and H.P. The large plow mixers can perform effective mixing function and the choppers are more effective for granulation. After this process, a swab soaked in 92% ethanol was spread on the jar or spheres surfaces, then placed in a test tube and diluted with 5 mL of 92% ethanol for the extraction of the APIs. Products of this type are made either with very expensive mixing methods, such as multiple step mixing and fluid-bed granulation, or having poor content uniformity. Many companies in the chemical process industries (CPI) experience flow problems and core flow behavior due to the cohesive nature of powders. In this paper, we evaluated the mixing efficacy of a new 3-axis mixer device and determined its optimal working conditions. sharing sensitive information, make sure youre on a federal In addition to the determination of the AV for each API in each formulation, a design of experiment (DOE) was performed to understand the homogenization process of the device, as well as to attempt to define the optimal working conditions. Accessibility The evaluation of the jars and spheres after the compounding and cleaning procedures proved that the cleaning method used was able to reduce the API amounts on their surface to non-detected levels by HPLC (limits of detection = 2.50 g mL1 for finasteride, 0.055 g mL1 for vitamin B12, 6.59 g mL1 for folic acid, 0.01 ng L1 for Cu, 4.0 ng L1 for Mg, and 0.4 ng L1 for Zn). For adding a solvent to slow dissolving powders, there is a time delay for binding effect to fully develop. The addition of a liquid to a powder in a mechanical mixer often has the following problems: 1. Dilip M. Parikh is president and CEO, Dpharma Group Inc., a pharmaceutical technology consulting organization in Ellicott City, MD. An automatic ice making freezer equipped with a ice milling machine and a temperature adjustable storage compartment can serve the basic need of this invention. The technologies for making such an equipment is well established but such a need has not been identified. This model showed no evidence of lack of fit within the 95% confidence interval for the samples tested, once the lack of first tests returned the Fcalculated value as lower than the Fcritical value. On the basis of the surface responses and the individual values obtained from each experiment, specific conditions were defined to be fixed and used to provide a comparison of the homogenization efficiency among the 3-axis mixer and the alternative methods (Y-mixer and plastic bag): for F1, X1 was at 1 and X2 was at 0 (2 min, 50 rpm); for F2, X1 was at 0 and X2 was at 1 (5 min, 10 rpm); and for F3, X1 was at +1 and X2 was at 0 (8 min, 50 rpm) (Figure 3). HPLC analyses for finasteride, folic acid, and vitamin B12 were performed on a qualified and calibrated chromatography system (Young Lin, Anyang, Korea) composed of a quaternary gradient pump (YL 9110), a photodiode array (PDA) detector (YL 9160), a 96-vial programmable autosampler (YL 9150), a column oven compartment (YL 9130), a variable sample loop up to 200 mL, and a software controller (Clarity). Because of this automation, the amount of collectible test data has risen considerably, thereby enabling a more comprehensive statistical analysis. It is difficult to mix liquid with highly soluble powder materials which instantly aggromerate by the liquid. (A) 3-axis mixer front side picture (B) 3-axis mixer top side scheme (right). This can be explained because the powders can have different particle size and size distribution, density, surface morphology, and particle shape, which are some of the factors that influence powder flow [11]. Number 8860726. Comparison of the use of the 3-axis mixer with other common methods used for homogenization in compounding pharmacies. Alternative equipment such as double-cone or V type blenders can often achieve a homogenous mixture, but clients have come to us with several cases where the time and energy imparted into the mix are outside of the scope for what is deemed a productively efficient process. Received 2021 Mar 30; Accepted 2021 Apr 15. This application is a continuation-in-part of U.S. application Ser. They are not usable by current liquid addition methods to mix with or to granulate powders. Chromatographic conditions for finasteride quantification were as follows: columnC18 4.6 100 mm, at 45 C; mobile phasephosphoric acid 2.5mM and acetonitrile (1:1); flux1.5 mL/min; volume of injection20 L; and UV detection at 240 nm. PATENT EXPIRED DUE TO NONPAYMENT OF MAINTENANCE FEES UNDER 37 CFR 1.362. It is difficult to add viscous liquid to and disperse