Quality by Design Based Formulation Study of Meloxicam-Loaded Polymeric Micelles for Intranasal Administration

Abstract

Our study aimed to develop an “ex tempore” reconstitutable, viscosity enhancer- and preservative-free meloxicam (MEL)-loaded polymeric micelle formulation, via Quality by Design (QbD) approach, exploiting the nose-to-brain pathway, as a suitable tool in the treatment of neuroinflammation. The anti-neuroinflammatory effect of nose-to-brain NSAID polymeric micelles was not studied previously, therefore its investigation is promising. Critical product parameters, encapsulation efficiency (89.4%), Z-average (101.22 ± 2.8 nm) and polydispersity index (0.149 ± 0.7) and zeta potential (−25.2 ± 0.4 mV) met the requirements of the intranasal drug delivery system (nanoDDS) and the targeted profile liquid formulation was transformed into a solid preservative-free product by freeze-drying. The viscosity (32.5 ± 0.28 mPas) and hypotonic osmolality (240 mOsmol/L) of the reconstituted formulation provides proper and enhanced absorption and probably guarantees the administration of the liquid dosage form (nasal drop and spray). The developed formulation resulted in more than 20 times faster MEL dissolution rate and five-fold higher nasal permeability compared to starting MEL. The prediction of IVIVC confirmed the great potential for in vivo brain distribution of MEL. The nose-to-brain delivery of NSAIDs such as MEL by means of nanoDDS as polymeric micelles offers an innovative opportunity to treat neuroinflammation more effectively.

A Systematic, Knowledge Space-Based Proposal on Quality by Design-Driven Polymeric Micelle Development

“…The thin film method is a production method based on complete solvent evaporation, where the drug and polymer system dissolved in any solvent (mixture) is recovered in the form of a thin film. It is then followed by hydration in water (or water-based buffer) and depending on the properties of the polymer, the process can also be followed by ultrasonication, mixing or even filtration, just like in the production process for liposomes [ 8 , 9 ]. Possible CPP elements and specific CMAs associated with each production method are collected in Table 4 .…”

“…In our previous work, the optimization of Meloxicam-loaded polymeric micelles via RA-based Box–Behnken factorial design was performed and a one-way ANOVA statistical analysis of the results was applied. The effect of the ethanol and sodium-hydroxide volume and the polymer concentration was investigated on particle size and particle size distribution with end results of 111.6 nm and a PdI of 0.114, allowing proper basis for nasal drug delivery [ 9 ]. In addition to these examples, many factorial/neural design studies are there in the literature for polymeric micelles; however, the lack of pre-optimization risk screening can be observed.…”

“…On the one hand, the reason for this is to be found in the production process, as conventional production line equipment is not necessarily suitable for the production of these products besides the need of special conditions and constant control. The opportunity is there in the hands of all developers to apply this method and in the course of our research group, the existence was proven on many occasions for nanoDDSs, such as liposomes [ 8 ], polymeric micelles [ 9 ] and human serum albumin nanoparticles [ 10 ]. On the other hand, safety must also be proven, as an increase in efficacy is expected due to the advanced properties of the systems, but in the case of improperly optimized preparations, it can lead to nanotoxicity and severe side effects [ 11 , 12 ].…”

Formulation and In Vitro and In Silico Characterization of “Nano-in-Micro” Dry Powder Inhalers Containing Meloxicam

“…The API was first released in the simulated lung fluid, and then diffused through the membrane to the phosphate buffer. The amount of diffused MX was determined real-time at λ = 362 nm until 60 min with sonda (FDP-7UV200-VAR, Avantes, Apeldoorn, The Netherlands) spectrophotometer (Avaspec-ULS2048-USB2, Avantes, Apeldoorn, The Netherlands) in the acceptor phase [29]. The samples were measured three times.…”

Lipid-Based Nanocarriers for Ophthalmic Administration: Towards Experimental Design Implementation

“…Quality by design and thus design of experiments have already been widely applied in the food or chemistry industries for product optimisation and process improvement [ 15 , 16 , 17 ]. Applications in the pharmaceutical field have been constantly growing in the past years: from solid dosage forms [ 18 ] to nanoparticulate systems such as liposomes, polymeric micelles or drug nanocrystals [ 19 , 20 , 21 ]. The number of specification requirements in a formulation intended for ocular administration can be demanding [ 22 ].…”