A Capsule History
YOU MAY AT SOME TIME, WHEN CLEARING A JAM IN A PHOTO copier or a laser printer, have gotten some of the toner powder on your hands or, even worse, your shirt. It’s natural at this point to expect a major cleanup, but the anticipated dire result is avoided when you find that the black smudge simply brushes off. This property of toners is more than just a boon to clumsy office workers; in fact it lies at the very heart of the process by which copiers and printers produce documents. Each toner particle consists of a speck of dye covered with a special fusible coating, together forming a microcapsule. The properties of microcapsules are central to many other technologies as well, including carbonless carbon paper, timedrelease drugs and agricultural products, and even perfume advertisements.
Microencapsulation is used to keep a substance separate from the outside world until the time is right to release it. The encapsulated substance may deteriorate with exposure to air, for example, or disperse too quickly, or be harmful to humans, or have an unpleasant taste or smell. The core can be released when the capsule is ruptured physically (as in a scratch-andsniff strip) or chemically (as in the digestive system), or the capsule walls may remain intact while the substance inside diffuses through them (as in timed-release drugs). Microencapsulation also provides a way to handle a liquid in the form of a powder. In some products the coating’s sole function is to contain the core; in others, such as toner, the coating forms part of the application.
One publication suggests, with perhaps a bit of hyperbole, that “the concept of controlled release or the regulated release of an active ingredient probably appealed to primitive man.” Unfortunately, the technology necessary to gratify this basic human urge was not available until the twentieth century. Starting in the late 1920s, companies experimented with microencapsulation techniques in a variety of products. For example, in 1942 James A. Raynolds of the Atlantic Coast Fisheries Company patented a process for microencapsulating fish oil or vitamins. It involved suspending droplets in a gelatin solution and then pushing them through tiny holes into an inert solvent. The solvent was drained away, leaving gelatin-coated microcapsules. This and most other early processes proved to be impractical on more than a small scale.
The modern science of microencapsulation, like so many areas of research, can be traced to a serendipitous observation. In 1902 the chemists Wolfgang Pauli (father of the physicist of the same name) and Peter Rona of Vienna added neutral salts to a lukewarm gelatin solution and noticed that the solution spontaneously separated into two layers. Investigation showed that one of the layers contained most of the gelatin and the other most of the salt, and that vigorous stirring or shaking caused the two layers to form a uniform emulsion.
In the 1920s H. G. Bungenberg de Jong of Leiden University in the Netherlands began investigating this phenomenon, which he named coacervation (after acervus , the Latin for “heap” or “aggregation”). In 1931 he pointed out the possibility of using coacervation to make microcapsules for drugs. While the concept is fairly straightforward, getting the conditions exactly right is exceedingly difficult, and since Bungenberg de Jong’s main interest was in theoretical and analytical chemistry, he did not pursue his suggestion. Other researchers, however, picked up on the idea.
In the late 1930s Barry Green began investigating coacervation at the National Cash Register Company, in Dayton, Ohio. (NCR’s early role in this technology explains why the Dayton area still has a cluster of microencapsulation-related businesses.) The company saw a potential application in office products. A purchase order, for example, could need to be communicated to several departments involved in processing it. Before xerography, a clerk might use multipage forms interleaved with carbon paper. These packets were inherently messy, since the carbon-paper pages had to be pulled out and discarded, and reading the last copy in the stack was often a challenge. If microencapsulated ink could replace the carbon paper, a much neater, more compact, and less wasteful product would result.
By 1942 Green had developed a working method of microencapsulating ink and a prototype of carbonless carbon paper. Over the next dozen years he painstakingly refined his methods, scaled them up to production levels, and worked with Thomas Busch of Appleton Coated Paper, in Appleton, Wisconsin, on the tricky process of applying the microcapsules to paper in a thin, flexible layer. In June 1953 Green and Lowell Schleicher applied for a patent on their microencapsulation technique (it was granted four years later), and in March 1954 the company began selling its “NCR paper,” with NCR here standing for “no carbon required.”
The product had three layers: the paper, a film of acidsensitive dye packaged in microcapsules, and a layer of acidic clay to develop the dye from transparent to dark blue or black. Pressure from writing broke the microcapsules of dye on the bottom of each sheet (except the last one), and when the dye was released, it reacted with the acidic layer on top of the next sheet. Considerable effort went into designing capsule walls that were sturdy enough to withstand processing but would rupture under the pressure of a pencil.
