scholarly journals Preparation and Characterization of Fenofibrate Microparticles with Surface-Active Additives: Application of a Supercritical Fluid-Assisted Spray-Drying Process

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2061
Author(s):  
Jeong-Soo Kim ◽  
Heejun Park ◽  
Eun-Sol Ha ◽  
Kyu-Tae Kang ◽  
Min-Soo Kim ◽  
...  
Keyword(s):  
Particle Size ◽  
Surface Layer ◽  
Dissolution Rate ◽  
Spray Drying ◽  
Supercritical Fluid ◽  
Water Soluble ◽  
Size Reduction ◽  
Particle Size Reduction ◽  
Surface Active ◽  
Poorly Water Soluble

In this study, supercritical fluid-assisted spray-drying (SA-SD) was applied to achieve the micronization of fenofibrate particles possessing surface-active additives, such as d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), sucrose mono palmitate (Sucroester 15), and polyoxyethylene 52 stearate (Myrj 52), to improve the pharmacokinetic and pharmacodynamic properties of fenofibrate. For comparison, the same formulation was prepared using a spray-drying (SD) process, and then both methods were compared. The SA-SD process resulted in a significantly smaller mean particle size (approximately 2 μm) compared to that of unprocessed fenofibrate (approximately 20 μm) and SD-processed particles (approximately 40 μm). There was no significant difference in the effect on the particle size reduction among the selected surface-active additives. The microcomposite particles prepared with surface-active additives using SA-SD exhibited remarkable enhancement in their dissolution rate due to the synergistic effect of comparably moderate wettability improvement and significant particle size reduction. In contrast, the SD samples with the surface-active additives exhibited a decrease in dissolution rate compared to that of the unprocessed fenofibrate due to the absence of particle size reduction, although wettability was greatly improved. The results of zeta potential and XPS analyses indicated that the surface-active additive coverage on the surface layer of the SD-processed particles with a better wettability was higher than that of the SA-SD-processed composite particles. Additionally, after rapid depletion of hydrophilic additives that were excessively distributed on the surfaces of SD-processed particles, the creation of a surface layer rich in poorly water-soluble fenofibrate resulted in a decrease in the dissolution rate. In contrast, the surface-active molecules were dispersed homogeneously throughout the particle matrix in the SA-SD-processed microparticles. Furthermore, improved pharmacokinetic and pharmacodynamic characteristics were observed for the SA-SD-processed fenofibrate microparticles compared to those for the SD-processed fenofibrate particles. Therefore, the SA-SD process incorporating surface-active additives can efficiently micronize poorly water-soluble drugs and optimize their physicochemical and biopharmaceutical characteristics.

scholarly journals Formulation and Particle Size Reduction Improve Bioavailability of Poorly Water-Soluble Compounds with Antimalarial Activity

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Hongxing Wang ◽  
Qigui Li ◽  
Sean Reyes ◽  
Jing Zhang ◽  
Lisa Xie ◽  
...  
Keyword(s):  
Particle Size ◽  
Solid Dispersion ◽  
Antimalarial Activity ◽  
Fold Increase ◽  
Water Soluble ◽  
Size Reduction ◽  
Particle Size Reduction ◽  
Physical Form ◽  
Poorly Water Soluble ◽  
Nanoparticle Formulation

Decoquinate (DQ) is highly effective at killing malaria parasites in vitro; however, it is extremely insoluble in water. In this study, solid dispersion method was used for DQ formulation which created a suitable physical form of DQ in aqueous phase for particle manipulation. Among many polymers and surfactants tested, polyvinylpyrrolidone 10, a polymer, and L-α-phosphatidylcholine or polysorbate, two surfactants, were chosen as DQ formulation components. The formulation particles were reduced to a mean size between 200 to 400 nm, which was stable in aqueous medium for at least three weeks. Pharmacokinetic (PK) studies showed that compared to DQ microparticle suspension, a nanoparticle formulation orally dosed to mice showed a 14.47-fold increase in area under the curve (AUC) of DQ plasma concentration and a 4.53-fold increase in AUC of DQ liver distribution. WR 299666, a poorly water-soluble compound with antimalarial activity, was also tested and successfully made into nanoparticle formulation without undergoing solid dispersion procedure. We concluded that nanoparticles generated by using appropriate formulation components and sufficient particle size reduction significantly increased the bioavailability of DQ and could potentially turn this antimalarial agent to a therapeutic drug.

Liquid antisolvent recrystallization and solid dispersion of flufenamic acid with polyvinylpyrrolidone K-30

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Rahul Kumar ◽  
Sanjay Kumar ◽  
Pranava Chaudhari ◽  
Amit K. Thakur
Keyword(s):  
Particle Size ◽  
Dissolution Rate ◽  
Solid Dispersion ◽  
Fine Particles ◽  
Xrd Analysis ◽  
Solution Concentration ◽  
Injection Rate ◽  
Size Reduction ◽  
Flufenamic Acid ◽  
Particle Size Reduction

Abstract Flufenamic acid (FFA) is a Biopharmaceutical Classification System- II (BCS-II) class drug with poor bioavailability and a lower dissolution rate. Particle size reduction is one of the conventional approaches to increase the dissolution rate and subsequently the bioavailability. The use of the liquid antisolvent method for particle size reduction of FFA was studied in this work. Ethanol and water were used as solvent and antisolvent, respectively. Experimental parameters such as solution concentration (10–40 mg/ml), flow rate (120–480 ml/h), temperature (298–328 K) and stirring speed (200–800 rpm) were investigated. Furthermore, the solid dispersion of FFA was prepared with polyvinylpyrrolidone K-30 (PVP K-30) with different weight ratios (1:1, 1:2, 1:3 and 1:4) and samples were characterized using SEM, FTIR and XRD techniques. The experimental investigation revealed that higher values of concentration, injection rate, stirring speed, along with lower temperature favored the formation of fine particles. SEM analysis revealed that the morphology of raw FFA changed from rock-like to rectangular-like after liquid antisolvent recrystallization. FTIR analysis validated the presence of hydrogen bonding between FFA and PVP in solid dispersion. XRD analysis showed no significant change in the crystallinity of the processed FFA.

