Tailoring the release of drugs having different water solubility by hybrid polymer-lipid microparticles with a biphasic structure.

The aim of this study is to investigate the potential of hybrid polymer-lipid microparticles with a biphasic structure (b-MPs) as drug delivery system. Hybrid b-MPs of Compritol®888 ATO as main lipid constituent of the shell and polyethylene glycol 400 as core material were produced by an innovative solvent-free approach based on spray congealing. To assess the suitability of hybrid b-MPs to encapsulate various types of APIs, three model drugs (fluconazole, tolbutamide and nimesulide) with extremely different water solubility were loaded into the polymeric core. The hybrid systems were characterized in terms of particle size, morphology and physical state. Various techniques (e.g. optical, Confocal Raman and Scanning Electron Microscopy) were used to investigate the influence of the drugs on different aspects of the b-MPs, including external and internal morphology, properties at the lipid/polymer interface and drug distribution. Hybrid b-MPs were suitable for the encapsulation of all drugs (encapsulation efficiency > 90 %) regardless the drug hydrophobic/hydrophilic properties. Finally, the drug release behaviors from hybrid b-MPs were studied and compared with traditional solid lipid MPs (consisting of only the lipid carrier). Due to the combination of lipid and polymeric materials, hybrid b-MPs showed a wide array of release profiles that depends on their composition, the type of loaded drug, the drug loading amount and location, providing a versatile platform and allowing the formulators to finely balance the release performance of drugs intended for oral administration. Overall, the study demonstrates that hybrid, solvent-free b-MPs produced by spray congealing are an extremely versatile delivery platform able to efficiently encapsulate and release very different types of drug compounds.

Solvent-Free Fabrication of Biphasic Lipid-Based Microparticles with Tunable Structure.

Lipid-based biphasic microparticles are generally produced by long and complex techniques based on double emulsions. In this study, spray congealing was used as a solvent-free fabrication method with improved processability to transform water-in-oil non-aqueous emulsions into spherical solid lipid-based particles with a biphasic structure (b-MPs). Emulsions were prepared by melt emulsification using different compositions of lipids (Dynasan®118 and Compritol®888 ATO), surfactants (Cetylstearyl alcohol and Span®60) and hydrophilic carriers (PEGs, Gelucire®48/16 and Poloxamer 188). First, pseudo-ternary phase diagrams were constructed to identify the area corresponding to each emulsion type (coarse emulsion or microemulsion). The hydrophobicity of the lipid mostly affected the interfacial tension, and thus the microstructure of the emulsion. Emulsions were then processed by spray congealing and the obtained b-MPs were characterized in terms of thermal and chemical properties (by DSC and FT-IR), external and internal morphology (by SEM, CLSM and Raman mapping). Solid free-flowing spherical particles (main size range 200-355 µm) with different architectures were successfully produced: microemulsions led to the formation of particles with a homogeneous internal structure, while coarse emulsions generated "multicores-shell" particles consisting of variable size hydrophilic cores evenly distributed within the crystalline lipid phase. Depending on their composition and structure, b-MPs could achieve various release profiles, representing a more versatile system than microparticles based on a single lipid phase. The formulation and technological strategy proposed, provides a feasible and cost-effective way of fabricating b-MPs with tunable internal structure and release behavior.