Layered double hydroxides-AINEs hybrids: physicochemical characterization and in vitro drug release

ROJAS DELGADO, R.; MANZO, RH.; GIACOMELLI, CE.; JIMENEZ KAIRUZ, AF.

Rósario

Congreso; 2ra. Reunión Internacional de Ciencias Farmacéuticoas RICiFa 2012.; 2012

Universidad Nacional de Rosario

Introduction Layered double hydroxides (LDHs) are inorganic solids with bidimensional structures and anion exchange properties that are currently used as inert excipients and antacids in pharmaceutical dosage forms1. Furthermore, the number of reports studying LDHs in drug delivery design has markedly increased in the last years due to their capacity to incorporate different pharmaceutically active drugs (antiinflamatories, antibiotics, antihypertensives, anticancerigens)2 and biomolecules (amino acids, peptides and DNA)3. Nevertheless, studies concerning LDHs as drug carriers have centered their attention on the incorporation of diverse anionic drugs and the structural characterization of the synthesized material while the study of their biopharmaceutical behavior has been almost exclusively restricted to drug release from particulate solid dispersions4. The aims of this work are the synthesis of LDH-anionic drug (LDH-D) hybrids, the determination of relevant physicochemical properties and the evaluation of in vitro drug release from LDH-D hybrids formulated as hydrophilic matrices. Particularly, LDHs of Mg and Al loaded with ibuprofen (Ibu), naproxen (Nap) or ketoprofen (Ket) were studied to correlate their structure and interfacial properties with their drug release profiles in simulated gastric (SGF) and intestinal (SIF) fluids. Methods The LDH-D hybrids were obtained by the coprecipitation method at constant pH5. The hybrids containing Ibu, Nap or Ket were named LDH-Ibu, LDH-Nap and LDH-Ket, respectively. The metal ions and drug content were determined by atomic absorption spectrometry and UV-vis spectrophotometry, respectively. Structural characterization was performed by X-ray diffraction (Phillips X’pert Pro) and FT-IR spectroscopy (Bruker IFS28). Contact angle (θ) measurements were performed by the sessile drop method using a homemade contact angle goniometer. Zeta potential (ζ) of the hybrid particles in aqueous dispersions were measured in a DelsaNano-C instrument (Beckman Coulter). Hydrophilic matrices were prepared by direct compression of an accurately weighted amount (around 400 mg) of LDH-D hybrids using a hydraulic press. In vitro drug release from these matrices was studied using a dissolution test station (Sotax, AT7smart), apparatus 2-paddles setting at 100±1 rpm on 900 mL dissolution media at 37 °C. The drug concentration was determined by UV-Vis spectrophotometry at the corresponding absorbance maximum. Results The XRD patterns and FT-IR spectra indicated that a single phase, corresponding to a LDH intercalated with the drug in its anionic form was obtained in all cases. All the samples presented, at least, an amount of drug to completely compensate the structural layer charge. Further, the loaded amount exceeded the interlayer capacity in the order LDH-Ket