Exploring the Solvent-Anti-solvent Method of Nanosuspension for Enhanced Oral Bioavailability of Lovastatin

Patil, Apurva; Hegde, Riya; Gadad, Anand Panchakshari; Dandagi, Panchaxari Mallappa; Masareddy, Rajashree; Bolmal, Uday

doi:10.4274/tjps.galenos.2020.65047

Cited by 16 publications

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“…As for PDI, the nanosuspensions turned out to be monodisperse (PDI < 0.5) throughout the stability study. HPMC has sufficient affinity for the particle surface and possesses a high enough diffusion rate to adequately cover the generated surface after ultrasound application, which provides sufficient steric repulsion between the particles to contribute to the stability during storage [ 22 ]. In turn, the zeta potential values also remained similar without significant variations.…”

Section: Resultsmentioning

confidence: 99%

“…[ 6 , 8 , 11 , 13 , 18 ]. Hence, in order to obtain an improved product, ultrasonication was introduced as an effective method, which has been combined with precipitation to control nucleation processes and crystal growth using confined jet mixers or multi-entry vortex mixers (flash nanoprecipitation) [ 19 , 20 , 21 , 22 ]. When ultrasonication is applied to liquids, ultrasound waves are characterized by a cyclical succession of expansion and compression phases.…”

Section: Introductionmentioning

confidence: 99%

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Formulation and Characterization of Ursodeoxycholic Acid Nanosuspension Based on Bottom-Up Technology and Box–Behnken Design Optimization

Boscolo,

Flor,

Salvo

et al. 2023

Pharmaceutics

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Background: Ursodeoxycholic acid (UDCA) is a therapeutic agent used for the treatment of cholestatic hepatobiliary diseases in pediatric patients. It is a bile acid that presents high lipophilicity, and it belongs to Class II of the Biopharmaceutical Classification System (BCS), which exhibits low water solubility and high intestinal permeability, which leads to poor oral absorption. The objective of this work was to design and optimize UDCA nanosuspensions by means of the precipitation-ultrasonication method to improve the solubility, dissolution, and oral bioavailability of UDCA. Methods: A three-level, three-factor Box–Behnken design was used to optimize formulation variables and obtain uniform, small-particle-size UDCA nanosuspensions. The independent variables were: stabilizer percentage (X1), amplitude (X2), and sonication time (X3), and the dependent variable was the particle size (Y1). In the precipitation–ultrasonication method, UDCA was dissolved in acetone:PEG 400 (1:1 v/v) and quickly incorporated into the antisolvent (pre-cooled aqueous dispersion of HPMC E-15 0.3%), by means of intense sonication at 50 W for 5 min, controlling temperature through an ice water bath. The lyophilization efficacy was evaluated by means of a cryoprotective efficacy test, working with 10% maltose at −80 °C. The nanosuspensions were characterized by dynamic light scattering (DLS), X-ray diffraction, and scanning electron microscopy (SEM). The physicochemical stability was determined at 25 °C and 4 °C at 7, 14, 30, and 60 days, and the UDCA content was analyzed via HPLC-UV. An in vitro dissolution assay and an oral bioavailability study were performed in male Wistar rats. Results: A significant impact was achieved in the optimized nanosuspension with 0.3% (stabilizer), 50 W (amplitude), and 5 min (sonication time), with a particle size of 352.4 nm, PDI of 0.11, and zeta potential of −4.30 mV. It presented adequate physicochemical stability throughout the study and the UDCA content was between 90% and 110%. In total, 86% of UDCA was dissolved in the in vitro dissolution test. The relative oral bioavailability was similar without significant statistical differences when comparing the lyophilized nanosuspension and the commercial tablet, the latter presenting a more erratic behavior. The pharmacokinetic parameters of the nanosuspension and the commercial tablet were Tmax (1.0 ± 0.9 h vs. 2.0 ± 0.8 h, respectively), Cmax (0.558 ± 0.118 vs. 0.366 ± 0.113 µM, respectively), ΔCmax (0.309 ± 0.099 vs. 0.232 ± 0.056, respectively), AUC (4.326 ± 0.471 vs. 2.188 ± 0.353 µg/mL.h, respectively, p < 0.02), and IAUC0–24h (2.261 ± 0.187 µg/mL.h vs. 1.924 ± 0.440 µg/mL.h, respectively). Conclusions: The developed nanosuspension presents an appropriate dosage and administration for pediatric patients. On the other hand, it exhibits an adequate absorption and UDCA oral bioavailability.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Formulation and Characterization of Ursodeoxycholic Acid Nanosuspension Based on Bottom-Up Technology and Box–Behnken Design Optimization

