RESUMEN
This study evaluated the ability of different sweeteners to improve dissolution and to form and stabilize supersaturated solutions of griseofulvin (GSF), comparing a eutectic mixture and amorphous formulations. Among the sweeteners tested, only saccharin (SAC) was able to delay drug precipitation in buffer (area under the curve (AUC) increase of 40%) and in fasted state simulated intestinal Fluid (FaSSIF, AUC increase of 20%) compared to pure media. GSF solubility was not affected by the presence of isomalt (ISO), maltitol (MALT) and SAC in buffer pH 6.5 but was reduced in FaSSIF. The quenched cooled amorphous formulation GSF-SAC QC -with the carrier that forms a eutectic mixture with GSF -provided higher drug release in buffer than amorphous formulations with ISO and MALT. In FaSSIF, SAC slightly changed the microenvironment's hydrophobicity (observed in fluorescence studies) and both its amorphous formulation (GSF-SAC QC) and its eutectic mixture (GSF-SAC EM) dissolved at concentrations above drug solubility, achieving supersaturation ratio (SR, Eq. (1)) of 4.14 and 3.15, respectively. The main finding of this study was that for the first time a eutectic mixture acted as a supersaturating drug delivery system, emphasizing the importance of investigating EMs during preformulation studies of fast-crystallizing poorly water-soluble drugs.
Asunto(s)
Griseofulvina , Sacarina , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , SolubilidadRESUMEN
Solid dispersions (SDs) of chlorthalidone (CTD) are promising systems to enhance drug dissolution rate, generate and maintain drug supersaturation levels in gastrointestinal fluids. In this work, SDs of CTD were prepared by spray drying using sodium alginate (SA) as carrier. Six formulations were prepared, varying the drug loading and composition, through the combination of SA with surfactants (sodium lauryl sulfate (SLS) or polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOL)). In all SDs, except when SA was used alone at low drug loading, CTD was in the amorphous form. At sink conditions, all SDs showed a faster dissolution rate than the crystalline drug. At non-sink conditions, the SDs prepared with SA and SLS at low drug loading exhibited the best performance to maintain supersaturating drug levels. All SDs, except those prepared with SA alone or SA-SLS at high drug loading, presented no drug recrystallization after 34 months of storage.