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.

Effective Management of Rare Lymphangioleiomyomatosis Using Sirolimus: Tablet Matrix with Hibiscus rosa sinensis Leave Mucilage

The authors aimed to extend the discharge of Sirolimus from the tablets with a blend of herbal and synthetic polymers. In this study, Sirolimus was taken as a model drug, Hydroxy Propyl Methyl Cellulose as a synthetic polymer and mucilage from Hibiscus rosa sinensis leaves as a natural polymer. Sirolimus is an orphan drug used to treat Lymphangioleiomyomatosis damage and to suppress body refuse towards the transplanted organs. Sirolimus matrix tablets made with the blend of Hibiscus rosa sinensis leaves mucilage and Hydroxy Propyl Methyl Cellulose. The blend was assessed for flow possessions and the designed tablets were categorized for official and non-official tests including Sirolimus discharge. The Sirolimus matrix tablets possess good Sirolimus content with passible pre and post-formulation parameters. The study concludes that there were no chemical interactions between Sirolimus with polymers used. The study also revealed that Hibiscus rosa sinensis leaves mucilage can be a good polymer in grouping with other polymers for prolonged drug discharge.

In vivo Evaluation of Theophylline Sustained Release Matrix Tablets Containing Low Viscosity Guar Gum

The present investigation was carried out to evaluate the utility of guar gum as a hydrophilic matrix carrier in the design of oral controlled drug delivery. Based on the earlier reports, the low viscosity guar gum appears to be superior to medium and high viscosity grades of guar gum in providing a sustained delivery of theophylline along the GI tract. Conducting in vivo studies on theophylline matrix tablets containing 10% of low viscosity guar gum as a representative formulation assessed the in vivo performance of the guar gum matrix tablets. The in vivo studies were carried out in dogs. The effective concentration of theophylline was sustained for a period of 16 hours. The extended tmax, reduced absorption rate constant, prolonged MRT, unchanged Cmax and unchanged bioavailability indicate a controlled release of theophylline from the guar gum matrix tablets resulting in a sustained absorption and prolonged blood levels of theophylline. The theophylline matrix tablets showed blood levels well below 15 ?g/mL indicating freedom from adverse effects. Based on the studies, guar gum appears to be a potential carrier in the design of oral controlled drug delivery systems.

Formulation and Evaluation of Gabapentin Sustained Release Matrix Tablet Using Hibiscus rosa sinensis Leaves Mucilage as Release Retardant

The major goal of this study was to develop and evaluate Sustained release matrix tablets of Gabapentin with Hibiscus rosa - sinensis leaves mucilage prepared by using wet granulation technique with microcrystalline cellulose as a diluents and magnesium stearate as a lubricant. Pre-compression and post-compression evaluation of physicochemical parameters were carried out and to be within acceptable limits. Drug and polymer compatibility were validated by FTIR measurements. Further, tablets were evaluated for in vitro release study. To get the sustained release of Gabapentin, the concentration of Hibiscus rosa- sinensis mucilage was tuned with a gas-generating agent. The % drug release of all formulation from F1 to F5 showed 91.24%, 80.24%, 70.53%, 62.12% and 49.83% respectively. All the dosage form release kinetics was computed using zero order, first order, Higuchi, and Korsmeyer–Peppas methods. From the above results, it is concluded that the n value of formulation F5 showed 0.78 suggesting anomalous (non-fickian) behavior of the drug. Mucilage from the leaves of Hibiscus rosa-sinensis has a great retarding effect in drug release from sustained release tablets.