To harden the cell walls, Green made use of another property of gelatins. Gelatin is a protein that consists of long chains of chemically linked amino acids. When gelatin is treated with a reactive chemical such as formaldehyde, glutaraldehyde, or tannic acid, new chemical links form between the chains. The result is a three-dimensional network called a cross-linked gelatin. Cross-linked gelatin is harder and less soluble than regular gelatin, yielding a tougher and more durable microcapsule. Cross-linking complicates the production process, though, because when a solution of cross-linked gelatin separates during coacervation, the gelatin-rich layer will no longer stay as an emulsion. Adding gum arabic to the mixture solves this problem.
To make the microcapsules, dye was dissolved in a highboiling organic solvent and the resulting solution was stirred at high speed in the presence of gelatin and gum arabic in water. As a result of the vigorous agitation, the oily dye solution formed a dispersion of very fine droplets in the water layer. Changing the acidity of the water solution made the gelatin and gum become less soluble and caused them to precipitate in the form of a coating on the droplets. Formaldehyde hardened the coatings, and the resulting microcapsules could be separated from the mixture with a sieve and dried.
Until the early 1970s the usual solvent for the dye consisted of polychlorinated biphenyls, the notorious PCBs that caused much harmful environmental pollution. These accounted for the characteristic odor of carbonless carbon paper. PCBs have now been replaced by more environmentally acceptable solvents, though NCR is still paying to clean up PCBs from its old industrial sites.
TODAY THOUSANDS OF TONS OF MICROCAPSULES ARE MANU factured yearly for carbonless carbon paper. Many improvements in both the product and the production processes have been made over the half-century since it was introduced. For instance, the outer coat of the capsule now often consists of a custom-designed synthetic polymer instead of cross-linked gelatin. Capsule sizes range from 1 to 20 microns (a micron is a thousandth of a millimeter), with most between 5 and 10. Their minute size means that each square inch of paper may hold 10 million or more microcapsules.
Another early research effort in microencapsulation, in a different industry, came at the Atlantic Gelatin division of General Foods. In the early 1950s American Chicle asked the company for help in making the mint flavor in its chewing gum last longer. At the time, confectioners simply added a mix of mint oils to the gum base, and almost all the flavor would get swallowed within a minute.
Frank Kramer of Atlantic Gelatin had the idea of enclosing tiny droplets of the powerful mint oils in gelatin shells. That way the flavor would be released more slowly. He hired Daniel Casper, a recent chemical-engineering graduate, to investigate the process. Casper, now a consultant at World Food Tech Services, in Maiden, Massachusetts, recalls his early trepidation: “Quite frankly, I did not comprehend what all the preliminaries had to do with the final product, but I was solely assigned to this project and given to understand that failure would not bode well for job longevity.” With luck and good instincts, he came up with a workable process. American Chicle was delighted with the result and used the microencapsulated flavors in a new product, Certs mints, which were introduced in 1956.
Since the process was still quite new, Kramer and Casper had to invent or improvise apparatus that is now standard equipment. After being unable for some time to measure the size of the particles, they finally managed to examine a sample using a microscope and etched-glass plates. They were pleased to find the size distribution very close to what they had wanted.
Another problem cropped up when Casper tried to grind production quantities of gelatin, which came in sheets, to a fine powder. “It gummed up the grinder, and I burned out two motors,” he recalls. “The first fix was to grind carbon dioxide ice and manually add it to the gelatin during grinding. This had to be ruled out because the ice was not very clean and gumming still occurred. With the help of our carbon dioxide supplier, we installed a manifold that allowed a measured amount of it to be added to the gelatin just at the grinding point.”
Kramer and Casper expanded into drug encapsulation for Warner-Lambert, Schering, and other companies. Casper continued his work in encapsulation of flavors and colors for food products, with the occasional mishap: “Once a 6,000-pound lot was lost and nothing was heard until a thunderous complaint from Schering that many of their capsules were mintflavored.” Atlantic Gelatin researchers figured out how to duplicate NCR’s carbonless carbon paper and did work for the U.S. Mint, the U.S. Department of Defense, and other agencies before General Foods management decided to eliminate nonfood research. “The only use of this technique in the company,” Casper recalls wistfully, “was to produce an exquisite Frenchmint chocolate pudding, which an ad agency judged too expensive to market under the Jell-O label.”
Meanwhile, within a few years of the introduction of carbonless carbon paper, microencapsulation made possible another technology that forever altered office procedures. In the late 1940s an inventor named Chester Carlson enlisted the aid of the Haloid Company, of Rochester, New York, to help commercialize his new copying process, known as xerography. The development work culminated in 1959 with the introduction of the revolutionary Xerox 914. Although it was bulky and needed frequent attention, this machine made it possible for the first time to produce faithful copies of virtually anything without resorting to messy wet processes.
