INVESTIGADORES
JIMENEZ KAIRUZ Alvaro Federico
congresos y reuniones científicas
Título:
Invitro evaluation of preabsortive events of oral multivitamin formulations by dynamic ligth scattering.
Autor/es:
PALENA, MC.; JIMENEZ KAIRUZ, AF.; MANZO, RH.
Lugar:
Córdoba
Reunión:
Congreso; 1ra. Reunión de Ciencias Farmacéuticas, RICiFa; 2010
Institución organizadora:
Dpto de Farmacia, FCQ-UNC - CONICET
Resumen:
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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 1. A reference solution (RS) having the same
proportion of polysorobate-80 glycerin and water was prepared.
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 37°C,
using Zetasizer (Beckman-Coulter). Diffusion coefficients and apparent
hydrodynamic diameters (dH)
were reported (table 2).
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 25°C
quite similar dH in P1 and
P2 and a higher one in P3. At 37°C,
dH became higher in P2 and
P3 while those of P1 and the RS dispersion remain unchanged. Samples 1/10
diluted with SGF and SIF showed similar dH
among P1, P2, P3 and the RS at 25°C.
At 37°C,
P2, P3 and RS rise their dH
while that of P1 remained unchanged, as observed in water. It?s known that a
polysorbate-80 aqueous dispersion at this concentration consist of spherical
micelles[2].
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.
Diluted samples exhibit dH close to that of the
polysorbate-80 reference dispersion. So, it appears that they also consist of
sferical micelles loaded with the lipophilic vitamins. Therefore, it?s expected
that the micellar supramolecular aggregates will be in contact with the
gastrointestinal membranes upon administration. It is worth mentioning that the
amount of polysorbate-80 contained in a newborne dose is higher than the WHO
recomended daily intake of polysorbate-80 (25 mg/Kg).