Despite a rising interest in controlled-release drug delivery systems, the most common tablets are those intended to be swallowed
whole, disintegrating and releasing their medicaments rapidly in the gastrointestinal tract. A disintegrant is a substance in a tablet formulation that enables the tablet to break up into smaller fragments upon contact with gastrointestinal
fluids. Such a rapid rupture of the tablet matrix increases the surface area of the tablet particles, thereby increasing the
rate of absorption of the active ingredient and producing the desired therapeutic action (1).
The proper choice of disintegrant and its consistency of performance are critical to formulation development of such tablets.
In the past, starch was one of the most widely used, inexpensive, and effective tablet disintegrants. A high concentration
of starch is required to bring about effective disintegration. Scientists' search for disintegrating agents with efficient
disintegrating properties at relatively low concentrations has led to the development of some new compounds with excellent
disintegrating properties.
Superdisintegrants generally are used at a low level in the solid dosage form, typically 1–10% by weight relative to the total
weight of the dosage unit. Examples of superdisintegrants are crosscarmelose, crospovidone, and sodium starch glycolate, which
are a crosslinked cellulose, crosslinked polymer, and a crosslinked starch, respectively. BASF is one manufacturer of crospovidone
under the trade name of insoluble "Kollidon" grades. Another manufacturer is ISP's "Polyplasdone XL" grade. Crosscarmelose
is marketed mainly as the brand name of "Ac-Di-Sol" by FMC BioPolymer and sodium starch glycolate as "Primojel" from DMV International.
Insoluble grades of Kollidon (crospovidone) are manufactured by a polymerization process that yields crosslinked insoluble
polyvinyl-pyrrolidone in the form of a "popcorn" polymer. The polymerization is performed using an aqueous system. No organic
solvents are involved at any stage. The crosslinking is of chemical and physical nature, which is mainly achieved by the entanglement
of the polymer chains and dominates the product's properties.
Unlike povidone, crospovidone is completely insoluble in solvents and the corresponding products cannot be named according
to a K-value or a molecular weight. The product differentiation is conducted mainly by the particle-size distribution. The
bulk density and swelling behavior also play an important role in disintegration behavior (2). (BASF supplies the following
insoluble grades of Kollidon: Kollidon CL, Kollidon CL-F, Kollidon CL-SF, and Kollidon CL-M, which all comply with current
monographs in the European, Japanese, and US pharmacopeias.)
Physical characteristics
Insoluble Kollidon grades are supplied as fine, white, and almost-white powders. They have a slight characteristic odor and
are practically tasteless. They are insoluble in all usual solvents.
Table I: Characteristics of various disintegrants.
|
Bulk and tapped densities of Polyplasdone XL are lower than those of Kollidon CL, perhaps because of the porous structure
of Polyplasdone XL or the smoother surface area of Kollidon CL. In consequence of the smaller particle size, bulk densities
of Kollidon CL-F and Kollidon CL-SF are lower than the bulk density of Polyplasdone XL grades. Because of its smooth particle
surface, Primojel had the highest bulk and tapped densities of all disintegrants. The density of Ac-Di-Sol is between those
of Kollidon CL and Primojel (3) (see Table I).
The average particle sizes of Kollidon CL-F and Kollidon CL-SF are significantly lower than those of Kollidon CL and Polyplasdone
XL. Kollidon CL-M has the lowest particle size. Polyplasdone XL-10 exhibits a similar particle size as Kollidon CL-F. Ac-Di-Sol
and Primojel are significantly finer than Kollidon CL and Polyplasdone XL but coarser than the other disintegrants (Particle
size was measured on a "Mastersizer," Malvern Instruments) (3) (see Table I).
