Invitro evaluation of preabsortive events of oral multivitamin formulations by dynamic ligth scattering.

PALENA, MC.; JIMENEZ KAIRUZ, AF.; MANZO, RH.

Córdoba

Congreso; 1ra. Reunión de Ciencias Farmacéuticas, RICiFa 2010; 2010

Facultad de Ciencias Químicas, Universidad Nacional de Córdoba.

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).