ABSTRACT
The reduction of particle size to nanometers has been an important tool used for efficient drug delivery. Solid drug nanoparticles can be conveniently prepared by nanocomminution. This process relies on mechanical energy and the selection of a proper polymeric stabilizer. The long chains of polymers provide steric stabilization for drug nanoparticles. In this research, itraconazole and hydroxypropyl cellulose were used to study the effect of the molecular weight of a polymer on particle size reduction. In principle, an increase in molecular weight produces two counteracting effects: a decrease in the diffusion rate of chains and an increase in the physical adsorption of a polymer. The effects of particle size reduction are more pronounced in systems involving smaller molecular weights, and the effects of changing molecular weights disappear with time. Systems of higher molecular weight show larger aggregates in their redispersion after drying. Based on the results of our research, it appears that polymers of smaller molecular weight are more suitable than larger polymers for efficient nanocomminution. This indicates that the kinetic aspects of molecular weight are important.
Subject(s)
Drug Delivery Systems , Itraconazole/administration & dosage , Nanoparticles , Polymers/chemistry , Cellulose/analogs & derivatives , Cellulose/chemistry , Chemistry, Pharmaceutical , Drug Compounding , Excipients/chemistry , Itraconazole/chemistry , Microscopy, Electron, Scanning , Molecular Weight , Particle Size , Powders , Solubility , Surface-Active Agents , Suspensions , WaterABSTRACT
The recent advance of particle size engineering in nanometer ranges has widened the formulation opportunities of relatively water-insoluble drugs. However, the 'nanoformulation' suffers from a lack of systematic understanding about the requirements of polymeric stabilizers. Furthermore, the polymers that can be used for the preparation of nanocrystals are so limited that finding a proper stabilizer for a given formulation is often difficult. In this study, amino acid copolymers whose properties can systematically be tailored are developed, and their morphological and compositional effects are investigated. Copolymers containing lysine (K) as their hydrophilic segments, and phenylalanine (F) or leucine (L) as their hydrophobic segments successfully produce stable nanocrystals (200-300 nm) in water, while copolymers of K and alanine (A) could not generate nanosized particles. Not the morphology but the hydrophobicity of copolymers seems to be a critical parameter in the preparation of drug nanocrystals by wet comminution. The effective stabilization performance of copolymers requires the hydrophobic moiety content to be higher than 15 mol%. Comminution for only 5 min is long enough for nanocrystal preparation, and the crystallinity of drug is found intact after the processing.
