Development of micro-fibrous solid dispersions of poorly water-soluble drugs in sucrose using temperature-controlled centrifugal spinning

• Published in: European journal of pharmaceutics and biopharmaceutics 2016-06, Vol.103, p.84-94
• Main Authors: Marano, Stefania, Barker, Susan Anne, Raimi-Abraham, Bahijja Tolulope, Missaghi, Shahrzad, Rajabi-Siahboomi, Ali, Craig, Duncan Q.M.
• Format: Article
• Language: English
• Subjects: Amorphous solid dispersion; Benzodiazepines - chemistry; Calibration; Calorimetry, Differential Scanning; Centrifugal spinning; Centrifugation; Dissolution enhancement; Microfiber; Microscopy, Electron, Scanning; Olanzapine; Poorly water soluble drug; Powder Diffraction; Research Paper; Solubility; Spectroscopy, Fourier Transform Infrared; Sucrose; Sucrose - chemistry; Supersaturation; Temperature; Water - chemistry
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2016.03.021

[Display omitted] Solid dispersion technology represents a successful approach to addressing the bioavailability issues caused by the low aqueous solubility of many Biopharmaceutics Classification System (BCS) Class II drugs. In this study, the use of high-yield manufacture of fiber-based dispersion is explored as an alternative approach to monolith production methods. A temperature-controlled solvent-free centrifugal spinning process was used to produce sucrose-based microfibers containing the poorly water-soluble drugs olanzapine and piroxicam (both BCS Class II); these were successfully incorporated into the microfibers and the basic characteristics of fiber diameter, glassy behavior, drug loading capacity and drug–sucrose interaction assessment were measured. Scanning electron microscopy revealed that bead-free drug-loaded microfibers with homogenous morphology and diameter in the range of a few micrometers were prepared using our process. Differential scanning calorimetric and X-ray diffraction analyses showed that both drug and carrier were present in the amorphous state in the microfibers, although in the case of piroxicam-loaded microfibers, the presence of small amounts of crystalline drug was observed under polarized light microscopy and in Fourier transform infrared spectra. Drug dissolution performance was evaluated under both sink and non-sink conditions and was found to be significantly enhanced compared to the corresponding crystalline physical mixtures and pure drugs, with evidence of supersaturation behavior noted under non-sink conditions. This study has demonstrated that microfiber-based dispersions may be manufactured by the centrifugal spinning process and may possess characteristics that are favorable for the enhanced dissolution and oral absorption of drugs.