ANALYSIS OF FORMULATION EFFECTS IN THE DISSOLUTION OF KETOPROFEN PELLETS

Abstract

In this work the effects of citric acid and two common fillers, lactose (soluble) and tricalcium phosphate
(insoluble) are examined on the release profiles from pellets, using ketoprofen as a model drug with pHdependent
solubility. Also studies were conducted on dependence of these profiles on the specific surface
area, bulk density, apparent density, porosity and porosity parameters (pore size distribution, total
pore surface area, mean pore diameter and pore shape), as determined by mercury intrusion porosimetry.
Pellets were prepared by the extrusion-spheronization method. Four different formulations were considered:
two ternary mixtures of ketoprofen (I), lactose (L) or tricalcium phosphate (P) and microcel (M) in
the relative proportions 2:3:5 (ILM or IPM) and two four-component mixtures of the same components
plus 5% citric acid (C) in the relative proportions 2:2.5:0.5:5 (CILM or CIPM). Pellets with high porosity
and total pore sur face area but small median pore diameter ( t r icalcium phosphate pellets IPM) are
found to produce similar dissolution results to those of low porosity and low total pore surface area, but
having a high median pore diameter ( lactose pellets I LM) , ir respect ive of the solubility of excipients.
Addition of citric acid causes a delay in the initial dissolution for both formulations. During dissolution,
however, citric acid reduces the median pore diameter of lactose-based pellets. In contrast, in tricalcium
phosphate/ cit r ic acid pellet s (CIPM) , this parameter increases considerably dur ing dissolut ion, when
compared to the IPM formulat ion. These findings may just ify the cont rast ing dissolut ion behaviors of
CIPM and CILM (lactose/citric acid) pellets, after their common behavior in the initial stages, and show
that porosity and its related parameters, along with physical properties of excipients such as solubility,
density and specific surface area, are helpful to predict pellet behavior in drug release profiles.