Preparation of nanoparticles consisting of methacrylic polymers and drugs by an aerosol flow reactor method: Dissertation

Drug-containing polymer nanoparticles are submicron-sized particles consisting of drug and stabilising or functional polymer. In this experimental study, methacrylic polymer nanoparticles with and without incorporated model drug were prepared using a novel method, namely, aerosol flow reactor method. This method involves first preparing a solution containing the drug and the polymer, followed by spraying the solution as nanosized droplets into a carrier gas stream, then drying the nanoparticles in a tubular laminar flow reactor tube, and finally collecting the nanoparticles. Model polymers used in this study were Eudragit L, Eudragit E, and Eudragit RS, which are commonly used methacrylic polymers in the pharmaceutical industry. Model drugs studied were beclomethasone dipropionate, ketoprofen, and naproxen. Various properties of the prepared nanoparticles were studied, such as particle size and size distribution, morphology, crystallinity, thermal properties, drug content, and drug release. It was found that this method could be used to produce amorphous, spherical, homogeneous matrix-type drug-polymer nanoparticles. The size of the particles was adjusted between 90 and 200 nm by the concentration of the solution. The morphology of the particles varied as a function of the properties and composition of the starting solution. The nanoparticles were collected as dry powders, but the stability of the powders in an amorphous form was found to be dependent on the interactions between the drug and the polymer. When the amount of the drug in the nanoparticles was below the solubility limit of the drug in the polymer, the amorphous nanoparticles were found to be stable and no crystallisation of the drug took place. When the amount of the drug was larger than the solubility limit, large crystalline structures were formed due to crystallisation of the drug. The crystallisation was also dependent on the thermal properties of the drug, as amorphous nanoparticles consisting of a drug having a high glass transition temperature could be collected at room temperature. A low glass transition temperature of the drug led to crystallisation of the drug at ambient conditions, when the drug amount in the nanoparticles was larger than the solubility limit. Drug release from the nanoparticles could be modified by using polymers having specific solubility properties.