Determination of Solid State Characteristics of Spray-Congealed Ibuprofen Solid Lipid Microparticles and Their Impact on Sustaining Drug Release

摘要

This study was used to find solid state characteristics of ibuprofen loaded spray-congealed solid lipid microparticles (SLMs) by employing simple lipids as matrices, with or without polymeric additives, and the impact of solid drug matrix miscibility on sustaining drug release. Solid miscibility of ibuprofen with two lipids, cetyl alcohol (CA) and stearic acid (SA), were investigated using differential scanning calorimetry (DSC). SLMs containing 20% w/w ibuprofen with or without polymeric additives, PVP/VA and EC, were produced by spray congealing, and the resultant microparticles were subjected to visual examination by scanning electron microscopy (SEM), thermal analysis using DSC, and hot-stage microscopy. Intermolecular interactions between lipids and drug as well as additives were investigated by Fourier-transformed infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR). X-ray diffractometry (XRD) was utilized to study polymorphic changes of drug and matrix over the course of a year. Ibuprofen was found to depress the melting points of CA and SA in a colligative manner, reaching maximum solubility at 10% w/w and 30% w/w for CA and SA, respectively. Drug encapsulation efficiencies and yields of spray-congealed SLMs containing 20% w/w ibuprofen were consistently high for both lipid matrices. CA and SA were found to adopt their stable gamma- and beta-polymorphs, respectively, immediately after spray congealing. The spray congealing process resulted in ibuprofen adopting an amorphous or poorly crystalline state, with no further changes over the course of a year. SEM, DSC, and hot stage microscope studies on the SLMs confirmed the formation of a solid dispersion between ibuprofen and CA and a solid solution between ibuprofen and SA. SA was found to sustain the release of ibuprofen significantly better than CA. PVP/VA and EC showed some interactions with CA, which led to an expansion of unit cell dimensions of CA upon spray congealing, whereas they showed negligible interactions with SA. PVP/VA and EC both hastened drug release in both CA and SA matrices, despite PVP/VA being hydrophilic and EC being hydrophobic. CA and SA are useful as lipid matrices that do not exhibit polymorphism when spray-congealed. Sustained release of ibuprofen was achieved with the formation of a solid solution with SA. Solid miscibility of drug in lipid matrix has a large impact on the ability of the SLMs to sustain the release of a drug. Polymeric additives generally disrupted structural integrity of SLMs and led to faster drug release.