Boscolo,

Flor,

Salvo

et al. 2023

Pharmaceutics

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“…The measured Z-average particle size after 60 min of grinding was 204.5 nm, the PDI value was 0.147, which is a marker of the narrow size distribution [ 54 ], and the zeta potential was −16.4 mV.…”

Section: Resultsmentioning

confidence: 99%

Systematic Screening Study for the Selection of Proper Stabilizers to Produce Physically Stable Canagliflozin Nanosuspension by Wet Milling Method

Pirincci Tok,

Mesut,

Güngör

et al. 2023

Bioengineering

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One of the crucial approaches to managing the low solubility and weak bioavailability of drugs is via nanocrystal technology. Through this technology, drug particles have an increased solubility and a faster dissolution rate due to high surface free energy, which requires an appropriate stabilizer(s) to prevent instabilities during the manufacturing process and storage of the nanosuspension. This study aimed to establish a scientific predictive system for properly selecting stabilizers or to reduce the attempts on a trial-and-error basis in the wet-milling method. In total, 42 experiments were performed to examine the effect of critical material attributes on the wettability of the drug, the saturation solubility in the stabilizer solutions or combinations thereof and the dynamic viscosity of stabilizer solutions. All data were evaluated by Minitab 19® and an optimization study was performed. The optimized formulation at a certain concentration of stabilizer combination was ground by Dyno Mill® with 0.3 mm beads for one hour. The optimized nanosuspension with a particle size of 204.5 nm was obtained in short milling time and offered 3.05- and 3.51 times better dissolution rates than the marketed drug product (Invokana® 100 mg) in pH 4.5 and pH 6.8 as non-sink conditions, respectively. The formulation was monitored for three months at room temperature and 4 °C. The parameters were 261.30 nm, 0.163, −14.1 mV and 261.50 nm, 0.216 and −17.8 mV, respectively. It was concluded that this approach might indicate the appropriate selection of stabilizers for the wet-milling process.

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Hydrodynamics and Transport Mechanism of Microfluidic Mixing in Precipitation of Nanodrugs: A Review

Behera

Patel

Parikh

2023

Cryst. Res. Technol.

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Poor aqueous solubility drugs are a concern of pharmaceutical industries due to low dissolution rates and low bioavailability. Various approaches and techniques address these issues by customizing drug micro–nanonization, as investigated by many researchers. Establishing a compelling synthesis of tailored nanoparticles with highly variable qualities intended for therapeutic applications needs the flexibility to vary particle size, content, crystallinity, and shape. Such an approach necessitates getting to the desired yield and developing a synthetic process that is durable, reproducible, and scalable. However, precipitation techniques to produce nanoparticles are more convenient than other approaches. Liquid antisolvent precipitation is one of the robust crystal manipulation approaches extensively used for producing nanoparticles, where mixing sets the basis to create supersaturation followed by corresponding quality precipitation. Various process intensification equipments are in use for adequate mixing‐based precipitation. Nowadays, microfluidic precipitation system is gaining interest in the production of nanodrugs. Further, the use of ultrasound in a microfluidic system improves the mixing quality by cavitation phenomena. This review focuses on the transport phenomena and hydrodynamics involved in mixing to enhance the mass transfer during antisolvent precipitation of synthesized nanodrugs in the microfluidic system.

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Exploring the Solvent-Anti-solvent Method of Nanosuspension for Enhanced Oral Bioavailability of Lovastatin

Cited by 16 publications

References 0 publications

Formulation and Characterization of Ursodeoxycholic Acid Nanosuspension Based on Bottom-Up Technology and Box–Behnken Design Optimization

Formulation and Characterization of Ursodeoxycholic Acid Nanosuspension Based on Bottom-Up Technology and Box–Behnken Design Optimization

Systematic Screening Study for the Selection of Proper Stabilizers to Produce Physically Stable Canagliflozin Nanosuspension by Wet Milling Method

Hydrodynamics and Transport Mechanism of Microfluidic Mixing in Precipitation of Nanodrugs: A Review

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