Study of the dissolution kinetics of drugs in solid dosage form with lisinopril and atorvastatin and intestinal permeability to assess their equivalence in vitro

Atorvastatin and lisinopril are a successful combination for the treatment of patients with chronic heart failure and hypertension. Study of the dissolution kinetics of drugs in solid dosage form with lisinopril and atorvastatin and intestinal permeability to assess their equivalence in vitro were described. In medium with hydrochloric acid pH 1.2, in the medium of acetate buffer solution with a pH of 4.5 and in the medium phosphate buffer solution with a pH of 6.8 for 15 min more than 85% of the active substance passes into solution, hence the dissolution profiles these drugs in these environments are similar, and the drugs in them are “very quickly soluble”. Among the in vitro models that make it possible to assess the degree of absorption of API, the most widely used culture of adenocarcinoma cells of the colon – Caco-2. The development of the analytical methodology and its validation is the final stage of both the dissolution study and the Caco-2 test, as well as the biowaver procedure. It plays the most important role in the reliability of the results for all the above procedures and tests. To study permeability, method LC-MS/MS was developed. According to the obtained results, atorvastatin and lisinopril showed low permeability. The values ​​of recovery of transport of test and control substances through the monolayer of cells of the Caco-2 line indicate that the results of the experiment can be considered reliable. The equivalence of the drugs “Lisinopril”, tablets of 10 mg and “Atorvastatin”, tablets of 10 mg, belongs to class III BCS proven by in vitro studies.

Simultaneous Adsorptive Stripping Voltammetric Analysis of Heavy Metals at Graphenated Cupferron Pencil Rods

Electroanalysis of heavy metal ions in the presence of cupferron ligands has been extensively studied due to its ability to form stable metallic coordination complexes. Herein, electrochemically reduced graphene oxide (ERGO) sheets were for the first time employed in conjunction with low-cost, disposable pencil graphite rods and in-situ plated thin mercury films (HgF) for the simultaneous detection of Cd2+, Cu2+, Pb2+, and Zn2+ in the presence of cupferron as a chelating agent by square-wave adsorptive cathodic stripping voltammetry (SW-AdCSV). The technique is based on the catalytic reduction of adsorbed cupferron-metal ion complexes at the surface of the ERGO-HgF-PGE at 0.1 V for 60 s in 0.1 M acetate buffer solution (pH 4.6). Owing to the improved electronic and surface effects associated with ERGO inclusion, improved sensitivity was further achieved. Under optimized conditions, the ERGO-HgF-PGE showed a linear relationship from 20 to 200 µg.L-1 with detection limits below the US-EPA of 0.17 μg.L-1 , 0.02 μg.L-1 , 0.17 μg.L-1 and 0.14 μg.L-1 for Cd2+, Cu2+, Pb2+ and Zn2+, respectively at a deposition time of 60 s. The ERGO-HgF-PGE exhibited highly reproducible results with negligible intermetallic interferences and applied successfully to the determination of trace metals in tap water with satisfactory results.

Electrochemically Activated Screen-Printed Carbon Electrode for Determination of Ibuprofen

In this study, we present a simple, sensitive and selective analytical procedure for the ibuprofen (IBP) analysis using the commercially available screen-printed carbon electrode electrochemically activated (aSPCE) by cyclic voltammetry in 0.1 M NaOH. The quantitative determinations of IBP were carried out in 0.25 M acetate buffer solution of pH 4.5 ± 0.1 using the differential-pulse voltammetry (DPV). Different experimental parameters for DPV analysis were optimized, including pH and concentration of supporting electrolyte, amplitude (ΔEA), scan rate (ν) and modulation time (tm). The linear ranges of calibration curve were from 0.50–20.0 and 20.0–500.0 µM. The detection and quantification limits were estimated to be 0.059 and 0.20 µM. The aSPCE displayed satisfactory repeatability, reproducibility, and selectivity. Furthermore, the DPV procedure with the use of aSPCE was used to determination of IBP in pharmaceutical formulations. The results achieved by DPV show satisfactory agreement with those obtained by manufacturers (the relative errors are in the range of 3.1–4.7%).

Screening of Electrolyte Complexes Formed Between Dextran Sulfate and Amine Structures of Small-Molecule Drugs

Formation of an electrolyte complex using the electrostatic interactions between a polyanionic polymer and a cationic drug is a simple and efficient method of preparing a colloidal drug carrier system. Dextran sulfate, with a negatively charged sulfate group, was reacted in an acetate buffer solution of pH 3 with positively charged 1° amine, 2° amine, 3° amine, piperazine, and piperidine structures from 24 small-molecule drugs. The electrolyte complex was formed from 15 drugs, 63% of those tested. The tendency to form the electrolyte complex was in the order of piperazine and piperidine >3° amine >>2° amine. The drugs with the 1° amine structure failed to form an electrolyte complex. The mean particle sizes were in the range of 50-740 nm, and most of them showed a submicron colloidal dispersion of <400 nm. Regarding drug encapsulation efficiency (%), 11 drugs with piperazine, piperidine, and 3° amine structures showed 60–98% efficiency, which was fairly high. The results suggest that directly forming the electrolyte complex with dextran sulfate yields promising structural attributes as a submicron colloidal drug carrier system.

