Biodegradable Polymers-Based Smart Nanocrystals for Loxoprofen Delivery with Enhanced Solubility: Design, Fabrication and Physical Characterizations.

ABSTRACT

Nanocrystals are carrier-free, submicron-sized, colloidal drug delivery systems with particle sizes in the mean nanometer range. Nanocrystals have high bioavailability and fast absorption because of their high dissolution velocity and enhanced adhesiveness to cell membranes. Loxoprofen, a nonsteroidal anti-inflammatory drug belonging to the Biopharmaceutical Classification System (BCS) II drug class, was selected as the model drug. The aim of this study was to formulate nanocrystals of loxoprofen. A total of 12 formulations (F1 to F12) were prepared. An antisolvent technique was used to determine the effects of various stabilizers and processing conditions on the optimization of formulations. The various stabilizers used were hydroxypropyl methylcellulose (0.5%), polyvinylpyrrolidone (0.5%), and sodium lauryl sulfate (0.1%). The various characterizations conducted for this research included stability studies at 25 °C and 4 °C, scanning electron microscopy, transmission electron microscopy (TEM), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), zeta potentials, polydispersity indexes, and dissolution studies. F10 was the optimized formulation that showed stability at room temperature, as well as at a refrigerated temperature, for 30 days. A high dissolution rate (100% within the first 10 min) was shown by comparative dissolution studies of nano-suspensions with the micro-suspension and raw loxoprofen. F10 formulation had a non-porous and crystalline morphology on evaluation by TEM and XRPD, respectively, and the average particle size was 300 ± 0.3 nm as confirmed by TEM. DSC recorded a reduction in the melting point (180 °C processed and 200 °C unprocessed melting points). The dissolution rate and solubility of the formulated loxoprofen nanocrystals were significantly enhanced. It can be concluded that selecting suitable stabilizers (i.e., polymers and surfactants) can produce stable nanocrystals, and this can potentially lead to a scaling up of the process for commercialization.