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

Abstract

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.

Solid Lipid Microparticles by Spray Congealing of Water/Oil Emulsion: An Effective/Versatile Loading Strategy for a Highly Soluble Drug

“…The transparency of some formulations can be attributed to a smaller size of the drops of their dispersed phase compared to those of the cloudy emulsions, hypothesizing that watery droplets at narrow nanoscale dimensions were generated. This is supported by other authors that obtained oil-in-water nano-emulsions characterized by a translucent appearance [26] or developed lipid-based microparticles by spray congealing starting from a W/O emulsion characterized by nano-sized droplets of the hydrophilic phase (PEG 400 and a pink dye) [6].…”

“…Another protein hydrolysate (soybean) was encapsulated by Salvim et al [25] in partially hydrogenated cottonseed oil. More recently, Bertoni et al [6] described the spray congealing of a water-in-oil (W/O) emulsion loaded with a water-soluble dye (rhodamine), in which the "aqueous phase" was a hydrophilic molten excipient (PEG 400), and the "oily phase" was a long chain glyceride.…”

“…The use of lipid excipients in pharmaceutical products offers interesting benefits: their costs are relatively lower than those of other excipients (e.g., polymers) obtained through complex chemical processes. Moreover, lipid excipients are biodegradable and GRAS (generally recognized as safe) substances [4,5] that can be used in solvent-free processes and this makes them suitable for large-scale production [6].…”

“…Based on the previous statements, it is clear that the use of a suspension is the most common approach when the spray congealing process is carried out because it is more flexible and easier to develop than when a solution is the starting point (i.e., it is not always possible to identify a lipid mixture able to solubilize a specific drug); moreover, the choice of the proper excipients can manage the API release. Conversely, using an emulsion as starting material for a spray congealing treatment is not so frequent; the literature offers only a few examples [6,24,25]. In this case, a water-in-oil emulsion, in which the oily phase is constituted by the melted lipid and the aqueous phase is an aqueous solution or a hydrophilic molten excipient in which the API could be solubilized, is prepared and submitted to the spray congealing process.…”

Propolis-Based Nanostructured Lipid Carriers for α-Mangostin Delivery: Formulation, Characterization, and In Vitro Antioxidant Activity Evaluation

“…Polysorbate 80 (Tween 80 ® ) was chosen as the surfactant due to its high emulsification capacity for lipid components and its non-irritating properties, particularly for topical applications [ 35 ]. Furthermore, the melt–emulsification method combined with ultrasonication was selected as it is more environmentally friendly, eliminating the need for organic solvents [ 36 , 37 ].…”