Paddle Stirrer Research Articles

Formulation and evaluation of extended-release floating tablets of labetalol hydrochloride 200 mg

The aim of present work is to formulate and evaluate extended-release floating tablets of Labetalol HCL to improve the bioavailability, Patient compliance and solubility on oral floating drug of Labetalol HCL. Labetalol HCL is mainly used in the treatment of hypertension, which is BCS Class Ⅰ drug i.e. Highly soluble and highly permeable. The tablets were prepared by wet granulation method by using different concentrations of HPMC polymer. The tablets were evaluated for Preformulation characteristics, Pre compression parameters and post compression parameters. In-vitro dissolution studies were performed for all prepared formulations by using dissolution test apparatus employing a paddle stirrer at 50 rpm and 37 ± 0.5°C, 0.1N HCL buffer was used as dissolution medium. Samples of 5ml each were withdrawn at different time intervals. Each sample withdrawn was replaced with an equal amount of fresh dissolution medium. Samples were diluted and assayed at 302 nm using Agilent UV Visible double beam spectrophotometer. The increased drug release is due to the presence of low concentration of HPMC K4 m. The drug release kinetics was calculated for all the formulations, among all the formulations F8 was taken as optimized formulation whose percentage drug release was found to be 96%. It indicates the release follows zero order and Hixon kinetics. Hence formulation F8 was Considered as the optimized batch and stability studies were conducted at 40oc±2oc/75±5%RH, Storage condition for 3 months and no change was observed.

Comparative Evaluation of Dissolution Performance in a USP 2 Setup and Alternative Stirrers and Vessel Designs: A Systematic Computational Investigation.

The dissolution testing method described in the United States Pharmacopeia (USP) Chapter ⟨711⟩ is widely used for assessing the release of active pharmaceutical ingredients from solid dosage forms. However, extensive use over the years has revealed certain issues, including high experimental intervariability observed in specific formulations and the settling of particles in the dead zone of the vessel. To address these concerns and gain a comprehensive understanding of the hydrodynamic conditions within the USP 2 apparatus, computational fluid dynamic simulations have been employed in this study. The base design employed in this study is the 900 mL USP 2 vessel along with a paddle stirrer at a 50 rpm rotational speed. Additionally, alternative stirrer designs, including the hydrofoil, pitched blade, and Rushton impeller, are investigated. A comparison is also made between a flat-bottom tank and the USP round-bottom vessel of the same volume and diameter. Furthermore, this work examines the impact of various parameters, such as clearance distance (distance between the bottom of the impeller and bottom of the vessel), number of impeller blades, impeller diameter, and impeller attachment angle. The volume-average shear rate (Stv), fluid velocity (Utv), and energy dissipation rates (ϵtv) represent the key properties evaluated in this study. Comparing the USP2 design and systems with the same stirrer but flat-bottom vessel reveals more homogeneous mixing compared to the USP2 design. Analyzing fluid flow streamlines in different designs demonstrates that hydrofoil stirrers generate more suspension or upward movement of fluid compared to paddle stirrers. Therefore, when impellers are of a similar size, hydrofoil designs generate higher fluid velocities in the coning area. Furthermore, the angle of blade attachment to the hub influences the fluid velocity in the coning area in a way that the 60° angle design generates more suspension than the 45° angle design. The findings indicate that the paddle stirrer design leads to a heterogeneous shear rate and velocity distributions within the vessel compared with the other designs, suggesting suboptimal performance. These insights provide valuable guidance for the development of improved in vitro dissolution testing devices, emphasizing the importance of optimized design considerations to minimize hydrodynamic variability, enhance dissolution characterization, and reduce variability in dissolution test results. Ultimately, such advancements hold potential for improving in vitro-in vivo correlations in drug development.

