A screening study of surface stabilization during the production of drug nanocrystals.
In order to establish a knowledge base for nanosuspension production, a screening was performed on 13 different stabilizers at 3 concentrations for 9 structurally different drug compounds. Concerning the stabilizers tested, the group of semi-synthetic polymers was the least performant (stable nanosuspensions were obtained in only 1 out of 10 cases). For the linear synthetic polymers, better results were obtained with povidones, however poly(vinyl alcohol) did not result in adequate stabilization. The synthetic copolymers showed even higher success rates, resulting in nanosuspensions in two out of three cases when applied at a 100 wt% concentration (relative to the drug weight). Finally, the surfactants gave the best results, with TPGS being successful at concentrations of 25 or 100 wt% of the drug weight for all compounds tested. From the point of view of drug compound, large differences could be observed upon evaluation of the relative number of formulations of that compound resulting in nanosuspensions. It was found that the hydrophobicity of the surfaces, as estimated by the adsorbed amount of TPGS per unit of surface area of nanosuspensions stabilized with 25 wt% TPGS, was decisive for the agglomeration tendency of the particles and hence the ease of nanosuspensions stabilization.
Van Eerdenbrugh
Bernard
B
Laboratory for Pharmacotechnology and Biopharmacy, K.U. Leuven, Gasthuisberg O&N2, Herestraat 49, Box 921, 3000 Leuven, Belgium.
Vermant
Jan
J
Martens
Johan A
JA
Froyen
Ludo
L
Van Humbeeck
Jan
J
Augustijns
Patrick
P
Van den Mooter
Guy
G
D004339:Drug Compounding; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D012995:Solubility; D012996:Solutions / Q000737:chemistry; D013499:Surface Properties; D013500:Surface Tension; D013501:Surface-Active Agents / Q000737:chemistry; D014783:Viscosity
D005079:Excipients; D011108:Polymers; D012996:Solutions; D013501:Surface-Active Agents