Extruders and devices for pharmacy
HME pharmaceutical extrusion has become a novel processing technology in the development of molecular dispersions of API (Active Pharmaceutical Ingredient) pharmaceutical ingredients into various polymer or lipid matrices. This technique enables time-controlled, modified and targeted drug delivery. active substances.
HME has received significant attention from both the pharmaceutical industry and academia for applications for pharmaceutical dosage forms such as tablets, capsules, films and implants for oral, transdermal and transmucosal drug delivery. These pharmaceutical extrusion capabilities make HME an excellent alternative to other available techniques In addition to being a proven manufacturing process, HME satisfies the US Food and Drug Administration (FDA) Process Analytical Technology (PAT) scheme to design, analyze and control the manufacturing process through quality control measurements during the active extrusion process Hot extrusion technique creates the prospect of developing various components, technologies for processing once materials and innovative formula design and development in its various applications in drug delivery systems.
In recent years, extrusion technology has shifted the focus of pharmaceutical research due to the versatile applications of technology. In the meantime, great effort has been devoted to the miniaturization of pharmaceutical extrusion equipment, especially with regard to the development requirements of new chemical entities and formulations. This has led to a reliable small-scale extrusion process.
Hot extrusion process technology (HME).
Hot extrusion (HME) technology has proven to be a robust manufacturing method for many drug delivery systems and has therefore proven useful in the pharmaceutical industry as well. transforming powder or granular mixtures into a uniformly shaped product During this process, polymers are melted and molded into products of various shapes and sizes.
Possibilities of pharmaceutical hot extrusion (HME) technology.
Extrusion is a technique with great potential for use in organic synthesisExtrusion provides a way to achieve mixing of reagents, it also allows fine tuning of the mixing range by modifying the configuration of the pharmaceutical extruder. The extruder itself can provide heating up to several hundred degrees and small amounts of solvent can be added to speeding up the reaction Extruders can be equipped with efficient cooling systemsTherefore, it can be said that the extruder provides most, if not all, of the parameters that conventional solvent-based synthesis can provideIn fact, with regard to the current move towards a more sustainable environment, the extruder is advantageous because the amount of solvent required is reduced or eliminated Moreover, usually reaction times are significantly shortenedHME provides medical product developers, creating soluble dosage forms and drug release devices with a processing option that maximizes the blending of API with polymer while minimizing API (Active Pharmaceutical Ingredient) degradation, and even opens the door to products that cannot be prepared by other means.
Pharmaceutical extruders.
The modular configuration of twin-screw extruders makes it possible to combine several unit operations in one machine.Feeding, mixing, extrusion and molding are performed simultaneously in the twin screw extruder due to the continuous process.
In recent years, twin screw extruders have been successfully applied to pharmaceutical applications through reduced size machines. The key factor is the size and in particular the volume of the plasticizing system of the pharmaceutical extruder.
Twin-screw extrusion has become an efficient and flexible technique due to advantages such as cost reduction, process efficiency improvement, and research and production capability flexibility also use in the development of new solid dosage forms for personalized medicine.
The high material throughput required by the continuous extrusion process is an advantage in production, but is a limitation in developing new formulations Especially in the early development period, new chemical units are not available or are too expensive in large volumes Therefore, there is a need for low throughput extruders for the development of pharmaceutical products obtained by pharmaceutical extrusion (HME).
In pharmaceutical production, small extruders are useful because they are more reliable when using small amounts of active ingredients. Small batches can be easily accessed and easily adjusted by a quick process changeover.
Technological and material limitations in constructing pharmaceutical extruders.
One of the dominant obstacles in the development of miniaturized extruders is the optimization of key parts of the equipment when downsizing The limitations are the available materials, specifically the availability of structural acid-resistant steels with the desired strength properties and approved for contact with pharmaceutical products Another limitation is the ability to design and build miniature extruders with high performance and technical parameters .
