The aim of this study was to develop a long-acting injectable formulation of risperidone using polylactic acid (PLA) or poly (lactic-co-glycolic acid) (PLGA), a biodegradable and biocompatible polymer. Risperidone microspheres (RMs) were prepared by creating an O/W emulsion using dichloromethane (DCM) as a solvent and then employing the solvent evaporation method. The RMs were prepared with four different risperidone-to-PLGA ratios (1:1, 1:1.3, 1:2, and 1:3 (w/w)), and each ratio was subjected to the same manufacturing process. The physicochemical properties of the prepared RMs, such as their shape, particle size, drug loading ratio, encapsulation efficiency, and in vitro degradation profile, were evaluated. The particle size of the RMs ranged from 30 to 100 μm, with larger PLGA ratios resulting in larger RM sizes. The drug loading ratio was inversely proportional to the increase in the PLGA ratio in the RMs, and all the formulations showed improved release profiles compared to the reference drug, Risperdal Consta^®. The release data modeling results showed that the RM-3 formulation with a 1:1 (w/w) ratio of risperidone and PLGA exhibited a release pattern close to zero-order kinetics. The manufactured RMs were confirmed to have the potential to be used as a long-acting risperidone injection with sustained and stable release as well as an extended dosing interval.

Background/Objectives: Tacrolimus has poor aqueous solubility and limited skin permeation, necessitating formulation strategies for effective topical therapy. This study aimed to develop tacrolimus-loaded solid lipid nanoparticles (SLNs) and an SLN-gel, comparing optimized SLNs prepared with three lipids—Compritol 888 ATO (C888), Compritol HD5 ATO (CHD5), and Stearic acid (St.a). Methods: Each SLN was optimized via Box–Behnken design (BBD) using factors X1 (lipid amount), X2 (surfactant amount), and X3 (homogenization speed). Morphological analysis was conducted using SEM and TEM, while the solid-state properties were evaluated by XRD and FT-IR. In vitro drug release was assessed using the dialysis bag method, and permeation was evaluated using Franz diffusion cells. The SLNs showing the highest cumulative permeation with a consistent release profile were tested in a 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis mouse model. Results: Optimized SLNs obtained from the BBD demonstrated particle sizes of 275.8, 190.9, 308.9 nm, PDIs of 0.35, 0.26, 0.14, zeta potentials of −15.2, −12.9, −24.0 mV, and encapsulation efficiencies of 84.6, 91.8, 92.5% for C888, CHD5, and St.a, respectively. In dialysis-bag studies, all SLNs showed higher cumulative release than drug solution and Protopic^® 0.1%. SEM/TEM revealed spherical morphology, while FT-IR/XRD confirmed drug incorporation within the lipid matrix. Franz diffusion showed higher permeation than API-gel and Protopic^® 0.1%, ranked St.a > C888 > CHD5, with 48 h cumulative amounts of 127.2, 96.8, 87.5 μg/cm². The St.a-SLN-gel significantly improved atopic dermatitis lesions in the DNCB-induced mouse model in vivo (score 14.5→1.75, n = 6, p < 0.001). Conclusions: Box–Behnken optimization produced an SLN-gel surpassing existing formulations in release, permeation, and in vivo efficacy, demonstrating tunable performance via lipid selection and offering a reproducible, translatable approach for topical tacrolimus.