Poly(amidoamine) dendrimer-mediated synthesis and stabilization of silver sulfonamide nanoparticles with increased antibacterial activity.

Silver sulfadiazine (AgSD) is a topical antibiotic with limited aqueous solubility. In this study, it was shown that poly(amido amine) (PAMAM) dendrimer complexes with SD (SDZ) and silver (Ag) could be used for a bottom-up approach to synthesize highly-soluble AgSD nanoparticles (NPs). These NPs were stabilized against crystal growth by electrostatic layer-by-layer (LBL) coating with various PAMAM dendrimers. Additionally, AgNPs can be incorporated in the dendrimer shells that augmented AgSD release. NP formulation in a cream base provided a topical drug-delivery platform with enhanced antibacterial properties against burn-wound infections, comprising three nanostructures i.e., nano-AgSD, AgNPs as well as PAMAM dendrimers, in one efficient, elegant nanosystem. FROM THE CLINICAL EDITOR: In this paper an elegant silver sulfadiazine-based nanoparticle complex is demonstrated with enhanced antibacterial properties and improved solubility for the treatment of burn-wound infections in a topical crème formulation.

Physicochemical properties of amorphous roxithromycin prepared by quench cooling of the melt or desolvation of a chloroform solvate.

Roxithromycin is a poorly soluble antibacterial drug. The aim of this study was to prepare and characterize an amorphous form of roxithromycin. The amorphous form was prepared by desolvation of its chloroform solvate, and by quench cooling a melt of the crystalline monohydrated solid. The X-ray powder diffraction pattern of the desolvated chloroform solvate was indistinguishable from that of the glass prepared by melting, which indicated that it was amorphous. The roxithromycin glass was determined to be a fragile glass, but due to its high Kauzmann temperature (approximately 8°C), it should remain fairly stable upon refrigeration or even at room temperature. It was also determined that this glass remains stable in the presence of moisture with no indication of crystallization.

Introduction to nanocoatings produced by layer-by-layer (LbL) self-assembly.

Studies on the adsorption of oppositely charged colloidal particles ultimately resulted in multilayered polyelectrolyte self-assembly. The inception of layer-by-layer constructed particles facilitated the production of multifunctional, stimuli-responsive carrier systems. An array of synthetic and natural polyelectrolytes, metal oxides and clay nanoparticles is available for the construction of multilayered nanocoats on a multitude of substrates or removable cores. Numerous substrates can be encapsulated utilizing this technique including dyes, enzymes, drugs and cells. Furthermore, the outer surface of the particles presents and ideal platform that can be functionalized with targeting molecules or catalysts. Some processing parameters determining the properties of these successive self-assembly constructs are the surface charge density, coating material concentration, rinsing and drying steps, temperature and ionic strength of the medium. Additionally, the simplicity of the layer-by-layer assembly technique and the availability of established characterization methods, render these constructs extremely versatile in applications of sensing, encapsulation and target- and trigger-responsive drug delivery.

Crystallization of toxic glycol solvates of rifampin from glycerin and propylene glycol contaminated with ethylene glycol or diethylene glycol.

This study was initiated when it was suspected that syringe blockage experienced upon administration of a compounded rifampin suspension was caused by the recrystallization of toxic glycol solvates of the drug. Single crystal X-ray structure analysis, powder X-ray diffraction, thermal analysis and gas chromatography were used to identify the ethylene glycol in the solvate crystals recovered from the suspension. Controlled crystallization and solubility studies were used to determine the ease with which toxic glycol solvates crystallized from glycerin and propylene glycol contaminated with either ethylene or diethylene glycol. The single crystal structures of two distinct ethylene glycol solvates of rifampin were solved while thermal analysis, GC analysis and solubility studies confirmed that diethylene glycol solvates of the drug also crystallized. Controlled crystallization studies showed that crystallization of the rifampin solvates from glycerin and propylene glycol depended on the level of contamination and changes in the solubility of the drug in the contaminated solvents. Although the exact source of the ethylene glycol found in the compounded rifampin suspension is not known, the results of this study show how important it is to ensure that the drug and excipients comply with pharmacopeial or FDA standards.

Preparation and characterization of directly compactible layer-by-layer nanocoated cellulose.

Microcrystalline cellulose is a commonly used direct compression tablet diluent and binder. It is derived from purified α-cellulose in an environmentally unfriendly process that involves mineral acid catalysed hydrolysis. In this study Kraft softwood fibers was nanocoated using a layer-by-layer self-assembling process. Powder flow and compactibility results showed that the application of nano-thin polymer layers on the fibers turned non-flowing, non-compacting cellulose into powders that can be used in the direct compression of tablets. The powder flow properties and tableting indices of compacts compressed from these nanocoated microfibers were similar or better than that of directly compactible microcrystalline cellulose powders. Cellulose microfibers coated with four PSS/PVP bilayers had the best compaction properties while still producing tablets that were able to absorb water and disintegrate and did not retard the dissolution of a model drug acetaminophen. The advantages of nanocoating rather than traditional pharmaceutical coating are that it add less than 1% to the weight of the fibers and allows control of the molecular properties of the surface and the thickness of the coat to within a few nanometers. This process is potentially friendlier to the environment because of the type and quantity of materials used. Also, it does not involve acid-catalyzed hydrolysis and neutralization of depolymerized cellulose.