Application of Central Composite Designs to the Preparation of Polycaprolactone Nanoparticles by Solvent Displacement

Abstract

Cyclosporin A (CyA) is a good candidate for incorporation in colloidal carriers such as nanoparticles (NP) that would diminish the adverse effects associated with its use under conventional pharmaceutical dosage forms and improve bioavailability after oral administration. In this study a composite rotational experimental design was used to evaluate the joint influence of five formulation variables: temperature of the aqueous phase, needle gauge, volume of the organic phase, and the amounts of polymer and surfactant on the micromeritic characteristics of the CyA-loaded NP obtained by the method of Fessi et al. The percentage of drug encapsulated in the NP was also evaluated for each formulation, and the yield, which was expressed as the ratio between the experimentally measured quantity of drug in the formulation and the theoretical content, was determined because CyA undergoes surface absorption. Potential variables such as stirring speed (500 rpm), final drug concentration (100 micrograms/mL), or injection rates (GRi = 0.379 mL/s) were maintained constant. The ANOVA corresponding to the experimental design showed that the amounts of polymer and surfactant, and the diameter of the needle used in the preparation of NP, significantly affected the percentage of entrapped drug (I2 = 0.8916). The mean particle size was significantly affected by all the formulation variables tested except for the amount of surfactant dissolved in the external aqueous phase (r2 = 0.9518). Neither the yield (mean value of 99.61%) nor the size distribution parameters (polydispersity and coefficient of variation) presented good correlation coefficients for the equations obtained, although some variables showed statistical significance. A second study was carried out to investigate the effects on the drug-loaded NP characteristics of varying the global injection rates (GRi) for the organic phase into the aqueous medium. The results showed a dramatic decrease in both particle size and drug incorporation in the carrier as the rate of mixing increased. From the results of both the experimental design and the second study, a theoretical model for nanoparticle formation is proposed that considers the most significant variables, and an empirical relationship to predict mean particle size is presented. Thus, particle size can be controlled by the injection rates (GRi), the needle gauge, and the polymer concentration.

Controlled Nanoparticle Formation by Diffusion Limited Coalescence

“…2, our results compare favorably to the data available in the literature [6] for the same system. As the experiments are performed in the mix > cls regime, the scaling obeys the 1=3 power law as expected.…”

“…Two relevant time scales, the mixing and the encounter and coalescence times, are identified in (6) and their ratio is shown to be of a critical importance for the NP final diameter. The latter is predicted to scale in a universal manner and be sensitive predominantly to the mixing time and the polymer concentration if the surfactant concentration is sufficiently high.…”

“…Scheme of a pressure driven injection device used in Ref. [6] (a) and an impinging jets mixer used in Ref. [7] (b).…”

Synthesis, Characterization and in vitro Anti-Tumoral Evaluation of Erlotinib-PCEC Nanoparticles

“…Size of particles decreased with decreasing the CL/PEG molar ratio of copolymer. A similar observation has been reported previously, where particle size of polymeric nanoparticles obtained through nanoprecipitation method was decreased by decreasing the molecular weight or concentration of copolymers in acetone and also by increasing the surfactant concentration (Molpeceres et al, 1996;Ge et al, 2000;Ge et al, 2002). In nanoprecipitation method, formation of smaller nanodroplets during emulsification leads to increased specific surface area.…”

‘Surfactant-free’ stable nanoparticles from biodegradable and amphiphilic poly(ε-caprolactone)-grafted dextran copolymers

“…Several publications highlighted the ability of nanoparticles to reduce adverse effects of various drugs released at non-target sites, typically hydrophobic ones [1][2][3][4][5]. Most commonly used methods for preparing polymer-based nanoparticles include emulsion-evaporation [6], in situ monomer polymerization [7], a method based on the salting out effect [8][9], and nanoprecipitation [10,11]. The latter originally developed by Fessi et al [11] represents an easy and reproducible technique, which has been quickly and widely explored by several research groups for producing both vesicle and matrix type nanoparticles, also termed nanocapsule and nanosphere, respectively [10,[12][13].…”