Diabetes is a known risk factor for sexual dysfunction in men; diabetic men have an increased risk of erectile dysfunction compared to non-diabetic men. Canagliflozin is one of the common antidiabetic drugs that is readily used in the treatment of type-2 diabetes. Concomitantly phosphodiesterase 5 inhibitors, such as tadalafil, can be given to the patient to alleviate erectile dysfunction. Canagliflozin is reported to be one of the cytochrome P450 3A4 enzyme inhibitors, that might seriously influence blood concentration levels of tadalafil but there is no study till now, discussing this interaction. Therefore, a fast, simple, and sensitive high-performance thin-layer chromatographic method was developed, validated, and applied for the simultaneous determination of tadalafil and canagliflozin in spiked and real human plasma. The limit of detection for tadalafil was 0.14 ng/band and for canagliflozin was 0.16 ng/band. The limit of quantitation value for tadalafil was 0.43 ng/band and for canagliflozin was 0.47 ng/band. Tadalafil and canagliflozin were determined simultaneously in real human plasma using the described procedure and the method was applied for in vivo pharmacokinetic drug interaction study between the studied drugs, which proved significant interaction between them when administered simultaneously.

Erectile dysfunction (ED) is one of the most common chronic diseases affecting men and its incidence increases with aging. Due to its substantial influence on the quality of life, phosphodiesterase type-5 (PDE5) inhibitors have been implemented to treat ED by increasing the penile blood flow that results in improving erection. PDE5 inhibitors is a class of drugs that affects many pharmacological sectors, and it is essential to review the different analytical methods described for their determination. Few reviews were published concerning this group of drugs. For this reason, this review article gathers the different analytical methods used to determine PDE5 inhibitors in pharmaceutical and biological samples over the past 20 years. Different analytical techniques were used to analyze these compounds in different matrices such as separation methods (capillary electrophoresis, LC-MS, UPLC-MS/MS, and GC-MS), spectroscopic methods (UV-visible methods, FT-IR spectroscopy and spectrofluorometry) and electrochemical methods (polarography, voltammetry and potentiometry). This review focuses on the different electrochemical methods and their use in analytical determination of PDE5 inhibitors in pharmaceutical dosage forms and biological samples. Moreover, it discusses the different modified electrodes used for their electroanalytical determination and the behavior of the studied drugs at different modified electrodes. Additionally, this review discusses the pharmacokinetics of the studied compounds and their interactions with other co-administered drugs especially the metabolic interactions between the studied compounds and other co-administered drugs in different matrices. This literature survey would provide a beneficial guide for future analytical investigation of PDE5 inhibitors.

Patients who receive anticancer drugs, might experience loss of sexual desire together with erectile dysfunction as one of cancer medications’ adverse effects. This might have a negative effect on their psychological functioning and quality of life and accordingly phosphodiesterase type 5 (PDE5) inhibitors as sex stimulants are used. One of the recently FDA-approved members of this class of drugs is avanafil (AVN) that is administered to assist in improving penile erection. Because of the seriousness of the cancer patient's health condition, it is mandatory to recognize the possible pharmacokinetic interactions in case of administering other drugs at the same time. Therefore, a sensitive sensor derived from carbon paste electrode (CPE) modified with anatase titanium dioxide nanoparticles (TiO₂-NPs) and multi-walled carbon nanotubes (MWCNTs) was designed for the simultaneous determination of AVN and the anticancer drug doxorubicin (DOX) in spiked and real rabbit plasma samples. X-ray powder diffraction (XRD), Fourier transform infrared (FT-IR), and scanning electron microscopy (SEM) were employed to fully characterize the fabricated electrode. The modified electrode offers a considerable improvement in voltammetric sensitivity toward oxidation of AVN and DOX, compared to the bare electrode. A good separation was achieved between the oxidation peak potentials of AVN (1.4 V) and DOX (0.8 V). The effect of different voltammetric parameters on the peak separation and sensitivity for both drugs was studied to select the optimum experimental conditions. It was found that the optimum pH for the simultaneous determination of both drugs was obtained utilizing a Britton-Robinson buffer (BR) of pH 3.0. Furthermore, the electrochemical oxidation of AVN and DOX was evaluated with different modified carbon paste electrodes using cyclic voltammetry (CV) and square-wave adsorptive anodic stripping voltammetry (SWAdASV). The analytical curves for the quantitative simultaneous determination of AVN and DOX exhibited acceptable linearity within the concentration range from (0.10–6.0 μmol L⁻¹ for AVN) and (5.0–35.0 μmol L⁻¹ for DOX) in spiked rabbit plasma. Detection and quantitation limits were determined to be 0.035 and 0.10 μmol L⁻¹ in the case of AVN and 1.3 and 4.0 μmol L⁻¹ in the case of DOX, respectively. The method was effectively applied for the analysis of AVN in real rabbit plasma samples after the coadministration of DOX. Moreover, the proposed voltammetric method was useful as a therapeutic drug monitoring method to investigate the possible pharmacokinetic interactions between AVN and DOX in real rabbit plasma. An increase in the level of AVN in rabbit plasma was observed after administering DOX, and accordingly, the dose of AVN should be adjusted and monitored.

