Sugar spheres: a versatile excipient for oral pellet medications with modified release kinetics

Sugar spheres are a widely used excipient for sustained-release pellet formulations.1 This paper reviews their development in the last decades, informs about the state of the art and provides the user with the necessary information for further processing. Finally, the article focuses on the possibilities of characterization related to the technological properties of the sugar spheres.
Apr 01, 2006

Pellets are a multiparticle, solid form of medication. The individual pellets are almost spherical with diameters usually between 100 and 2000 μm.

Their history is related to two important development trends in pharmaceutical technology: the hard gelatine capsule as an alternative to tablets, and biopharmacy and its concept of modified release.

The hard gelatine capsule provided a method of oral medication, which made it possible to put powders or granules directly in a patient-friendly form with specific dosage.2 By mixing various components before filling the capsules or with sequential filling of the capsule with these components, it was possible to combine partial quantities that differ in appearance, are incompatible with each other, or have differing release behaviour, in one single dose. Pellets with their almost ideal spherical shape offer optimum mixing and flow behaviour, making them ideal for this application.

At the same time, since the 1950s, biopharmacy has developed concepts for optimum control of active pharmaceutical ingredient (API) release in the gastrointestinal tract, in terms of location and time.3,4 In particular, the sustained release from a single application over a longer period of time (during the day) resulted in the development of mixtures whose individual components were given different quantities of a sustained release coating to ensure that the active substances are released accordingly at different points in time. Pellets with their reproducible, smooth surface were again the solution of choice.

These two developments together resulted in numerous pellet preparations. There were suitable pellet solutions for nearly all requirements, with a rapid increase in the market share of corresponding products. Formulas with pellets are still a modern form of medication, which offers an elegant solution even for new requirements.

Production technology

Figure 1
There are numerous procedures for pelletization, with two fundamentally competing concepts.5 On the one hand, the use of sugar spheres, which are then coated with the active substance, and on the other, direct pelletization of active substance/excipient mixtures. Figure 1 illustrates these two alternatives.

In the first option, sugar spheres (also called neutral pellets, nonpareil seeds, microgranules or sugar beads) are produced, preferably using a layered sugar-coating structure.6 The result is sugar spheres with sufficient mechanical stability for further processing. The ideally rounded sugar spheres classed in closely graduated particle sizes are then coated with the active substance and sustained release additives. The core of the finished pellet contains no active substance itself so that this solution is used for low-dose substances or substances with a high effect/dose relation. But the use of small sugar spheres and corresponding procedures also makes it possible to use this method to produce pellets containing more than 75% active substance.

In the second concept, pelletization already includes the active substance itself. The procedures developed here consist of fluidized bed granulation, rotor granulation, or extrusion followed by spheronization, whereby the initially cylindrical particles are then rounded out in a second step.7–9 The advantage of this procedure is that the whole pellet contains the active substance.

There are numerous applications for both alternatives on the market, so it is still not possible to ascertain any clear preference of one over the other. Each solution offers its own pros and cons, depending on the specific product. The following points outline certain aspects where the two concepts differ, to make it easier for the user to decide which one to choose:

  • The use of sugar spheres means that the drug producer can outsource pelletization to a specialist and concentrate on processing the API. This will produce sugar spheres as a spherical excipient of uniform size.

  • The shaping process involved in pelletization entails thermal load and contact with a solvent (usually water). This can cause stability problems, depending on the susceptibility of the active substance.

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