Polymeric Nanoparticles for Increased Oral Bioavailability and Rapid Absorption Using Celecoxib as a Model of a Low-Solubility, High-Permeability Drug

Abstract

PurposeTo demonstrate drug/polymer nanoparticles can increase the rate and extent of oral absorption of a low-solubility, high-permeability drug.MethodsAmorphous drug/polymer nanoparticles containing celecoxib were prepared using ethyl cellulose and either sodium caseinate or bile salt. Nanoparticles were characterized using dynamic light scattering, transmission and scanning electron microscopy, and differential scanning calorimetry. Drug release and resuspension studies were performed using high-performance liquid chromatography. Pharmacokinetic studies were performed in dogs and humans.ResultsA physical model is presented describing the nanoparticle state of matter and release performance. Nanoparticles dosed orally in aqueous suspensions provided higher systemic exposure and faster attainment of peak plasma concentrations than commercial capsules, with median time to maximum drug concentration (Tmax) of 0.75 h in humans for nanoparticles vs. 3 h for commercial capsules. Nanoparticles released celecoxib rapidly and provided higher dissolved-drug concentrations than micronized crystalline drug. Nanoparticle suspensions are stable for several days and can be spray-dried to form dry powders that resuspend in water.ConclusionsDrug/polymer nanoparticles are well suited for providing rapid oral absorption and increased bioavailability of BCS Class II drugs.

Beta-casein nanocarriers of celecoxib for improved oral bioavailability

“…This increase in systemic exposure, which was accompanied by lower T max values of Cx/bCN, indicates that this formulation was characterized by more rapid and efficient Cx dissolution in the GI tract. This outcome may stem from the fact that the Celebra ® formulation contained micron-sized crystalline drug (11,38) while Cx in Cx/bCN is nano-sized and amorphous (15). Enhanced dissolution rate and oral bioavailability of Cx in an amorphous nano-formulation was previously reported (12).…”

“…At concentrations above its critical micellization concentration (CMC, 0.5-2 mg/mL at pH∼7, 25°C), bCN self-assembles in water into nanometric micelles (∼20-25 nm in diameter) having a hydrophobic core and a hydrophilic corona (17). The bCN structural and physicochemical properties facilitate its application in drug delivery (18)(19)(20), and bCN has been used for encapsulation of hydrophobic chemotherapeutics (21)(22)(23), However, our formulation is quite different from these, and also from the Cx and casein-based formulation described recently (11). We assumed that in our formulation, bCN can allow high drug loading and encapsulation efficiency since the drug is encapsulated within bCN micelles present in significantly higher concentrations than its CMC.…”

“…Examples include the use of co-solvents (1), cyclodextrin (6), a self-microemulsifying drug delivery system (7), salt formation combined with precipitation inhibitors (8), reduction in particle size (9,10) and formation of amorphous nanoparticles (10)(11)(12)(13).…”

Ethyl cellulose nanoparticles as a platform to decrease ulcerogenic potential of piroxicam: formulation and in vitro/in vivo evaluation

“…This complies with the typical nature of solid particles formed using emulsion or precipitation methods, due to the favorable energetics associated with minimization of surface area. 30 It was also reported that spherical nature of the formed NPs itself provided favorable controlled release of incorporated drug where it provided a long diffusion pathway. 17 Differential scanning calorimetry DSC thermograms of PX, P188, EC, their PM, and P188/0.2 are presented in Figure 3.…”

Innovative pharmaceutical formulations and excipients for nasal delivery of drugs to target the systemic circulation

“…Nanonization of pharmacons offers a great possibility to increase their solubility (Ambrus et al, 2009) and to enhance permeability through mucosal barriers (Morgen et al, 2012). Nano-sized drug particles with carriers can overcome the resistance offered by biological barriers .…”