Granulation Technology Research Articles

Development of technology for obtaining tablets by double granulation method with Pipsissewa (Chimaphila Umbellata) extract

The use of the therapeutic potential of medicinal plants is currently considered a physiological method of prevention and treatment, which affects the normalization of metabolic processes and the restoration of the body's functional capabilities. Medicinal products created based on plants can be used for a longer period, including in the treatment of chronic diseases. The aim of the work is to select a technology to produce tablets containing wintergreen umbrella herb liquid extract, considering the pharmaco-technological properties of the resulting dosage form. Materials and methods. The objects of the study were pipsissewa herb liquid extract and experimental model samples of mixtures of this plant substance with excipients permitted for medical use. The research on the analysis of the liquid extract and pharmaco-technological indicators of test samples of tablet mass and tablets was carried out according to the methods of the State Pharmacopoeia of Ukraine (SPhU). Determination of the optimal technology for obtaining and quantitative composition of excipients of tablets from pipsissewa herb liquid extract was carried out using mathematical design of experiments (MDE) by the method of a four-factor experiment based on the Greco-Latin square. Results. The analysis of the liquid extract of pipsissewa showed the presence of 47.0±1.0 % of extractive (dry residue) substances. It was determined that the use of Liquid-Solid technology in the technology of obtaining tablets with plant extract based on the amorphous form of magnesium aluminometasilicate (Neusilin US2) requires the use of a combined approach that will ensure the quality of the finished product. During experimental studies, the use of three interrelated production strategies was proposed. In the process of applying the proposed strategy, it was determined that microcrystalline cellulose effectively performs the function of an adsorbent and filler; the consistency of the mixtures significantly depends on the ratio of MCC 101:extract. It was investigated that the use of double granulation will allow for the increase of the amount of active ingredient in the granulate without changing the volume of MCC 101, which will allow for the achievement of a higher extract content in the finished tablets. The use of double granulation technology can also ensure uniform distribution of the active ingredient and maintain the necessary flowability of the mixture for subsequent tabletting. The use of mathematical, experimental planning in the development of double granulation (drying) technology and the composition of excipients based on studies of the fluidity of the tabletting mass; attrition, disintegration, resistance of tablets to crushing, and organoleptic indicators became the basis for the development of the composition of the medicinal product in the form of tablets containing pipsissewa liquid extract. Conclusions. The adsorption property and its influence on the tabletting process of the synthetic amorphous form of magnesium aluminometasilicate (Neusilin US2) and microcrystalline cellulose 101 (MCC 101) were determined when using these substances as a carrier for pipsissewa grass liquid extract. The possibility of conducting a double granulation process using microcrystalline cellulose 101 (MCC 101) according to a given amount of liquid extract was proven. Using mathematical planning of the experiment, the drying conditions of the granulate and the quantitative composition of excipients were selected

METHODS OF OBTAINING AMMONIUM PHOSPHATE AND ITS AREAS OF APPLICATION

Ammophos is an effective mineral fertilizer that combines nitrogen and phosphorus, widely used in agriculture. Its production is mainly carried out by reacting phosphorous raw materials with ammonia. Granulation technology ensures the product is prepared in a convenient form. This fertilizer plays a significant role in increasing crop yields and improving soil fertility. Ammophos is utilized in agriculture for various crops, including grains, vegetables, and fruit trees. Additionally, it is applied in the chemical industry and environmental sectors. Due to its optimal composition and efficiency, ammophos is highly valued as a universal fertilizer [3-4].

Technological approaches to improve the bioavailability of the poor soluble substance Candesartan Cilexetil in mini-tablets