Stability testing of an active substance or final product is very crucial to ensure drug efficacy during shelf life.
Simple and specific monitoring of β-lactam antibiotic combinations (with β-lactamase inhibitors) under ambient
storage conditions was performed to better understand the kinetics of their degradation in powder for injection.
The stored samples were analysed using HPTLC/MS and HPTLC/UV. The method employed HPTLC aluminum
pre-coated plates with silica gel 60 F254 as the stationary phase. The used mobile phase systems consisted of ethyl acetate: acetonitrile: glacial acetic acid: water (5.5:3.0:2.0:1.0, v/v/v/v), for Magna-biotic® and ethyl acetate:
acetonitrile: glacial acetic acid: water (5.0:3.0:2.0:1.0, v/v/v/v) for Unasyn® and Sulbacef®. The investigated
mixtures were subjected to conditions resembling those found in a storage facility during different time intervals.
The degradation behavior of powders for injection of the investigated mixtures, was found to be fitted to first order kinetics, which is measured by observing the drug’s starting concentration drop over time. The obtained
results ensure the method’s ability to assess the degradation kinetics of the tested combinations in the presence of their degradation products. The current study examines the drug’s stability against high storage temperatures.
MS detection was employed to elucidate the chemical structures of degradants and to confirm the suggested
degradation pathway of the investigated mixtures in powder of injection. As a result, it is recommended that
suitable protection measures against high temperatures must be followed during storage and handling of the
investigated powder for injection of β-lactam antibiotics mixtures in order to maintain their biological efficiency.
 

Extraction of highly hydrophilic compounds from biological fluids including urine or plasma samples is a
dilemma due to high hydrophilicity of the matrix itself. The main aim of the current work is to explore the
competence of ionic liquid (IL)-based surfactant-coated mineral oxide nanoparticles (NPs) in dispersive solidphase microextraction (d-SPME) of highly hydrophilic analytes taking cefoperazone (CPZ) as a model analyte for the study. The IL-based surfactant coated Fe3O4 NPs is utilized as an innovative adsorbent for the separation and pre-concentration of CPZ after intramuscular injection (I.M) in rabbits. The utilized magnetite NPs were synthesized via simple and reliable co-precipitation procedure, which doesn’t require any air-free environment and depends on a single iron (III) salt. Characterization of the as-synthesized NPs was achieved by X-ray powder diffraction (XRD), Fourier transform infrared (FT-IR) and energy dispersive X-ray (EDX). Surface area measurements show that Fe3O4 NPs have large surface area of 75 m2 g- 1. The developed approach utilizes the unique properties of the IL-based surfactant including multiple polar interaction types provided by the polar head in addition to merits of Fe3O4 nanoparticles, which include large adsorptive capacity and magnetic properties, to improve separation, save time, and achieve satisfactory recovery. Comprehensive study was developed for the factors, that affect the adsorption capacity such as pH, NPs amount, IL-based surfactant concentration, ionic strength, adsorption time, and desorption conditions. Moreover, the adsorption data was fitted to Langmuir and second-order kinetic models as reflected by the reasonable determination coefficients of 0.9319 and 0.9726, respectively. Under the optimized conditions, the developed approach achieves good correlation coefficient of 0.9975, and 0.9981 over linearity range of 0.7–12.0 and 4.0–50.0 µg mL- 1 for both CPZ standard solutions and spiked rabbit plasma, respectively. It also provides good sensitivity expressed by the low values of limit of detection (LOD) of 0.2 and 1.2 µg mL- 1 and limit of quantitation (LOQ) of 0.7 and 4.0 µg mL- 1 for both the  standard solutions and spiked plasma, respectively. The developed approach was also applied successfully for monitoring CPZ in rabbit plasma samples with satisfactory recovery % (83–110). In addition, a detailed pharmacokinetic study is performed where pharmacokinetic parameters of CPZ in rabbit plasma samples were
calculated.
 

Dry eye disease (DED), keratoconjunctivitis sicca or dysfunctional tear syndrome, is the most prevalent
ophthalmic disease which affects a substantial segment of people worldwide with increasing frequency. It is
considered a multifactorial disease of the ocular surface and tear film, characterized by a variation of signs and
symptoms. The symptoms range from mild to severe itching, burning, irritation, eye fatigue, and ocular
inflammation that may lead to potential damage to the cornea, conjunctiva and even vision loss. Correspondingly,
depending on the different manifestations and pathophysiology, the treatment must be tailored specifically
to each patient by targeting the specific mechanisms implicated in their disease. Currently, there are several
medical products and techniques available or under investigation for the treatment of DED. The present article
focused on the pathophysiology of DED, the new diagnostic approach and the recently developed drug delivery
systems or devices reducing the progress of the disease and treating the causes.

This work aimed to optimize a celecoxib (CXB)-loaded solid lipid nanoparticles (SLN) colon delivery system for the enhancement of anticancer activity. An ultrasonic melt-emulsification method was employed in this work for the preparation of SLN. The physical attributes were characterized for their particle sizes, charges, morphology, and entrapment efficiency (%EE), in addition to DSC and FTIR. The in vitro drug release profiles were evaluated, and the anticancer activity was examined utilizing an MTT assay in three cancer cell lines: the colon cancer HT29, medulloblastoma Daoy, and hepatocellular carcinoma HepG2 cells. All of the prepared SLN formulations had nanoscale particle sizes ranging from 238 nm to 757 nm. High zeta-potential values (mv) within −30 s mv were reported. The %EE was in the range 86.76–96.6%. The amorphous nature of the SLN-entrapped CXB was confirmed from SLN DSC thermograms. The in vitro release profile revealed a slow constant rate of release with no burst release, which is unusual for SLN. Both the F9 and F14 demonstrated almost complete CXB release within 24 h, with only 25% completed within the first 5 h. F9 caused a significant percentage of cell death in the three cancer cell lines tested after 24 h of incubation and maintained this effect for 72 h. The prepared CXB-loaded SLN exhibited unique properties such as slow release with no burst and a high %EE. The anticancer activity of one formulation was extremely significant in all tested cancer cell lines at all incubation times, which is very promising.