Effect of adsorption-catalytic deformation and partial deactivation on the determination of the absolute activity of a liquid phase hydrogenation catalyst

Objectives. To take into account the change in the number of active sites during the adsorptioncatalytic deformation and deactivation of a catalyst surface by means of a catalytic poison when calculating the turnover frequency (TOF) of a hydrogenation catalyst.Methods. The activity was determined by a static method, using a titanium reactor having a volume of 400 mL, an experimental temperature controlled using a liquid thermostat with an accuracy of 0.5 K, with a paddle stirrer rotation speed of 3600 rpm and system hydrogen pressure equal to atmospheric. The consumption of hydrogen used to reduce the model compound was taken into account via the volumetric method. The heats of hydrogen adsorption were determined using a reaction calorimeter with an operating mode close to that of a chemical reactor. After measuring the specific surface area using low temperature nitrogen adsorption, the results were processed using Brunauer–Emmett–Teller theory approximations. Deactivation was carried out by introducing dosed amounts of catalytic poison into the system in titration mode.Results. A kinetic experiment for the reduction of a multiple carbon bond in a sodium maleate molecule using aqueous solutions of sodium hydroxide with additions of monohydric aliphatic alcohols as solvents under conditions of partial deactivation of the catalyst was carried out. The obtained values of heats of hydrogen adsorption on skeletal nickel in the course of the experiment are given. The described approach is used to calculate TOF values taking into account changes in the number of active surface sites during the course of a catalytic reaction and upon the introduction of a deactivating agent. A refined equation for the correct calculation of TOF is proposed along with its mathematical justification. The results of TOF calculations under various assumptions for a number of catalytic systems are shown.Conclusions. When calculating absolute activity values, a change in the number of active sites has a significant effect on the obtained values. The physical meaning of a number of constants in the proposed equation relates the activity of the catalyst to the distribution of hydrogen on its surface in terms of heats of adsorption.

Development and Study of Antibacterial <i>In situ</i> Coatings for Processing Implants

Introduction. Periprosthetic infections are a major problem in orthopedic surgery. The most optimal way to influence the bacterial film is to suppress the early stages of its formation. The use of hydrogel coatings for the prevention of periprosthetic infections is an effective measure, while the process of coating the implant can be simplified due to the use of in situ systems.Aim. The purpose of the research is to develop and study antibacterial in situ coatings for preoperative treatment of implants.Materials and methods. In the experiment we used poloxamers Kolliphor® P 407 and Kolliphor® P 188 (BASF, Germany), hyaluronic acid high-molecular PrincipHYAL® (1400–1800 kDa), low-molecular PrincipHYAL® (400–600 kDa), mixture of high, medium and low-molecular acids PrincipHYAL® Cube3 (ROELMI HPC Srl, Italy). As screening methods for identifying the optimal composition, we used gelation temperature measurements, pH measurements, studies of rheological properties, and microbiological tests.Results and discussion. During the experiment, we found the optimal concentration of hyaluronic acid 1400–1800 kDa – 0.5 %, at which the studied composition at a temperature of 4.5 ± 0.5 °C was a homogeneous liquid, and it made a sol-gel transition when heated. It was revealed that hyaluronic acid had no significant effect on the gelling temperature, so we added poloxamer 188. We also established the influence of the hyaluronic acid molecular weight on the in situ systems characteristics. High molecular weight hyaluronic acid stabilized the viscosity values and improved the adhesive properties of the system, samples with medium and low molecular weight hyaluronic acid showed lower dynamic viscosity values at the phase gel-sol transition end. We tested the optimal composition (containing 18.0 % poloxamer 407, 2 % poloxamer 188, and 0.5 % hyaluronic acid (1400–1800 kDa) adhesion to the titanium plate. When exposed to the paddle stirrer (rotation speed 20 rpm) for 15 minutes and stored in the thermostat (37,0 ± 0,5 °C) for a week, the analyzed composition showed adhesion strength, which makes it possible to use it for coating.Conclusion. By multistage screening a sample was selected for introduction of a model antibacterial component representing a cocktail of bacteriophages Klebsiella pneumonia, Staphylococcus aureus, Escherichia coli. Microbiological studies showed good compatibility of the immunobiological substance with excipients, which indicated the prospects for further preclinical studies.

A sampling platform incorporating 3D-printed paddles-stirrers coated with metal-organic framework MIL-100(Fe) for in-situ extraction of phenolic pollutants in biodigester supernatant and wastewater effluent samples

In this work, a portable paddle stirrer platform for solid-phase extraction of chlorophenols, p-nitrophenol, and bisphenol A is presented. These compounds are important environmental pollutants and toxic inhibitors of the anaerobic treatment of wastewater. The platform integrates 3D-printed paddle stirrers coated with the metal-organic framework MIL-100(Fe), which is prepared in 10 min using a green microwave-assisted synthesis. This coated stirrer serves as an adsorbent for the preconcentration of phenols. The device is assembled with an electric motor that agitates the sample in a sample container. The sampler can be used for in-situ extraction of the analytes, eliminating the need for transporting samples to the laboratory. The analytes are eluted through ultrasonic desorption before analysis by HPLC-DAD. An exhaustive study of the stirring and extraction parameters was conducted. Under optimum conditions, the detection limits ranged from 0.3 to 1.7 μg L−1, and the precision, expressed as the relative standard deviation, showed intraday and interday ranges of 1.2–5.1% and 4.5–6.8%, respectively. The accuracy was evaluated using spiked samples of wastewater effluent and biodigester supernatant, and it provided relative recoveries in the range of 91.5–108.5%.