Along with the reduction of the dimensions of the pharmaceutical extruder, there are objective physical and technical factors leading to a reduction in the possibility of supplying mechanical energy to the plasticizing system. the capacity of the extruder to transport such materials is compromised The throughput of the extruder must be reduced to a lower value, which is often a challenge in terms of feed uniformity Cohesive powder materials place high mechanical stress on the extruder, generating a high need for mechanical power This affects the residence time of the material in the extruder and sometimes the properties The iconic issue is the ability to scale down equipment in such a way that it is efficient to general due to varying process conditions for the products under testFactors affecting upscaling or downscaling include volume, heat transfer, and mass transfer spreading and homogenizing mixingThese factors affect both the delivery equipment and the design of the plasticizing system of the pharmaceutical extruder, which is responsible for the course and quality of the extrusion process.
Downscaling the process, along with reducing the geometries of the barrel and screws of a pharmaceutical extruder, is a key factor as general scaling concepts used in large extruders fail. For example, the concept of geometric similarity has a range that becomes invalid when using small extruders.One of the main problems is the surface area to volume ratio of the components that affect friction and heat transfer Another problem when scale-down is that the properties of the substance, such as particle size and viscosity, remain constant while the machine gets smaller This can also affect for the pharmaceutical extrusion process.
Our company has put a lot of effort into the process of miniaturization of components in the pharmaceutical extrusion technology. We offer various types of miniaturized extruders that differ in diameter and length of the plasticizing system, but also in design.
Small-scale extruders can be divided into two groups:
- The first group of machines was designed for early development as it can be started with just a few grams of material RES-2PN 2x12mm-Pharma, RES-2PB 2x12mm-Minilab, RES-2PM-Minilab.
- The second group of our extruders includes reduced size extruders RES-2PN 2x16 mm-Pharma, RES-2PM 2x20 mm-Pharma, RES-2PM 2x24 mm-Pharma.
All our extruders intended for pharmaceutical extrusion are connected by high functionality, high technical parameters and, which is a unique possibility of operation as co-rotating and counter-rotating extruders. The process of changing the direction of rotation of the extruder screws is automated thanks to the developed Vertex II technology.
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Processing of plastics by extrusion
Extrusion using extruders is a method of processing polymeric materials that is of great economic importance, as more than 50% of plastic materials produced are processed through this process. Extrusion (extrusion) is not a simple process to be carried out in practice.
It is impossible to build a good extruder without in-depth knowledge of the phenomena occurring in the plasticizing system of the extruder. Knowledge in the field of material science and technology in the field of plastics processing is necessary. The extrusion device is a difficult object to control. Problems may appear in the plasticizing system of the extruder or in the process of forming a polymer material. in the extruder, such as high temperature, high pressure, significant shear stresses and the presence of various fillers, can cause accelerated wear of components of plastics processing machines. The extruder is built of three basic systems: drive, control and plasticizing, as well as auxiliary components.
In the extrusion process, a very important role is played by the plasticizing system of the extruder, built of a cylinder and a screw [screws], which is a key component of each extruder The specific type of the plasticizing system of the extruder is selected adequately to the specificity of the processed material The screw of the extruder is responsible for the quality and consistency of the extruded material There are many possible configurations of screws used in extruders The key parameters of the extruder are the quality of the plasticization of the material and its homogenization, i.e. thorough mixing of the ingredients In the cylinder, as a result of the rotation of the screw [screws, the material is transported towards the head The material moving in the extruder cylinder enters the heated zone, where it is melted and then homogenized material and thermal The plasticized and mixed melt is fed with the appropriate efficiency and pressure to the extruder head, where the material is formed y taking the shape of the mouthpiece.
The complexity of plastics extrusion issues is evidenced by a large number of design solutions used in the design and manufacture of extruders.
In the extrusion technology, plasticization is of decisive importance, i.e. the appropriate transition of the input material as a result of heating, compression, movement and forces from a generally solid state to a plastic state. This process is the most important factor determining the extrusion efficiency and the quality of the obtained extrudate. specific parameters, i.e. temperature, pressure, degree of homogenization, speed of movement and flow rate. There are larger or smaller fluctuations of these values, characterized by a specific period and a given amplitude.
The plasticizing system of the extruder performs four basic functions:
- heating of the material, carried out in order to ensure the desired course of changes in the physical states of the processed material, determined by temperature and its fluctuation. Supply the thermal energy necessary to heat the material to the temperature required by the process, in order to melt the polymer.
- mechanically compressing the plastic to remove air from between its granules.And then create a stable pressure in the molten material in order to obtain a given course of pressure changes in the processed material, determined by the value of pressure and its pulsation.
