Modern pharmaceutical products manufactured by extrusion.

Interest in hot extrusion techniques in pharmaceutical applications is growing rapidly. Many articles have been published in the pharmaceutical scientific literature in recent years. Hot extrusion (HME) is a widely used technique in the plastics industry and has recently been shown to be a viable method for preparing many types of dosage forms and drug delivery systems. Hot extruded dosage forms are complex mixtures of active drugs, functional intermediates and processing aids.

Description of the pharmaceutical extrusion process.

Hot extrusion (HME) is one of the most widely used processing techniques in the plastics industryHot extrusion is the process of extruding raw materials using a single or twin screw extruder at elevated temperature through a die into a uniformly shaped product Today, more than half of all plastic products, including plastic bags, sheets, and tubes is produced by this processHME was first introduced to the plastics industry in the mid-19th century to prepare polymeric insulating coatings for wiresCurrently, interest in HME techniques for pharmaceutical applications is growing rapidlyThe number of HME patents issued for pharmaceutical systems continues to growResearch has shown that HME processes are a viable method for the preparation of pharmaceutical drug delivery systems, including granules, cylinders and foilsHME technology is an attractive alternative to traditional processing methodsHME offers many advantages over and Other pharmaceutical techniques Molten polymers during the extrusion process can function as thermal binders and act as drug stores or drug release retarders after cooling and solidification Solvents and water are not necessary, thus reducing the number of processing steps and eliminating time-consuming drying steps Matrix can be pressurized to obtain a higher density of the matrix Intense mixing and shear imposed by the rotating extruder screws breaks up and distributes aggregates of suspended particles in the molten polymer This process results in a more uniform dispersion, is continuous and efficient HME has been used to improve the bioavailability of medicinal substances, especially those with low water solubility by forming molecular dispersions, HME requires a pharmaceutical grade polymer that must be processed at relatively low temperatures due to the thermal sensitivity of many drugs.

For this reason, pharmaceutical extruders must be equipped with plasticizing systems that provide high-end temperature control and regulation. Pharmaceutical grade extruders have evolved and have been engineered to mix drugs with carriers for various solid dosage forms, as well as for the production of wet granulations. The main differences between the extruder for plastics plastics and a pharmaceutical grade extruder are contact parts that must meet regulatory requirements Typically contact metallurgy must not be reactive, additive or absorptive with the product In addition, the equipment is configured for the cleaning and validation required in the pharmaceutical environment By utilizing laboratory pharmaceutical extruders, you can stay one step ahead of the competition by developing new products pharmaceuticals Laboratory extruders for extrusion of new pharmaceutical products.

Laboratory extruders are small versions of production extruders. However, there are many differences between laboratory and production extruders. Laboratory extruders are more extensively equipped with functions that allow testing many materials, which makes them very versatile devices. They have functionalities that facilitate and accelerate the research process. Laboratory extruders are equipped with a rich set of precise measuring sensors.

• Lab extruders are ideal for short delivery and response times for low volume batches or pilot trials. They can be tailored to suit all applications.
• They are designed to enable the efficient development of new products and the testing of new extrusion processes can be critical to a manufacturing company or research lab.Laboratory extruders can be used to reduce time to market for new products.
• Different formulations can be tested with laboratory extruders to find out how they behave during extrusion. The amount of extruded samples is usually sufficient to be easily made for testing and evaluation of a newly developed product.
• Continuous research and development ensure continuous improvement and optimization of final products. Final products require quality control. This is most easily done on a laboratory scale.
• Universal laboratory extruders designed for small batches of product, with the possibility of a quick change of the research process, can be effectively used in the training process. They allow you to effectively use time and maximize the effectiveness of training.

Scalability from lab to pharmaceutical production.

Laboratory extruders are a valuable research and development tool for performing research that will eventually be scaled up to production. In addition to preventing the use of valuable production resources, significant material cost savings can be achieved by making small batches of product. The key to scale-up is the flexibility of the laboratory extruder. The versatile laboratory extruder allows you to test and modify processes for the best results prior to scaling Another factor in successful scaling is ensuring that the material has exactly the same experience in the production equipment as in the lab extrusion lines Zamak Mercator Lab Extruders are fully customizable and can be equipped with specialized process control instrumentation to continuously measure and record parameters to accurately replicate the process The technical parameters of these extruders are high Compact and versatile, and At the same time, stable and precise, Zamak Mercator laboratory extruders turn out to be a very profitable investment in equipment intended for research.

