Wednesday, June 24, 2009

Local Delivery of Modified Paclitaxel-Loaded Nanoparticles

Images of paclitaxel-loaded DMAB-modified PCL/F68 nanoparticles.

The purpose of this research was to test the possibility of localized intravascular infusion of didodecyldimethylammonium bromide (DMAB)-modified paclitaxel-loaded poly(∑-caprolactone)/Pluronic F68 (PCL/F68) nanoparticles to achieve long-term inhibition of hyperplasia in a balloon-injured rabbit carotid artery model.
Paclitaxel-loaded nanoparticles were prepared by the modified solvent displacement method using commercial poly(lactide-co-glycolide) (PLGA) and self-synthesized PCL/F68, respectively. DMAB was adsorbed on the nanoparticle surface by electrostatic attraction between positive and negative charges to enhance arterial retention. Nanoparticles were found to be of spherical shape with a mean size of around 300 nm and polydispersity of less than 0.150.
The surface charge was changed to positive values after the DMAB modification. The in vitro drug release profile of all nanoparticle formulations showed a biphasic release pattern. Drug release from DMAB-modified PCL/F68 nanoparticles (DPNP) was significantly slower than DMAB-modified PLGA nanoparticles (PGNP). After 90 days, the DPNP group showed very significant inhibition of neointimal proliferation (P <>

Mei L, Sun H, Song C. Local delivery of modified paclitaxel-loaded poly(∑-caprolactone)/pluronic F68 nanoparticles for long-term inhibition of hyperplasia. J Pharm Sci. 2009;98:2040-2050. Correspondence to Hongfan Sun, The Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Peking Union Medical College & Chinese Academy of Medical Sciences at or +86-22-87892052.

Surface Stabilization During Drug Nanocrystal Production

Success rate (%) in nanosuspension production for the high-viscosity stabilizers (black bars = 10 wt%, dark gray bars = 2.5 wt%, light gray bars = 1 wt%, white bars = accumulated results for all concentrations).

In order to establish a knowledge base for nanosuspension production, a screening was performed on 13 different stabilizers at three concentrations for nine structurally different drug compounds. Concerning the stabilizers tested, the group of semi-synthetic polymers was the least performant (stable nanosuspensions were obtained in only one 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 B, Vermant J, Martens JA, et al. A screening study of surface stabilization during the production of drug nanocrystals. J Pharm Sci. 2009;98:2091-2103. Correspondence to Guy Van den Mooter, Laboratory for Pharmacotechnology and Biopharmacy, K.U. Leuven at or +32-16330304.

Minitablets as Gastroretentive Floating Drug Delivery Systems

Design of floating multiple-unit dosage forms.

A gastroretentive floating drug delivery system with multiple-unit minitablets based on a gas formation technique was developed for furosemide. The system consists of core units (solid dispersion of furosemide: povidone and other excipients), prepared by direct compression process, which are coated with two successive layers, one of which is an effervescent (sodium bicarbonate) layer and another that is an outer polymeric layer of polymethacrylates.
The formulations were evaluated for pharmacopoeial quality control tests and all the physical parameters evaluated were within the acceptable limits. Only the system using Eudragit RL30D and a combination of them as polymeric layer could float within an acceptable time. The time to float decreased as the amount of the effervescent agent increased and when the coating level of the polymeric layer decreased. The drug release was controlled and linear with the square root of time. By increasing the coating level of the polymeric layer, drug release was decreased.
The rapid floating and the controlled release properties were achieved in this study. The stability samples showed no significant change in dissolution profiles (f2 = 81). Radiograms were used to examine the in vivo gastric residence time and it was observed that the units remained in the stomach for about six hours.

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