Introduction. The polypill in the form of a hard gelatin capsule containing mini-tablets of the original antihypertensive combination is being developed at the Saint-Petersburg State Chemical and Pharmaceutical University. One of the components of the polypill is Candesartan, which has high antihypertensive activity and organoprotective properties. The active pharmaceutical ingredient (API) of Candesartan Cilexetil is characterized by low solubility in water and gastrointestinal tract media, therefore increasing the solubility of this substance can lead to a significant improving the bioavailability.Aim. Comparative analysis of technological approaches to increasing the bioavailability of the poor soluble API Сandesartan Сilexetil in a mini-tablet dosage form.Materials and methods. API Сandesartan Сilexetil, β-cyclodextrin (β-CD), copolymer of polyvinylpyrrolidone and vinyl acetate and excipients for the production of mini-tablets, such as diluents, binders, disintegrant, dusting components were used. The release profiles of Candesartan Cilexetil from the developed mini-tablets were assessed in comparison with the original drug Atacand®, 8 mg tablets. The complex of candesartan cilexetil with β-CD in a 1 : 1 ratio was prepared by three methods: dry mixing, paste method and lyophilization. A solid dispersion (SD) of candesartan was obtained by hot melt extrusion. The API complexes with β-CD and SD were characterized by FTIR-spectroscopy and differential scanning calorimetry. Tablet mixtures were produced by dry mixing and wet granulation technology. Mini-tablets were obtained on a laboratory automatic single-punch tablet press. Quality control of the mini-tablets was conducted by the methods of State Pharmacopoeia of the Russian Federation XV ed. and United State Pharmacopeia methods.Results and discussion. Comparative analysis of technological approaches to increasing the bioavailability of Candesartan Cilexetil showed, that preparation of a complex including API with β-CD in a 1 : 1 ratio using the paste method with further using of wet granulation technology allowed to obtain mini-tablets with improved release of poor soluble API compared to the original drug. On the contrary, the use of TDS in mini-tablet technology led to a slower release of API compared to the original drug. The developed mini-tablets of Candesartan composition № 7 met pharmacopoeial requirements by all acceptance criteria.Conclusion. The creation of complex of Candesartan Cilexetil with β-CD by the paste method with further using of wet granulation technology is the optimal technological approach to increasing the bioavailability of the poor soluble API Candesartan Cilexetil in mini-tablets.

The methodology for developing modified release granules based on phytoextracts for the treatment of mastopathy

Aim. To substantiate the scientific and methodological approach to the development of the composition and technology of granules based on phytoextracts with modified release of active substances for the complex treatment of mastopathy. Materials and methods. The research was conducted by processing electronic and paper sources of information on the etiopathogenetic factors of mastopathy, the concept of developing medicinal products with modified release of active pharmaceutical ingredients (APIs), the market analysis of medicines and dietary supplements (DS) for the treatment of mastopathy. Results. An information search has been conducted to study the etiology, pathogenesis, clinical manifestations and pharmacotherapy of breast diseases. The article presents and substantiates the stages of experimental research on the development of a medicinal product in the form of granules based on phytoextracts with a modified release of active substances, including marketing and statistical research methods of electronic and paper sources of information on the prevalence and consequences of mastopathy, development of granules based on phytoextracts with a modified release of APIs, standardization, preclinical studies of the medicinal product developed. Conclusions. The scientific and methodical approach to the development of the composition and technology of granules based on phytoextracts with a modified API release for the complex pharmacocorrection of mastopathy and prevention of the appearance of malignant neoplasms in breast tissues has been substantiated.

Study on preparation technology of Qi Yu constitution Yangsheng granules.

Understanding how pharmaceutical formulas target specific illnesses is crucial for developing effective treatments. Enriching ion channel data is a critical first step in comprehending a formula's mechanism of action. This study aims to explore the effective disease spectrum of the Qi Yu granule formula through network pharmacology analysis and backtracking, and analyze its potential curative effects on liver and spleen system diseases, particularly depression and breast cancer. Using pharmacological tools and database analysis, the ion channel data of the formula's components were investigated. The effective disease spectrum was determined, and diseases related to liver and gallbladder, liver depression, and spleen deficiency were identified. Network pharmacology analysis was conducted to backtrack diseases, target gene proteins, and drug compositions. The extraction technology of volatile oil from medicinal herbs was experimentally studied to optimize the preparation process. The effective disease spectrum analysis identified potential curative effects of the Qi Yu granule formula on various diseases, including breast cancer. Backtracking revealed relationships between diseases, target gene proteins, and drug compositions. Experimental studies on volatile oil extraction provided insights into optimizing the preparation process. The study underscores the potential therapeutic benefits of the Qi Yu granule formula for liver and spleen system diseases. By integrating network pharmacology analysis and experimental research, this study offers valuable insights into the formulation and efficacy of the Qi Yu granules, paving the way for further exploration and optimization of TCM formulations.