- mixing, ensuring homogenization, i.e. homogenization of the composition and properties, mainly thermal and mechanical, as well as the structure of the processed material and uniform heating of the alloy to the required temperature
- transporting, enabling the material to be moved through the system, obtaining at its end the required flow rate of the material with a specific intensity and a fixed fluctuation and pulsation.
Sometimes the plasticizing system is designed to also perform auxiliary functions, which can be, for example, degassing or foaming. Most often used in single-screw extruders is the classic three-zone screw
Three-zone screw of a single-screw extruder.
The processing zones of the extruder screw are defined by the changing height of the screw channel:
- In the feeding zone, the height of the screw channel is constant and is the highest,
- In the compression zone, the height of the screw channel decreases, most often it is a linear change.
- In the dosing zone, the channel height is constant and has the lowest value.
Geometrical dimensions that characterize the extruder screw:
- L/D – length of the working part represented by the number of calibers [extruder cylinder diameter] npL/D=32.
- D - outer diameter.
- H – canal height (0.12-0.2D).
- W – canal width (0.75-1.2D).
- S – helix pitch of the helix,
- φ – coil inclination angle.
- e – roll width).
- R – compression ratio.
Figure 1 geometrical dimensions of the extruder screw
Extruder screw pitch angle [helix angle] and volumetric efficiency
In extrusion, the angle of the helix is the angle between the helix and a plane transverse to the axis of the extruder screw. For most applications, the pitch of the extruder screw is equal to its diameter. Volumetric capacity depends on the angle of the helix. ), then the volumetric efficiency is 45.4%.
The energy used to rotate and pump the plastic forward of the extruder's plasticizing system is converted to heat Since the material is also sheared, the heat generated is known as shear heat Shear heat is not evenly distributed throughout the material, but is greatest where the shear rate is highest The amount of heat released can be high enough to cause localized overheating and decomposition of the material or its degradation For a given material, the amount of shear heat generated depends on the speed and diameter of the screw If possible, the size of the extruder should be matched to the expected capacity It is possible to achieve the required capacity with a small diameter of the extruder screw operating at high speed or with a larger diameter machine running slower It is generally stated that a larger machine will melt at a much lower temperature and achieve higher resultsFor this reason extruders running at high RPM should be equipped with efficient cylinder zone cooling systems.
Screw pitch of a plastic extruder.
The pitch of the extruder screw is defined as the distance between two consecutive turnsThe pitch of the screw is directly related to the angle of the screw helix, which is the angle between the pitch of the screw and the plane perpendicular to the axis of the screw If the pitch is to be equal to the diameter of the screw, it is called square pitchNote that square pitch is not always the optimal pitch for the screw design.In fact, the optimum pitch or alternatively the optimum helix angle can be calculated based on the rheology of the extruded materials.
Compression ratio of the plastic extruder screw.
The compression ratio is an important parameter to evaluate when designing extruder screws. It can be determined by the ratio of the channel depth (or alternatively channel volume) in the feed section to the depth in the dispense section. The former is known as the depth compression ratio and the latter is the volumetric compression ratio. For special screws such as like barrier bolts, the inclusion of the volumetric compression ratio (VCR) is a more reliable design parameter than the depth compression ratio (CR) because the pitch of the driver also changes from the feeding section to the transition and gauge sections in their screw design It is worth mentioning that the CR value can also be a confusing parameter in screw designFor example, if the channel depth changes from 16mm in the feed section to 4mm in the dispense section, the CR is 4:1 However, the same compression ratio will be achieved if the channel depth changes from 12mm in the delivery section up to 3 mm in the dosing sectionThese two screws behave completely differently despite the fact that they have the same compression ratioAn important parameter in the design of extruder screws, closely related to the compression ratio, is the inclination of the transition section.
In order to obtain efficient melting, the compression ratio and the inclination of the transition section should be carefully matched to the melting rate of the polymer being processed. The compression ratio of the screw also depends on the compressibility of the materials being processed. for the extrusion of highly compressible materials, it is generally recommended to use a high compression screw.
Length to diameter ratio (L/D) of extruder screws.
