score, and Green Analytical Procedure Index, as three assessment tools.

Alfuzosin hydrochloride-loaded low-density gastroretentive sponges: development, in vitro characterization and gastroretentive monitoring in healthy volunteers via MRI.

The current work aimed to develop low-density gastroretentive sponges loaded with alfuzosin HCl (ALF) to sustain the rate of drug release, improve its oral bioavailability and deliver it to the main site of absorption. Sponges were developed, according to a 23 full factorial design, by compression of the lyophilized ALF-loaded hydroxypropylmethylcellulose (HPMC) or chitosan (CH) solutions. The influences of the polymer type, grade and concentration on the appearance, topography, porosity, density, in vitro ALF release, floating behavior, swelling, erosion, and mucoadhesive potential of the developed sponges were explored. Based on the desirability value, the best achieved system was selected. The gastroretentive potential of this system was evaluated in healthy male volunteers via MRI. Soft and flexible sponges were developed. They were characterized with interconnecting pores and channels and had excellent floating properties with respect to floating lag time and duration. Compared to HPMC-based sponges, CH-based ones exhibited higher porosity, larger pore diameters, lower bulk densities, higher drug release rates, larger swelling ratios, faster erosion rates and better mucoadhesive properties. MRI of magnetite-loaded best-achieved CH-based system (F8) ascertained the development of a promising gastroretentive system; exhibiting a gastric residence period of at least 5 h.

Design and optimization of gastric floating sustained-release mini-tablets of alfuzosin hydrochloride based on a factorial design: in vitro/in vivo evaluation.

The purpose of this research was to develop multiple-unit gastric floating mini-tablets and to evaluate the possibility of using these mini-tablets as a delivery system to improve the drug absorption for drugs with a narrow absorption window. Mini-tablets were prepared using hydroxypropyl methylcellulose (HPMC K100M) and carbopol 971P as release retarding agents and sodium bicarbonate (NaHCO3) as gas-forming agent. The properties of the prepared mini-tablets in terms of floating characteristic parameters and in vitro release were evaluated. Furthermore, in vivo gastric retention study in rats and in vivo pharmacokinetic study in rabbits of the optimized formulation were performed. The optimized mini-tablets containing 45% HPMC K100M, 15% stearyl alcohol, 13% carbopol 971P, and 12% NaHCO3 were found to float immediately within 1 min and duration more than 9 h. The in vivo gastric retention study results indicated that the mini-tablets could retain in the stomach for more than 6.67 h. Furthermore, the AUC0-t of the floating mini-tablets (6849.83 ± 753.80 h ng·mL-1) was significantly higher than that of marketed sustained-release tablets XATRAL®XL (4970.16 ± 924.60 h ng·mL-1). All these results illustrated that the gastric floating mini-tablets might be a promising drug delivery system for drugs with a narrow absorption window.

Development and Evaluation of Compression Coating Gastro-Floating Tablet of Alfuzosin Hydrochloride for Zero-Order Controlled Release.

Alfuzosin hydrochloride is an appropriate candidate drug to prepare a gastro-retention controlled release dosage form since it demonstrates a narrow absorption window in the proximal section of the gastrointestinal tract with a short half-life. The purpose of the present study was to develop and optimize a gastro-floating tablet of alfuzosin hydrochloride by using the compression coating method for controlling drug release in a controlled manner. The floating tablets were developed utilizing hydroxypropyl methylcellulose and carbomer as matrix materials. The impact of formulation factors on buoyancy property and in vitro drug release of the floating tablet was investigated. The "similarity factor" (f2) was used as the indicator for the optimization of the formulations. Furthermore, in vivo pharmacokinetic study in rabbits and correlation of in vitro/in vivo study were also performed. It was found that the optimized formulation F9 could float immediately less than 2 min and remain lastingly buoyant over 24 h and follow zero-order release kinetics well. In comparison with the commercially available prolonged release tablets XATRAL® XL, the prepared floating tablet exhibited similar pharmacokinetic parameters (Cmax, Tmax, t1/2, and AUC0 - t) and plasma concentration versus time profile. Moreover, it indicated from the correlation of in vitro/in vivo study that the floating tablets exhibited a good correlation of in vitro/in vivo. In summary, the compression coating gastro-floating tablets might be a promising drug delivery system for alfuzosin hydrochloride to control drug release.

