Distrontium Cerate as a Radiopaque Component of Hydraulic Endodontic Cement

This study aimed to synthesize distrontium cerate (2SrO·CeO2: S2Ce) and evaluate its properties as an alternative component of the endodontic cement. S2Ce cement was prepared through calcination of strontium hydroxide and cerium carbonate. Subsequently, the crystal phase was confirmed using X-ray diffraction. S2Ce cement exhibited a rapid setting time (121 min) and achieved a high compressive strength (72.1 MPa) at 1 d after mixing, comparable to the compressive strength of a commercial mineral trioxide aggregate (MTA) cement (ProRoot MTA) after 28 d post mixing. However, the compressive strength decreased after 28 d of storage when the W/P ratio was 0.30–0.40 (p < 0.05). Ion dissolution test of the S2Ce cement showed that strontium ions were released after immersion in water (5.27 mg/mL after 1 d), whereas cerium dissolution was not detected. S2Ce exhibited approximately three times higher radiopacity (9.0 mm aluminum thickness equivalent) compared to the commercial MTA (p < 0.05). These findings suggest that S2Ce is a possible component for hydraulic endodontic cement that demonstrates a rapid setting and high radiopacity.

Effect of soft beverages on the in vitro dissolution of gastro-resistant tablets containing low dose Acetylsalicylic acid

The need for additional fluids for easy absorption is typical for elderly patients and those with dysphagia. Most often, these patients take their medication with a glass of orange juice or another liquid instead of a glass of water. We conducted a dissolution test with gastro-resistant tablets acetylsalicylic acid where different kind of orange juice or soft drink wеre added to the release medium. As a control, release medium - buffers 1.2, 4.5 and 6.8 were used. The released aspirin was determined after HPLC analysis. The obtained data were fitted to different kinetic models. The results of the dissolution test in medium buffers with added different beverage showed results similar to those obtained in pure buffer, where it is used an artificial sweetener and different, when sugar or glucose-fructose syrup was used to sweeten the beverage. The most significant change was observed in the release kinetics of the active substance.To exclude the possibility that the other beverage ingredients or excipients used to make the tablets affect the release profile of acetylsalicylic acid, we conducted a beverage-like dissolution test. Instead of a original beverage, we used water and sugar syrup, in a concentration that is declared on the label of the original beverages. The results obtained confirm that different sugar concentrations alter the release profile of acetylsalicylic acid from gastro resistant tablets when they are taken with a glass of sugar-containing beverage instead of a glass of water.

Development of the "Dissolution" Test Method for Tablets of Sodium 4,4'-(propanediamido)dibenzoate with Sustained Release

Introduction. Non-alcoholic fatty liver disease is one of the most common chronic diseases of this parenchymal organ among the adult population. The search and creation of supporting drugs is an urgent task of modern pharmacy. The malonic acid derivative, sodium 4,4'-(propanediamido) dibenzoate, synthesized by the employees of the Department of Organic Chemistry of the SPСPU, has antisteatous activity, is a potential agent for the treatment of liver diseases. Sustained release tablets were prepared based on sodium 4,4'-(propanediamido)dibenzoate. An integral part of the pharmaceutical development of a medicinal product is the development of a method for conducting the Dissolution test and the selection of optimal conditions, which became the purpose of this study.Aim. To develop the "Dissolution" test method for the sustained-release tablets based on sodium 4,4'-(propanediamido)dibenzoate.Materials and methods. The objects of research are the active pharmaceutical ingredient sodium 4,4'-(propanediamido)dibenzoate, as well as sustained-release tablets based on this substance. Equilibrium biopharmaceutical solubility was determined by UV-spectrophotometry. To establish the conditions for the "Dissolution" test, an ERWEKA DT-620 dissolution tester (ERWEKA GmbH, Germany) was used.Results and discussion. The suitability of the UV-spectrophotometry method for the quantitative determination of sodium 4,4'-(propanediamido) dibenzoate in solutions was determined. The established high biopharmaceutical solubility of sodium 4,4'-(propanediamido)dibenzoate in a buffer solution with a pH of 6,8, as well as in a 0,01 M solution of hydrochloric acid with a pH of 2,6, determined the choice of these media for the "Dissolution" test of the dosage form. The apparatus "Rotating basket" (rotation speed of 100 rpm in a dissolution medium with a volume of 1000 ml) was reasonably chosen for the test on the basis of the obtained linear dependence of the rate of release of the substance on time, as well as the best test results by the end of the experiment.Conclusion. A study of the biopharmaceutical properties of the original substance with antisteatous activity has been carried out. High biopharmaceutical solubility was established in media with pH 2,6 and pH 6,8. The conditions of the "Dissolution" test for sustained-release tablets based on the original sodium 4,4'-(propanediamido)dibenzoate were experimentally substantiated.

