Industry Experts Speak On Blending and Processing
Blending and processing techniques are crucial to turning out a reliable, high-quality, homogenous, shelf-stable, finished product each day. Physical properties including particle size, moisture content, ingredient percentages and bulk density are primary considerations, as are potential ingredient interactions. INSIDER conducted a question and answer session with a variety of companies involved in contract manufacturing to find out how blending and processing techniques ensure product consistency.
How important is blending/processing of ingredients to the efficacy of a finished product?
Ram Chaudhari, Ph.D., senior executive vice president at Schenectady, N.Y.-based Fortitech Inc.: A product must conform to its label claims and certain quality standards such as homogeneity and shelf life. A consistent blending/processing procedure is critical in the prevention of segregation of certain micronutrients and ingredients during processes including manufacturing and shipping and ensures a product delivers what is stated on the label.
Jay Kaufman, chief executive officer of Torrance, Calif.-based Paragon Laboratories: Content uniformity is a critical issue for dietary supplements. In order to have ingredients at their proper potencies, a homogenous mix is required. A homogeneous mix helps assure label claims are being met.
George Simpson, executive advisor (and plant manager emeritus) at Bellingham, Wash.-based Rhema Industries Inc.: Blending/processing is critical in achieving a successful finished product. Binders and lubricants must be evenly distributed in the blend for effective compression and flowability. Active ingredients must be homogenously mixed to pass finished assay tests. Flavors and colors must be evenly mixed to result in consistent taste and appearance throughout the batch. Regardless of whether formulations contain two ingredients or 50 ingredients, blending is critical in achieving a successful finished product.
Robin Koon, vice-president sales & marketing, and Jeff Hensley, production manager, with City of Industry, Calif.-based Best Formulations Inc.: Blending is vital to the efficacy of a finished product. It is the determining factor as to the uniformity of ingredients throughout a batch.
What are important considerations in determining whether liquid-state ingredients and/or blends are better freeze dried, spray dried or tray dried? How does the drying technique impact the efficacy of the ingredient/formula?
Kaufman: Many ingredients are temperature sensitive. Ingredients that are sensitive to heat may be better protected if those ingredients are freeze-dried. Spray drying may be a better alternative for flavors where the dispersion of an ingredient onto a carrier is indicated.
Koon & Hensley: Important factors in determining which drying processes are used include product stability, feasibility and economics.
- Spray drying: Must be a pumpable solution (slurry, emulsion, etc.) that can be atomized. It is applicable for drying heat-sensitive products because the evaporative process keeps products cool. Spray drying is also economical, because it produces a dry powder with uniform particle size, without further processing.
- Freeze drying: Advantages include enhanced stability for products that are subject to degradation caused by heat or oxidation. The cost of equipment and increased time and handling make it expensive and somewhat uneconomical, so it is usually reserved for products that require it for stability reasons.
- Tray drying: Tray drying is not very suitable for liquid-state materials, due to the amount of heat and time that most liquid-state would require to dry to a suitable level. In essence, cooking would occur. It can be used for heat stable products, such as minerals. However, another concern would be mold and bacterial growth in a media that is an incubation setting.
In what situations would ingredients be indicated for microencapsulation during processing, and how does that impact final delivery form options?
Kaufman: Microencapsulation is the process of encapsulating a very small particle in a shell of inert material. Microencapsulation can help protect the ingredient from environmental considerations or interaction with other ingredients. With microencapsulation, it is also possible to create particles of a particular size, which can help with overall homogeneity of a mix.
Simpson: Microencapsulation may be indicated in cases where you need increased stability, taste masking and to facilitate certain production processes. Microencapsulation is especially indicated for ingredients that are used in chewable tablets, drink mixes and nutritional bars. Microencapsulation is widely used in oil-soluble products that need to be converted to powdered form such as lutein, vitamin D, vitamin A, beta-carotene and lycopene.
Koon & Hensley: Microencapsulation is normally indicated for one of three scenarios: 1) to protect the material from either atmospheric conditions or from reactive materials within the matrix that might cause degradation, 2) to mask flavor, 3) for time-released purposes. The impact on the final delivery form is producing a more stable product, a more palatable product or a delayed/sustained dissolution.
When would pre-blending be important in developing a nutritional pre-mix?
Chaudhari: When you have a small amount of nutrients, in microgram quantities, for example, they are prone to getting lost in manufacturing process. Putting those micronutrients into a pre-mix will bulk them up, ensuring homogeneity and even distribution in the final product.
Simpson: Pre-blending is important when you have some materials in large percentages and some in small percentages (for example, vitamin D, which represents a very small input quantity in a multi vitamin blend). Through a process of pre-blending or trituration you can achieve a homogenous mix.
Koon & Hensley: Pre-blending is important when trying to disperse a small percentage of materials uniformly throughout a matrix. At times, it is necessary to make and/or use triturations, which are premanufactured dilutions of ingredients, to be able to obtain reasonable uniformity. An example would be vitamin B12 or biotin ingredients typically added in micrograms to a finished product. In some cases, safety is an issue; many of the trace minerals used in nutritional blends are toxic in relatively small amounts and you must be certain these are properly diluted and dispersed.
Are some types of ingredients and formulas more suited to agglomeration versus dry granulation? How is that determination made?
