The fine grinding done most often by pharmaceutical manufacturers tends to fall into just a few categories. The industry's fine grinding machines are proven to be the most effective for their processing needs. Not only must pharmaceutical manufacturing equipment ensure that medications obtain the desired fineness, particle size, and surface area during processing, but these fine grinding machines must also keep chemical and physical alterations to a minimum.
Additionally, such pharmaceutical equipment must be built to enable easy cleaning and reduce the risk of contamination, particularly if the machinery is meant to process multiple products. Upfront costs and return on investment (ROI) also present a factor, making decisions about which grinding machinery to include in a pharmaceutical processing system even more complex. Understanding the role these fine grinding machines play in the processing of medicines is important for anyone involved in the pharmaceutical and other related industries.
Fine Grinding Machines for the Pharmaceutical Industry
Studies examined various aspects of the materials used to make medications as far back as 1990. For the active ingredients within pharmaceutical medicines to be fully effective, their biochemical properties, crystallinity, porosity, and particle size needed to be considered. Researchers found drug efficacy differed depending on how it was processed. Various processing methods were found to produce different types of particles that would make drugs more or less effective.
Studies on drug efficacy indicated that smaller-sized particles allowed drugs to dissolve more readily in medicinal solutions, as these finer particles had proportionally more surface area. The better solubility of particles with greater proportional surface area is directly related to their absorption by the human body. However, fine particles can agglomerate to create a barrier that hinders dissolution and absorption. For this reason, it’s imperative in the production of pharmaceuticals that particle size is optimized rather than simply reduced.
Fine grinding machines are used by the pharmaceutical industry in the follow ways:
- As certain pharmaceutical materials are heat-sensitive, fine grinding machines that produce less heat or operate at low temperatures are used to prevent certain ingredients from degrading.
- Specific fine grinding machines are used for particular applications, such as producing homogenous granules or formulations at the nanoparticle level.
- For active ingredients with poor solubility in water, processes that micronize particles are necessary to increase surface area to ensure they’re properly absorbed within the body.
- To augment bioavailability, consistency, and dissolution within drug formulas through particle size reduction.
- Uniformly blend ingredients so that they’re equally distributed within a mixture, which ensures drugs will be reliably potent and effective.
The rate at which drugs are absorbed into the body is the basis of bioavailability, which relates to the proportion of an active ingredient that can enter the circulatory system. The more bioavailable a drug, the smaller the dose needed to be effective. Fine grinding machines are imperative for this process, as well as milling and micronizing powders to create micro-sized and nanosized particles that can be processed into powders for capsules and pills and even dissolved into emulsions.
Importance of Particle Size in Pharmaceutical Manufacturing
How a drug is processed affects the dosage needed to produce the desired effects, with particle size, shape, and distribution all playing important roles. Regardless of the type of medication, a pharmaceutical drug’s particles must be small enough for the body to absorb the active ingredients. Since smaller particles feature larger proportional surface areas, they help active ingredients more readily adhere to cell membranes. These smaller particles, with their larger proportional surface area, are also more soluble, reducing biological barriers and enhancing absorption.
As with any material, particles reduced by fine grinding machines can differ markedly in shape. While spheroid-shaped particles are measured using their diameter, irregular or ovoid-shaped particles often require measurements based on width and length. As already noted, accurate particle size determination helps ensure the efficacy of pharmaceutical products. It’s for this reason that particle size distribution also requires careful evaluation. To determine whether particles are correctly sized, pharmaceutical manufacturers will usually use various types of measurement, including dynamic image analysis, dynamic light scattering, laser diffraction, or sieve analysis.
Importance of Particle Size Distribution in Pharmaceuticals
Particle size distribution simply refers to the amount of variation in particle size in a material sample. Narrower particle size distribution ranges mean more particles within a pharmaceutical formulation will meet specifications. The more particles that fall closer to the ideal size range, the more bioavailable the medication. To measure this, pharmaceutical manufacturers use something referred to as “D-values” to calculate how tight this distribution is.
