Continuous and Size-Controlled Preparation of Ibuprofen Nanosuspension by Antisolvent Crystallization Method Using Hollow Fiber Membrane

Ibuprofen first came to market about 50 years ago and rapidly moved to over-the-counter (OTC) sales. In April 2019, the National Agency for the Safety of Medicines and Health Products (ANSM) of France issued a warning for NSAID uses by patients with infectious diseases based on an analysis of 20 years of real-world safety data on ibuprofen and ketoprofen. Nevertheless, ibuprofen remains a mainstay in the analgesic armamentarium and with numerous randomized clinical trials, head-to-head studies, and decades of clinical experience. The authors offer a review of the safety of ibuprofen and how it may differ from other NSAIDs. Ibuprofen is associated with certain well-known gastrointestinal adverse effects that are related to dose and patient population. Among nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen has a comparatively low risk of cardiovascular adverse effects. It has been associated with renal and hepatic adverse effects, which appear to depend on dose, concomitant medications, and patient population. The association of ibuprofen with infections is more complex in that it confers risk in some situations but benefits in others, the latter in cystic fibrosis. Emerging interest in the literature is providing evidence of the role of ibuprofen as a possible endocrine disrupter as well as its potential antiproliferative effects for cancer cells. Taken altogether, ibuprofen has a favorable safety profile and is an effective analgesic for many acute and chronic pain conditions, although it-like other NSAIDs-is not without risk. After 50 years, evidence is still emerging about ibuprofen and its unique safety profile among NSAIDs. FUNDING: The Rapid Service Fee was funded by Abbott Established Pharmaceuticals Division (EPD).

Polymeric nanoparticles (PNPs) are promising drug carriers in cancer treatment. Size of the particles has a significant impact on drug loading, in vivo distribution, extravasation, intratumor diffusion and cell uptake, and thus is critical for the successful development of a drug delivery regime. However, methods for manufacturing PNPs of defined size are yet to be established. The goal of this study is to establish a method that can be used to fabricate PNPs with controlled size. We systematically investigated the factors that could impact the size of PNPs fabricated by nano-precipitation. The factors studied include polymer concentration, organic solvent, temperature, aqueous phase ionic strength, organic phase injection rate, aqueous phase agitation rate, gauge of the needles and final polymer concentration. Polymer concentration, the choice of organic solvent, temperature, and the ionic strength of the aqueous phase were shown to have a significant impact on the size of PNPs, and the effect of these factors can be attributed to a single parameter, the diffusion coefficient of the solvent in water, D pw . It is possible that by tightly control these four parameters, nanoparticles with highly predictable and desirable size with narrow size distribution can be fabricated.