Limits...
Effect of formulation variables on preparation of celecoxib loaded polylactide-co-glycolide nanoparticles.

Cooper DL, Harirforoosh S - PLoS ONE (2014)

Bottom Line: The use of 0.1, 0.25, and 0.5% w/v didodecyldimethylammonium bromide resulted in a more than 5-fold increase in zeta potential and a more than 1.5-fold increase in entrapment efficiency with a reduction in particle size over 35%, when compared to stabilizer free formulation.In conclusion, formulations using 5 mg celecoxib with 0.25% w/v didodecyldimethylammonium bromide concentrations produced nanoparticles exhibiting enhanced size reduction and entrapment efficiency.Furthermore, emulsifier free formulations demonstrated improved zeta potential when compared to formulations containing emulsifier (p<0.01).

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, Gatton College of Pharmacy, East Tennessee State University, Johnson City, Tennessee, United States of America.

ABSTRACT
Polymer based nanoparticle formulations have been shown to increase drug bioavailability and/or reduce drug adverse effects. Nonsteroidal anti-inflammatory drugs (e.g. celecoxib) reduce prostaglandin synthesis and cause side effects such as gastrointestinal and renal complications. The aim of this study was to formulate celecoxib entrapped poly lactide-co-glycolide based nanoparticles through a solvent evaporation process using didodecyldimethylammonium bromide or poly vinyl alcohol as stabilizer. Nanoparticles were characterized for zeta potential, particle size, entrapment efficiency, and morphology. Effects of stabilizer concentration (0.1, 0.25, 0.5, and 1% w/v), drug amount (5, 10, 15, and 20 mg), and emulsifier (lecithin) on nanoparticle characterization were examined for formula optimization. The use of 0.1, 0.25, and 0.5% w/v didodecyldimethylammonium bromide resulted in a more than 5-fold increase in zeta potential and a more than 1.5-fold increase in entrapment efficiency with a reduction in particle size over 35%, when compared to stabilizer free formulation. Nanoparticle formulations were also highly influenced by emulsifier and drug amount. Using 0.25% w/v didodecyldimethylammonium bromide NP formulations, peak zeta potential was achieved using 15 mg celecoxib with emulsifier (17.15±0.36 mV) and 20 mg celecoxib without emulsifier (25.00±0.18 mV). Peak NP size reduction and entrapment efficiency was achieved using 5 mg celecoxib formulations with (70.87±1.24 nm and 95.55±0.66%, respectively) and without (92.97±0.51 nm and 95.93±0.27%, respectively) emulsifier. In conclusion, formulations using 5 mg celecoxib with 0.25% w/v didodecyldimethylammonium bromide concentrations produced nanoparticles exhibiting enhanced size reduction and entrapment efficiency. Furthermore, emulsifier free formulations demonstrated improved zeta potential when compared to formulations containing emulsifier (p<0.01). Therefore, our results suggest the use of emulsifier free 5 mg celecoxib drug formulations containing 0.25% w/v didodecyldimethylammonium bromide for production of polymeric NPs that demonstrate enhanced zeta potential, small particle size, and high entrapment efficiency.

Show MeSH

Related in: MedlinePlus

TEM images illustrating morphology of 0.25% w/v DMAB NP formulations with emulsifier at A) 5 mg drug amount, B) 10 mg drug amount, C) 15 mg drug amount, and D) 20 mg drug amount.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4264745&req=5

pone-0113558-g004: TEM images illustrating morphology of 0.25% w/v DMAB NP formulations with emulsifier at A) 5 mg drug amount, B) 10 mg drug amount, C) 15 mg drug amount, and D) 20 mg drug amount.

Mentions: To study the effect of drug amount on NP characteristics, formulations consisting of 0.25% DMAB concentrations were chosen based on their sufficient size and general representation of drug entrapment and zeta potential. In conjunction with previously formulated NP systems using 20 mg CEL, new NPs with or without emulsifier were formulated with increasing amounts (5, 10, and 15 mg) of CEL (Table 3). Morphological characterization of NPs formulated with (Fig. 4) and without (Fig. 5) emulsifier at various drug amounts showed spherical shape and size similar to what was noticed in previous formulation studies [23], [24], [54]–[58]. All NP formulations without emulsifier displayed significantly higher zeta potential compared to formulations with emulsifier (Fig. 6A) (p<0.01). Maximum zeta potential was reached in formulations of 20 mg CEL without emulsifier (25.00±0.18 mV). Formulations with emulsifier reached peak zeta potential using 15 mg CEL (17.15±0.36 mV). These results further indicate that use of emulsifiers such as lecithin, can function to mask surface charge of the incorporated stabilizer thereby reducing overall cationic charge associated with DMAB formulated NPs [44].


