Pelletization – An Effective Multiple Unit Drug Delivery System

Oral modified drug delivery systems can be classified into two broad groups: Single-unit dosage forms & Multiple-unit dosage forms. Multiple-unit dosage forms (MUDFs), such as granules, pellets, or mini tablets.
The concept of MUDFs was initially introduced in 1950s. The production of MUDFs is a common strategy to control the release of drug as shown by the reproducibility of the release profiles when compared to the ones obtained with SUDFs. The development of mini matrices is a promising area in pharmaceutical research concerned with a high control over the release rate of the drug combined with a high flexibility on the adjustment of both the dose and the release of drugs and has attracted some attention in the 1990s. Like other MUDFs, several mini tablets can either be filled in to hard capsules or compacted in to bigger tablets. Then after disintegration, they release these sub-units as multiple dosage forms. There has been increasing interest in the development of MUDF’S incorporated into tablets instead of hard gelatin capsules in order to overcome the higher production costs of capsules. In contrast to Monolithic dosage forms multiple unit dosage forms offer several advantages.
Pellets
Pellet has been used to describe a variety of systematically produced, geometrically defined agglomerate obtained from diverse starting materials utilizing different processing conditions. They contain multiples of free-flowing, spherical or semi-spherical solid units which are smaller in size (0.5 mm to 1.5 mm), and are intended mostly for oral administration. The small sterile masses which are obtained from the compression of implants or sterile cylinders are termed as pellets in pharmacy.
Regardless of which manufacturing process is used, pellets have to meet the following requirements:
 Spherical shape and smooth surface is considered as desired characteristics for uniform film coating.
 The particle size of pellets should be in range of 600-1000μm.
 The quantity of the active ingredient in pellets should be maximum in order to maintain size of pellet.
For the past two decades, pellets made their use promising due to some ideal characteristics. Due to free-flowing character of pellets they are packed easily without any difficulties and hence flexibility in design and development of a uniform solid dosage form with uniform weight of capsules and tablets. The spherical shape and a low surface area-to-volume ratio of pellets make for a uniform film coating. Two or more drugs can be formulated in a single dosage form, chemically compatible or incompatible, at the same sites or different sites in the gastrointestinal tract. Different release rates of the same drug can be supplied in a single dosage form.
Multiple-unit dosage forms show a number of advantages over the single-unit dosage systems like suspensions, capsules or disintegrating tablets. With pellets, the mentioned goals can be obtained through the application of coating materials (mainly different polymers), providing the desired function, or through the formulation of matrix pellets to provide the desired effect.
Therapeutic Advantages of Multiple Units over Single Units
When taken orally, multiple unit dosage forms
 Disperse freely in the gastro intestinal tract.
 Maximize drug absorption, reduce peak plasma fluctuations, minimize local irritation of the mucosa by certain irritant drugs and minimize potential side effects without appreciably lowering drug bioavailability.
 Offer reduced variation in gastric emptying rate and transit time which is less dependent on the state of nutrition.
 Provides less risk of dose dumping.
 Reduces localized concentration of irritative drugs.
 Improves safety and efficacy of a drug.
 Reduce inter and intra patient variability.
 More suitable for fabrication of formulations with acid-sensitive drugs.
Desirable Properties of Pellets
Uncoated pellets
 Uniform spherical shape and smooth surface
 Optimum size, between 600 and 1000 μm
 Improved flow characteristics
 High physical strength and integrity
 Good hardness and low friability
 High bulk density
 Ease and superior properties for coating
 Reproducible packing of beds and columns
Coated pellets
 Maintain all of the above properties
 Contain as much as possible of the active ingredient to keep the size of the final dosage form within reasonable limits
 Have desired drug release characteristics
Advantages of Pellets
 The smooth surface and the uniform size of the pellets allow uniform coating not only for each pellet but also from batch to batch. Coating of pellets can be done with different drugs to enable a controlled release rate.
 In case of immediate release products, larger surface area of pellets enables better distribution.
 Chemically incompatible products can be formed into pellets and delivered in a single dose by encapsulating them.
 The beads or granules of different thickness of coatings are blended in the desired proportions to give the desired effect.
 The thickness of the coat on the pellets dictates the rate at which the drug or contents are released from the coated particles.
 By selecting the proper formulation, processing conditions and processing equipment, it is possible to attain smooth surfaced and uniform pellets.
 Improved appearance of the product and the core is pharmaceutically elegant.
 They offer high degree of flexibility in the design and development of oral dosage form like suspension, tablet and capsule.
 Recently, coated pellets are compressed to rapidly disintegrating tablets. For this purpose small pellets with the mean diameters below 0.5 mm are most suitable. Such pellets can be produced by direct pelletization methods.
Disadvantages of Pellets
 The manufacturing of multiple unit dosage forms is more complicated and more expensive.
 The filling into gelatin capsules is difficult to accomplish, especially in the case where different subunits are involved.
Pelletization
Pelletization is a novel drug delivery system; a technique which converts fine powder particles into pellets. It represents an efficient pathway in the scope for different oral immediate or controlled delivery systems. Because of its simple design, high efficiency of producing spherical pellets and fast processing, pelletization has found a special position in pharmaceutical industry and especially in case of production of multi-particulate oral controlled release dosage forms as compared to granulation.
Pelletization technique produces more spherical pellets and offers more advantages than granulation process. In addition, hot-melt extrusion method has provided a new, wider platform to produce spherical pellets of drugs which are not stable or have compatibility problems in presence of solvents.