it in powders. Some frozen powder of gelatinized corn starch paste is added and immediately started to mix for about 1 minute. Contact our engineers today to discuss how high shear mixers from Lancaster Products can solve your problem. Differences in particle size, density, shape, and resilience are the properties most responsible for segregation. A mechanical mixing granulation method, meanwhile, produces denser and harder granules than a fluid-bed granulation method. The issue is further compounded in cases where the ratio of ingredients can be significantly unbalanced with 95% of the mixture containing ingredient A and the other 5% consisting of ingredients B, C, D. They can also be added through a insulated feeder to the powder in a mixer during mixing. will also be available for a limited time. The ice cubs in a double layered plastic bag is powdered by a hammer and stored in a freezer before use. Spray Drying:Illustration of a granule formation inside a spray dryer. A simplified mechanical mixing method for adding an amount of liquid to a powder selected from the group consisting of polydextrose, maltodextrin, sugar, sugar alcohol, starch and modified starch for improved homogeneity of mixing and reduced processing time comprising the step of mixing frozen particles of said liquid with said powder in a mechanical mixer to melt said frozen particles to form an uniformly wetted powder product. It is also worth remarking that the finished products presented adequate content uniformity even with small mixing times, such as 2 min. We take great pride in seeing their faces light up when we show them the results that can be achieved using a Lancaster Products High Shear Counter-Current mixer! This confirmation provides additional safety validation for using the 3-axis mixer device, as cleaning the critical parts that contact the API is sufficient to prevent cross-contamination among different formulations produced. Mixing times for the three methods were the same to allow for comparisons, and the speed of rotation was also kept the same for the 3-axis mixer and the Y-mixer. Ferreira A.D.O., Brando M.A.F., Polonini H.C. Lakshman P., Cooney C.L. Corn starch powder is widely used in cooking to add thickness to the soup of cooked dishes. HHS Vulnerability Disclosure, Help For vitamin B12, the conditions were as follows: columnC18 4.6 150 mm, at 25 C; mobile phasemethanol and water (35:65); flux0.5 mL/min; volume of injection100 L; and UV detection at 361 nm. In addition, the device was superior to classical mixing methods (such as the use of manually shaken plastic bags) and equivalent to well-established ones (Y-shaped mixer). After 3 additions and mixings, very fine spherical granules are formed. The powdery contents of 20 Wyler's unsweetened Orange soft drink mix packets are emptied into the food processor. The liquid is added by pumping in through the inlets, which often equipped with spraying nozzles. Having trouble producing homogeneous mixes or experiencing long mix processing times? It can be used in a shaker to sprinkle in foods while cooking without dusting and forming lumps. The main motivation for producing free-flowing pharmaceutical powders is the establishment of consistent feed from bulk storage containers into feed mechanisms of subsequent processing operations. All active pharmaceutical ingredients (finasteride, vitamin B12, folic acid, copper chelate, magnesium citrate, and zinc chelate) and hard-shell capsules were obtained from Fagron Brasil (So Paulo, Brazil), and the standardized excipient (Celulomax HG) was obtained from Excipienta (So Paulo, Brazil). 6. To obtain the continuous, beneficial effect of the products, every dosage form needs to contain the same amount of ingredients, and then a mixture can be defined as homogenous if every sample of it has the same quantitative composition as the others [4]. Serhan M., Sprowls M., Jackemeyer D., Long M., Perez I.D., Maret W., Tao N., Forzani E. Total iron measurement in human serum with a smartphone; Proceedings of the 2019 AIChE Annual Meeting, American Institute of Chemical Engineers; Orlando, FL, USA. Contrast matrix containing factors and levels for the 32 experimental design, with 10 replicates in each level. Mixing frozen liquid particles with powder instead of spraying liquid on powder in a mechanical mixer results in improving mixing homogeneity, reducing processing time, and simplifying mixing equipment and method. 