Effect of pH on Homogeneous Photodegradation of Eosin Y Dye

Eosin Y (EY), an anionic dye, also known as Eosin Yellow or Bromoeosin, or Acid red 27 is an industrial dye. The residual dye, discharged as one of the components of the untreated effluent, into the adjacent surface and causes water pollution. Photodegradation of EY was investigated at 29 oC in homogeneous aqueous media using UVA light (≈400 – 320 nm) in acetate buffer solution as a function of pH (3.08-7.08). At higher pH, there was no effect of this light on the dye in the solution. Results show that the initial rate of photocolorization increased with decreasing the pH of the dye solution.

The use of photogenerated iodine in determination of the dibazol content in solid and liquid dosage formulations

A rapid method for the determination of Dibazol (bendazol hydrochloride) in liquid and solid dosage forms (DF) has been developed. The method is based on converting the drug into an analytical form and titrating the physiologically active compound (PAC) with a solution of photogenerated iodine obtained by irradiation of an auxiliary solution containing potassium iodide, a mixture of sensitizers (sodium eosinate: fluorescein: auramine, taken in a molar ratio of 1:1:1) and an acetate buffer solution (pH 5.6). A decrease in the titrant content in the cell due to interaction with Dibazol was recorded by a decrease in the current in the amperometric circuit. Stabilization of the current in the circuit indicated the completeness of the reaction, thus providing for estimation of the PAC content in a DF. Further irradiation of the solution and measurement of the generation time required to replenish the titrant loss in the cell also ensure the quantitative estimation of the PAC content in the preparation. The method has been tested on solid dosage form and sterile solutions of Dibazol intended for intramuscular and intravenous administration. A slight effect of stabilizers (hydrochloric acid, ethanol) and auxiliary substances (potato starch) present in the DF on the photogeneration of the titrant was observed. The determined Dibazol content in solid and liquid DF falls within the range recommended by the order of the Ministry of Health of the Russian Federation (26.10.2015 No. 751n) and OFS.1.4.2.0009.15, which indicates that the quality of the drug meets the GMP standards. The linear dependence of the analytical signal on the Dibazol concentration is observed in the range of 13.5 – 134.7 mg for the drug «Dibazol-UBF, tablets, 20 mg». The calculated limits of Dibazol detection and quantitative determination by changes in the current strength and generation time are (4.71; 3.56) and (14.26; 10.77) mg, respectively. The use of developed technique in the analysis of drugs containing Dibazol reduces both the time of single determination due to the absence of the need for standardization of solutions, and the cost of a single analysis, since it does not require the use of expensive equipment and reagents.

SIMULTANEOUS ESTIMATION OF CLONAZEPAM AND METRONIDAZOLE IN PHARMACEUTICAL TABLETS BY REVERSED-PHASE HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY MODE WITH UV DETECTION

Clonazepam (CLO) plays a significant role in treating seizures, myoclonic seizures, and other clinical infections, while metronidazole (MTZ) is an antiprotozoal, antibacterial drug. The reversed-phase high performance liquid chromatographic (RP-HPLC) technique has provided greater precision and sensitivity over other methods, especially the colorimetric and spectrophotometric. This study aimed to implement a simple method in pure and pharmaceutical tablets for the simultaneous determination of CLO and MTZ. The RPHPLC method's development and optimization for validating a separation method for the simultaneous estimation of both drugs in pharmaceutical formulation involved studying the optimum mobile phase, buffer concentration, and the pH value. Under the chromatographic conditions, RP-HPLC system achieved excellent separation on a Phenomenex HyperClone BDS (250 x 4.60 mm, 130A, and 5μ) at a temperature of 45°C and the following conditions: 65:35% acetonitrile:acetic acid and sodium acetate buffer solution (NaOAc/HAc) as mobile phase (pH 3.5); 20 μL injection volume at a flow rate of 0.75 mL/min and detection wavelength of 310 nm. The proposed RP-HPLC procedure demonstrated high precision (RSD% 1%), as well as the good linear relationship of the calibration graph at concentration ranges of 50-160, 35-100 ppb with a coefficient of determination (r2) of the regression line of 0.9996 and 0.9997 for metronidazole and clonazepam respectively. The proposed method offered excellent validated values for both LOD (4.24 and 3.06 ppb) and LOQ (14.15– 10.21 ppb) for both metronidazole and clonazepam drugs, respectively. The RP-HPLC method has been successfully applied to estimate metronidazole and clonazepam in the well-known commercial pharmaceutical tablets and gave an excellent recovery> 98% for both drugs. The results of the method was compared with the standard pharmacopeial method for both drugs using statistical tests, which indicated no difference in accuracy between the methods

Detection of carious lesion by laser speckle analysis using the first order moment