Comparative Evaluation of Metformin and Metronidazole Release from Oral Lyophilisates with Different Methods

The aim of this study is to compare three different dissolution methods to assess the drug release from oral lyophilisates, based on interpolyelectrolyte complexes (IPECs). IPECs were prepared by mixing solutions of a linear polymer, Eudragit® EPO, with a polymer with a cross-linked structure, Noveon® AA-1 or Carbopol® 10 Ultrez (in ratios of 1:2 and 1:1, respectively). Metformin or metronidazole were used as model drugs to achieve a systemic or local effect. A comparative assessment of the drug release kinetics was carried out using artificial saliva and three different set-ups: a paddle stirrer (USP apparatus 2), a flow cell (USP apparatus 4) and a Franz diffusion cell. The results demonstrated that oral lyophilisates disintegrated within 1 min. In the case of metformin, the drug release was completed in about 90 min independently of the set-up. The static conditions in the Franz diffusion cell and USP apparatus 2 permitted the aggregation of the IPEC; therefore, the release profiles show a significant difference compared to the USP apparatus 4.

Simulation of the hydrodynamics in polymerizers based on the CFD model for the synthesis of rubbers and plastics using the method of the solution polymerization

Mixing in a viscous medium, such as in polymerization processes, is worth noting. To control the polymerization process for improving the product quality, it is important to understand the mixing process. Also, it is essential to understand the flow behaviour in the stirred-tank reactor for the equipment design and from the point of view of the large-scale transition of the process. Local and general characteristics of mixing in the reactor are related to the design and selected speed of the agitator. 3D-modeling of the flow in the cylindrical reactor with the paddle stirrer was carried out using the potential of a supercomputer. Numerical results showed good consistency with experimental results and correlation developed by other researchers. To determine the best mode of introduction into the paddle space of the stirrer, two efficiency criteria were used: with respect to power and mixing time.

Study of the effectiveness of wet biodiesel purification

The efficiency of wet cleaning of fatty acid methyl esters (FAE), also called biodiesel, was studied by conducting volumetric, bubble and aerosol washing. The volumetric washing of FFAs was carried out using a three-blade paddle stirrer with a shaft and a four-blade stirrer with inclined blades. The shaft speed of the paddle agitator was 100, 200, 300, and 400 rpm, and that of the four-blade agitator with inclined blades was 200, 350, 500, and 650 rpm. The foam washing of the MWC was carried out at an air flow rate of 20 and 60 l/h at a MWC temperature of 20, 40, and 60°C. Three types of turbulizers were used for the experimental study of aerosol flushing of the ESP: DS-31-CER with one hole, DS-33-CER with two holes and DS-56-CER with four holes. The time of the experiments was 4 hours. Sampling of the MEMC to determine its alkalinity was carried out every hour. Also, every hour, contaminated water was replaced with clean water. Volumetric flushing for four hours unsatisfactorily removes potassium citrate from the CIP. When foam flushing the CIP with an air flow rate of 20 l/min, its alkalinity decreases by 2-3 times during 1-2 hours of bubbling. Further bubbling is impractical, as the alkalinity does not decrease but increases. At an air flow rate of 60 l/h for 3-4 hours of bubbling, the alkalinity of the CIP is reduced by 4.5 times, but then some increase is observed. The resulting alkalinity of the CIP during its aerosol washing decreases by about 2 times, and there is a tendency to its decrease over a longer washing time. Of the three studied methods of CIP washing, the aerosol method can be recommended for practical use, and medium- and large-droplet washing should be carried out for at least 4-5 hours, while small-droplet washing should be carried out for a longer time

