DBPapers
DOI: 10.5593/SGEM2014/B61/S24.021

PREPARATION AND THERMAL STABILITY EVALUATION OF SOLID LIPID PARTICLES LOADED WITH ALENDRONATE

L. Ochiuz, A. Tomoiaga, A. Grigoras, C. Grigoras, L. Profire, C. Peptu, G. Popa
Wednesday 1 October 2014 by Libadmin2014

References: 14th International Multidisciplinary Scientific GeoConference SGEM 2014, www.sgem.org, SGEM2014 Conference Proceedings, ISBN 978-619-7105-20-9 / ISSN 1314-2704, June 19-25, 2014, Book 6, Vol. 1, 151-158 pp

ABSTRACT
Sodium alendronate (AL) is a therapeutical agent in the bisphosphonate (BFs) class. The main biomedical applications of BFs are the inhibition of bone resorption, its use as carrier and bone targeted delivery agent of other drugs, and restenosis inhibition and osteogenesis stimulation near bone implants. Currently, AL is used in conventional release tablets. Its low oral bioavailability (1-3%) is caused by several factors such as low permeability determined by the negatively charged molecules, the short plasma half-time (T½ = 0.5 – 2 h) and its chelatation by Ca2+ ions resulting in non-absorbable complexes. Aiming at increasing AL bioavailability both on oral and on other routes of administration (e.g. nasal and rectal mucosa), we have decided to load AL in solid lipid particles (SLPs). This research intends to assess AL stability when associated with lipidic excipients and during lyophilization. We prepared 8 self-emulsifying lipidic mixtures based on Compritol 888 (glyceryl behenate), Gelucire 44/14 (a mixture of glycerol and PEG1500 esters of long fatty acids) and Cremophor A 25 (the 25 mole ethoxylate of a blend of cetyl and stearyl alcohols). The hydrophilic-lipophilic balance of those mixtures ranges from 10.4 to 11.4. The aqueous AL solution was dispersed by ultrasonication in these mixtures. The obtained emulsions were lyophilized at – 57 °C and 0.016 mbar for 15 hours. The stability of AL was evaluated by 3 specific methods: differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and FTIR spectroscopy (FTIR). DSC was carried out with a Perkin Elmer device under the following conditions: the samples (4-4.5 mg) sealed in an aluminum pan and placed in inert atmosphere were dynamically analyzed at a temperature ranging between 50 and 300°C. TGA was performed on 3-6 mg samples using a derivatograph Mettler Toledo in a nitrogen atmosphere with a flow rate of 20 mL/min, a heating speed of 10°C/min (25- 600°C). FTIR spectra were obtained with a Vertex 70 equipment using KBr pellets technique, and obtained spectra were compared with those available in literature. The results have confirmed the stability of AL in association with the selected lipidic excipients. All three thermal analysis methods have shown identical characteristics for AL both in its raw and in its SLPs loaded state.

Keywords: alendronate, solid lipid particles, Cremophor