Carious lesion is one of the most prevalent diseases in humankind, affecting nearly all human beings at least once in a lifetime. Early carious lesion (ECL, also known as white spot lesion) is part of the caries process in which the enamel surface loses mineral but the subsurface layer overlying the mineral-poor region remains intact. In its early stages, the detection of the carious lesion is currently still a major challenge because it is based on visual inspection, thus with an inherent subjectivity. In this work, we present a method to detect and assess the severity of ECLs using a computer-assisted laser speckle imaging technique. Forty-five polished and cut bovine incisors samples allow a paired t-test by exposing half of the surface while protecting the other half. The samples, included in a PVC tube, were immersed in 50ml of a solution (pH 5.0) containing 0.05M acetate buffer solution and 50% saturated hydroxyapatite enamel powder at 37°C. The etching time is 24h; 48h and 72h; each group contain 15 samples. We illuminate each sample with a laser and analyse the first momentum of the laser speckle images with a computer. Our results shows that the first momentum of the LSI of the sound region statistically differs from the decay region of the samples for all groups (p<0.0001). We also found a strong correlation between the acid etch duration (severity of the decay) and the shift in LSI contrast (Pearson’s correlation coefficient ρ=0.9989, R²=0.9978). Detecting decay in its early stages is still a challenge in the clinical practice, however this work demonstrates that the analysis of the statistical features of the laser speckle image in the spatial domain allows for the detection of microstructural changes in the enamel associated with the presence of the lesion even before any intervention is required.

Effect of physicochemical properties on the pharmacokinetic parameters of the new representative of benzothiazinones antituberculosis drug macozinonе

Introduction.Tuberculosis (TB) is one of the top ten causes of death worldwide. Improvement of the treatment options via development of new drugs and treatment regimens that would be more convenient for patients is one of key options of improving the effecacy of the TB prevention and careis. Since the creation of new treatment regimens by minimizing the number of the drugs used and reducing the duration of treatment is the most promising and correct direction, macozinone, a new candidate of the benzothiazinone series, can become the basis for development of new chemotherapy regimens for drug-resistant forms of TB including the combination of macozinone with the most effective modern anti-TB drugs. Aim.Comparative evaluation of the pharmacokinetic properties of macozinone capsules 80 mg and the new dosage form a dispersible tablet for preparation of oral solution. Materials and methods.Solubility of the substance macozinone in biorelevant media in vitro, permeability of macozinone in the test Caco-2 in vitro, as well as pharmacokinetics of macozinone in dogs in vivo were evaluated. Results.The solubility assessment in biorelevant media showed that the average limit of macozinone substance dissolution in the pH 5.0 acetate buffer solution was from 6 to 9 mg/l, in FaSSIF medium (fasted) from 2.5 to 4 mg/l, and in FeSSIF medium (after meals) from 16.8 to 29 mg/l. It is established that the cell permeability of the pharmaceutical substance macozinone in the CACO-2 test system is on average 2.510-6cm/s in the forward direction from the apical to basolateral cell membrane, and 1.510-6cm/s in the reverse direction, which corresponds to low permeability. The main pharmacokinetic parameters of macozinone dispersable tablets 160 mg, after dosing with food and on an empty stomach, as well as capsules 80 mg, when administered on an empty stomach in vivo studies in dogs are presented. Discussion.The specific physicochemical properties of macozinone, the problems of developing the new dosage form, as well as ways of solving some of them are presented. Conclusion.In the process of new dosage forms development, the existing chemical properties of the macozinone substance should be considered. One of the promising ways of increasing bioavailability and, consiquently, efficacy is development a fundamentally new drug form with modified release within the absorption window.

Initial and pulp chamber concentration of hydrogen peroxide using different bleaching products

Objective: This study’s aim was to quantify the hydrogen peroxide (HP) penetration into the pulp chamber of teeth submitted to different protocols of bleaching. Material and Methods: Ninety premolars were randomly divided into nine groups according to the bleaching agent protocol (n = 10): control (no bleaching), carbamide peroxide 10% [10% CP], carbamide peroxide 16% [16% CP], carbamide peroxide 22% [22% CP], hydrogen peroxide 4% [4% HP], hydrogen peroxide 6% [6% HP], hydrogen peroxide 7.5% [7.5% HP], hydrogen peroxide 10% [10% HP] and hydrogen peroxide 35% [35% HP]. The penetration of HP was measured via spectrophotometric analysis of the acetate buffer solution from the pulp chamber. The absorbance of the resulting solution was determined in a spectrophotometer and converted into equivalent concentration of HP (μg/ mL). To analyze the concentration of HP, the titration of bleaching agents with potassium permanganate was used. Data were subjected to ANOVA and Tukey’s test for pairwise comparison (α = 0.05). Results: Higher concentration of HP in the pulp chamber was found in the HP 35% group (p < 0.0001). No significant difference between at-home protocols were observed (p = 0.64). Titration values showed that the concentration of the products was similar to that claimed by the manufacturer. Conclusion: It follows that the amount of HP that reaches the pulp chamber is not proportional to the concentration of whitening gels, but depends on the application time recommended by the manufacturers.KEYWORDSAt-home bleaching; Dental enamel permeability; Inoffice bleaching; Tooth bleaching.