Influence of Solvent Evaporation Technique Parameters on Diameter of Submicron Lamivudine-Poly-ε-Caprolactone Conjugate Particles

Abstract

The size of active pharmaceutical ingredient carrier is one of the key properties considered during design of submicron drug delivery systems. Particle diameter may determine drug biodistribution, cellular uptake, and elimination path. Solvent evaporation technique is a flexible method of particle preparation, in which various macromolecules and drugs may be employed. Parameters of emulsion obtained as first step of particle preparation are crucial in terms of particle size, drug loading, and morphology. The aim of the study was to investigate the influence of emulsion preparation parameters on diameter of resulting particles. Impact of surfactant type and concentration, homogenization time, homogenization rate, phase ratio, and conjugate concentration were evaluated. Model drug lamivudine was covalently bound to polymer and applied in solvent evaporation method in order to overcome issues related to drug loading and provide method-independent incorporation. Synthesized drug–polymer conjugate and obtained particles were evaluated via dynamic light scattering, chromatography, scanning electron microscopy, and spectroscopic methods. Covalent bonding between drug and polymeric chain was confirmed, estimated drug content per milligram of conjugate was 19 μg. Among employed colloid stabilizer, poly(vinyl alcohol) was proven to be most effective. Homogenization rate and surfactant concentration were identified as crucial parameters in terms of particle diameter control.