RESUMEN
Despite recent advances, the drug development process continues to face significant challenges to efficiently improve the poor solubility of active pharmaceutical ingredients (API) in aqueous media or to improve the bioavailability of lipid-based formulations. The inherent high intra- and interindividual variability of absorption of oral lipophilic drug leads to inconsistent and unpredictable bioavailability and magnitude of the therapeutic effect. For this reason, the development of lipid-based drugs remains a challenging endeavour with a high risk of failure. Therefore, effective strategies to assure a predictable, consistent, and reproducible bioavailability and therapeutic effect for lipid-based medications are needed. Different solutions to address this problem have been broadly studied, including the approaches of particle size reduction, prodrugs, salt forms, cocrystals, solid amorphous forms, cyclodextrin clathrates, and lipid-based drug delivery systems such as self-emulsifying systems and liposomes. Here, we provide a brief description of the current strategies commonly employed to increase the bioavailability of lipophilic drugs and present Advanced Lipid Technologies® (ALT®), a combination of different surfactants that has been demonstrated to improve the absorption of omega-3 fatty acids under various physiological and pathological states.
RESUMEN
Sucrose octaacetate (SOA) is a United States National Formulary (NF) monograph compendial material (U.S. Pharmacopeia, 2008), and, as shown in Fig. 1, has eight acetate groups attached to a sucrose moiety. It is a natural product that has been extracted from the seeds of Annona cornifolia (Lima et al., 2011). It is nontoxic (Sigma-Aldrich, 2016) and has a number of uses based on its bitter taste. For example, sugar is rendered too bitter is eat at a concentration of 0.06% (w/w) SOA (Mann et al., 1992). SOA can form 255 different possible isomers and degradation products, all of which have a very low molar absorptivity. Its ultraviolet molar absorptivity at 210nm has been reported to be 439 absorption units/cm/M in water and 442 absorption units/cm/M in 30:70 acetonitrile-water.
Asunto(s)
Annona/química , Sacarosa/análogos & derivados , Gusto , Semillas/química , Sacarosa/químicaRESUMEN
A sucrose octaacetate (SOA) gradient HPLC evaporative light scattering detection (ELSD) and low-wavelength UV-diode array detection (UV-DAD)-specific stability-indicating method development and validation comparison is reported. A central composite response surface design and multicriteria optimization was used to maximize molten SOA area-under-the-curve response and signal-to-noise ratio. The ELSD data were also analyzed using multivariate principal component analysis, analysis of variance, and standard least squares effects modeling. The method suitability and validation parameters of both methods were compared. To the authors' knowledge, this is the first report that validates an ELSD method using a molten analyte. SOA exhibited a low molar absorptivity of 439 absorption units/cm/M in water at 210 nm requiring low-wavelength UV-DAD detection. The low-wavelength UV-DAD method provided substantially better intraday and interday precision, intraday and interday goodness-of-fit, detection limit, and quantitation limit than ELSD. ELSD exhibited a 60-fold greater area-under-the-curve response, better resolution, and 58% more theoretical plates. On balance, the UV-DAD method was chosen for SOA chemical kinetic studies. This study illustrates that ELSD may not always be the best alternative to gradient HPLC low-wavelength UV detection.