ВИЗНАЧЕННЯ ЕНЕРГЕТИЧНО ЕФЕКТИВНОГО РІВНЯ ШВИДКОСТІ ПЕРЕМІШУВАЛЬНОГО ОРГАНУ ЕЛЕКТРОМЕХАНІЧНОЇ СИСТЕМИ

Purpose. Today, biomass fermentation in biogas plants is one of the most advanced, environmentally and economically viable solutions for energy production from waste. However, the process of anaerobic digestion of waste is long, so the main process of intensification is mixing. Analysis of well-known studies of domestic and foreign scientists indicates the urgency of reducing energy consumption for the mixing process. The aim of the study is to determine the energy-efficient speed of a paddle stirrer with blades set at an angle of 450 for small biogas reactors. Methodology. At the decision of the set tasks the general methods of physics, three-dimensional modeling, processing and visualization of the received results in the SolidWorks Flow Simulation and Wolfram Mathematica programs are applied. Results. Using 3D modeling, the influence of the stirrer speed on the picture of the distribution of the velocity vectors of the substrate flows in the biogas reactor was studied. Graphs of power consumption at the beginning of mixing for different stirrer speeds were obtained and analyzed, and the levels of energy consumed for mixing biomass during the start-up period and the whole mixing period were compared. A method for determining the energy efficient rotation speed of the stirring mechanism of the electromechanical system of biogas reactors is proposed. Practical value. The results can be used in the construction and modernization of biogas plants to reduce energy consumption of the substrate mixing process. Conclusion. Based on the research, it was concluded that for a paddle two-tier mixer with blades set at an angle of 450 energy-efficient speed, is 40 rpm. At this speed, careful and intensive mixing of the biomass is observed throughout the volume of the tank. The average velocity of flow vectors in the biomass volume is 0,273 m/s. The energy consumed per cycle of biomass mixing is 2471,3 J, and the percentage of energy consumed during the start-up period from the energy consumed during the entire mixing period is 0,62 %. References 19, figures 5.

Technologic Considerations of Creation Dosage Form of Original Substance 3,7-diazabicyclo[3.3.1]nonane

Introduction. An innovative pharmaceutical substance based on the 3,7-diazabicyclo[3.3.1]nonane derivative provides long-term activation of AMPA receptors and the production of neurotrophic factors, which makes it possible to use it for the treatment of cognitive impairments and rehabilitation of patients who have undergone acute brain hypoxia. Given that this substance is able to be absorbed through the walls of the gastrointestinal tract and pass through the blood-brain barrier, there are no restrictions on the development of an oral dosage form. In addition, the oral dosage form has significant advantages when used in geriatric and pediatric practice.Aim. The aim of the work was to carry out a comparative study of the possibility of using gelatin and hypromellose capsules for the development of the composition and technology for obtaining a dosage form containing a pharmaceutical substance based on a 3,7-diazabicyclo[3.3.1]nonane derivative.Materials and methods. The study of the «Dissolution» test of gelatinous and hypromellose capsules was carried out on an ERWEKA DT 720 «Paddle stirrer» apparatus at a stirrer rotation speed of 50 rpm in three media: pH 1.2, pH 4.5 and pH 6.8. The content of the substance in each sample was determined by high performance liquid chromatography with UV detection.Results and discussion. The results of the development and testing of capsules containing an original pharmaceutical substance of nootropic action based on a derivative of 3,7-diazabicyclo[3.3.1]nonane, which has low pharmaceutical and technological characteristics and is practically insoluble in water, are presented. The D/S value was ≥250.00 ml in each physiological pH range. The results of determining the dissolution of the developed dosage form in three media at pH values of 1.2, 4.5 and 6.8 showed a positive effect of the technology used on the solubility of the substance.Conclusion. A significant increase in the solubility of the practically insoluble substance of the 3,7-diazabicyclo[3.3.1]nonane derivative in the developed dosage form was shown, which is the result of the use of a well-founded complex of excipients and the technology of moisture-activated granulation. According to the results obtained, (77.60 ± 2.50) % of the substance passes into the dissolution medium with a pH of 4.5 in 45 minutes. The research results are used to develop a technological scheme for obtaining a finished dosage form, its indicators and quality standards.

The impact of addition of xanthan gum and guar gum on rheological properties of foams produced by continuous method

The paper presents the effect of the addition of hydrocolloids – xanthan gum and guar gum – on the rheological properties of ovoalbumin-based food foams, produced by continuous method. The foaming was carried out in a column apparatus with additional aeration equipped with a paddle stirrer. In order to determine the rheological parameters, a hysteresis loop test was carried out. The results of the study were described using the Ostwald-de Waele equation. The effect of the addition of hydrocolloid on the rheological properties of the obtained foams was characterized, and the synergistic effects between the hydrocolloids used were described.

