Encapsulation of alendronate sodium by nanoprecipitation and double emulsion: From preparation to in vitro studies

• This original research article contains a systematic study that deals with encapsulation of a hydrophilic active molecule, alendronate sodium. The latter is indicated as first regimen for osteoporosis treatment. Encapsulation of hydrophilic molecules is a challenging task because operating conditions has to be well monitored. Sodium alendronate was successfully encapsulated in nanoparticles via two techniques: nanoprecipitation and double emulsion. Various operating conditions exerted effects on nanoparticles properties. It was shown that double emulsion ensured better encapsulation efficiency of alendronate. Invitro studies showed that prepared particles ensured sustained released of the active molecule and that active release mechanism from particles relied on a combination of drug diffusion and polymer relaxation phenomena.

Alendronate sodium is an active molecule indicated as first line regimen for osteoporosis treatment. Use of this drug presents, however, some shortcomings such as low oral bioavailability and gastrointestinal mucosa irritation. Nanotechnology remains an attractive approach to overcome such limitations of conventional pharmaceutical forms. However, encapsulation of hydrophilic molecules like alendronate represents a real challenge. Preparation, characterization and drug release behavior of polycaprolactone based nanoparticles loaded with alendronate sodium were investigated in this work. Two strategies were used to prepare these nanocarriers: double emulsion evaporation and nanoprecipitation. Operating conditions were monitored to produce biocompatible nanoparticles with good properties. Both techniques gave nanoparticles with mean diameter in the range of 200–450 nm. Encapsulation efficiency of selected formulae reached 34% for double emulsion and 18% for nanoprecipitation, respectively. Highest drug loading was 20.7% for double emulsion and 8.2% for nanoprecipitation, respectively. For both methods, an increase of polymer molecular weight and polymer amount led to an increase of particle size. For nanoprecipitation, oil to water phase exerted also a significant effect on particle size. The increase of stabilizer amount or the use of rotoevaporation rather than continuous stirring at ambient temperature decreased particles size. Prepared nanoparticles exhibited sustained release of alendronate. When the same polymer amount and molecular weight was used, drug release of the selected formulae was faster for nanoparticles formulated by the nanoprecipitation method. However, release profiles were similar for both techniques with a first rapid release phase followed by a more prolonged phase. Analysis of in vitro release data showed also that active release mechanism relied on a combination of drug diffusion and polymer relaxation phenomena.