Another key parameter in screw design is the length to diameter (L/D) ratio. It is defined as the ratio of the length of the screw to its diameter. Typical screw L/D ratios range from 20:1 to 36:1 and even up to 52:1. lengths considered in screw design, which in turn depends on the application and the materials being processed. For conventional screws with three functional zones (i.e. feeding, compression and dispensing zones), the typical L/D ratio is 24:1 to 32:1. However, for processes where where a highly homogeneous and gel-free melt and melting at constant temperature and pressure are required, the need for additional sections is unavoidable. For example, one or more additional mixing elements are often added to the design of these screws to ensure uniform delivery of the melt to the die. Therefore, in these applications, the screw should be longer to accommodate added sections then typical L/D ratio for auger that used in extrusion processes is 32:1. In processes where outgassing is required (so-called two-stage screw), screws with an L/D ratio greater than 32:1 are usually recommended.
Clearance between the screw and the extruder barrel.
The clearance between the screw and the extruder barrel is a measure of the space between the outer diameter of the screw and the cylinder wall of the plasticizing system Incorrect clearance will adversely affect the performance of the plasticizing system A small clearance can cause excessive wear on the screw, while a large clearance can reduce the melting efficiency of the screw to the accumulation of a thick molten layer on the surface of the cylinder, which reduces the thermal conductivity through the cylinder.A large clearance between the screw and the extruder barrel can also reduce the pumping capacity of the screw due to excessive material backflow.
Mixing of plastic in a screw extruder.
The extruder screw does not always ensure very good mixing of the extruded plastic This is due to the way the plastic flows or is transported along the plasticizing system The plastic transported in the direction of the longitudinal axis of the extruder screw may not be properly mixed For this reason, the material coming out of the machine will not be of uniform quality It will be heterogeneous because it has a non-uniform shear history Therefore, it is important that the plasticizing system breaks up agglomerates, ensuring good dispersion mixing. The second important action of the plasticizing system is to create a random spatial distribution of the processed material, ensuring distributional mixing.
To ensure high quality extruded material, there is a trend to use longer extrusion systems with a length to diameter ratio [L/D ratio] in excess of 25/1 Long plasticizer systems are used where high flow rates and excellent melt uniformity are required They will produce the same throughput as shorter layouts, but at lower extruder screw speeds This is especially important when a lot of heat is generated that needs to be removed from the system The use of a longer plasticizer gives greater flexibility in operation as there are more options for using shear and mixing elements Some extruders are 32 D to 52 D length.
Elements of intensive shearing and mixing of material used in screws of boring machines.
Obtaining a product of the required quality with high efficiency is possible thanks to extruder screws equipped with appropriate material homogenizing elements, i.e. shearing and mixing, which are usually placed in the end part of the extruder screw. The purpose of the spreading elements is to homogenize the plasticized material leaving the shearing element. Homogenization is achieved thanks to the use of a mixing system located in the relaxation zone, i.e. the zone with increased channel height. configurations, which results in intensive mixing of the plasticized material. It should be noted that the use of these elements increases the power consumed by the drive e This element acts as a choke, reducing the extrusion efficiency, but allows the process to be carried out at higher rotational speeds of the screw and ensures obtaining a properly homogenized material and optimal product quality.
Currently, many screws used in extrusion processes have a mixing element. dispersion mixing and distributive mixing In extrusion processes, dispersion mixers are mainly used to remove gels in the melt Distribution mixers are used to homogenize the melt, in particular to obtain a thermally homogenized melt This is an important problem in extrusion processes because poor homogenization has a detrimental effect on the final product quality, especially its homogeneity.
Many types of mixing elements have already been developed for both dispersion and distribution mixing, which are used in the construction of extruder screws.Generally, high shear mixing elements are mainly used for dispersion mixing It should be noted that the high shear rate and consequently the high shear stress applied to the polymer melt as it travels through the small gap of the barrier run can raise the temperature of the polymer melt Twisted Maddock mixer, also called spiral shear mixer, properly optimized can reduce the effect of shear on melt temperature rise Pineapple mixer, typically used as a distribution mixer, continuously separates and combines different melt streams to produce a homogeneous polymer melt Known as a low shear mixing elementFor extrusion processes where the molten plastic is homogenized thermally, this mixer can be of great help.
Mixing elements used in extruder screws.
The geometry of the mixing and shearing elements of the extruder screw should be appropriately selected to the properties of the processed material. It should be taken into account when selecting the properties of the extruder's plasticizing system, including the head shaping the extruded profile. The length of the extruder's screw shearing and mixing elements is usually 2-3 DE. at a distance of 5-7 D from its end.