scholarly journals Dissolution rate and bioavailability enhancement of co-ground mixtures of paliperidone, with different hydrophilic carriers

2013 ◽  
Vol 2 (3) ◽  
pp. 70-77 ◽  
Author(s):  
Anuja Pandey ◽  
Bhabagrahi Rath ◽  
Anil Kumar Dwivedi
Keyword(s):  
Particle Size ◽  
Dissolution Rate ◽  
Methyl Cellulose ◽  
Pharmaceutical Journal ◽  
Water Soluble ◽  
Vinyl Pyrrolidone ◽  
Particle Size Reduction ◽  
Bioavailability Enhancement ◽  
Ground Mixture ◽  
Crystalline Nature

Co-ground mixtures of poorly water soluble drug Paliperidone (PAL) with different hydrophilic carriers [Polyvinylpyrrolidine (Plasdone K-25 and Plasdone S-630), Hydroxypropyl methyl cellulose (HPMC), Hydroxypropylcellulose (HPC) and Sodium alginate were prepared to improve the dissolution rate of PAL. Co-grinding with PVP, especially with PVP- S630 (Vinyl pyrrolidone/ vinyl acetate co-polymer), was more effective in reduction of particle size than milling of drug alone. DSC studies indicated that crystalline nature of drug was reduced after co-grinding with PVP grades as compared to their corresponding physical mixtures. The hydrophilic carriers other than PVP did not reduce the crystalline nature of the drug significantly. X-ray diffraction (XRD) was carried out for selected batches to confirm DSC results. Significant enhancement in dissolution rate as well as extent was observed with co-ground mixtures of drug and PVP. Among all the prepared batches in this study, co-ground mixture of PAL and Plasdone S-630 in 1:1 ratio showed best results in terms of extent of dissolution as well as dissolution rate in water. This effect was not only due to particle size reduction, but also loss of crystalline nature of the drug during co-grinding. PVP was found to be a better carrier among the different hydrophilic carriers used in the study for improving the dissolution characteristics of PAL. The extent of the mean plasma exposures of PAL was 7-fold higher in animals treated with co-ground mixture of PAL, Plasdone S630 (1:1) compared to animals treated with Pure PAL.DOI: http://dx.doi.org/10.3329/icpj.v2i3.13632 International Current Pharmaceutical Journal, February 2013, 2(3): 70-77 

scholarly journals Formulation and Evaluation of Nanosuspension as an Alternative Approach for Solubility Enhancement of Simvastatin

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Mohini E. Shinde ◽  
Mitesh P. Sonawane ◽  
Avish D. Maru
Keyword(s):  
Particle Size ◽  
Average Particle Size ◽  
Entrapment Efficiency ◽  
Water Soluble ◽  
Average Particle ◽  
Particle Size Reduction ◽  
Drug Effectiveness ◽  
Saturation Solubility ◽  
Drug Content ◽  
Poorly Water Soluble

Solubility is an essential factor for drug effectiveness. Simvastatin is poorly water-soluble drug and its bioavailability is very low. Nanosuspension is one of those approach which can tremendously enhance the effective surface area of drug particles by reducing the particle size and there by increases the rate of dissolution and hence improve bioavailability. The main purpose of the present investigation was to increase the saturation solubility of simvastatin by preparation of nanosuspension. Nanosuspension of simvastatin were prepared by nanoprecipitation method using hydroxypropyl cellulose as stabilizer and sodium lauryl sulphate as surfactant. Prepared nanosuspension was evaluated for its particle size, total drug content, entrapment efficiency and saturation solubility study. On the basis of the evaluation, the best batch F8 formulation demonstrated highest drug content and entrapment efficiency with average particle size of 0.004µm. The saturation solubility studies show the solubility of the prepared nanosuspension has increased as compared to the pure drug due to the particle size reduction. The nanosuspension of simvastatin could be successfully prepared and can be concluded that the nanosuspension formulation is a promising approach to enhance the solubility. The nanoprecipitation is a simple and effective method to produce nano sized particles of poorly water-soluble drugs with enhance solubility.

Microstructural effects of high-energy grinding on poorly soluble drugs: the case study of efavirenz

2017 ◽  
Vol 32 (S1) ◽  
pp. S135-S140 ◽  
Author(s):  
Elisa Cappelletto ◽  
Luca Rebuffi ◽  
Alberto Flor ◽  
Paolo Scardi
Keyword(s):  
Particle Size ◽  
Grain Size ◽  
Mechanical Activation ◽  
Morphological Changes ◽  
Domain Size ◽  
High Energy ◽  
Water Soluble ◽  
Size Reduction ◽  
Dissolution Behavior ◽  
Particle Size Reduction

In this work, a poorly water-soluble drug (efavirenz) was mechanically activated by ball-milling. The effect of the mechanical activation on the dissolution behavior was investigated considering changes in the particle size and morphology. The powder diffraction was used to follow the comminution process, verifying phase compositions, and crystalline domain size. The interplay between domain and grain size was studied in relation to the solubility rate, through specific dissolution tests. Finally, the morphological characterization has allowed to complete the physical–chemical characterization of the milled powders. This study demonstrated that the mechanical activation of the drug leads the particle size reduction and, with a long milling time, morphological changes. The grain size reduction is not always sufficient to increase the solubility: morphology and agglomeration grade play an important role in the dissolution process.

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