The Development and the Validation of a Novel Dissolution Method of Favipiravir Film-Coated Tablets

The aim of this study was to develop and validate a dissolution test for favipiravir release in a tablet dosage form using ultra-high performance liquid chromatography (UHPLC). The dissolution method was developed by testing the solubility of favipiravir in media with different pH values. The results demonstrated that the best dissolution was achieved in phosphate buffer with a pH of 6.8. The amount of favipiravir that was released was about 100% after 30 min. The UHPLC method presented linearity (R = 1.000) in the concentration range of 0.044–0.44 mg/mL. The recovery parameter that was achieved ranged from 102.5% to 104.2%. The system suitability, repeatability, and intermediate precision RSD% results were found to be 0.36%, 1.99%, and 2.49%, respectively. In addition to these parameters and results, an F-test was performed using the Minitab 18 Statistical Software program for the intermediate precision and repeatability results. The standard and sample solutions were found to be stable for 2 days in their respective dissolution medium. This analytical method was also found to be selective for favipiravir. In conclusion, a simple and feasible dissolution method with a short run time of 2.5 min was developed and validated successfully. The obtained results demonstrated that the dissolution test developed here is adequate for its purpose and can be applied as the dissolution method for favipiravir in film-coated tablets for release analyses.

IMPROVEMENT OF THE DISSOLUTION PROFILE OF SIMVASTATIN TABLETS WITH THE ADDITION OF CREMOPHOR-EL USING WET GRANULATION METHOD

Objective: Simvastatin is a drug used as a first-line anti-cholesterol in the treatment of dyslipidemia. Low solubility will affect its ability to penetrate the digestive tract membrane and will affect the amount of drug levels in the plasma. The use of Cremophor-EL as a surfactant has been shown to inhibit the action of P-glycoprotein so that it can increase the bioavailability of a drug and can increase the effect of a drug. Methods: The preparation of simvastatin tablets was carried out using the wet granulation method. The dissolution test used the paddle method, a speed of 50 rpm at a temperature of 37±0.5 ° C with a phosphate buffer pH 7.0 as the dissolution medium. Results: The results showed that at 30 min the generic simvastatin tablets had 81.52% dissolution and the Simvastatin Tablets with Cremophor-EL were 85.520%. Conclusion: Simvastatin cremophor-EL tablets are more dissolved than generic simvastatin at 30 min so that cremophor-EL simvastatin tablets have a better dissolution rate than generic simvastatin tablets.