Chaudhari: It depends on the delivery form of the final product. In the case of a product in powdered form, agglomeration makes the product more soluble, yielding a nice, uniform mixture. Agglomeration increases the surface area of particles, which allows them to be homogeneously dissolved in a medium without sediment. Granulation is a different process altogether. It increases the compactability or binding properties of a nutrient to be dissolved. The two processes yield different properties. For tablets, granulation is very important, whereas agglomeration applies to products such as foods, beverages or powdered supplements.
Kaufman: Granulation/agglomeration is used to change the characteristics of powder that has many fine particles to one with particles of a larger size. Granulation is used for better flowability of a powder.When a powder is granulated, it is possible to better control content uniformity.Granulation can also protect ingredients from environmental factors.
Simpson: It depends on the characteristics of the material and the nature of the finished dosage form. Herbs are notoriously difficult to compress so agglomeration may be indicated to improve compaction during tableting, or to improve their flowability in encapsulation. Also, materials that are agglomerated will go into solution, so agglomeration is popular for ingredients like whey that are used in drink mixes.
Koon & Hensley: Dry granulation is always preferred as it requires less handling. Agglomeration/wet granulation is sometimes necessary to achieve desired particle size, binding characteristics, or to add liquid materials to a solid matrix.
In dealing with hydroscopic ingredients, how do you ensure proper distribution throughout an ingredient blend?
Chaudhari: The addition of excipients or carrierswhich are usually inert ingredientspicks up moisture from the mixture and prevents the mixture from caking or solidifying.
Kaufman: Hydroscopic ingredients can at times benefit from microencapsulation or granulation. These two techniques offer protection to ingredients that are sensitive to heat and moisture.
Simpson: First, make sure that your manufacturing environment is extremely dry by controlling temperature and humidity. You also need a well-designed blending protocol where you mix the hydroscopic ingredient(s) with a moisture-absorbing ingredient or something very dry such as dibasic calcium phosphate. You will benefit from including a glidant as it facilitates subsequent blending.
Koon & Hensley: The proper handling of these materials is important. One needs to keep these materials appropriately dry and away from moisture. This also applies when blending or mixing these materials. In dealing with hydroscopic ingredients, it is sometimes necessary to premix them with dessicants or lubricants to keep them from agglomerating before being dispersed through a matrix.
What are the key equipment requirements for blending and processing?
Chaudhari: Blending and processing necessitates equipment that reduces particle size. Such equipment can include micropulverizers, which ensure uniformity and prevent segregation; and blending machines that ensure homogeneity, including V-blenders, which combine ingredients of different sizes in a cyclonic motion, plough (Littleford) blenders, or delumpers. A key benefit of blending equipment is that it makes homogeneity possible in minutesnot hours.
Kaufman: Large and small dry and wet blenders, mills, screens, drying ovens and, most importantly, well trained and competent personnel.
Simpson: You want equipment that will provide a homogenous blend in an efficient, cost effective amount of time. For optimal homogenous blends you need more than a good blender; you also need milling and screening capabilities, as well as proper containers in which to store the blend after mixing so as not to disrupt its homogeneity.
Koon & Hensley: Key equipment requirements are certainly product and process dependent. An example in the case of blending would be a tablet granulation. One would look for a moderately high-intensity yet low-shear blender with capacity suitable for the majority of products produced. One wants to be able to produce a uniform blend, while minimizing destruction of particle structure. An important characteristic that would be universal with regard to blending equipment is elimination or attention to dead spots. These are areas in which materials can either be trapped or segregated.
What types of processing aids are commonly used, and how important are they to the finished product?
Chaudhari: Processing aids are essential. Processing aids prevent interactions between ingredients and other potential processing problems. For example, a flow agent helps certain ingredients to flow smoothly, producing a uniform distribution.
Kaufman: Years of experience and technical knowledge are required to choose the right ingredients and at the right proportions. One most know the chemical as well as physical properties of each active ingredient in order to choose the right inactive ingredients. Common excipients (inactives) include cellulose, dicalcium phosphate, magnesium stearate, stearic acid and silicon dioxide.
Simpson: Commonly used processing aids include binders, lubricants, glidants, disintegrants and coating solutions (for dry dosage forms). They are frequently essential to the finished product, but not all of them are always needed.
Koon & Hensley: Processing aids are product/process dependent. Commonly used aids in tablet formulations include lubricants, binders, disintegrants, and granulating and bulking agents. Lubricants and binders are used to facilitate processing and improve characteristics such as flowabilility, tablet hardness and friability. Disintegrants are used to accelerate disintegration of tablets. Granulation agents are necessary to ensure good granulation occurs. Bulking agents are used to increase tablet size.
Can processing aids influence bioavailability or negatively impact the nutritional value of a finished good?
Chaudhari: Processing aidsthe last line of defense in causing a product to flow and bind easilydo not normally affect bioavailability because they are in general inert and very stable. They would not usually cause chemical reactions.
Simpson: Processing aids can influence the bioavailability of the finished product and at times it is possible that they could negatively impact the nutritional value.
Koon & Hensley: If not properly used, processing aids can have a negative influence on bioavailability. The improper use of soluble/insoluble materials can inhibit dissolution, and reduce absorption and the availability of nutrients/active ingredients.
For more discussion surrounding topical issues in contract manufacturing, dont miss the upcoming Manufacturing Focus in the Jan. 3, 2005 issue of INSIDER.