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Microcapsules >>
A brief history of microencapsulation >>
Why microencapsulation >>
Core and coating >>



The majority of micronutrients and other pharmacologically active substances are extremely sensitive to the surrounding environment. Oxygen, humidity, microelements, peroxides and so on are among the many factors that contribute to degradation of these active constituents: so far, the most cost-effective technique to protect the most delicate components of food products for productive livestock is microencapsulation. This technology was already known in the 1930s but it has been thoroughly developed only in the last years and not only for protection of active ingredients from chemical and environmental stress factors. Presently microencapsulation is used in the majority of Drug Delivery Systems (DDS). The diffusion of this technology can be explained with the wide choice of potential applications: hundreds of drugs have been microencapsulated and used for controlled released systems. Last but not least, the studies of the last thirty years on the degradation of some additives and micronutrients in the rumen (due to resident micro-organisms and the peculiar biochemical conditions), have increased the use of this technique in the bovine and ovine sector with the aim to “by-pass” rumen of sensitive ingredients.

Microcapsules
The most “classical” form of microcapsules (for example those of the products obtained with simple coacervation) consists in a small sphere surrounded by an uniform wall. The material within the capsule may be called nucleus, core, internal phase, active substance and so on while the wall is also called covering, external phase, coating, membrane.
There are several types of microcapsules depending on the type of technology used to obtain them, and they are described as coated granules, coated pellets, microspherules and so on .(Fig. 1)
The capsules have extremely variable sizes ranging from a few microns to some millimetres (the size of the majority of products used in the livestock feeding and veterinary therapy ranges from 400 μm to 1 mm).
Capsules smaller than 1 micron are called nanocapsules since their size is measured in nanometres.
To be more precise, when there is no true distinction between core and coating the microcapsules are actually called microparticles or microgranules (Fig. 2). The name “microencapsulates” can refer actually, to all products with these features.
The different types of microencapsulated products differ between each other in size, materials used for coating, technological procedures used to obtain them, thickness of capsule and controlled delivery properties.

A brief history of microencapsulation
The first studies on microencapsulation and on its possible applications in pharmaceuticals industries date back to 1931 (Bundeburg, de Jong and Kaas).
From 1931 to 1940, Green and his colleagues of NCR developed a process of microencapsulation with gelatin (coacervation).
Since then many other coating materials and other encapsulation processes have been developed by pharmaceutical industries.
During the last 30 years there have been many registration of patents of encapsulation processes to be used for active principles - medicinal or not - like sulphonamides, antibiotics, vitamins and so on.
Besides pharma, there are several other industry sectors that use this technique, from cosmetics to food industry, to producers of photographic materials, computers, fertilizers and pesticides.

Why microencapsulation
There are many different reasons for encapsulating an active principle or a chemical substance.
The different reasons that may lead to encapsulate a substance, especially in the veterinary and feed sectors, are:

1. Protection from chemical-physical agents like oxygen, humidity, acid pH, light and heat (vitamins, pigments, micro-organisms, penicillins).
2. Conversion from liquid to solid state of products to be inserted in feed (cod-liver oil, vitamin A, vitamin E, vitamin D3);
3. Reduction of potential gastric damages (acetylsalicylic acid and other non-steroid anti-inflammatory drugs);
4. Reduction of corrosiveness (malic acid, ortophosphoric acid, some essential oils);
5. Taste-masking (propylene glycol, fish oil, antibiotics, anionic salts);
6. Physical separation of the active principles from incompatible substances (some vitamins with trace elements and choline, strong acids with vitamins and micro-organisms, antibiotics with micro-organisms);
7. Controlled release in the gastrointestinal tract (acidifiers, micro-organisms, some antibiotics);
8. Rumen bypass (choline, methionine, lysine, vitamin A, vitamin C, folic acid);
9. Removal of powders and electro-static charges (antibiotics, sulphonamide, olaquindox, carbadox, nicarbazine).

An especially important feature is the microcapsules capacity to delay the delivery of the drug and increase its capacity to interact with the body. The active principle of a drug is encapsulated within a particle that can be as small as one μm. A common tablet can contain millions of microcapsules: each one of them can deliver the drug in the body. Compared to other pharmaceutical product types in which the active principle is simply agglomerated, the microcapsules have a broader contact surface (which increases its interaction with the factors involved in the delivery). The “theoretical” kinetics of release is influenced by the resultant between the physical-chemical features of the ingredient and the choice of coating. Coating control allows microencapsulation to become a true release device. Microcapsules can be built to release drugs gradually or to reach the preferential area of drug absorption. The release processes for microcapsules include: breaking due to heat, solvation, coating emulsion or it enzymatic digestion, diffusion (due to shearing stress produced by the coating’s sliding on the core) or by mechanical stress (pressure).


Fig. 1 Types of microcapsules


Fig. 2. Microcapsules or microspheres.

Hundreds of different substances are used to form the coating of a microencapsulation (see picture). In case the product is to be used for human or animal foods or for pharmaceutical products, only the additives included in allowed additives lists can be used.

Core and coating

The core, that is the substance that needs to be microencapsulated, may belong to the most diverse categories of chemical substances, it can be either liquid or solid, acid or basic, in fine powder or coarse crystals.
These different features require the microencapsulation process and coating choice to depend on the reason for which each active principle is microencapsulated.
The most common substances used for microcapsule films include:

agar
polypropylene glycols
polystyrene
Acacia
hydrogenated fats
polyvinyl alcohol
mono-and diglycerides
polyamides
acrylic polymers

polyvinylpyrrolidone
cellulose and derivatives
gelatines
stearic acid
starch
stearyl, myristyl alcohols
paraffins
waxes
polyesters

In many cases coatings are made using mixes of these substances in order to achieve more complex results (Rumen bypass + resistance to mixing).

Most common technological procedures for microencapsulation
The technologies used to produce microcapsules are different and varied and each technique has undergone several changes and improvements to adapt the standard process to the most diverse objectives. Therefore microencapsulation is not a “fixed” technology but it changes and evolves each day thanks to countless companies and inventors working in this field.

However, the most common processes used to build microcapsules belong to three main groups:

1) CHEMICAL MICROENCAPSULATION
a – simple coacervation in aqueous medium
b – complex coacervation in aqueous medium
c – coacervation in non-aqueous medium

2) MICROENCAPSULATION WITH PHYSICAL METHODS
a – pan-coating
b – coating on fluid bed
c – Wurster procedure (air-suspended coating)

3) MICROENCAPSULATION WITH MATRIX SOLIDIFICATION
a – spray drying
b – spray cooling
c – spray embedding
d – spray polycondensation

Methods 1 and 2 produce “classic” microencapsulates; some of the methods of the third group have been successfully used in the last twenty years in the zoo-technical industry in which they represent a valid technology in terms of costs and efficacy.


Effects of a mixture of organic acids (Lactiplus) on productive performances and health status of weaning piglets
V. Bontempo et al., 2005
Dept. of Veterinary Science and Technology for Food Safety
University of Milan

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