Study on Preparation Technology and Quality Standard of Acne Granules

AbstractThe study aimed to optimize the preparation process of acne granules and establish their quality standards. In this work, the extraction process of Chinese herbal extract was optimized by the amount of water added, the number of decoction, the extraction time, and the soaking time with extraction yield as an evaluation index. The indexes of the acne granules such as molding rate, dissolvability, angle of repose, moisture content, and ease of preparation were evaluated. Thin-layer chromatography (TLC) was used to identify Salviae, Scutellaria baicalensis, and Indigowoad Leaf. High-performance liquid chromatography (HPLC) was used to determine the baicalin content in the granules. Based on orthogonal and single-factor experiments, the optimized extraction process of the prescription of nine medicinal materials was as follows: soaked in cold water for 2 hours, boiled three times, decocted with eight times the amount of water for 1.5 hours for the first time, and six times the amount of water for 1 hour for the second and third times. The combined extracts were concentrated to a relative density of 1.30 to 1.40 (20–30°C), and mixed evenly according to the mass ratio of extract to excipient 1:5, and dextrin: powdered sugar = 1:3. The mixture was granulated, dried, prepared into granules, and the acne granules were formed at a molding rate of 95.52% and a critical relative humidity of 82%. The spots in TLC were clear and easy to identify. The HPLC result showed that the content of baicalin was not less than 1.0 mg/g. The study provides a valuable reference for the production and preparation of the granules through optimization of the wet process and the excipient dosage. Furthermore, the established TLC method for the identification and the HPLC method for baicalin quantification laid the foundation for the quality control of the preparation in future studies.

An Advanced Twin-Screw Granulation Technology: The use of Non-Volatile Solvents with High Solubilizing Capacity

PurposeTwin-screw wet granulation (TSWG) is a manufacturing process that offers several advantages for the processing of water-insoluble active pharmaceutical ingredients (APIs) and has been used for increasing the solubility and dissolution rates. Here we introduce a novel TSWG approach with reduced downstream processing steps by using non-volatile solvents as granulating binders.MethodsHerein, TSWG was carried out using Transcutol a non-volatile protic solvent as a granulating binder and dissolution enhancer of ibuprofen (IBU) blends with cellulose polymer grades (Pharmacoat® 603, Affinisol™, and AQOAT®).ResultsThe physicochemical characterisation of the produced granules showed excellent powder flow and the complete transformation of IBU into the amorphous state. Dissolution studies presented immediate release rates for all IBU formulations due to the high drug-polymer miscibility and the Transcutol solubilising capacity.ConclusionsOverall, the study demonstrated an innovative approach for the development of extruded granules by processing water-insoluble APIs with non-volatile solvents for enhanced dissolution rates at high drug loadings.Graphical

Converting municipal solid waste incineration bottom ash into the value-added artificial lightweight aggregates through cold-bonded granulation technology

To effective recycle the Municipal solid waste incineration bottom ash (MSWIBA), this study adopts cold consolidation granulation technology to develop eco-friendly artificial lightweight aggregates (ALCBAs), and the materials are over 50 % dosage of MSWIBA, less 50 % fly ash (FA) or ground granulated blast furnace slag (GGBFS), and 10 % ordinary Portland cement (OPC). This study investigated the effects of different binder types and dosages on the properties of ALCBAs, including compressive strength, water absorption rate, bulk density, microstructures, pore development, heavy metal leaching behavior, and sustainability. The feasibility of ALCBAs to design green concrete was also explored. The results show that with higher content of MSWIBA and binders of FA, GGBFS and OPC, the ALCBAs with compressive strength greater than 2.5 MPa, bulk density of about 1000 kg/m3 and water absorption rate greater than 12 % was successfully developed. Increasing the content of FA/GGBFS is beneficial to improve the compressive strength and reduce the water absorption rate and the total porosity and lower the air bubbles percentage of ALCBAs. More importantly, both FA and GGBFS are mixed into ALCBAs, the compressive strength is at 2.5 MPa-3.0 MPa, the water absorption rate is significantly reduced, and the energy consumption, carbon footprint and cost are also significantly reduced. As the content of ALCBAs increases, although the compressive strength and splitting tensile strength are not as good as concrete with natural aggregates, the density of low-carbon concrete with ALCBAs gradually decreases, and the interface transition zone is gradually improved. Overall, ALCBAs can be beneficial to the conservation of natural resources (natural aggregates) and effectively solve the shortage of natural aggregates, and can be used to deal with the accumulation of solid waste in a green way, and it also can open up new channel for solid waste recycling.