5. Granulation is achieved by mixing a powder with its binder liquid. This article provides some illustrations of the characteristics of two different mixing methods for powders. These forces are responsible for the cohesive properties of fine powders and their tendency to form aggregates or agglomerates. and H.P. As the 3-axis mixer is a new mixing method that has not yet been fully evaluated and, as it claims to be time-saving for the compounding pharmacies, this study was designed to evaluate whether this device can be of added value for the mixing process on a small scale and provide homogeneous mixtures with small, required mixing times. The spheres are important because the shape variations in powders are relevant, as they can range from very irregular particles to almost spheres or well-defined crystals [13]. It is, therefore, surprising that a simple and economical method exists to solve them. This way, all of the ingredients are added into water and the mobility of the individual particles in this slurry is higher compared to a dry mixing process. Since the binder liquid is added to only a small portion of the powder at a time, only this wetted powder portion forms granules. In this sense, the F2 formulation contained very different APIs: one amorphous (folic acid) and another crystalline (vitamin B12); because of this, the porcelain spheres were added to help reduce the particle size, so that they could mix better as a function of their size. It may have two types of mixing devices, such as a set of large plow mixers and a set of choppers, such as the Mixmill of Processall.
The uniformity of granulation depends, partially, on how fine the binder liquid spraying particles are atomized. It also extends the application to homogenously mix liquid with highly soluble powders in a mechanical mixer, since direct adding liquid to such powders immediately forms aggromerates. All high shear energy granulators, which are mechanical mixers having essentially optimized mixing efficiency, still have problems to homogeneously mix some liquids and powders. The mechanical mixing method of claim 1 wherein said frozen liquid particles are made with (a) an automatic ice making freezer equipped with an ice milling machine and a temperature adjustable storage compartment. Gilbertson M.A., Eames I. Water and water solutions of solids, liquids, and gases are, however, the most useful and practical frozen liquids of this invention. They can be dissolved in water or water-alcohol mixtures to form binder liquids. The mechanical mixing method of claim 1 wherein said frozen liquid particles have a spherical shape made by freezing fine liquid droplets dropping out of fine needle holes. The powder and the liquid are mixed and/or granulated continuously in its intense mixing chamber, which contains fast rotating bars or pins, such as the Turbulizer of Bepex. The frozen liquid and powder mixing method of this invention requires an equipment to make desired particle size range granular and/or powder particles of frozen liquid and store them at desired temperature ready for utilization. The same compact food processor of EXAMPLE 1 is used. Web page addresses and e-mail addresses turn into links automatically. For more information, call 410-900-8489. The .gov means its official. The https:// ensures that you are connecting to the The mechanical mixing method of claim 1 wherein said frozen liquid is selected from the group consisting of ice, frozen water solution and frozen water alcohol solution of an intense sweetener, a high potency drug, a flavoring agent, a fertilizer, or a pesticide. When the powder is highly soluble to form sticky liquid, even a very slow liquid addition or time consuming granulation process can not avoid failures, e.g., from extensive agglomeration. According to both references, the individual values are used to calculate the acceptance value (AV) using the formula AV=|Mx|+ks, in which x is the mean of individual contents, expressed as a percentage of the label claim; M = x for the cases where 98.5% x T, M = 98.5 if x < 98.5, and M = T, if x > T, where T is the target content per dosage unit, expressed as a percentage of the label claim; k is the acceptability constant (=2.4); and s is the sample standard deviation. Benefits of Tumble Blenders and Dryers
Every handling or processing operation, therefore, gives rise to conditions in which segregation can take place. Consideration of these factors will minimize the segregation potential.
Segregation occurs where differential forces act on different fractions of the mass of bulk material. Liquid is added to only a small portion of the powder particles close to one another at any time resulting in uneven mixing.
