Celecoxib nanosuspension: single-step fabrication using a modified nanoprecipitation method and in vivo evaluation

Abstract

Conventional nanoprecipitation process involves addition of water miscible organic solvent containing drug to an aqueous phase containing hydrophilic surfactants to yield drug nanosuspension. However, nanosuspensions obtained with conventional nanoprecipitation process have very low colloidal stability. The objective of the present investigation was to fabricate drug nanosuspensions with good colloidal stability using a modified nanoprecipitation method. Celecoxib, a hydrophobic anti-inflammatory agent with low oral bioavailability, was used as a model drug for this investigation. The conventional nanoprecipitation method did not result in the nanosizing of the celecoxib. Incorporation of surface active lipophiles such as Labrafil 1944 CS (oleolyl macrogol glycerides) along with hydrophilic surfactants during nanoprecipitation process could successfully nanosize the celecoxib. The particle size of the nanosuspensions was influenced by the various parameters of the nanoprecipitation process and also by the concentration of the lipophilic stabilizer. The celecoxib nanosuspension was characterized by transmission electron microscopy, differential scanning calorimetry, and X-ray diffraction. Saturation solubility of celecoxib was dramatically improved in pH 1.2 buffer when formulated as nanosuspensions. The celecoxib nanosuspesnsion showed significantly higher in vitro dissolution rate and in vivo anti-inflammatory activity as compared to that of celecoxib-marketed formulation.

Single-step and low-energy method to prepare solid lipid nanoparticles and nanostructured lipid carriers using biocompatible solvents

“…We used 4 chemically different biocompatible solvents for the preparation of GMS nanoparticles. However, unlike earlier observations (Date, Srivastava, et al, 2011;Malkani et al, 2014), we did not see a significant change in the size of the GMS nanoparticles as a function of the change in the biocompatible solvent. This may be in part due to equivalent solubility of GMS in all the biocompatible solvents which may have overcome the contribution of solvent-water interaction parameter while preparing GMS nanoparticles.…”

“…Finally, unlike a considerably high amount of organic solvent used in the conventional nanoprecipitation process, we use only 0.5 mL of biocompatible solvents. The ratio of the organic to aqueous phase also influences the nanoprecipitation process (Malkani, Date, & Hegde, 2014) and could also be a contributing factor for the results obtained with Compritol and Precirol. We decided to focus our further studies on the development and optimization of GMS SLN and NLCs using biocompatible solvents.…”

Preparation and Characterization of Celecoxib Agglomerated Nanocrystals and Dry Powder Inhalation Formulations to Improve its Aerosolization Performance

“…Celecoxib is a poorly water-soluble drug classified as biopharmaceutical classification system class II drug (high permeability and low solubility) and poor oral bioavailability (22-40 %). 20 High oral or intravenous dose should be administered to obtain a therapeutic drug level at the site of lung carcinoma, which improves the incidence of undesirable side effects. Hence, pulmonary drug delivery application is considered as an alternative and potential delivery route to the cure of lung cancer.…”

Particle size control and the interactions between drug and stabilizers in an amorphous nanosuspension system

“…Crystalline nanoparticles, also called nanocrystals, are usually prepared by top-down approaches, including wet milling [5,6] and high pressure homogenization [7]. Amorphous nanosuspensions are often produced by bottom-up techniques, among which, antisolvent precipitation [6][7][8][9][10][11][12] are typically used. Nanocrystals could also be formed in a bottom-up process in case the crystallization is not inhibited effectively [13].…”

“…Accordingly, polymer stabilizers that can interfere with crystallization in a competitive manner, are indispensable for amorphous nanosuspensions. In most cases, ultrasonication [6,8,9] or high-speed stirring [10][11][12] should be incorporated in a precipitation procedure to minimize the particle size, which adds to the complexity and difficulty of scale-up.…”