Alternative Methods for Dissolution Profile Comparison in the Dissolution Test

Introduction. The article discusses the problem of assessing the similarity of the dissolution profiles of two batches of the nebivolol. The use of a generally accepted similarity factor for assessing equivalence is unacceptable in some cases, for example, for drugs with a high variability in the values of the release of the active substance from the formulation. At the same time, at present, there are no generally accepted approaches to comparing the profiles of the dissolution kinetics of drugs, with the exception of the method for assessing the comparability of profiles based on the mathematical calculation of the similarity factor f2, which has certain criteria that limit its application.Aim. To demonstrate alternative methods for assessing the similarity between the dissolution profiles of two drugs using a practical example.Materials and methods. The results of the comparative dissolution test of two series of nebivolol at a dosage of 5 mg. Five model-independent methods for assessing the equivalence of drug dissolution were used. Statistical data processing was performed using Microsoft Excel software.Results and discussion. The paper presents a practical example of using five alternative model-independent methods for assessing the equivalence of the dissolution profile. An example is used to illustrate the proposed equivalence limits and statistical methodology. Also, various approaches to determining the boundaries of equivalence have been proposed to assess the similarity of the dissolution profiles of an active substance.Conclusion. According to the results of the comparative dissolution test of two batches of nebivolol, it was shown that the use of the similarity factor as a criterion for assessing dissolution profiles led to a false positive result. In such cases, the possibility of using alternative methods for assessing the equivalence of dissolution profiles described in the article, or other methods presented in the scientific literature, should be considered, with a justification of their acceptability in each specific case.

Combined Methodologies for Determining In Vitro Bioavailability of Drugs and Prediction of In Vivo Bioequivalence From Pharmaceutical Oral Formulations

With the aim of developing an in vitro model for the bioavailability (BA) prediction of drugs, we focused on the study of levonorgestrel (LVN) released by 1.5 mg generic and brand-name tablets. The developed method consisted in combining a standard dissolution test with an optimized parallel artificial membrane permeability assay (PAMPA) to gain insights into both drug release and gastrointestinal absorption. Interestingly, the obtained results revealed that the tablet standard dissolution test, combined with an optimized PAMPA, highlighted a significant decrease in the release (15 ± 0.01 μg min−1 vs 30 ± 0.01 μg min−1) and absorption (19 ± 7 × 10–6 ± 7 cm/s Pe vs 41 ± 15 × 10–6 cm/s Pe) profiles of a generic LVN tablet when compared to the brand-name formulation, explaining unbalanced in vivo bioequivalence (BE). By using this new approach, we could determine the actual LVN drug concentration dissolved in the medium, which theoretically can permeate the gastrointestinal (GI) barrier. In fact, insoluble LVN/excipient aggregates were found in the dissolution media giving rise to non-superimposable dissolution profiles between generic and brand-name LVN tablets. Hence, the results obtained by combining the dissolution test and PAMPA method provided important insights confirming that the combined methods can be useful in revealing crucial issues in the prediction of in vivo BE of drugs.

IN VITRO ASSESSMENT OF PHYSICOCHEMICAL PARAMETERS OF FIVE GENERICS AMLODIPINE BESYLATE TABLETS MARKETED IN YEMEN

Objective: The present paper aims to evaluate the quality of five different brands (local and imported) of oral film-coated tablets of generic Amlodipine besylate 5 mg marketed in Sana`a-Yemen, through physiochemical parameters. Methods: Different physicochemical parameters, including the uniformity of tablet weight, hardness, thickness, disintegration time, and an assay of active ingredients, were conducted to validate the quality of generics Amlodipine Besylate 5 mg according to USP specification. Results: From the obtained results, it was observed that all the brands of Amlodipine Besylate 5 mg have passed the tests and met the specifications of USP. Results of weight variation, hardness, thickness, and disintegration time were ranged from-3.8 % to+5.13 % to-1.25 % to+3.25 %, 5.06±0.31 to 13.21±1.5, 2.682±0.04 to 3.676±0.01 and 25 s to 2 min: 30 s, respectively. The dissolution test and the assay results of all the brands are also ranged within the acceptable label claim 93.7±2.24 to 98.4±0.85 and 93.22±0.38 to 100.15±0.33, respectively. However, there is no relation was found between the disintegration time and the dissolution test. Conclusion: According to the finding, all the selected Amlodipine Besylate 5 mg brands are met pharmacopeia standards and USP specifications. Therefore, the local and imported Amlodipine Besylate 5 mg can be used safely to get the desired therapeutic efficiency.