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.

Prediction of the composition of prolonged release tablets based on 4,4'-(propandiamido) sodium dibenzoate using the SeDeM method

Introduction. Direct compression technology is one of the most common tablet technologies. As known, many active pharmaceutical ingredients are not suitable for this technology without the addition of special excipients. A useful tool for determining the suitability of powdered materials for direct compression technology is the Sediment Delivery Model (SeDeM) method, based on the concept of Quality by Design. The presented method allows not only to assess the suitability of a material for direct compression, but also helps to predict the composition of a solid dosage form in the form of a tablet, which, in turn, leads to a significant reduction in experimental work carried out in the development of a new drug.Aim. Prediction of the compositions of matrix tablets based on sodium 4,4'-(propanediamido)dibenzoate with prolonged release, obtained by direct compression using the method of mathematical modeling SeDeM.Materials and methods. The objects of the study were the original substance sodium 4,4'-(propanediamido)dibenzoate, as well as a number of auxiliary substances, which included polymers used for dosage forms with prolonged release, a dusting component – magnesium stearate, and a filler – lactose monohydrate. Physicochemical and technological properties of APIs, explosives, obtained tablet mixtures and tablets were studied in accordance with the requirements of the State Pharmacopoeia of the Russian Federation XIV ed. and EP 9th ed.Results and discussion. The properties of the substance and excipients were assessed in accordance with the SeDeM method. It was found that the substance 4,4'-(propanediamido) sodium dibenzoate is not suitable for direct pressing due to poor flowability and low compressibility. Hypromellose Methocel K4M had good compressibility, but it did not have sufficient flowability. The other tested polymers had satisfactory properties for the direct compression technology. The composition of the tablet mixtures was calculated using the SeDeM method, the obtained tablet mixtures had satisfactory technological characteristics for obtaining tablets by direct compression. The tablets obtained as a result of the experiment also met the pharmacopoeial requirements.Conclusion. Prediction of the composition of sustained-release tablets based on the original substance sodium 4,4'-(propanediamido)dibenzoate was carried out using the SeDeM method. It was found that this method is suitable for the development of the composition of tablets based on sodium 4,4'-(propanediamido)dibenzoate.

Formulation Development and In-vitro Evaluation of Sustained Release Tablets of Metoprolol Succinate

Metoprolol succinate is a β1 selective antagonist used an anti-arrhythmic, antiagina, antihypertensive. sustained release tablet of metoprolol succinate were formulated using polymers. The half-life of drug is relatively 4-6 hours. The formulation of metoprolol succinate tablet were produced by direct compression or wet granulation method. The formulations were evaluated for thickness, hardness, weight variation, friability and dissolution, drug content all the physical characteristics of the formulated tablets were within acceptable limits. The dissolution studies of Metoprolol succinate sustained release tablets reflects USP specification NMT 25%by 1 hours, 20-40%by 4 hours,40-60%by 8 hours and more than 80% by 20 hrs.

Formulation Development and Evaluation of Doxofylline Sustained-Release Tablets by Using Chitosan and Guar Gum

The sustained-release dosage form is a well-characterized and reproducible dosage form that is designed to control drug release profile at a certain rate to reach desired drug concentration in blood plasma or at the target site. There is immense demand in the market for new sustained-release formulations used for new drug molecules which release the drug at a sustained rate. Doxofylline is one of the widely useful drugs in the market and needs to be given in a single dose for a long duration of time. For the same, we have prepared a sustained released Doxofylline tablet. Aim: This research was done to design, formulate and evaluate Doxofylline sustained-release tablets by using different concentrations of Chitosan and Guar Gum. Methods: The factorial design was used to prepare Doxofylline sustained-release tablet. Doxofylline sustained-release tablets were prepared to employ different concentrations of Chitosan, Guar Gum, Lactose, and Magnesium Stearate in different combinations by wet granulation technique. Total 9 formulations were designed, formulated, and evaluated for the hardness, thickness, friability, % drug content, and in-vitro drug release. Results: A study of the release of drug by in-vitro found that F8 is to be the best efficient formulation which consists of both Chitosan and Guar Gum helped in delayed the release of drug up to 24 hours and performs excellent release of drug in starting hours of drug release in the body. The drug released from the F8 formulation indicates the kinetic model of First Order, by anomalous diffusion. The formulation F8 shows optimum thickness, hardness and at 40ºC±2 99.35% drug release after 24 hours shows optimum formulation. Conclusion: This study concludes that better drug release was observed by using natural polymers. Doxofylline with natural polymer shows good release and better dissolution rate as compared with a single synthetic polymer. Synthetic drug with natural polymer shows more future scope and this work will help the researcher in the future.

Formulation Development and Characterization of Darunavir and Ritonavir Sustained Release Tablets Using Quality by Design Approach

Darunavir is a nonpeptidic inhibitor of protease and is primarily metabolized by cytochrome P450 3A (CYP3A) isoenzymes. It is usually coadministered with low-dose ritonavir (Darunavir/r). Ritonavir is an inhibitor of CYP3A isoenzymes and pharmacologically enhances Darunavir which leads to increased plasma concentrations of darunavir and allows for daily lower dose. Here, we have developed combination SR formulation of Darunavir and Ritonavir and evaluated. In vitro drug release of all formulations was carried out in dissolution medium 900ml of pH 3.0, 0.05 M Sodium Phosphate Buffer + 2% Tween 20 for 75 RPM USP II apparatus (paddle). The results shown that, all the formulations of matrix tablets shown the good release of drug from trialed formulations however all formulations were not releasing the drug in enough amount. In matrix tablets F6, the release of drug shows NLT 80%. So, the formulation F6 have been considered as suitable for the SR tablet of Darunavir and Ritonavir. Tablets were also evaluated though Quality by Design (QbD) method.

Transitory restless arms syndrome in a patient with antipsychotics and antidepressants: a case report

Background Restless arms syndrome (RAS) is characterized by uncomfortable aching or burning sensations in the arms. RAS is regarded as an upper limb variant of restless legs syndrome (RLS). The lack of specific diagnostic criteria makes it difficult to recognize the RAS. Therefore, RAS is usually neglected in clinical practice. Moreover, when a patient was diagnosed with RAS, the adjustment of medications was the first choice for doctors, which may make the patient’s condition unstable. Case presentation A 33-year-old woman was diagnosed with schizophrenia and major depressive disorder. Starting with 0.6 g/d amisulpride, 0.1 g/d quetiapine, 75 mg/d venlafaxine sustained-release tablets, the patient reported symptoms of RAS (itching arms) on the fourth day since the latest hospitalization. After ruling out other factors, her RAS was suspected to be induced by antidepressants or antipsychotics. Without medication adjustment, RAS spontaneously remitted. Conclusions This case suggests that psychiatrists should pay attention to RAS when using antipsychotics and/or antidepressants. Moreover, RAS may be transitory. When a patient manifests RAS, observation may be one choice instead of an immediate medication adjustment.