Formulation and Optimization of Omeprezole Floating Tablet by Wet Granulation Technique

Omaprezole is a proton pump inhibitor, antacid drug. It is categorized as class II in BCS system of classification of drugs. Omaprazole inhibits the H(+)-K(-) ATPase in the proton pump of gastric parietal cells and highly effective inhibitor of gastric acid secretion. Floating tablet is nowadays considered as one of the best method to enhance the retention time of tablet in stomach. To get a better dissolution rate, the retention time of Omaprazole is enhanced by the floating technique. The aim of the work is to formulate the floating tablet of Omaprazole and evaluation of tablets invitro performance. The floating tablets are prepared by using two different polymers; HPMC K15, HPMC K100. Wet granulation method was used to prepare tablet. The polymers added in different ratios. The increasing concentration of polymers is responsible for enhancement of drug content and percent yield due to increase in the swallability of polymer.Invitro drug release study was performed using United State Pharmacopoeia (USP) type II dissolution test apparatus employing paddle stirrer at 50 rpm using 900ml of 0.1 N HCL buffer maintained at 37⁰C±0.5⁰C as the dissolution medium. The FTIR, DSC studies of Omaprazole floating tablet indicated the phase inversion of Omaprazole from crystalline to amorphous form. The F3 formulation show increased drug release as compare to pure drug in 24 hrs. It can be concluded that the floating tablet of Omaprazole prepared with mixture of HPMC K15 and HPMC K100 has greater retention time than pure drug and marketed formulation.

Glipizide Loaded Gastro Retentive Floating Tablets: Formulation and in vitro Evaluation

The objective of this research was to formulate and evaluate hydro dynamically balanced controlled drug delivery system of Glipizide. Initially, considering buoyancy as the main criteria, blank tablets were compressed for different formulae with various polymers like Carbopol-940p, HPMC, Citric acid and sodium bi carbonate. The formula selected for design had a combination of Glipizide, Carbopol-940p, HPMC, Citric acid. The tablets were prepared by direct compression method and evaluated for Glipizide content, in vitro release profile and buoyancy. The dissolution study was carried out in simulated gastric fluid using USP dissolution test apparatus employing paddle stirrer. Duration of buoyancy was observed simultaneously when the dissolution has carried out. The Glipizide content of F9 batch 97.87±0.16% and in-vitro release was found to be in the range of 98.85% and from the above result it was concluded F9 was the optimized formulation. This indicates the suitability of the technique chosen for the present dosage form.

In vitro equivalence evaluation of betahistine generic medicinal products as a tool potentially determining the efficacy of pharmacotherapy

To compare release parameters of various betahistine drugs in vitro using a comparative dissolution kinetics test. Objects of research are solid dosage forms (tablets) containing betahistine in a dose of 24 mg permitted for medical use in the Russian Federation. A method of comparative dissolution kinetics test was carried out as follows. The study was performed on a paddle stirrer at a speed of 50 rpm in three different pH dissolution media (pH 1.2, 4.5, 6.8), simulating the main sections of the digestive tract in which the active ingredient was decomposed, released and absorbed. This was performed in a quality controlled environment using a citrate buffer solution with pH 6.8. The time points for sampling the medium were 10 min, 15 min, 20 min and 30 min. The results of betahistine release were significant (RSD<10%) for all time points, except the first time point (RSD<20%). Regardless of pH, there was a complete release (≥85% over 15 minutes, <10%) of betahistine from betaserc, 24 mg, tablets (manufactured by Mylan Laboratories SAS). The dissolution profiles of betahistine in other investigational drugs did not show complete drug release (parameter <85% in 15 minutes, <10%) in different pH media. Therefore, dissolution profiles of the studied drugs were not comparable to the reference profile. Starting from 10 minutes, the reference drug of betahistine (betaserc, 24 mg) has a consistently higher release at different pH levels (representing the various stages of gastric digestion), vs. other studied generic analogues showing significantly lower levels of betahistine release. None of the studied drugs were found to be equivalent in vitro.