The key step in xerography consists of projecting an image of the object to be copied onto a charged, photosensitive plate. The light causes the charge to dissipate from the portions of the plate that are illuminated. The plate is then brushed with an oppositely charged, pigment-containing powder, the toner. The powder particles adhere to the areas that still retain charge but not to the discharged areas, thus re-creating the image. The toner is then transferred electrostatically to a sheet of paper. Brief exposure of the paper to a high temperature fuses the toner to the paper, providing a permanent copy of the original document.
The demands of the xerographic process ruled out the use of traditional printing inks, since they could not have been selectively distributed to the electrostatic image. It was also important that the image-forming pigment leave no marks until it was ready to be permanently recorded. Carlson used lycopodium powder, a natural plant-spore product, in his early research. The first xerography machine (which was unsuccessful), introduced in 1949, used a mixture of powdered iron, ammonium chloride, and a plastic dust. But Haloid researchers needed a better toner, one that would yield a sharper image and would melt and bond with the paper more easily. Microencapsulation fitted the requirements very nicely.
IN PHOTOCOPIER TONER, THE CAPSULE COATING ACTS AS a dry, charge-bearing vehicle for the pigment and at the same time forms a protective coating around it. The coating consists of a specially designed synthetic resin selected for its melting point and dielectric properties. It may contain additional ingredients such as lubricants to help it flow freely. The pigment for black toners consists of solid carbon black.
Advances in computing made necessary the next major application. As computers became more powerful and increasingly ubiquitous, the need arose for a faster and more reliable way to create hard copies than the mechanical printers of the 1960s and 1970s. Haloid had long since changed its name to Xerox, and researchers at the company’s Palo Alto Research Center (Xerox PARC) recognized that the photosensitive plate at the heart of the xerographic process could also accept electronic data almost instantaneously.
This was done by sweeping a charged, photosensitive drum with a laser beam that turned on and off at very high speed to reflect the digital data being output by a computer. The procedure resulted in a pattern of fine, electrically discharged dots. The drum was then exposed to the same microencapsulated toner as that used for copiers, and the toner was fused to the paper with heat. The first commercial laser printer, the Xerox 9700, was introduced in 1977; desktop machines arrived in 1984. An important step in making them easy to use came when the toner was packaged with the photosensitive drum in a replaceable cartridge.
Since the 1920s pharmaceutical companies have worked on microencapsulating drugs to mask unpleasant tastes and for other reasons. If a drug cannot stand up to the highly acidic conditions of the stomach, a microcapsule coating can resist acid but dissolve in the nearly neutral environment of the small intestine, which is where most drugs are absorbed into the blood-stream. If they do not dissolve immediately, the rate at which the drug leaches out of the microcapsules can be controlled by the choice of capsule wall material. It is often possible in this way to provide a steady outflow of a drug for as long as 24 hours.
The author of this article was once involved in microencapsulation research for pharmaceuticals. My company’s vice president for marketing regularly bemoaned the fact that the research division failed to provide him with innovative products. One of our existing lines consisted of potassium supplements for patients who took diuretic drugs to control their blood pressure. Since potassium chloride has a severe bitter taste, quite unlike its close cousin sodium chloride (table salt), one company in the early 1960s came up with a coated tablet that bypassed the taste buds. This product unexpectedly injured a number of patients by irritating tissues in the gastrointestinal tract with localized high potassium concentrations. The Food and Drug Administration then decreed that future potassium supplements had to be liquid solutions or forms that would release the salt slowly.
Our company had several liquid forms and one antiquated slow release. By the mid-1980s these were under intense competition from newly introduced formulations that consisted of conventional capsules filled with microencapsulated potassium salt. Developing a similar capsule was out of the question because the existing products were surrounded by a veritable hedge of patents. Instead we produced a candylike chewable wafer that contained microencapsulated potassium chloride along with a good slug of citric acid to stimulate the flow of saliva and wash the microcapsules into the stomach.
When given a sample of the product, the vice president showed initial interest. He even allowed that it tasted pretty good. Then he asked, “Who else has something like this?” When told that no one did, he replied, “That worries me,” and that was the end of the project.