6. In addition, parameters such as moisture and temperature can also play a role in flowability [7,12]. X1 (Mixing time (min)): (1): 2; (0): 5; (1): 8; X2 (Speed (rpm)): (1): 10; (0): 50; (1): 100. Granulation technology has been extensively utilized to reduce dust, improve flow character, increase or reduce dissolution rate, reduce interactions among ingredients, and change bulk density by various industries including pharmaceutical, food, and agriculture industries.
After setting the working conditions for the 3-axis mixer, a comparison study was conducted. Because variations in powder blend samples would probably be a function of particle size distribution, it is not possible to measure the absolute efficiency of the technique. This can be understood by the Van der Waals forces, which affect the flowability of powders due to adhesive forces between individual particles [12,15]. In general, the larger the difference in particle size, the larger the extend of segregation. esters or ethers, SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS, Shaping or working of foodstuffs characterised by the products, PATENT EXPIRED DUE TO NONPAYMENT OF MAINTENANCE FEES UNDER 37 CFR 1.362, Process for making flowable powders for coating applications, Dried marshmallow methods of preparation for increasing bowl life, Multi-colored aerated confectionery products, Process for Preparing Ammonic Glyphosate Granules, Material moisture content adjustment method, Methods for determining mixedness of batch material and for obtaining substantially consistent mixedness of batch material, Method and apparatus for cooling concrete mixture components, Method of and device for continuous preparation of granular material, such as foundry sand, Vane and chilling systems for tumble mixers, Process for preparing ammonic glyphosate granules, Agglomerated food product and method for making the same, Particulate composition for preparing bouillon, soups, sauces, gravies or for use as a seasoning, Preparing granulated sugar blends and products, Convenient to use aspartame and method of making, Method of agglomerating a dry pulverulent flour base material, Hydrothermally degradable binder based on fat-coated starch particles, Formed cream substitute and process for producing thereof, Process for making a bouillon tablet or bouillon cube, Powdery or granular oil and fat, and its manufacturing method, Recent advances in granulation technology and equipment, A kind of emamectin-benzoate water dispersible granules and preparation method thereof, Lapse for failure to pay maintenance fees, Lapsed due to failure to pay maintenance fee, Information on status: patent discontinuation.
This method produces a broad range of granular particle sizes which means low yield for obtaining a desired narrow range particle size product. In sequence, the results presented in Table 2 were modeled and, after multiple regression analyses through the least-squares method were performed, the following models were obtained: where Equation (1) is finasteride, Equation (2) is vitamin B12, Equation (3) is folic acid, Equation (4) is copper chelate, Equation (5) is magnesium citrate, Equation (6) is zinc chelate, X1 represents the mixing time, and X2 is the speed of rotation. The frozen liquid mixing method of this invention eliminates the need of a liquid delivery system, such as spraying nozzle with pressurized air atomizing system and its associated problems, such as dust, expenses, and time consuming. Even when the large frozen particles stay intact during mixing, since they release binder liquid slowly, they also result in homogeneous mixing with entire powder. The required amount of frozen liquid particles can be added all at once to the powder in the granulator right before starting to mix and to granulate. About 200 g of corn starch powder is added into the food processor. Copyright 2022. ; Validation, B.M., H.P. In other words, these two granulation methods are different in their applications. The drying equipment used by conventional mechanical mixing granulation methods, such as tray dryer, fluid-bed dryer, and turbo-dryer, can be used. A preferred continuous granulation method is to pre-mix a frozen liquid particles with a powder in a batch mechanical mixer to achieve complete melting of frozen liquid particles resulting in even mixing of liquid and powder then feed the mixture into a continuous mechanical mixing granulator to granulate. https://creativecommons.org/licenses/by/4.0/. Biased sample selection is avoided if potential samples are selected using random numbers. This addition method is dusty. Thus, dusting segregation occurs due to the difference in particle size between coarser and fine particles and their ability to suspend in the air as the blend material is discharged from the mixer or charged and discharged from the storage bin. Informa PLC's registered office is 5 Howick Place, London SW1P 1WG. Pharmaceutical industries need to provide evidence of the validation of the production process, and this includes objective parameters that attest to the homogeneity of the mixtures and the consequent uniformity of the final dosage forms. 7. In this sense, a mixture can be considered homogeneous when any fraction of it contains all components in the same proportion as the total preparation [5]. All volumetric glassware and the analytical balance used were calibrated. The mechanical mixing method of claim 1 wherein said mechanical mixer is selected from the group consisting of a high shear energy granulator, a mechanical mixer equipped with choppers, a mix pelletizer (or) and a continuous mixer. 3. All authors have read and agreed to the published version of the manuscript.
