The model retinoid adapalene was formulated in a novel solid lipid microparticle (SLM) dispersion as a topical drug delivery system for transport of the active pharmaceutical ingredient (API) into hair follicle orifices. The aims of the investigations were the solid-state characterization of the lipid matrix (LM) with wide angle X-ray diffraction (WAXD) and hot-stage light microscopy (HS), the design space analysis of the developed SLM dispersion with a Box–Behnken design, the stability study of the manufactured formulation for particle size with laser diffraction and polarization intensity differential scattering (LD/PIDS) and thermal behavior with differential scanning calorimetry (DSC), and the structure analysis of the SLM dispersion with light microscopy, transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The formulation showed a constant mean particle size (MPS) of 4.2 μm over 24 weeks with a melting point of about 56 °C. The potential for dermal application was determined by a follicular penetration (FP) study with porcine ear skin and thermal analysis of the interaction with artificial human skin lipids like sebum and stratum corneum lipid mixture. The in vitro studies confirmed both the follicular penetration potential and a targeted erosion or dissolution of the particles in sebum.