Design, optimization and pharmaceutical characterization of wound healing film dressings with chloramphenicol and ibuprofen.

OBJECTIVE: The aim of the present study was to develop and optimize a wound dressing film loaded with chloramphenicol (CAM) and ibuprofen (IBU) using a Quality by Design (QbD) approach. SIGNIFICANCE: The two drugs have been combined in the same dressing as they address two critical aspects of the wound healing process, namely prevention of bacterial infection and reduction of inflammation and pain related to injury. METHODS: Three critical formulation variables were identified, namely the ratios of Kollicoat SR 30D, polyethylene glycol 400 and polyvinyl alcohol. These variables were further considered as factors of an experimental design, and 17 formulations loaded with CAM and IBU were prepared via solvent casting. The films were characterized in terms of dimensions, mechanical properties and bioadhesion. Additionally, the optimal formulation was characterized regarding tensile properties, swelling behavior, water vapor transmission rate, surface morphology, thermal behavior, goniometry, in vitro drug release, cell viability, and antibacterial activity. RESULTS: The film was optimized by setting minimal values for the folding endurance, adhesive force and hardness. The optimally formulated film showed good fluid handling properties in terms of swelling behavior and water vapor transmission rate. IBU and CAM were released from the film up to 80.9% and 82.5% for 8 h. The film was nontoxic, and the antibacterial activity was prominent against Micrococcus spp. and Streptococcus pyogenes. CONCLUSIONS: The QbD approach was successfully implemented to develop and optimize a novel film dressing promising for the treatment of low-exuding acute wounds prone to infection and inflammation.

Lipid-microparticles for pulmonary delivery of active pharmaceutical ingredients: Impact of lipid crystallization on spray-drying processability.

Spray-drying is an extensively used technology for engineering inhalable particles. Important technical hurdles are however experienced when lipid-based excipients (LBEs) are spray-dried. Stickiness, extensive wall deposition, or simply inability to yield a solid product have been associated to the low melting points of LBEs. In this work, solutions containing polyglycerol esters of behenic acid (PGFA-behenates), or other high melting point LBEs, were spray-dried to produce ibuprofen (IBU)-loaded inhalable lipid-microparticles. Prior to spray-drying, rational boundaries for the outlet temperature of the process were defined using LBE-IBU phase diagrams. Despite spray-drying the solutions at outlet temperatures below the boundaries, process performance and yield among LBEs were entirely different. Lipid crystallization into polymorphs or multi-phases negatively impacted the yield (10-47%), associated to liquid fractions unable to recrystallize at the surrounding gas temperature in the spray-dryer. The highest yields (76-82%), ascribed to PGFA-behenates, resulted from monophasic crystallization and absence of polymorphism. Lipid-microparticles, composed of a PGFA-behenate, were characterized by a volume mean diameter of 6.586 µm, tap density of 0.389 g/cm3 and corrugated surface. Application as carrier-free dry powder for inhalation resulted in high emitted fraction (90.9%), median mass aerodynamic diameter of 3.568 µm, fine particle fraction of 45.6% and modified release in simulated lung fluid.