Antónia Gonçalves, Cláudia Costa, Rui Pinho, Susana Saldanha
Hovione FarmaCiência, Campus do Lumiar, Edifício R, Estrada do Paço do Lumiar, 1649-038 Lisboa, Portugal
Summary
Nasal drug delivery presents a non-invasive, rapid, and effective alternative for both local and systemic therapies, with the added advantage of bypassing first-pass metabolism and potentially enabling brain targeting. Polymeric lipid hybrid nano-in-microparticles (PLNiM) represent an innovative strategy that merges polymer stability with lipid biocompatibility, offering enhanced drug protection, sustained release, and modifiable surface properties for targeted delivery. This study aimed to develop stable amorphous PLNiM for nasal administration, incorporating piroxicam, a poorly soluble drug, maximizing drug loading and bioavailability. Piroxicam solubility was evaluated in various lipids and in a lipid/ dichloromethane (DCM) system, yielding 1.6 and 6.6% w/w, respectively. High-shear mixing (HSM) parameters were optimized to produce nanoparticles with particle size distribution (PSD) under 200 nm and polydispersity index (PDI) below 0.3, critical for nasal delivery efficacy [[i]]. Emulsion stability was achieved using a combination of Tween® 80 and Methocel* E5 Premium LV Hydroxypropyl Methylcellulose (HPMC E5), minimizing surfactant concentration to safe nasal limits. Spray drying was employed to produce an amorphous PLNiM powder with hydroxypropyl methylcellulose HPMC-AS (as stabilizer and bulking agent) and a drug load up to 10.8% w/w, demonstrating suitable particle size distribution for nasal delivery (> 10 µm). Analytical characterization confirmed solid-state, and homogeneity. These findings validate the potential of PLNiM systems as a versatile nasal drug delivery vehicle, particularly for poorly soluble drugs like piroxicam, enhancing therapeutic outcomes through improved bioavailability and patient compliance.
[[i]] Costa, C, Moreira, J N, Amaral, M H, Lobo, J M S, Silva, A C: Nose-to-brain delivery of lipid-based nanosystems for epileptic seizures and anxiety crisis. Journal of Controlled Release 2019; 295: pp 187-200.