Temperature influencing permeation pattern of alfuzosin: an investigation using DoE.

BACKGROUND AND OBJECTIVE: There has been relatively little investigation of the effect of temperature on skin permeation compared to other methods of penetration enhancement. A principal physicochemical factor which controls the passive diffusion of a solute from a vehicle into the skin arises from the skin temperature. The aim of this ex vivo study was to probe into the effect of heat on transdermal absorption of alfuzosin hydrochloride from ethyl cellulose-polyvinyl pyrrolidone (EC-PVP) based transdermal systems. MATERIALS AND METHODS: Principles of design of experiment (DoE) were used to systematically study the influence of temperature on transdermal permeation of alfuzosin. Ex vivo transdermal permeation studies were carried out at varied donor compartment temperatures. Permeation data analysis was carried out and activation energy for transdermal permeation was estimated. RESULTS: Temperature found to enhance ex vivo permeation parameters of alfuzosin hydrochloride from its transdermal systems. It was also noted that chemical permeation enhancers potentiate permeation enhancing effect of temperature. The permeation flux values approximately doubled after exposure to 45°C. The activation energy for transdermal permeation was found lower for the runs with chemical permeation enhancers indicating existence of a lower energy barrier in the presence of chemical permeation enhancers. CONCLUSION: The method reported here is a simple and useful tool for studying the effect of heat on percutaneous absorption. Such temperature dependent enhancement of flux can be more pronounced at skin surface temperatures >45°C.

Utilization of absorbance subtraction and ratio difference green spectrophotometric methods for the quantification of alfuzosin hydrochloride and tadalafil in their binary mixture.

Alfuzosin hydrochloride and tadalafil fixed-dose combination tablets were recently formulated for the treatment of individuals with lower urinary tract symptoms caused by benign prostatic hyperplasia. Herein, the first spectrophotometric methods for quantitative analysis of alfuzosin hydrochloride and tadalafil in their binary mixture were established. The spectral overlapping of alfuzosin hydrochloride and tadalafil made direct simultaneous analysis unfeasible. Therefore, two mathematical methods were used to solve these overlapping spectra: absorbance subtraction and ratio difference. The absorbance subtraction method manipulates the zero absorption spectra of the studied drugs at the isoabsorptive point (272 nm) and uses the absorbance factor of pure ALF to calculate the absorbance of the studied drugs in the mixture at the isoabsorptive point. The ratio spectra method, on the other hand, manipulates the ratio spectra of the studied drugs, which are obtained by dividing each drug's zero absorption spectra by a divisor spectrum from the second drug. The ratio amplitude difference between 251 nm and 211 nm was directly proportional to alfuzosin hydrochloride, whereas between 292 nm and 222 nm it was directly proportional to tadalafil. The methods used were verified in accordance with the recommendations of the ICH and demonstrated adequate linear regression in working ranges of 1-15 µg/mL for alfuzosin hydrochloride and 3-40 µg/mL for tadalafil. The methods were accurate, precise, and selectively employed to quantify alfuzosin hydrochloride and tadalafil in their combined tablets.

Micellar-enhanced and green-assessed first-derivative synchronous spectrofluorimetric approach for concurrent determination of alfuzosin hydrochloride and solifenacin succinate in different matrices: Docking simulation.

Alfuzosin hydrochloride (AZH) is co-formulated with solifenacin succinate (SOS) in Solitral® capsules for treating prostate hyperplasia in patients with overactive bladder syndrome. Herein and for the first time, an ultrasensitive synchronous spectrofluorimetric approach coupled with first-order derivative signal processing was designed for simultaneous determination of AZH and SOS in their pure forms, newly-released pharmaceutical capsules, and human biological fluids. AZH and SOS showed their conventional emission spectra in bi-distilled water at 382 nm and 294 nm after excitation at 325 nm and 250 nm, respectively. The native fluorescence intensities of AZH and SOS were greatly enhanced through micellar formation using sodium dodecyl sulfate surfactant (2%). The proposed approach included the use of synchronous mode at Δλ of 60 nm where the overlap between the studied analytes' fluorescence spectra wasn't completely resolved. The complete resolution was achieved by derivatization of the synchronized spectra to the first-order yielding two zero-crossing points which allowed the determination of AZH and SOS simultaneously without interference at 408 nm and 321 nm, respectively. Under optimum experimental circumstances, good linearities were accomplished over the concentration ranges of (1-24) ng/mL and (4-250) ng/mL with LOD of 0.26 ng/mL and 1.31 ng/mL for AZH and SOS, respectively. The proposed approach was validated successfully according to guidelines adopted by the ICH and compared statistically with the reported LC method with no discernible differences concerning accuracy or precision at p = 0.05. Successful application of the proposed approach achieved with excellent recovery percentages for analysis of the studied analytes in different matrices (pharmaceutical capsules and biological fluids) confirms its suitability for use in QC laboratories and other bioanalytical applications. The proposed approach's greenness was evaluated using two tools namely; penalty points scoring system and green analytical procedure index (GAPI) divulging excellent greenness of this approach relative to the reported LC method. The proposed approach relied chiefly on water as the cheapest and greenest solvent.

