Nanosuspension for improving the bioavailability of a poorly soluble drug and screening of stabilizing agents to inhibit crystal growth

Ghosh, Indrajit; Bose, Sonali; Vippagunta, Radha; Harmon, Ferris

doi:10.1016/j.ijpharm.2011.02.051

Cited by 232 publications

(127 citation statements)

References 11 publications

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“…The higher MW of Poloxamer 407 (MW 14,600 g/mol) increased its ability to cover RIF particle surfaces more than that of Poloxamer 188 (MW 7,680 g/mol). These results were in accordance to those reported by Ghosh et al 39 From Table 1, HPMC (4,000 cp) of higher viscosity resulted in the formation of smaller particles (473.5±2.192 nm) but with a larger particle distribution index (0.610±0.079) compared to that of the lower viscosity. HPMC polymers are able to induce steric stabilization of the NS through their absorption on the drug particle surface via their hydrophilic and hydrophobic components, namely, hydroxy propyl and methoxyl groups, respectively.…”

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confidence: 92%

The relevancy of controlled nanocrystallization on rifampicin characteristics and cytotoxicity

Mohyeldin

Mehanna

Elgindy

2016

IJN

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Purpose This article investigated the influence of novel rifampicin nanosuspension (RIF NS) for enhancing drug delivery properties. Methods RIF NS was fabricated using the antisolvent precipitation technique. The impact of solvent type and flow rate, stabilizer type and concentration, and stirring time and apparatus together with the solvent–antisolvent volume ratio on its controlled nanocrystallization has been evaluated. NSs were characterized by transmission electron microscopy, particle size and zeta potential analysis, solubility, and dissolution profiles. The compatibility between RIF and the stabilizer was investigated via Fourier transform infrared spectroscopy and the differential scanning calorimetry techniques. The shelf-life stability of the RIF NS was assessed within a period of 3 months at different storage temperatures. Cell cytotoxicity was evaluated using 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on lung epithelial cells. Results Polyvinyl alcohol at 0.4% w/v, 1:15 methanol to deionized water volume ratio and 30-minutes sonication were the optimal parameters for RIF NS preparation. Nanocrystals were obtained with a nanometeric particle size (101 nm) and a negative zeta potential (−26 mV). NS exhibited a 50-fold enhancement in RIF solubility and 97% of RIF was dissolved after 10 minutes. The RIF NS was stable at 4±0.5°C with no significant change in particle size or zeta potential. The MTT cytotoxicity assay of RIF NS demonstrated a good safety profile and reduction in cell cytotoxicity with half maximal inhibitory concentration values of 0.5 and 0.8 mg/mL for free RIF and RIF NS, respectively. Conclusion A novel RIF NS could be followed as an approach for enhancing RIF physicochemical characteristics with a prominence of a safer and better drug delivery.

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confidence: 92%

The relevancy of controlled nanocrystallization on rifampicin characteristics and cytotoxicity

Mohyeldin

Mehanna

Elgindy

2016

IJN

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“…Solid state characterization by DSC of the freeze dried nanocrystalline formulation showed that the crystallinity of PTX was not affected by the wet milling process, thus avoiding possible stability issues due to crystalline-to-amorphous transitions induced by the friction generated during the high-intensity wet milling process (10).…”

Section: Physico-chemical Characterization Of Ptx Nanocrystalsmentioning

confidence: 99%

Development of a Nanocrystalline Paclitaxel Formulation for Hipec Treatment

et al. 2012

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Purpose: To develop a nanocrystalline paclitaxel formulation with a high paclitaxel-to-stabilizer ratio which can be used for hyperthermic intraperitoneal chemotherapy (HIPEC).Methods: Paclitaxel (PTX) nanocrystals were prepared via wet milling using Pluronic F127 ® as stabilizer. The suitability of paclitaxel nanosuspensions for HIPEC treatment was evaluated by analyzing the cytotoxicity of both stabilizer and formulation, and by determining the maximum tolerated dose (MTD) and bioavailability. The effect on tumor growth was evaluated by magnetic resonance imaging (MRI) at day 7 and 14 after HIPEC treatment in rats with peritoneal carcinomatosis of ovarian origin.Results: Monodisperse nanosuspensions (±400 nm) were developed using Pluronic F127 ® as single additive. The cytotoxicity and MTD of this nanocrystalline formulation was similar compared to Taxol ® , while its bioavailability was higher. MRI data after HIPEC treatment with a PTX nanocrystalline suspension showed a significant reduction of tumor volume compared to the nontreated group. Although no significant differences on tumor volume were observed between Taxol ® and the nanosuspension, the rats treated with the nanosuspension recovered faster following the HIPEC procedure.Conclusion: Nanosuspensions with a high paclitaxel-to-stabilizer ratio are of interest for the treatment of peritoneal carcinomatosis of ovarian origin via HIPEC.

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“…4,6,[15][16][17] However, the preparations used were stabilized by surfactants or polymers, so may not truly reflect the effects of particle size. Until now, investigations of the particle size effect using naked nanocrystals (ie, 100% drugs without any stabilizer) have rarely been reported.…”

Section: Introductionmentioning

confidence: 99%

Effect of particle size on solubility, dissolution rate, and oral bioavailability: evaluation using coenzyme Q10 as naked nanocrystals

Sun¹,

Wang²,

Sui³

et al. 2012

IJN

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In this paper work, four naked nanocrystals (size range 80–700 nm) were prepared without any surfactant or polymer using the solvent/nonsolvent method. The effects of particle size on their solubility, dissolution, and oral bioavailability were investigated. Solubility and dissolution testing were performed in three types of dissolution medium, and the studies demonstrated that the equilibrium solubilities of coenzyme Q 10 nanocrystals and bulk drugs were not affected by the dissolution media but the kinetic solubilities were. Kinetic solubility curves and changes in particle size distribution were determined and well explained by the proposed solubilization model for the nanocrystals and bulk drugs. The particle size effect on dissolution was clearly influenced by the diffusion coefficients of the various dissolution media, and the dissolution velocity of coenzyme Q 10 increased as particle size decreased. The bioavailability of coenzyme Q 10 after oral administration in beagle dogs was improved by reducing the particle size. For 700 nm nanocrystals, the AUC 0–48 was 4.4-fold greater than that for the coarse suspensions, but a further decrease in particle size from 700 nm to 120 nm did not contribute to improvement in bioavailability until the particle size was reduced to 80 nm, when bioavailability was increased by 7.3-fold.

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Nanosuspension for improving the bioavailability of a poorly soluble drug and screening of stabilizing agents to inhibit crystal growth

Cited by 232 publications

References 11 publications

The relevancy of controlled nanocrystallization on rifampicin characteristics and cytotoxicity

The relevancy of controlled nanocrystallization on rifampicin characteristics and cytotoxicity

Development of a Nanocrystalline Paclitaxel Formulation for Hipec Treatment

Effect of particle size on solubility, dissolution rate, and oral bioavailability: evaluation using coenzyme Q10 as naked nanocrystals

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