Recovery of Lithium from Industrial Li-Containing Wastewater Using Fluidized-Bed Homogeneous Granulation Technology

In this study, a novel fluidized-bed homogeneous granulation (FBHo-G) process was developed to recover lithium (Li) from industrial Li-impacted wastewater. Five important operational variables (i.e., temperatures, pH, [P]0/[Li]0 molar ratios, surface loadings, and up-flow velocities (Umf)) were selected to optimize the Li recovery (TR%) and granulation ratio (GR%) efficiencies of the process. The optimal operational conditions were determined as the following: a temperature of 75 °C, pH of 11.5, [P]0/[Li]0 of 0.5, surface loading of 2.5 kg/m2·h, and Umf of 35.7 m/h). The TR% and GR% at optimal condition could be as much as 90%. The material characterization of the recovery pellet products showed that they were highly crystallized Li3PO4 (purity ~88.2%). The pellets had a round shape and smooth surface with an average size of 0.65 mm, so could easily be stored and transported. The high purity enables them to be further directly reused as raw materials for a wide range of industrial applications (e.g., in the synthesis of cathode materials). Our calculation shows that the FBHo-G process could recover up to 0.1845 kg of lithium per cubic meter of Li-containing wastewater, at a recovery rate of ~90%. A brief technoeconomic analysis shows that FBHG process had economic viability, with an estimate production cost of USD 26/kg Li removed, while the potential gained profit for selling lithium phosphate pellets could be up to USD 48 per the same volume of wastewater and the net profit up to USD 22/m3 Li treated. In all, fluidized-bed homogeneous granulation, a seedless one-step recovery process, opens a promising pathway toward a green and sustainable recycling industry for the recovery and application of the resource-limited lithium element from nonconventional water sources.

A Review: Novel Granulation Technology

All the pharmaceutical Active pharmaceutical Ingredients (API) and Pharmaceutical excipients will have different particle size. While formulating a dosage form, particles from raw materials will tend to separate from other due to their rheological properties. There could be a condition where fine particles separate from the larger particles causing demixing or uneven distribution of active with its excipients leading to tablet content uniformity issue. To overcome this problem, particle enlargement or particle cohesiveness with or without additional aid is necessary, which could be achieved by granulation. Hence granulation technology is important in the formulation of pharmaceutical oral solid dosage form. Granulation is the process of adhering fine particles agglomerate into a large particle using two most common methods i.e. wet granulation and dry granulation/compaction. Day by day technological innovation is happening in all fields and pharmaceutical granulation process is also not an exemption. The objective of present review is to focus the novel granulation technology and how it is differing from the conventional granulation technology.

Characterization and pharmacokinetics of cinnamon and star anise compound essential oil pellets prepared via centrifugal granulation technology

Cinnamon and star anise essential oils are extracted from natural plants and provide a theoretical basis for the development and clinical application of compound essential oil pellets. However, cinnamon oil and star anise oil have the characteristics of a pungent taste, extreme volatility, poor palatability, and unstable physical and chemical properties, which limit their clinical use in veterinary medicine. In this study, the inhibitory effects of cinnamon oil and star anise oil on Escherichia coli and Salmonella were measured. Compound essential oil pellets were successfully prepared by centrifugal granulation technology. Subsequently, the in vitro dissolution of the pellets and their pharmacokinetics in pigs were investigated. The results showd that, cinnamon and star anise oils showed synergistic or additive inhibitiory effects on Escherichia coli and Salmonella. The oil pellets had enteric characteristics in vitro and high dissolution in vitro. The pharmacokinetic results showed that the pharmacokinetic parameters Cmax and AUC were directly correlated with the dosage and showed linear pharmacokinetic characteristics, which provided a theoretical basis for the development and clinical application of compound essential oil pellets.

The Aerobic Granules Process for Wastewater Treatment: From Theory to Engineering

Aerobic granules are small, dense aggregates of microbial cells that form naturally in aerobic wastewater treatment systems. They are characterized by their spherical shape, strong structural integrity, and ability to rapidly settle. These granules are formed through a self-immobilization process where different microbial species coalesce to degrade organic and inorganic compounds in wastewater. This study summarizes the development of aerobic granulation technology in wastewater treatment and the mechanism of aerobic granules’ formation, analyzes the characteristics and the factors affecting the aerobic granules’ formation, and presents practical engineering examples of its application from pilot-scale to full-scale operation.