3D-Printed Coating of Extended-Release Matrix Tablets: Effective Tool for Prevention of Alcohol-Induced Dose Dumping Effect

Tablets used for extended drug release commonly contain large amounts of drugs. The corresponding drug release mechanism thus has to be well-known and invariable under numerous conditions in order to prevent any uncontrolled drug release. Particularly important is the stability and invariability of the release mechanism in the presence of alcohol due to the possible occurrence of the dose dumping effect. The effect of 3D printing (3DP) coating on the drug release mechanism and the drug release rate was studied as a possible tool for the prevention of the alcohol-induced dose dumping effect. Three types of matrix tablets (hydrophilic, lipophilic, and hydrophilic-lipophilic) were prepared by the direct compression method and coated using 3DP. The commercial filament of polyvinyl alcohol (PVA) and the filament prepared from hypromellose by hot melt extrusion (HME) were used as coating materials. Both coating materials were characterized by SEM, DSC, Raman spectroscopy, and PXRD during particular stages of the processing/coating procedure. The dissolution behavior of the uncoated and coated tablets was studied in the strongly acidic (pH 1.2) and alcoholic (40% of ethanol) dissolution media. The dissolution tests in the alcoholic medium showed that the Affinisol coating was effective in preventing the dose dumping incidence. The dissolution tests in the acidic dissolution media showed that the Affinisol coating can also be useful for the delayed release of active substances.

Formulations of sustained release matrix tablets of Furosemide using natural and synthetic polymers

The primary benefit of a sustained release dosage form compared to a conventional dosage form, is the consistent drug plasma concentration and consequently uniform therapeutic effect. Matrix system are preferential because of their ease, patient compliance etc, than traditional drug delivery which have several drawbacks like reiterated administration, variation in blood concentration level etc. The aim of the present research study was to develop and evaluate sustained release matrix tablets of furosemide using direct compression method using natural gummy and waxy materials (Xanthan gum, bees wax) and synthetic polymers (HPMC K4M). The matrix tablet formulations were prepared by using different drug: polymer ratios (1:1, 1:2 and 1:3). All formulations were assessed using micromeritics studies of powder blend and diverse physicochemical tests. All the physicochemical characters of the formulated tablets were within acceptable limits. The release pattern of the drug was viewed over a period of 12 hours and determined the amount of drug by the UV-Visible spectroscopic method. Dissolution data demonstrated that the formulated tablets with Xanthan gum and hydroxyl propyl methylcellulose (HPMC) provided sustained release of the drug up to 12 hrs. Therefore inexpensively it may be appropriate for the pharmaceutical industries to employ this kind of simple technologies for the expansion of advanced formulations. Hence, we conclude that the purpose of this study was to formulate a sustained release matrix tablet of furosemide using diverse polymers and their dissimilar proportions have been attained. Keywords: Furosemide, Direct compression, Natural, Synthetic polymers, Sustained release tablets.

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.

Interpolymer Complex of Chitosan and Eudragit L-100: Preparation, Characterization and Drug Release Behavior

Aims: The aim of the present investigation was to prepare interpolymer complex between Chitosan and Eudragit L100, and to evaluate its performance as a matrix for controlled release of drugs, using Diclofenac sodium as a model. Methodology: Interpolymer complex were prepared by combining different % chitosan solutions with different % Eudragit L100 solutions in different ratios. The formation of interpolyelectrolyte complexes (IPEC) between carbopol and Chitosan was investigated, using turbidimetry and viscosity measurement. The structure of the prepared IPEC was investigated using FTIR spectroscopy and DSC. A Rotary compression press was used to formulate matrix tablets of diclofenac sodium using polymers in physical mixture and IPECs.The amount of Diclofenac Sodium released in the dissolution medium was determined spectrophotometrically at 276 nm. Results: The results of the present investigation confirmed the formation of an interpolyelectrolyte complex between Chitosan and Eudragit L 100. The release of the model drug Diclofenac sodium was significantly controlled from tablets made up of the IPEC as compared with polymers alone and in combination. Release profiles were represented by a mathematical model, which indicates that the prepared system releases drug in a zero-order manner by changing the ratio of the IPEC in the tablets. Conclusion: Controlled release drug delivery systems designed to manipulate the drug release to achieve specific clinical objectives that are unattainable with conventional dosage forms.