Effect of formulation variables on preparation of celecoxib loaded polylactide-co-glycolide nanoparticles.

Cooper DL, Harirforoosh S - PLoS ONE (2014)

TEM images illustrating morphology of 0.25% w/v DMAB NP formulations with emulsifier at A) 5 mg drug amount, B) 10 mg drug amount, C) 15 mg drug amount, and D) 20 mg drug amount.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4264745&req=5

pone-0113558-g004: TEM images illustrating morphology of 0.25% w/v DMAB NP formulations with emulsifier at A) 5 mg drug amount, B) 10 mg drug amount, C) 15 mg drug amount, and D) 20 mg drug amount.
Mentions: To study the effect of drug amount on NP characteristics, formulations consisting of 0.25% DMAB concentrations were chosen based on their sufficient size and general representation of drug entrapment and zeta potential. In conjunction with previously formulated NP systems using 20 mg CEL, new NPs with or without emulsifier were formulated with increasing amounts (5, 10, and 15 mg) of CEL (Table 3). Morphological characterization of NPs formulated with (Fig. 4) and without (Fig. 5) emulsifier at various drug amounts showed spherical shape and size similar to what was noticed in previous formulation studies [23], [24], [54]–[58]. All NP formulations without emulsifier displayed significantly higher zeta potential compared to formulations with emulsifier (Fig. 6A) (p<0.01). Maximum zeta potential was reached in formulations of 20 mg CEL without emulsifier (25.00±0.18 mV). Formulations with emulsifier reached peak zeta potential using 15 mg CEL (17.15±0.36 mV). These results further indicate that use of emulsifiers such as lecithin, can function to mask surface charge of the incorporated stabilizer thereby reducing overall cationic charge associated with DMAB formulated NPs [44].

Bottom Line: The use of 0.1, 0.25, and 0.5% w/v didodecyldimethylammonium bromide resulted in a more than 5-fold increase in zeta potential and a more than 1.5-fold increase in entrapment efficiency with a reduction in particle size over 35%, when compared to stabilizer free formulation.In conclusion, formulations using 5 mg celecoxib with 0.25% w/v didodecyldimethylammonium bromide concentrations produced nanoparticles exhibiting enhanced size reduction and entrapment efficiency.Furthermore, emulsifier free formulations demonstrated improved zeta potential when compared to formulations containing emulsifier (p<0.01).

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, Gatton College of Pharmacy, East Tennessee State University, Johnson City, Tennessee, United States of America.

ABSTRACT
Polymer based nanoparticle formulations have been shown to increase drug bioavailability and/or reduce drug adverse effects. Nonsteroidal anti-inflammatory drugs (e.g. celecoxib) reduce prostaglandin synthesis and cause side effects such as gastrointestinal and renal complications. The aim of this study was to formulate celecoxib entrapped poly lactide-co-glycolide based nanoparticles through a solvent evaporation process using didodecyldimethylammonium bromide or poly vinyl alcohol as stabilizer. Nanoparticles were characterized for zeta potential, particle size, entrapment efficiency, and morphology. Effects of stabilizer concentration (0.1, 0.25, 0.5, and 1% w/v), drug amount (5, 10, 15, and 20 mg), and emulsifier (lecithin) on nanoparticle characterization were examined for formula optimization. The use of 0.1, 0.25, and 0.5% w/v didodecyldimethylammonium bromide resulted in a more than 5-fold increase in zeta potential and a more than 1.5-fold increase in entrapment efficiency with a reduction in particle size over 35%, when compared to stabilizer free formulation. Nanoparticle formulations were also highly influenced by emulsifier and drug amount. Using 0.25% w/v didodecyldimethylammonium bromide NP formulations, peak zeta potential was achieved using 15 mg celecoxib with emulsifier (17.15±0.36 mV) and 20 mg celecoxib without emulsifier (25.00±0.18 mV). Peak NP size reduction and entrapment efficiency was achieved using 5 mg celecoxib formulations with (70.87±1.24 nm and 95.55±0.66%, respectively) and without (92.97±0.51 nm and 95.93±0.27%, respectively) emulsifier. In conclusion, formulations using 5 mg celecoxib with 0.25% w/v didodecyldimethylammonium bromide concentrations produced nanoparticles exhibiting enhanced size reduction and entrapment efficiency. Furthermore, emulsifier free formulations demonstrated improved zeta potential when compared to formulations containing emulsifier (p<0.01). Therefore, our results suggest the use of emulsifier free 5 mg celecoxib drug formulations containing 0.25% w/v didodecyldimethylammonium bromide for production of polymeric NPs that demonstrate enhanced zeta potential, small particle size, and high entrapment efficiency.

Show MeSH
Related in: MedlinePlus