Utilization of a micellar matrix for simultaneous spectrofluorimetric estimation of alfuzosin hydrochloride and vardenafil hydrochloride.

A sensitive and direct spectrofluorimetric method was developed for simultaneous quantitation of two co-administered drugs, namely, alfuzosin hydrochloride (AFH) and vardenafil hydrochloride (VRH). Both drugs exhibited native fluorescence properties that could be exploited to assay them in biological fluids with high sensitivity. Spectrofluorimetric analysis of AFH and VRH is based on excitation of both drugs at 265 nm where emission spectra were recorded separately for AFH and VRH at 380 and 485 nm, respectively. Micellar trends in analytical chemistry were adopted to minimize both environmental and occupational hazards, using distilled water and sodium dodecyl sulphate (serves as a micellar medium that enhanced the sensitivity of AFH and VRH) for analysis of both drugs in their raw materials, tablets, and human biological fluids (plasma and urine). Linearity ranges were 1.0-16.0 and 10.0-700.0 ng mL-1 for AFH and VRH, respectively. The proposed method was successfully assessed for analysis of AFH and VRH in spiked human plasma and urine samples over the following concentrations: 1.0-12.0 ng mL-1 and 4.0-400.0 ng mL-1 for both drugs, simultaneously with mean recoveries of 101.08 % and 102.06 % in plasma and 96.75 % and 92.8 % in urine. Statistical analysis of the practical results has proved quite good agreement and revealed there were no significant differences in the accuracy and precision with those obtained by the comparison methods. The proposed method was applied successfully to Prostetrol® and Powerecta® commercial tablets without interference with tablet additives.

Development of green differential pulse voltammetric strategy for the determination of alfuzosin hydrochloride at pencil graphite and modified carbon paste electrodes.

A sensitive and inexpensive differential pulse voltammetric technique was applied to investigate the electrochemical behavior of alfuzosin hydrochloride at two different working electrodes: silica gel modified carbon paste and pencil graphite electrodes (PGE). The voltammetric conditions were optimized using cyclic voltammetry, showing an irreversible anodic peak in Britton-Robinson buffered medium (pH 6) at 0.86-0.90 V. The electrochemical responses were linearly correlated with alfuzosin concentrations (R2> 0.999) in the ranges of 0.6-20 and 0.3-20 µM, exhibiting higher electrocatalytic activity at PGE with a low detection limit/ detectability of 0.099 µM. In addition, this study was a successful attempt for the drug determination in tablets and spiked urine samples with green profile evaluation, employing the National Environmental Methods Index, analytical Eco-Scale score, and Green Analytical Procedure Index.

Assessment of column selection systems using Partial Least Squares.

Column selection systems based on calculation of a scalar measure based on Euclidean distance between chromatographic columns, suffer from the same issue. For diverse values of their parameters, identical or near-identical values can be calculated. Proper use of chemometric methods can not only provide a remedy, but also reveal underlying correlation between them. In this work, parameters of a well-established column selection system (CSS) developed at Katholieke Universiteit Leuven (KUL CSS) have been directly correlated to parameters of selectivity (retention time, resolution, and peak/valley ratio) toward pharmaceuticals, by employing Partial Least Squares (PLS). Two case studies were evaluated, separation of alfuzosin, lamotrigine, and their impurities, respectively. Within them, comprehensive correlation structure was revealed, which was thoroughly interpreted, confirming a causal relationship between KUL parameters and parameters of column performance. Furthermore, it was shown that the developed methodology can be applied to any distance-based column selection system.