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Introduction. In the modern world, there are many pharmaceutical substances that have various structure. During the development of finished dosage forms (FDPs) it is necessary to take into account many factors, such as physicochemical and technological properties of substances and excipients, manufacturing technology and others. This work is focused on the application of these approaches in practice in relation to a substance with anisodiametric crystal shape. Rebamipide was chosen as an example of such substance with poor technological characteristics for investigation and manufacturing technology selection.Aim. Research of approaches to examine a substance with anisodiametric crystal shape (Rebamipide in this case) to determine its physicochemical and technological properties in purpose of theoretical substantiation of the best method of manufacturing mass for tabletting.Materials and methods. In this study were used such materials as Rebamipide substance (α-[(4-chlorobenzoyl)amino]-1,2-dihydro-2-oxo-4-quinolinepropanoic acid) (experimental sample). Also were used such equipment as flowability tester ERWEKA GT (Erweka GmbH, Germany), powder density tester ERWEKA SVM 122 (ERWEKA GmbH, Germany), vibrating sieve CISA RP 200N (CISA Cedaceria Industrial S.L., Spain), powder diffractometer D8 ADVANCE (Bruker Corporation, USA), calorimeter DSC 204 F1 (NETZSCH, Germany), Hitachi TM-100 electron microscope (Hitachi, Japan).Results and discussion. The properties of Rebamipide substance were evaluated, such as polymorphism, melting point, microscopy and evaluation of technological characteristics. Application of the SeDeM method allowed to determine the critical parameters of the substance that need to be corrected.Conclusion. It was found out experimentally that Rebamipide substance has polymorphism, high melting point, needle-shaped crystals, poor bulkiness and compactability, which was confirmed by the use of SeDeM method.

Carbamazepine is a medicine used to manage epilepsy and partial or tonic-clonic seizures. This study aimed at formulating and obtaining carbamazepine orodispersible tablets for paediatric use at a 50 mg dose, with a diameter not greater than 6 mm and a tablet weight of 80 mg, through a direct compression process. The SeDeM pre-formulation/formulation method was used to define the characteristics of both carbamazepine and the selected excipients for direct compression. This study succeeded in formulating and obtaining the proposed tablets. Following the application of the SeDeM method, the tablets met the mass uniformity test and showed appropriate hardness values for orodispersible tablets. The tablets also met the United States Pharmacopeia (USP) test specifications at t = 60 min. The orodispersible tablets obtained may improve compliance with paediatric treatment with carbamazepine, ensuring the safety and effectiveness of the medicine.

Carbamazepine is a medicine used to manage epilepsy and partial or tonic-clonic seizures. This study aimed at formulating and obtaining carbamazepine orodispersible tablets for paediatric use at a 50 mg dose, with a diameter not greater than 6 mm and a tablet weight of 80 mg, through a direct compression process. The SeDeM pre-formulation/formulation method was used to define the characteristics of both carbamazepine and the selected excipients for direct compression. This study succeeded in formulating and obtaining the proposed tablets. Following the application of the SeDeM method, the tablets met the mass uniformity test and showed appropriate hardness values for orodispersible tablets. The tablets also met the United States Pharmacopeia (USP) test specifications at t = 60 min. The orodispersible tablets obtained may improve compliance with paediatric treatment with carbamazepine, ensuring the safety and effectiveness of the medicine. [ABSTRACT FROM AUTHOR]

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.

A new method of mathematical modeling called Sediment Delivery Model (SeDeM) is reviewed. This method is a convenient tool for determining the suitability of powdered material for direct compression. The method identifies unsatisfactory properties of the material and also determines the type and amount of excipients that should be added to the tablet formulation to neutralize the unsatisfactory properties of the active pharmaceutical ingredient (API). The principles of application of the SeDeM method are considered. The parameters to be determined for application of this method, the equations for calculations, and the constructed diagrams are presented. The methods for application of SeDeM to the pharmaceutical industry and the advantages of such use of the system are described. The SeDeM method is used to optimize and calculate the composition of tablets obtained by direct compression. This system takes into account all the characteristics of the bulk material and provides recommendations for the selection of excipients. The method makes it easier to develop a new drug and simplifies the manufacturing process by eliminating unnecessary excipients. In addition, the method is used for quality control of single APIs and excipients. [ABSTRACT FROM AUTHOR]

The deep understanding of products and processes has become a requirement for pharmaceutical industries to follow the Quality by Design principles promoted by the regulatory authorities. With this aim, SeDeM expert system was developed as a useful preformulation tool to predict the likelihood to process drugs and excipients through direct compression. SeDeM system is a step forward in the rational development of a formulation, allowing the normalisation of the rheological parameters and the identification of the weaknesses and strengths of a powder or a powder blend. However, this method is based on the assumption of a linear behavior of disordered systems. As percolation theory has demonstrated, powder blends behave as non-linear systems that can suffer abrupt changes in their properties near to geometrical phase transitions of the components. The aim of this paper was to analyze for the first time the evolution of the SeDeM parameters in drug/excipient powder blends from the point of view of the percolation theory and to compare the changes predicted by SeDeM with the predictions of Percolation theory. For this purpose, powder blends of lactose and theophylline with varying concentrations of the model drug have been prepared and the SeDeM analysis has been applied to each blend in order to monitor the evolution of their properties. On the other hand, percolation thresholds have been estimated for these powder blends where critical points have been found for important rheological parameters as the powder flow. Finally, the predictions of percolation theory and SeDeM have been compared concluding that percolation theory can complement the SeDeM method for a more accurate estimation of the Design Space. [ABSTRACT FROM AUTHOR]