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Nevertheless, they confirmed that the full range tested could potentially provide results with acceptable AVs and capsule content (90100%). Many of the mix requirements presented to our engineers start with the need to blend powders of dissimilar properties into a homogeneous mix. 5. The process employed by counter-current, rotating pan high shear mixers from Lancaster Products is perfectly equipped to satisfy the critical specifications demanded in technical ceramics manufacturing processes as well as in other applications that call for homogenous mixes of dissimilar powders. Bethesda, MD 20894, Web Policies The new PMC design is here! Asachi M., Nourafkan E., Hassanpour A. In most cases, however, the binding effects start as soon as the liquid binder contacts the powder particles and the binder liquid needs to be sprayed in while mixing.
This method requires long granulation time since slow addition of binder liquid is required to achieve homogeneous granulation. For this, the jar was washed with water and neutral detergent, then rinsed with 70% ethanol; the porcelain spheres were brushed with water and neutral detergent, and then rinsed with 70% ethanol. In the pharmaceutical industry, blend homogeneity is of prime importance to assure that the drug substance is distributed uniformly in the powder/granule mix. All the other flow properties (angle of internal friction, cohesion, flow function, kinematic angle of wall friction, etc.) Flowability is the result of the combination of a materials physical properties that affect material flow and the equipment used for handling, storing, or processing the material. A uniform size fine granules, 80-120 mesh, is obtained. . Federal government websites often end in .gov or .mil. Morin G., Briens L. The effect of lubricants on powder flowability for pharmaceutical application. It is often desirable to mix a powder and its frozen binder liquid particles at a below granulation speed to obtain a homogeneous powder mix and then increase mixing speed to achieve homogeneous granulation. 08/103,704 filed on Aug. 9, 1993. Schulze D. Flow properties of powders and bulk solids (fundamentals). official website and that any information you provide is encrypted Many drugs, food additives, sweeteners, etc, have very high potencies. Segregation occurs within a mixer when differences in particulate properties cause a preferential movement of particles to certain regions of the mixer. For that, the capsules were compounded again using the optimal condition previously defined for the device, and two alternative methods were used to verify which one provided the best homogeneity (in terms of the AV) for the formulations. 
For folic acid, the conditions were as follows: columnC8 4.6 250 mm, at 25 C; mobile phasemethanol and phosphate buffer (12:88); flux0.9 mL/min; volume of injection20 L; and UV detection at 280 nm. Such applications often require only homogeneous mixing of a powder with a very small quantity of liquid, without changing its powder's form. 2. In other words, a frozen liquid powder mixing process can achieve more uniform mixing and granulation level with significantly shorter processing time than a liquid spraying mixing process. Powder Mixing Challenges and How to Overcome Them, FDA Conducting Evaluation of Key Agency Activities, SME Review Course to Help Professionals Taking PE Exam, Amys Kitchen Closing Factory, Eliminating 300 Jobs, Leybold Introduces Central Vacuum System for Food, Packaging Applications, US Chemical Production Dipped Slightly in June, Biogen to Pay $900 Million to Resolve Kickback Claims, Conagra Brands Recognized for Disability Inclusion, Mixing Strategies for High-Solids Applications, International Powder & Bulk Solids Conference & Exhibition, Allowed HTML tags: