Ds. Desai et al., PHYSICAL INTERACTIONS OF MAGNESIUM STEARATE WITH STARCH-DERIVED DISINTEGRANTS AND THEIR EFFECTS ON CAPSULE AND TABLET DISSOLUTION, International journal of pharmaceutics, 91(2-3), 1993, pp. 217-226
Overmixing of magnesium stearate with granules in the hopper of a caps
ule filling machine can slow down their dissolution because of coating
by magnesium stearate, which acts as a water repellant. This phenomen
on was systematically investigated using three active ingredients repr
esenting a wide range of solubility in 0.1 N hydrochloric acid, the di
ssolution medium. The active ingredients were hydrochlorothiazide, an
antiviral agent SQ32756 (BV-araU), and aztreonam, with solubilities in
0.1 N hydrochloric acid of 0.6, 5.0 and 12 mg/ml, respectively, at 37
-degrees-C. When capsules of an aqueous wet granulated formulation con
taining one of the aforementioned active ingredients, hydrous lactose,
pregelatinized starch, microcrystalline cellulose, and 1% w/w magnesi
um stearate were filled using the MG2 Futura capsule filler, capsules
from the latter part of the filling run exhibited significantly slower
dissolution compared to those from the beginning. The extent of slowd
own in dissolution of the capsules varied depending upon the aqueous s
olubility of the active ingredient. The slowdown was maximum for hydro
chlorothiazide capsules followed by SQ32756 and aztreonam capsules, re
spectively. Further studies using SQ32756 as the active ingredient ind
icated that replacement of magnesium stearate in the formulation with
other hydrophobic lubricants such as calcium or zinc stearate gave sim
ilar results. However, replacement of magnesium stearate with hydrophi
lic lubricants such as Stear-O-Wet(R) or sodium stearyl fumarate did n
ot result in a slowing of dissolution. Among the hydrophobic lubricant
s, magnesium stearate caused the maximum slowdown in dissolution, foll
owed by zinc and calcium stearates, respectively. This observed rank o
rder was correlated to the surface area of these lubricants. Furthermo
re, optimization of magnesium stearate concentration to 0.25% w/w prov
ided enough lubrication for capsule filling while resulting in a capsu
le with satisfactory dissolution. Replacement of pregelatinized starch
by starch-derived superdisintegrants such as Explotab(R) or Primojel(
R) also resulted in no slowing of dissolution of capsules, even after
overmixing with 1% w/w magnesium stearate. Although the granules overm
ixed with 1% w/w hydrophobic lubricants exhibited slow down in dissolu
tion when filled into capsules, tablets compressed from these granules
dissolved rapidly.