Development and evaluation of raloxifene hydrochloride-loaded subdermal implants using hot-melt extrusion technology

Implantable drug delivery systems are known to provide great patient compliance and allow for controlled delivery of drugs over a prolonged period of time. This study aimed to prepare novel polycaprolactone/polyethylene glycol-based raloxifene hydrochloride subdermal solid cylindrical implants using a single-step hot-melt extrusion (HME) continuous process, for the provision of a sustained and prolonged release of RX-HCl as a cornerstone and alternative treatment and prevention option of osteoporosis, most especially post-menopausal osteoporosis, and invasive breast cancer, while providing better clinical outcomes by circumventing clinical and biopharmaceutical hurdles like first-pass metabolism and patient non-adherence and incompliance associated with the oral dosage forms of raloxifene hydrochloride. The 11-mm co-rotating twin-screw extruder was used to prepare the implants. The prepared cylindrical-shaped solid implants with dimensions of 10 mm (length) by 2 mm (diameter) were characterized by DSC, PXRD, FTIR, SEM, and in vitro dissolution analysis. Based on the physicochemical characterization of the prepared implants, the HME fabrication technology and optimized process parameters were determined to be acceptable and suitable. The prepared implants showed no obvious burst release and no significant amounts of drug on the surface of the implants. F-1, F-2, and F-3 implant batches showed a maximum cumulative percent drug release of 82.9%, 42.2%, and 20.6%, respectively, in a period of 30 days, and 100% drug release would be expected in a period of about 40 days (F-1), 72 days (F-2), and up to 150 days (F-3) by simple extrapolation. Interestingly, implant batches with a low drug load exhibited a relatively faster and higher rate of release of the drug compared to implant batches with high drug loading. In the present study, a single-step HME process was successfully used to fabricate RX-HCl-loaded subdermal implants, that could potentially be used as a cornerstone regimen in the treatment and prevention of osteoporosis, most especially post-menopausal osteoporosis, by providing release of RX-HCl over a long time period, and avoiding the clinical inconveniences and possible patient incompliance caused by daily administration of the drug.