Study of plasmochemical processing effect on the properties of polymer films based on polyvinylchloride

Subject of Research.The paper deals with characteristics study of polymer composites based on commercially available polyvinyl chloride and biopolymer filler pectin in various weight ratios (1.5 and 10 mass%) for the usage as biodegradable packaging. Method. Biopolymer composite films were obtained by rolling at the temperature of 165-170 ℃and pre-mixing of all composition components with a paddle stirrer at a stirring speed of 6000 rpm for four minutes. The introduction of natural materials into the polymer matrix facilitates the decomposition of plastics during disposal, and the processing of composite polymeric materials for five and ten minutes by low-temperature plasma in argon: oxygen modifies the surface of the material, ensuring access of microorganisms for biodegradation. Samples of composites were studied by the methods of infrared Fourier spectroscopy and optical microscopy, depending on the content of the filler and etching time of the samples. Main Results. The effect of plasma-chemical treatment on the surface of polymeric composites has been experimentally proved; an increase in roughness, craters and other discontinuities may be explained by structural changes confirmed by infrared spectra. It is shown that composites containing 1% by weight of pectin are subjected to the greatest degree of material oxidation. Practical Relevance. The resulting biopolymer composites can be used as a package that decomposes during disposal and does not harm the environment. The introduction of a biodegradable component, natural polysaccharide of pectin, in small amounts does not change the chemical structure of the polymer material. Plasma-chemical treatment can be used as a method for surface treatment of industrial polymer materials before disposal.

Production of Concentrated Pickering Emulsions with Narrow Size Distributions Using Stirred Cell Membrane Emulsification.

Stirred cell membrane emulsification (SCME) has been employed to prepare concentrated Pickering oil in water emulsions solely stabilized by fumed silica nanoparticles. The optimal conditions under which highly stable and low-polydispersity concentrated emulsions using the SCME approach are highlighted. Optimization of the oil flux rates and the paddle stirrer speeds are critical to achieving control over the droplet size and size distribution. Investigating the influence of oil volume fraction highlights the criticality of the initial particle loading in the continuous phase on the final droplet size and polydispersity. At a particle loading of 4 wt %, both the droplet size and polydispersity increase with increasing of the oil volume fraction above 50%. As more interfacial area is produced, the number of particles available in the continuous phase diminishes, and coincidently a reduction in the kinetics of particle adsorption to the interface resulting in larger polydisperse droplets occurs. Increasing the particle loading to 10 wt % leads to significant improvements in both size and polydispersity with oil volume fractions as high as 70% produced with coefficient of variation values as low as ∼30% compared to ∼75% using conventional homogenization techniques.

Evaluation of chamber effects on antenna efficiency measurements using non‐reference antenna methods in two reverberation chambers

In this study, the evaluation of chamber effects on antenna efficiency measurements using non-reference antenna (NRA) methods is presented. Two reverberation chambers have been employed and they differ in dimensions and paddle stirrer configurations, therefore the corresponding electrical characteristics such as quality factors, decay constants, and enhanced backscatter coefficients are envisaged to be different. However, it is found that these differences have little influence on the efficiency measurement of antennas-under-test (AUTs). The AUTs used for this study were a directional antenna and an omnidirectional antenna. The discrepancy in the efficiency of the two antennas measured between the two chambers is <10% within their operational frequency bands. These results demonstrate that the NRA measurement techniques are robust. Further investigation shows that the directional antenna is slightly more prone to polarisation mismatch than the omnidirectional antenna is. Therefore, polarisation stirring should be implemented when using the NRA methods for antenna efficiency measurement especially for directional antennas.

Quiescent and Agitated Redispersion as a Tool for Evaluating Dispersant Effectiveness in Dissolution Enhancement of Drug-Laden Nanocomposites.