Pharmaceutical twin screw extruders.

Extrusion is an umbrella term for a family of processes that involve the movement of material through a limited space, most commonly along an assembly of a cylinder and a screw or two located within that cylinder which provides what is known as screw extrusion. There are two main types of extrusion: single screw extrusion (SSE) and Twin Screws (TSE) As the names suggest, SSE involves the movement of material with one screw, while TSE, which is more commonly used, involves the movement of material which is transported, mixed, kneaded and modified by two screws As indicated, twin screw extruders use two side by side and interpenetrating screws The use of two segmented screws in a pharmaceutical extruder allows for many different configurations and imposes different operating conditions on the extruder zones In a twin-screw extruder, the screws can rotate in the same direction (co-rotating extruder) or in opposite directions h (counter-rotating extruder).

Co-rotating twin screw extruders are the most important type of pharmaceutical extruder They can operate at high rotational speeds and achieve high outputs while maintaining good mixing and conveying characteristics The extruder operates on a first-in-first-out basis as the material does not rotate with the extruder screws Non-interlocking extruders, on the other hand, are often used for processing where large amounts of volatiles need to be removed and when processing high viscosity materials Non-tangle extruders allow the discharge of large volumes of volatile components through vents usually located at the top of the cylinder.Twin-screw extruders have many advantages compared to single-screw extruders, such as easier material feeding, high kneading and dispersing efficiency, less tendency to overheat the material.

Both extrusion techniques process materials through mixing, heating, and also through the application of mechanical energy The main forces present in the extrusion process are pressure, kneading and shear However, the methodology of each technique varies greatly as well as the applications they are applied to For example, SSE is typically used for perform hot melt and pressurize Extrusion (TSE), where the emphasis is on melting the material for thorough mixing, kneading and processing Process can be customized by changing the configuration of the screws to make the process more efficient Laboratory single screw extruder is typically 12 to 32 in diameter mm Laboratory twin screw extruder typically has screw diameters from 2x12 to 2x24 mm.

TSE uses two intertwining screws that provide movement of the material along the barrel The configuration of two extruder screws is generally more complex and usually consists of a series of alternating transport and kneading segments The main advantage of using segmented screws is that the configuration can be adapted to each process Material conveying segments have a generally quite large channel depth i.e. radial distance between flight tip and core In addition, the kneading segments can be set at 30o, 60o and 90o angles to each other, with the latter angle providing the greatest kneading and shearing, resulting in variations in material properties .

Twin screw extruder screws are typically designed to provide different types of mixing and conveying conditions in different zones of the extruder plasticizing system. During product development, modular extruder screws with multiple components mounted on a common shaft allow the extruder screw design to be customized and optimized for each product. Screw sections can be designed to performing particle size reduction, mixing and conveying functions. The length of the screw in relation to the barrel diameter (L/D ratio) is selected to optimize the degree of mixing and the number of zones required to achieve the final product characteristics.

The rotation of the extruder screws causes dispersive and dispersive mixing Distributive mixing maximizes the partitioning and recombination of materials while minimizing energy input by mixing with low planar stretching and shearing effects.

Dispersion mixing uses tensile and planar shear fields to break dispersed materials into smaller sizes, ideally using energy at or just above the threshold level needed to break them apart.
The use of different mixing elements allows the twin screw extruder to both reduce particle size and mix so that the API can be introduced into the polymer in dispersed form or, if the solubility of the API in the polymer is high enough, in dissolved form. API that is dissolved in the polymer at the mixing temperature may not be able to recrystallise upon cooling, leading to supersaturated solid solutions.In such cases, product stability must be closely monitored as API recrystallization is possible over a long period of time, especially at elevated storage temperatures and high API loadings, which can affect the shelf life of the final product.
There are two families of twin screw extruders: high energy input (HSEI) twin screw extruders, which are primarily used for compounding, reactive processing, and/or degassing, and low melt rate (LSLF) twin screw extruders, which are designed for low melt rate mixing Shear and uniform pressure pumping Screws can be co-rotating (self-cleaning), which is the most common, or counter-rotating.