“D-values” calculate the volume of particle size distribution as follows:
- D90: This value relates to the 90 percent of particles smaller than the target particle size within the distribution.
- D50: This value relates to the median particle size, with half of the particles sized above a certain size and half falling below it.
- D10: This value relates to the 10 percent of particles smaller than the target particle size within the distribution.
The more closely related these measurements are, the narrower the distribution curve. Tighter distributions tend to be best, indicating a more uniform distribution, though optimal distributions can vary depending on the pharmaceutical medication. Particle size distribution may also affect the surface area and porosity, directly affecting the product’s bioavailability, effectiveness, manufacturability, performance, and shelf life. Additionally, particles that don’t meet specifications can hamper production by limiting flowability, lowering throughputs, and decreasing a manufacturer’s profitability. Because of this, fine grinding machines for the pharmaceutical industry need to ensure that particle size distribution is as accurate as possible.
How Fine Grinding Machines Are Used in Pharmaceutical Manufacturing
Much of the theory behind the operation of fine grinding machines comes from the mineral processing sector, where size reduction equipment was first used to maximize production while optimizing energy efficiency. Yet size reduction methods used by pharmaceutical manufacturers tend to correspond more appropriately to the animal feed and food processing industries, where bioavailability is also important. When it comes to fine grinding, machines in the pharmaceutical industry tend to use only certain types of fine grinding techniques.
The main options for fine grinding include:
- Cone milling: Cone mills use both shear and compressive strain to simultaneously pulverize and crush materials while not producing much heat or dust; this type of high-throughput milling produces uniform particles while also customizing particle size and shape of particles as well as producing tight particle size distributions.
- Cryogenic grinding: Certain pharmaceuticals require equipment that can work with heat-sensitive materials at cryogenic temperatures to keep ingredients from degrading; used when it’s impractical for traditional dry or wet fine grinding, machines break down material made brittle by the extremely low temperatures.
- Micronization: This method normally refers to reducing particle diameters down to the micrometer or even nanometer range, which can be achieved by certain types of hammer mills, jet mills and other fine grinding machines; producing little to no heat and minimizing contamination, micronization is only used for production of specific types of pharmaceuticals.
- Pulverization: Including a broad range of mill types that include impact and grinding mills, this milling method is widely used within the pharmaceutical industry for high-capacity fine grinding; machines like these feature generally smaller footprints so tend to work well for smaller production facilities.
With particle size reduction, the best grinding techniques depend on the fineness or surface needed. These methods must break down ingredients without causing any chemical or physical changes, which could reduce the efficacy of the medication. As noted earlier, fine grinding machines used for multiple products should be especially easy to clean to keep each product free from contamination.
Prater Fine Grinding Machines
Prater Industries makes fine grinding machines that use high-speed impact to break down raw materials meter-fed into the mill’s center. Once inside the grinding chamber, rotor blades impact the processed material, creating centrifugal acceleration that causes additional shear and impact as the material strikes the screens and the stationary jaw face. Once ingredients strike these immobile surfaces, they decelerate and rebound back into the path of the rotor blade. Once properly sized, material is pulled through the screen’s apertures, continuing to the next processing stage.
The two types of fine grinding machines Prater makes are:
- Prater M-Series Fine Grinder: The extremely efficient design of Prater’s M-series fine grinding machines can grind free-flowing product to a fineness of 400 mesh (37 microns), while also producing incredibly tight particle size distributions.
- Prater 10-Bar Fine Grinder: Certain pharmaceutical ingredients can be both flammable and explosive. Prater’s 10-bar fine grinding machine may be more appropriate for certain applications. It’s designed to resist shock from explosions up to 10 bar (145 psi) and handle heat-sensitive materials.
To learn more about Prater’s fine grinding machines and other equipment used for pharmaceutical manufacturing, contact the material handling specialists at Prater today.