Enhancement of the Classification Performance of Fuzzy C-Means through Uncertainty Reduction with Cloud Model Interpolation

As an information granulation technology, clustering plays a pivotal role in unsupervised learning, serving as a fundamental cornerstone for various data mining techniques. The effective and accurate classification of data is a central focus for numerous researchers. For a dataset, we assert that the classification performance of a clustering method is significantly influenced by uncertain data, particularly those situated at the cluster boundaries. It is evident that uncertain data encapsulate richer information compared with others. Generally, the greater the uncertainty, the more information the data holds. Therefore, conducting a comprehensive analysis of this particular subset of data carries substantial significance. This study presents an approach to characterize data distribution properties using fuzzy clustering and defines the boundary and non-boundary characteristics (certainty and uncertainty) of the data. To improve the classification performance, the strategy focuses on reducing the uncertainty associated with boundary data. The proposed scheme involves inserting data points with the cloud computing technology based on the distribution characteristics of the membership functions to diminish the uncertainty of uncertain data. Building upon this, the contribution of boundary data is reassigned to the prototype in order to diminish the proportion of uncertain data. Subsequently, the classifier is optimized through data label (classification error) supervision. Ultimately, the objective is to leverage clustering algorithms for classification, thereby enhancing overall classification accuracy. Experimental results substantiate the effectiveness of the proposed scheme.

Исследование параметров производства гранулированного топлива из торфа

Granulation technology is becoming an increasingly attractive one for the energy use of biomass. The problem to find a suitable method of compaction of various types of biomasses has existed for decades. The purpose of this study is to select the optimal mode to produce pellets from peat fuel. Peat samples collected in the Mezen district of the Arkhangelsk region have been selected as the data for study. Elemental analysis of the studied samples of peat and peat pellets has been carried out using X-ray fluorescence spectroscopy on an EDX-8000 spectrometer. Experiments on peat granulation have been carried out in a press granulator of the German company Amandus Kahl. The authors describe the procedure of selection of the operating mode of a press granulator to produce pellets from peat fuel. Optimal regime of pellets production has been selected corresponding to the national standard. An elemental analysis of the studied samples of peat and peat pellets has been carried out using X-ray fluorescence spectroscopy. The results have shown that the ash content of peat fuel from the Arkhangelsk region is no more than 2 %. Production of environmentally friendly high-calorific pellets from peat corresponding to the National Russian standards allows increasing the energy potential of the Arkhangelsk region. When converting peat into the pellets, the content of carbon, nitrogen, and hydrogen (C+N+H) increases, and the content of sulfur and oxygen (O+S) decreases, which leads to the increase of the heat of fuel combustion. Advantages of the use of peat to produce energy are low sulfur content, low ash content and high softening ash temperature.

Computational Fluid Dynamics Numerical Simulation on Flow Behavior of Molten Slag–Metal Mixture over a Spinning Cup

Centrifugal granulation technology using a spinning cup opens a potential way to recycle steel slag that is currently difficult to reuse. The objective of this research was to study the flow characteristics of a molten slag–metal mixture that was produced during smelting reduction in molten steel slag, passing over a spinning cup, so as to explore the feasibility of using centrifugal granulation technology to treat the steel slag. This was achieved by developing and implementing a computational fluid dynamics (CFD) model that incorporated free-surface multiphase flow to predict the thickness of the liquid slag film at the edge of the spinning cup (slag film thickness for short), which was an important parameter for estimating the size of the slag particles resulting from centrifugal granulation of the molten slag–metal mixture. The influences of various relevant parameters, including spinning cup diameter, slag feeding rate, cup spinning speed, etc., on the slag film thickness were analyzed. Additionally, hot experiments on centrifugal granulation of a molten slag–metal mixture were conducted to verify the results of the numerical simulations. The experimental results indicated a progressive reduction in the Sauter mean diameter of the slag particles as the metallic iron content in the slag increased. Specifically, when the iron content rose from 5% to 15% at a cup spinning speed of 2500 RPM, the Sauter mean diameter decreased by 13.77%. The numerical simulation results showed that the slag film thickness had a positive relationship to the slag feeding rate but a negative relationship to the spinning cup diameter and the cup spinning speed. Furthermore, the ratio between the mean slag particle diameter and the slag film thickness decreased nearly linearly with the increase in the metallic iron content in slag, with the average ratio being approximately 4.25, and this relationship was useful for estimating the slag particle size from the slag film thickness. Therefore, the present research results can provide theoretical guidance for the industrial application of spinning cup centrifugal granulation technology to effectively treat and recycle steel slags.