Construction elements of the pharmaceutical extruder:

• Feeding tank (gravimetric or volumetric feeding)
• Temperature controlled cylinder (heating and/or cooling)
• Matrix (different matrix configurations available)

Additional equipment:

• Process analysis technology
• Vacuum pumps for degassing extruders
• Pelletizing equipment
• Calendering equipment

The pharmaceutical extruder should ensure the measurement and monitoring of at least the following parameters in the extrusion process using standard instrumentation:

• Melt pressure
• Melt temperature
• Measurement of the axial force acting on the screws
• Temperature of the extruder barrel zones
• Torque of the extruder screws
• Electricity consumption
• Die temperature
• Rotational speed of the extruder screws
• Ambient temperature
• Ambient relative humidity
• Vent vacuum level (if applicable)

By monitoring these parameters, it is possible to effectively conduct research on the extrusion process. The condition must be met that the measurements made are reliable and the operation of the regulators is reliable and repeatable. In this way, the research process can be maintained and optimized and can be characterized by important aspects. can be determined by these parameters.

The extruder instrumentation mentioned above allows the operator to control the extruder in an optimal way. Some critical quality attributes can be combined using the parameters of the extrusion system with values monitored by the extruder instrumentation. It is important that changes in the operating parameters of the extruder are reliable.

Zamak Mercator laboratory extruders are modular in design to facilitate various configurations Configuration has a significant impact on the extrusion process and can be designed to achieve high or low shear Di is the internal diameter of the extruder screw and D is the external diameter of the extruder screw The ratio Do/D is very important and indicates available free volume of extruder screwsExtruder barrel length, is given as a multiple of the outer diameter [To] This means that an extruder with a functional length of 40 L/D has a length equal to 40 times the outer diameter of the extruder screws For scaling purposes, it is important to keep the functional length constant and the To/D ratio.The configuration of the screws can be varied depending on the number and arrangement of transport, kneading and mixing elements.

Advantages of pharmaceutical hot extrusion [HME].

In the pharmaceutical industry, hot melt extrusion is used for a variety of purposes, such as:

• Increasing the rate of dissolution and bioavailability of the drug
• Controlling or modifying drug release
• Taste masking
• Stabilizing the API
• Parenteral storage and topical delivery systems
• Modification or addition of a functional group
• Controlled degradation and cross-linking of polymers to produce a product with a controlled molecular weight distribution
• Reactive blending which involves the extrusion of two or more compatible polymer blends leading to the formation of a polymer-polymer complex
• Increasing the dissolution rate and bioavailability of APIs that are poorly soluble in water are important challenges in the development of dosage forms. One approach is to form a solid dispersion solution of the drug with hydrophilic excipients. thermodynamic barrier to dissolution.

Once formulated, hot extrusion is a reliable and robust process offering cost-effectiveness advantagesCompared to other solid solution manufacturing processes, the extrusion process is much less complex The production of such dosage forms requires only a few steps and avoids the use of organic solvents.

Hot extrusion also has advantages over solid solution/dispersion forming methods using solvent methods:

• There is no need to handle flammable solvents
• No residual solvents
• Possibility of continuous processing
• Fewer process steps
• High product density
• Non-dusty granules
• The equipment takes up little space
• The extrusion process does not require water

In addition to oral medicinal preparations, the hot extrusion technique can be used to produce parenteral depots such as implants and stents, and topical delivery systems such as dermal or transdermal patches. For these applications, the extrusion process is often combined with a shaping or injection molding step.

A look into the future of pharmaceutical extrusion.

The value of 'continuous processing' in the pharmaceutical industry is recognized Hot extrusion (HME) is a manufacturing process widely used in the plastics industry and has considerable potential as a continuous pharmaceutical process.

New chemical entities that exhibit poor bioavailability due to solubility problems are prime candidates for hot extrusion. This technology can be used to disperse such drugs in a given matrix at the molecular level by forming a solid solution. Combined with the use of dispersed, amorphous and molecularly dissolved systems, it can be apply a range of other formulation techniques using a melt extrusion approach. HME has also been shown to provide many different advantages in the production of thin films for both drug delivery and wound care. Hot extrusion technologies can offer numerous advantages over traditional methods. Shorter and more efficient lead times to the final productEnvironmental benefits resulting from the elimination of solvents in processing (including the possibility of recycling).The increased efficiency of drug delivery to the patient makes hot extrusion an exciting challenge for pharmaceutical scientists.

