Introduction
The development of
methodologies to evaluate in vitro
the events that take place in the upper gastrointestinal tract upon
administration of an oral dosage form have received considerable attention
along time. In fact, well defined official tests are available to appraise
disintegration and drug dissolution on tablets, hard capsules and some oral
suspensions. Less attention has been paid to evaluate preabsorptive events of aqueous
formulations consisting of supramolecular aggregates loaded with active
pharmaceutical ingredients. Within this kind of dosage forms, mixtures of
lipophilic and hydrophilic vitamins (A, D and C) dispersed in a water/glycerin/polysorbate-80
vehicle are formulated as oral drops, widely used in the pediatric population
(newborns and infants, usual dose 0.3 mL).
In this report, a
methodology to follow the contact of the drops with simulated gastrointestinal
fluids was designed based on dynamic light scattering (DLS).
Materials and methods
Three multivitamin
supplements with marketing authorization in Argentine[1], Trivisol®
(P1), Ostelin® (P2) and Tanvimil® (P3), were selected and
their composition is reported in table
To mimmic the
preabsorptive events, the formulations were appropriately diluted (1/2, 1/5 and
1/10 v/v) with water, simmulated
gastric fluid (SGF) and simmulated intestinal fluid (SIF). DLS and
electrokinetic ζ-potential of all samples were
performed, at 25 and
Results and Discussion
As table 1 reports,
there are only minor differences among formulations and therefore they may be
considered as essentially similar products, in which the main components are
polysorbate-80 (19.5%), glycerin (42.0%) and water to complete 100%.
Undiluted formulations. The DSL analysis of the products showed monodisperse supramolecular
aggregates, with a polydispersity index ≤ 0.1 and diffusion coefficients ranging
from 2.7 to 16.3E10-9 cm2/s. The complexity of the
systems prevents the assignment of a physical meaning to dH values (table 2). However, they were useful to follow
a comparative analysis since the formulations exhibited differences in dH (P3 > P2 > P1).
Diluted formulations. 1/2 to 1/10 dilutions with
water exhibited at
All diluted samples
exhibited negative close to cero ζ-potentials,
(-0.6 to -2.0 mV), which is consistent with the non-ionic character of polysorbate-80.
Conclusions.