Microcapsule technology has applications in agriculture as well. A number of pesticides are now available in encapsulated form to control the release rate. A further benefit is that some pesticides, such as the corn-borer insecticide fonofos, are highly toxic to humans. Because of this, application of the normally formulated compound requires stringent protective measures. Microencapsulation provides a barrier between the operator and the pesticide and decreases the applicator’s exposure.
Another important application is in liquid crystals. In the early 1970s NCR researchers succeeded in microencapsulating thermochromic (temperaturesensitive) liquid crystals. When the microcapsules are dissolved in a solvent and sprayed onto a surface, the liquid crystals they contain will indicate the temperature of the surface by changing color. This is useful for many diagnostic procedures in engineering and medicine as well as in thermometers. Without microencapsulation, the crystals would deteriorate from contact with the surface and the surrounding air.
In food technology full lines of encapsulated flavors and essences are available. My wife tells me that her favorite packaged lemon pie filling used to include the lemon flavor as a separate gelatin capsule. The most recent package she bought contained only a powder. The flavor in this new version was almost certainly enclosed in micro- capsules. The shells in which these flavors are encapsulated melt at specific temperatures to protect the flavor elements from prolonged exposure to high heat. The same procedure is also used with leavening agents, which are often encapsulated in vegetable shortening to keep them from reacting too early (during storage, for example). Nutritional additives can be microencapsulated too. Examples include L-arginine (an amino acid with a bitter taste) and dietary fiber, which could make a product too viscous if added in naked form.
As demand for microencapsulated products has grown, a variety of new methods have been developed for creating them, some using entirely different principles from coacervation. One of the earliest was invented in the late 1940s. This solventfree method, named the Wurster process after its inventor, Dale Wurster, a pharmacy professor at the University of Wisconsin, is used mainly for pharmaceuticals. It starts by floating a batch of finely ground drug particles in a cylinder in a high-speed stream of air. This arrangement is known as a fluidized bed. The liquid coating material is then introduced as a spray from the opposite direction. Drug particles pick up the coating as they circulate in the airstream, and they are routed to a zone where the coating is dried quickly by solidification or evaporation. Particles can be cycled through this process as many times as necessary to get a coating of the desired thickness.
Spray drying may be the oldest microencapsulation method, dating back at least to 1927. First the core material, usually an oil, is suspended in a solution of some inert substance, such as starch. Droplets of the suspension are sprayed into a heated chamber, where they dry rapidly through evaporation. Spray drying can yield irregular aggregates with multiple nuclei and a lower ratio of core to coating than the Wurster process or other methods; it can also leave patches of free core material on the surface. For applications where these things are not a problem, however, spray drying is fast, easy, and reliable. Another simple microencapsulation method involves suspending the core material in a liquid solution of resin. Evaporation of the solvent leaves a coat of resin on the particles.
One of the more unusual techniques for preparing microcapsules with liquid centers is coextrusion. The main part of the apparatus is a pair of very fine concentric nozzles. The solution to be coated is extruded at high pressure from the central nozzle while the shell material is pumped through the outer nozzle. Proper adjustment of flow rates will cause material from the central nozzle to break up into fine droplets. When the rate of flow is right, shell material covers the droplet as it departs the nozzle. This outer coat then solidifies into a shell. The Southwest Research Institute, in San Antonio, Texas, which started its work in microencapsulation in the 1940s, is a leader in researching this technique.
Other substances that have been microencapsulated include adhesives, vaccines, enzymes, fish food, and even living cells. While a full compilation of the uses of microencapsulation is beyond the scope of this article, the reader will almost certainly have come across one very common, and to some annoying, application. Microencapsulation makes possible the fragrance ads that are inserted in magazines. These consist of small capsules filled with a solution of the perfume being sold. The technology was developed in the 1950s, and by 1972 it had spread to the music world, with a scratch-and-sniff sticker of raspberry aroma attached to the cover of the Raspberries’ debut album.
The capsule coat was meant to be rugged enough to contain the scent until it was ruptured by a scratch. Often, however, it was released prematurely. Fragrance ads became their most intrusive in the 1980s, causing consumers to recoil (sometimes because of allergies) and some publications to institute strict standards for “scent containment.” In response, the industry developed peel-apart tabs and other more reliable delivery methods. While these solutions are still not perfect, magazines today are a lot less odorous than they were as recently as a decade ago.
In an odd twist, market researchers have found that around half the buyers who encounter scent strips like them so much that they keep them for days, rubbing them on their skin until all the scent is gone. This finding has led to the development of “dry perfume,” which contains no alcohol and can be refreshed when needed with a simple rub. It’s one more example of the unexpected paths that a versatile technology like microencapsulation can take.