A wide range of dosage forms and applications from oral to topical can be prepared Solid dispersions or solid dissolutions of drug embedded in carrier matrices can allow for sustained release and improved dissolution rates A wide range of functional excipients are available Potential drug and matrix degradation may be hampered by high Process temperatures and shear forces However, these challenges can be overcome through formulation and equipment design and engineering approach Selection of low-melt carriers or use of compatible plasticizers can lower process temperatures Extruder and screw design can also reduce shear forces and settling time HME enables mixing of API with polymer with minimal stresses and thermal stresses, thus limiting process-related degradation of APIsAntioxidants are often included in the formulation, and the short residence time in the plasticizing system (usually in the order of minutes) also helps to minimize thermal degradation, especially when compared to batch blending and other compounding processes. Interest in hot extrusion as a pharmaceutical process continues to grow.

In conclusion, extrusion is a technique that has great potential for 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 if necessary to speed up the reaction Extruders can be equipped with efficient cooling systems Therefore, it can be concluded that the extruder provides most, if not all, of the parameters that conventional solvent-based synthesis can provide In 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, typically reaction times are significantly reduced and oral doses and drug release devices with a processing option that maximizes mixing of API with polymer while minimizing API degradation and even opens the door to products that cannot be prepared by other means.

Professional research twin screw extruders you can rely on

Zamak Mercator is a manufacturer of twin-screw research extruders with screw diameters of 2 x 12/2 x16/2 x 20/2 x 24 mm, co-rotating and counter-rotating, with a range of L/D up to 48, with a modular and non-modular structure. The construction of the extruders is based on innovative design assumptions, modern components and is based on many years of experience gained in the plastics processing industry.

Due to the high complexity of the extrusion process, the research extruder should have all the capabilities of industrial extruders and even exceed them.

Our research extruders are reliable and repeatable. The preparation time for subsequent tests is short. In the practice of a research laboratory, meeting this assumption means that in a short time the extruder must reach and stabilize the working parameters set by the scientist. Changes of the set parameters must be reliable, repeatable and fast.All measurement data must be reliable.

The first key factor determining the quality and credibility of research on the extrusion process is the control and reliable measurement of temperature in each zone of the extruder.

The following requirements must be met in total:

The cylinder of a research extruder is divided along the longitudinal axis, often with multiple ports for side feeders and ports in the top of the cylinder, e.g. for dispensing liquids or gases.

The heaters are arranged in such a way that the heat is evenly distributed in each heating and cooling zone.

Temperature sensors are positioned to provide reliable measurement and limit thermal interference from heaters operating at a higher temperature than the plasticizing system.

To avoid uncontrolled temperature rises, each zone of the cylinder is equipped with an efficient and fast cooling system that works in conjunction with the heating system.

The whole is controlled by a precise multi-zone temperature controller. The control system has the ability to calibrate and shape the heating and cooling characteristics of the plasticizing system by the researcher.

The second important factor is the technical parameters and the ability to adapt the device to research on various materials.

The basic technical parameters are:

Maximum torque per worm, maximum revolutions, drive motor power and maximum operating temperature.

The technical parameters of twin-screw extruders enable operation with virtually all available materials, provided that the material from which the screw and cylinder is made allows it.

We designed cylinders with exchangeable inserts constituting the working surface of the cylinder. In practice, this means that we can adapt the extruder to work with other materials in a short time, moreover, exchangeable inserts allow for quick and relatively cheap regeneration of the plasticizing system. In principle, inserts can be made of any material and technology, which is suitable for the purpose. A set of augers is easy to replace with another. Virtually all materials can be researched, including the medical, pharmaceutical and food industries.

The Vertex II geared extruder replaces two extruders, extending your research capabilities.

Our extruders are equipped with torque dividing gears that can work as co-rotating and counter-rotating, the change of the direction of rotation is made automatically from the operator's panel This unique feature allows us to test such materials in full scope Zamak Mercator research extruders can be equipped with a precise strain gauge measurement force acting on the screws lengthwise, this mechanism further extends the possibilities of conducting research.

You can get reliable scale-up, reduced time-to-market Our twin-screw extruders offer flexible configurations from small batches to pilot scale or low-volume production and are ideal for research and development in the polymer, pharmaceutical, biology and nanotechnology sectorsPharmaceutical manufacturers need precise and reliable twin-screw extruders you can rely on to create new material blendsOur instruments meet a wide range of process requirements, even with the most challenging formulations.