RESUMO
Administration of enrofloxacin tablets concealed in improvised morsels to elude the unpleasant flavor of this drug is likely to diminish maximum plasma concentrations (Cmax ) reached by this drug, jeopardizing treatment efficacy. To avoid this, the hypothesis that alginate dried beads containing enrofloxacin (ADBE) could modify the pharmacokinetics of enrofloxacin in dogs was tested. ADBE were manufactured and pharmaceutically defined as having high entrapment efficiency (>90%) and a drug loading capacity of 56%-67%. Based on the hydrophilic nature of alginate and its interaction with the anionic charge of the amino groups of enrofloxacin, a novel modified release system was obtained in which ADBE give place to both a rapid diffusion releasing of enrofloxacin and a maintained release. The ADBE concealed in a sausage (ADBEs) achieved both the highest Cmax (5.1 µg/ml ± 0.3 SD) and the area under the concentration versus time (AUC0-24 ) (41.2 µg hr-1 ml-1 ± 6.9 SD). The tablet administered alone had a Cmax of 1.9 µg/ml ± 0.3 SD and an AUC0-24 = 16.5 µg h-1 ml-1 ± 3.5 SD, while the tablet concealed in a sausage reached a Cmax of 1.2 µg/ml ± 0.3 SD with an AUC0-24 = 12.3 µg hr-1 ml-1 ± 3.8 SD (p < .05 in both cases when confronting ADBEs vs. tablets). Consequently, Cmax /MIC and AUC0-24 /MIC ratios are higher for ADBEs. Other PK parameters were statistically indistinguishable, and other morsels containing enrofloxacin as a tablet or as ADBE rendered less favorable PK parameters. Due to ease of administration and favorable PK for ADBE concealed in a sausage, this pharmaceutical design can be regarded as PK/PD consistent and worthy of clinical studies.
Assuntos
Alginatos , Animais , Área Sob a Curva , Disponibilidade Biológica , Cães , Enrofloxacina , ComprimidosRESUMO
In this work, we prepared a novel composite based on hybrid gelatin carriers and montmorillonite clay (MMT) to analyze its viability as controlled drug delivery system. The objective of this research involves the characterization of composites formed by structured lipid-gelatin micro-particles (MP) and MMT clay. This analysis included the evaluation of the composite according to its rheological properties, morphology (SEM), particle size, XRD, FT-IR, and in vitro drug release. The effect of pH in the properties of the composite is evaluated. A novel raspberry-like or armor MP/MMT clay composite is reported, in which the pH has an important effect on the final structure of the composite for ad-hoc drug delivery systems. For pH values below the isoelectric point, we obtained defined morphologies with entrapment efficiencies up to 67%. The pH level controls the MP/MMT composite release mechanism, restringing drug release in the stomach-like environment. Intended for oral administration, these results evidence that the MP/MMT composite represents an attractive alternative for intestinal-colonic controlled drug delivery systems.