Sustainability vs suitability in granulation

Little is known about the sustainability of competing granulation technologies, despite them being key and widespread industrial processes. This study has evaluated the sustainability of four prominent granulation technology pathways with respect to material wastage (Yield %), Specific Time (Hours/kg) and Specific Energy (kWh/kg). The Fluidised Bed Granulator proved to be the most material efficient while the Roller Compactor was the most time efficient. The energy efficiency of the granulators improved in the following order: Twin Screw Granulator, Fluidised Bed Granulator, High Shear Granulator and Roller Compactor. The wet granulation techniques proved to be the more energy inefficient technologies due to energy expensive sub stages such as drying. This was especially the case with the Twin Screw Granulator and High Shear Granulator where the actual granulating equipment only accounted for around 13% and 15% of the total energy consumed by the entire production pathway. Comparatively, the drying stage accounted for around 45% and 84% of the Twin Screw Granulation and High Shear Granulation production pathways. The different granulation technologies were shown to produce granules with significantly varying properties due to changing granule shape and porosities. The use of visual tools such as parallel co-ordinate graphs and radar plots alongside analytical methods such as priority scoring are suggested as important tools to help manufacturers choose the optimum process pathway based on these varying sustainability and granule suitability factors.

Evaluation of tribological properties of silane‐treated rapeseed straw fiber reinforced friction polymer composites prepared by wet granulation

AbstractReinforcing fibers play a key role in improving the tribological properties of friction polymer composites. Cellulose reinforcing fibers were extracted from rapeseed straw waste and prepared as friction composites based on wet granulation, and the effects of heat and rapeseed straw fiber (RSF) additions on the tribological properties were systematically investigated. The addition of RSF induced an important transformation of the major wear mechanism to abrasive wear, especially at 9 wt%, where the abundant tribo‐films contributed to the stability of the friction coefficients (fade rate 6.8%, recovery rate 106.6%), resulting in a 37.5% increase in wear resistance compared to no addition. Furthermore, XRD, FTIR and SEM analyses showed that the silane‐ethanol solution modification contributed to the good performance of RSF.Highlights Rapeseed straw fiber (RSF) and granulation technology for polymer composites. Addition of RSF transforms adhesive and fatigue wear into abrasive wear. Friction models are developed to clarify the wear mechanism transformation. A 37.5% increase in wear resistance was achieved when RSF was added at 9 wt%.

Novel wind-speed prediction system based on dimensionality reduction and nonlinear weighting strategy for point-interval prediction

In the context of today’s energy shortage, wind energy plays a crucial role as one of the most widely used renewable energy sources. However, in order to fully utilize the potential of wind energy, it is necessary to build a precise and reliable wind-speed prediction system. Conventional wind-speed prediction models frequently rely on a solitary model for forecasting, and sometimes these models cannot accurately fit the nonlinear characteristics of the data, resulting in poor prediction performance. Therefore, to address this deficiency, a new wind-speed point-interval prediction system is proposed in this study. The fuzzy information granulation technology is adopted in this system to reduce the dimension of data and solve the problem of redundancy in wind-speed data. In addition, this paper uses the multi-objective dragonfly algorithm and combines sub-models using the multi-nonlinear weight strategy to address the issue of inadequate precision exhibited by an individual prediction model. In order to verify the effectiveness of this wind-speed prediction system, the Penglai wind farm in Shandong Province is used as the dataset to construct the model, and several reference models are selected to conduct point prediction and interval prediction comparison experiments respectively. The experimental results show that the combined prediction system has the best prediction performance, with MAPE values of 14.16%, 15.02% and 15.74%, respectively. Compared with other benchmark models, the average improvement rates for the multi-step prediction were 14.97%, 16.48% and 19.11%, respectively.

