Determination of solid state characteristics of spray-congealed Ibuprofen solid lipid microparticles and their impact on sustaining drug release.

Abstract

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 γ- and β-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.