Nanocomposite microparticles (NCMPs) have been used in various solid dosage forms with the goal of enhancing the dissolution rate and bioavailability of poorly water-soluble drugs. Nanoparticle recovery from NCMPs, i.e., redispersion, is the preliminary step in drug dissolution. This study aims at exploring aqueous redispersion of NCMPs with various dispersants under quiescent vs. agitated conditions as potential dispersant screening tool in the development of fast-dissolving NCMP formulations. NCMPs were prepared by coating wet-milled suspensions of a poorly water-soluble drug, griseofulvin (GF), formulated with the dispersants hydroxypropyl cellulose (HPC), sodium dodecyl sulfate (SDS), as-received/wet co-milled croscarmellose sodium (CCS), and mannitol, onto Pharmatose® carrier particles in a fluidized bed dryer. The NCMPs were added to quiescent water kept in a cuvette, and the redispersion was visualized and investigated by turbidimetry and dynamic light scattering. The morphological evolution of a single NCMP exposed to a drop of water was studied via optical microscopy, which provided further insight into the self-redispersibility. As a comparison, the NCMPs were also redispersed in water agitated by a paddle stirrer followed by centrifugation and drug assay of the resultant supernatant, which yielded the percentage of GF recovered as nanoparticles. Both quiescent and agitated redispersion methods yielded similar rank-ordering of the dispersants: NCMPs with either HPC/SDS or HPC/CCS exhibited effective nanoparticle recovery and fast dissolution, whereas those with HPC or HPC/mannitol led to poor redispersibility and slow dissolution. This study demonstrates that both quiescent and agitated redispersion tests could be used for screening/optimizing dispersants for fast-dissolving drug NCMP formulations.

Development, Internal and External Validation of Naproxen Sodium Sustained Release Formulation: an Level A In Vitro-In Vivo Correlation.

The aim of the present study was to develop and validate an in vitro-in vivo correlation (IVIVC) for naproxen sodium-sustained release tablets and to compare their plasma concentrations over time with the immediate-release tablets. In vitro release rate data were obtained for each tablet by using the USP Apparatus II, paddle stirrer at 50 rpm in pH 7.4 phosphate buffer. A four-way crossover study was conducted in 6 healthy subjects by administering naproxen sodium sustained release 375 mg and 500 mg of immediate release tablets. Series of blood samples were collected over 24 hours and estimated by using the validated liquid chromatography tandem-mass spectrometry method. The similarity factor was calculated and it was found that values between, 50 and 100 indicates similarity of the profiles. Assessment of predicted and observed bioavailability was performed and prediction errors (PE) % calculated, as per the Food Drug Administration guidelines, the average absolute PE% of Cmax and AUC of individual formulation was found below 15% for establishment of IVIVC, based on internal prediction strongly suggesting that the naproxen sodium IVIVC models are valid. During external validation the predicted curve for the naproxen sodium sustained-release tablets was found to be identical to immediate release tablets and considered as valid. IVIVC can serve as a surrogate for in vivo bioavailability study and supports biowaivers, supports and validates the dissolution methods and specification settings and assists in quality control during scale-up and post-approval changes. It may be used to predict the variation in site change, process changes and to predict the absorption performance of naproxen sodium products with different release rates.

ВЛИЯНИЕ ДЛИТЕЛЬНОСТИ СМЕШИВАНИЯ И ДОЛИ МЕНЬШЕГО КОМПОНЕНТА НА ПОКАЗАТЕЛИ РАБОТЫ МЕШАЛКИ ЛОПАСТНОГО СМЕСИТЕЛЯ С ДОПОЛНИТЕЛЬНЫМИ ЛОПАТКАМИ

The purpose of research is justification of area efficiency of the proposed mixer with vertical shaft and paddle stirrer, the edges of the blades which are fixed sinusoidal blades. Research has shown that, by virtue of the kinetics of mixing all the mixers in the early period mixing significantly improve the quality of the mixture, after which stabilization of the quality indicators, and in some cases starts and segregation of the mixture. The nature of the change of the uniformity of the mixture is kind of exponential time mixing. In this connection there is the task of identifying areas of efficiency and opportunities the application of paddle mixer proposed design for the preparation of dry feed mixtures. Important manufacturing concentrate mixtures (compaund feeds, feed concentrates or forage medicinal mixtures) based on the purchase of BVD and your own forage. Purpose: the establishment of functional dependence between the technological parameters of the mixer (the proportion of the control component and the duration of mixing) and process performance (uneven mix and adjusted intensity of mixing taking into account the uniformity of the mixture); identifying rational values of technological parameters of the mixer, providing the desired quality mix and minimum energy intensity of mixing. It is provided the description and structural diagram mixer dry material batch. The technique is described and results of experimental studies of the mixer. It is presented the expressions describing the unevenness of the mix and the energy intensity of stirring, depending on the proportion of the control component and the duration of mixing; the required duration of mixing depending on the proportion of the control component. It is built two-dimensional section of the surface response in the studied parameters. Based on the analysis of the given graphs justifies the area efficiency of the mixer: the proportion of the control component is not less than 3%; when the portion of the control component 5% duration of mixing – 300 s, when the portion of the control component 10% the duration of the mixing – 200 s.