Technology Criteria for the Manufacturing of Rebamipide Film-coated Tablets

Introduction. The current growth of the pharmaceutical market and stiff competition require from drug manufacturers make a more detailed and thorough fine-tuning of existing production lines. Direct compression technology is a modern and cost-effective technology for solid dosage form drug manufacturing. Roll-compaction tehnology (dry granulation) can be an alternative approach to optimize the manufacturing of formulations, for which the use of wet granulation or direct compression technologies is not possible due to their physical and chemical properties.Aim. The goal of this work is to investigate the possibility of manufacturing Rebamipide tablets by using direct compression technology and dry granulation technology (roll-compaction), avoiding such complicated and more ex-pensive technology as wet granulation. Also aim of this work is study the impact of production methods on such quality factors as disintegration and dis-solution time.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), MCC-102 (J. Rettenmaier & Söhne (JRS), Germany), Starch pregelatinized (Colorcon LTD., England), Kollidone SR (BASF, Germany), Croscarmellose sodium (J. Rettenmaier & Söhne (JRS), Germany), Anhydrous citric acid (Scharlau), Sodium lauryl sulfate (BASF, Germany), Aerosil 200 vv Pharma (Evonik Industries AG, Germany), Sodium stearyl fumarate (J. Rettenmaier & Söhne (JRS), Germany), Calcium stearate (FACI, Italy), Film coating VIVACOAT® PA-1P-000 (J. Rettenmaier & Söhne (JRS), Germany). Also were used such equipment as Y shape blender («AZT FARMA K.B.», Russia), roll compactor LGC100 (Beijing Gylongli Automation Tech. Co., Ltd, China), rotary tablet press PG16G (Beijing Gylongli Automation Tech. Co., Ltd, China), tablet coating system Labcoat™ M (O'Hara Technologies lnc, Canada), ionising air gun Simco Cobra (SimcoIon, Netherlands), 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), tablet hardness, thickness and height tester SOTAX HT 10 (SOTAX AG, Switzerland), dissolution tester DT 626/1000HH (ERWEKA GmbH, Germany) and disintegration tester ZT321 (ERWEKA GmbH, Germany).Results and discussion. In a series of experiments were obtained tablet’s cores and film coated tablets by direct compression and roll-compaction methods. Experimentally it was found, that in tablets with similar formulations roller compaction technology provides slower disintegration and dissolution time, compared to direct compression method. This fact should be taken into account during drug development when planning the rate of release of the active ingredient.Conclusion. As a result of the experiments it was shown a direct correlation between the use of a certain technology and its impact in such quality indicators as disintegration and dissolution time of tablets. It was also found that dry granulation technology provides a more technologically suitable tablet mass.

Study of the Effect of Matrix-forming Polymers on the Release Rate of Sodium 4,4'-(propanediamido)dibenzoate from Tablets

Introduction. Wet granulation technology is a process of directed particle aggregation of powder materials to obtain required properties of tablet masses and, as a consequence, to achieve satisfactory characteristics of tablets. In this addition, as a result of wet granulation technology, if special excipients are used, it becomes possible to control the rate and kinetics of release of active pharmaceutical substances from tablets to achieve the desired therapeutic effect.Aim. To study the effect of matrix-forming components included in the composition of mixtures for granulation on the rate of release of sodium 4,4'-(propanediamido)dibenzoate from tablets.Materials and methods. The original substance sodium 4,4'-(propanediamido)dibenzoate, as well as a number of excipients, which included polymers used for prolonged-release dosage forms, lubricant – sodium stearyl fumarate, as well as pore-forming agents – PVP and MCC, were the objects of the study. The key parameters of tablets and dissolution kinetics were studied in accordance with the requirements of State Pharmacopoeia of the Russian Federation XIV edition and Pharmacopeia of the Eurasian Economic Union.Result and discussion. Prolonged release was achieved for all tablets, but more than 90 % of the substance was released after 12 hours in tablets containing ethylcellulose as a matrix-forming polymer. The release of APS from tablets of this formulation was the most prolonged.Сonclusion. The effect of matrix-forming components included in the composition of mixtures for granulation on the rate of release of 4,4'-(propanediamido)sodium dibenzoate from tablets has been studied. The most uniform and complete release of ASF from tablets in which the matrix-forming polymer is ethylcellulose in the amount of 27.7 %.