The aim of this study was to relate the composition of the W/O emulsion used as a starting fluid in the spray-drying process to the quality of the dry polymer particles obtained in terms of physical–chemical properties, compatibility and drug release performance. Four W/O emulsions containing vancomycin hydrochloride (VAN), an encapsulating PLGA polymer and Poloxamer^® 407, chitosan and/or sorbitan monooleate as stabilisers were spray-dried using an ultrasonic atomising nozzle. The microparticles obtained were micron-sized, with a volume mean diameter between 43.2 ± 0.3 and 64.0 ± 12.6 µm, and spherical with a mostly smooth, non-porous surface and with high drug loading (between 14.5 ± 0.6 and 17.1 ± 1.9% w/w). All formulations showed a prolonged and biphasic VAN release profile, with diffusion being the primary release mechanism. Microparticles prepared from the emulsions with Poloxamer^® 407 and sorbitan monooleate released VAN rapidly and completely within one day. The release of VAN from microparticles prepared from the emulsion without additives or with chitosan in the inner aqueous phase was significantly decreased; after four days, a cumulative release of 65% and 61%, respectively, was achieved. Microparticles with encapsulated chitosan had the largest mean particle diameter and the slowest release of VAN.

Background/Objectives: This study investigates the stabilisation mechanisms of azelaic acid nanosuspensions (AZA-NS) prepared by wet media milling (WMM) using hydroxypropyl methylcellulose (HPMC) and chitosan as stabilisers. The aim was to elucidate the physical interactions relevant for stabilisation and to evaluate the effectiveness of a dual stabiliser approach to improve AZA-NS stability. Methods: AZA-NS were characterised using Fourier transform infrared spectroscopy (FTIR) to evaluate the chemical interactions, differential scanning calorimetry (DSC) for thermal properties, atomic force microscopy (AFM) to analyse the adsorption of the stabiliser on the AZA surface and X-ray diffraction (XRD) to evaluate the crystallinity. Contact angle and immersion studies were performed to evaluate wettability, and alternative stabilisers were tested for comparison. Results: Highly concentrated AZA-NS (up to 20% drug loading) were successfully produced with particle sizes between 326.8 and 541.2 nm, which are in the optimal range for follicular drug delivery. FTIR confirmed stabilisation by adsorption and not by chemical interaction. DSC revealed a melting point depression, indicating a partial disorder of the crystal lattice. AFM imaging showed different adsorption patterns for HPMC and chitosan, suggesting better surface coverage compared to alternative stabilisers. XRD confirmed the retention of the AZA crystalline form after milling. Contact angle and immersion studies showed improved wettability due to the synergistic effects of HPMC and chitosan. Alternative stabilisers showed suboptimal performance, highlighting the superior stabilising potential of the HPMC–chitosan combination. Conclusions: This study provides important insights into the dual stabilisation mechanisms and highlights the importance of combining steric and electrostatic stabilisers for the formulation of stable nanosuspensions of medium soluble drugs such as AZA. These results support the development of optimised nanosuspensions with increased stability and improved pharmaceutical applicability.