Mixing elements are used as below:
- torpedo element.
- Maddock element.
- element with transverse barriers.
- Maillefer element.
- element with mixing protrusions.
- discontinuous winding element.
- rheotoic element.
- Dulmage (Dow) element.
- component Saxton (DuPont).
The plasticizing system of the extruder should first provide dispersion mixing, and then produce distribution mixing. These two mixing processes can be repeated more than once.
Dispersion mixing sections.
A large number of dispersion mixing sections are available. They can be divided into three main groups:
- shear rings or blisters.
- corrugated mixers such as Egan, Maddock mixing sections.
- cross barrier mixers such as EVK or simple cross barrier mixing sections.
Distribution mixing sections.
There are many distribution mixing sections available, which can be divided into four main groups:
- slotted mixers.
- pin mixers.
- cavity mixers.
- variable depth mixers
Barrier extruder screw
The barrier screw of the extruder is considered a state of the art design which includes a separate melt channel to ensure full plasticization before the dispensing section. a melt zone in the primary channel that slows down the efficient melting of the raw material. This screw also uses a full circumferential barrier at the end of the transition section to ensure plasticization of the fully molten material prior to final mixing and pumping.
In the case of a barrier-free extruder screw, some of the bed of plastic pellets will disintegrate and be melted first The remaining unmelted pellets can only be melted by heat convection from the surrounding melt Heat convection melting is not an efficient melting mechanism for polymeric materials due to their limited thermal conductivity Therefore, unmelted polymer may still flow through the discharge end of the extruder, resulting in unwanted product.Barrier augers can solve this problem by separating the molten and solid channels by using a secondary scraper called a barrier scraper. The barrier section where the main part of melting takes place is placed between the feeding and dispensing sections. The barrier section usually replaces the transition section; however, there are auger designs with separate transition and barrier sections.
There are two main designs for barrier augers; constant depth and constant width As the name suggests, the channel depth for unmelted polymer pellets and molten polymer pellets remains the same in a constant depth design Channel width for unmelted pellets becomes narrower along the length of the screw, while the melt channel becomes wider In contrast, constant depth barrier screws widths have channel width for molten and unmelted polymer unchanged throughout the barrier section, while their depths are different; the depth of the solid material channel decreases and the depth of the melt channel increases.
Principles of selection of screws for the extrusion process.
The length of the extruder screw feeding zone should be the longer, the higher the softening temperature of the material, and sometimes its length is reduced at the expense of preheating the material. The length of the compression zone should be the greater, the higher the softening temperature and its range. softeningCrystalline plastics, melt in a small range of temperatures It may be only a few degrees, therefore, screws with a short (1-2D) compression zone are used for their extrusion. The situation is slightly different in the case of easily deformable plastics, such as LDPE, where even two-zone screws with a long compression zone can be used compression zone, in which the plastic granules, which have not yet been melted, are slowly compressed from the beginning.
The optimum compression ratio of the screw (the ratio of the height of the screw channel in the feed zone to its height in the dosing zone) should be greater than the ratio of the density of the solid material to its bulk density. it also depends on the viscosity of the material in the extrusion conditions, and so for amorphous materials with high melt viscosity, low compression ratio screws are recommended to avoid overheating of the intensively sheared material and excessive load on the screw drive system.
Small screw compression ratios, of the order of 2, are recommended for the processing of thermally unstable plastics. Such materials include PVC, for which too high a compression ratio could cause material degradation. For thermally stable semi-crystalline plastics, such as PE or PP, high compression ratios of the order of 4 and more can be used. to the need to have a large number of screws to obtain optimal extrusion conditions with each change of raw material.
In practical applications, this is a costly solution. In certain conditions, it is possible to adjust the screws to other materials by changing the adjustable operating parameters of the extruder, such as the rotational speed of the screw or the temperature of the heating zones. The screw for LDPE can be used for extruding PP at slightly higher speeds. The screw for PS can also be used for processing of PC after increasing the temperatures of the heating zonesThe screw of a general purpose extruder is designed to suit the widest possible range of plasticsThe screw used in an extruder is not the ideal answer to the processing of any particular material.
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