CONTINUOUS PRODUCTION OF RALOXIFENE HYDROCHLORIDE LOADED NANOSTRUCTURED LIPID CARRIERS USING HOT-MELT EXTRUSION TECHNOLOGY.

The aim of this study was to utilize a continuous process for the production of orally administered raloxifene hydrochloride (RX-HCl) loaded nanostructured lipid carrier (NLC) formulations for extended drug release using hot-melt extrusion (HME) technology coupled with probe sonication, and also to evaluate the in vitro characteristics of the prepared NLCs. Preparation of the NLCs using HME technology involved two main steps, first formation of a pre-emulsion after extrusion and then size reduction of the pre-emulsion using probe sonication to obtain the NLCs. A screw speed of 100 rpm and a barrel temperature of 85 °C, were used in the extrusion process. NLCs prepared by HME technology showed a lower particle size compared to those prepared by the conventional probe sonication method. The prepared NLCs had high entrapment efficiency values (>90 %). In vitro drug release was evaluated using dialysis bag diffusion technique and USP apparatus I. Overall, the RX-HCl loaded NLCs had a higher rate of drug release than the pure drug. The release profile for the F4-3 NLC formulations and pure drug at the beginning and end of the stability study were comparable. The particle size of the prepared NLCs remained stable over the storage period and all PDI and zeta potential values were ≤ 0.5 and in the range of -15 to -30 mV, respectively, indicating good physical stability of the formulations. In summary, HME technology and probe sonication were successfully used to prepare RX-HCl loaded NLC formulations with shorter processing times as compared to the conventional probe sonication method, which makes this technique a uniquely more industry-friendly method.