title: Cast lipid implants for controlled drug delivery: importance of the tempering conditions.
abstract: Lipid implants prepared by melting and casting offer a great potential for advanced drug delivery. However, care must be taken with respect to the solid state of the lipid(s) and potential changes thereof during storage. Generally, a thermal aftertreatment is required. However, little is known about the impact of the curing time and temperature on drug release. The aim of this study was to better understand the importance of these parameters for different types of implants containing propranolol hydrochloride. Hydrogenated cottonseed oil and hydrogenated soybean oil were used as matrix formers. The implants were characterized with respect to their in vitro release kinetics, water uptake, thermal properties, and morphology. On the basis of these experimental results, a mechanistic mathematical model was used to gain further insight into the underlying mass transport mechanisms. Both the curing time and the temperature strongly affected the resulting drug release patterns. Importantly, in most cases, these effects could not be attributed to polymorph transformations but to changes in the implants' microstructure. The size of the lipid particles depended on both the curing time and the temperature, and determined the size of the pores/channels through which water and drug diffuse. The importance of this aspect is often underestimated.
authors.affiliation: Univ. Lille Nord de France, College of Pharmacy, 59006 Lille, France; INSERM U 1008, Controlled Drug Delivery Systems and Biomaterials, 59006 Lille, France.
authors.forename: Frauke
authors.initials: F
authors.lastname: Kreye
authors.affiliation: Univ. Lille Nord de France, College of Pharmacy, 59006 Lille, France; INSERM U 1008, Controlled Drug Delivery Systems and Biomaterials, 59006 Lille, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Siepmann
authors.affiliation: Univ. Lille Nord de France, College of Pharmacy, 59006 Lille, France; INSERM U 1008, Controlled Drug Delivery Systems and Biomaterials, 59006 Lille, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Zimmer
authors.affiliation: Univ. Lille Nord de France, College of Pharmacy, 59006 Lille, France; Univ. Lille Nord de France, Department of Physics, UMR CNRS 8024, 59655 Villeneuve d'Ascq, France.
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Willart
authors.affiliation: Univ. Lille Nord de France, College of Pharmacy, 59006 Lille, France; Univ. Lille Nord de France, Department of Physics, UMR CNRS 8024, 59655 Villeneuve d'Ascq, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Descamps
authors.affiliation: Univ. Lille Nord de France, College of Pharmacy, 59006 Lille, France; INSERM U 1008, Controlled Drug Delivery Systems and Biomaterials, 59006 Lille, France. Electronic address: juergen.siepmann@univ-lille2.fr.
authors.forename: Juergen
authors.initials: J
authors.lastname: Siepmann
mesh_terms: D002152:Calorimetry, Differential Scanning; D003369:Cottonseed Oil / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D004343:Drug Implants; D008855:Microscopy, Electron, Scanning; D008956:Models, Chemical; D010316:Particle Size; D044367:Phase Transition; D011208:Powders; D011433:Propranolol / Q000008:administration & dosage / Q000737:chemistry; D012995:Solubility; D013024:Soybean Oil / Q000737:chemistry*; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D003369:Cottonseed Oil; D004343:Drug Implants; D011208:Powders; D014867:Water; D013024:Soybean Oil; D011433:Propranolol