The Preparation and Evaluation of Water-Soluble SKLB610 Nanosuspensions with Improved Bioavailability

Huang, Yun-Chuang; Luo, Xun; You, Xinyu; Xia, Yong; Song, Xinhang; Yu, Luoting

doi:10.1208/s12249-013-0005-7

Cited by 18 publications

(7 citation statements)

References 26 publications

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“…However, the result correlates with the particle size studies in that the particle size increased when two stabilizers were used in combination. As reported, reductions in particle sizes increased the drug uptake not only by increasing the solubility but also by other mechanisms, including increasing drug adhesion to gastrointestinal mucous surfaces (Huang et al, 2013). Hence, the relationship between particle size, saturation solubility, and in vivo absorption should be carefully considered when a nanosuspension formulation with a proper stabilizer is established.…”

Section: Parametersmentioning

confidence: 93%

Effects of stabilizing agents on the development of myricetin nanosuspension and its characterization: An in vitro and in vivo evaluation

Hong

Dang

Lin

et al. 2014

International Journal of Pharmaceutics

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Section: Parametersmentioning

confidence: 93%

Effects of stabilizing agents on the development of myricetin nanosuspension and its characterization: An in vitro and in vivo evaluation

Hong

Dang

Lin

et al. 2014

International Journal of Pharmaceutics

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“…The melting peak of SKLB610 in nanosuspension was relatively blunt as compared to that of pure SKLB610, apparently due to the preparation process. Amorphous domains were also generated on the particle surface [ 23 ].…”

Section: Characterization Of Nanocrystalsmentioning

confidence: 99%

Performance Parameters and Characterizations of Nanocrystals: A Brief Review

2016

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Poor bioavailability of drugs associated with their poor solubility limits the clinical effectiveness of almost 40% of the newly discovered drug moieties. Low solubility, coupled with a high log p value, high melting point and high dose necessitates exploration of alternative formulation strategies for such drugs. One such novel approach is formulation of the drugs as “Nanocrystals”. Nanocrystals are primarily comprised of drug and surfactants/stabilizers and are manufactured by “top-down” or “bottom-up” methods. Nanocrystals aid the clinical efficacy of drugs by various means such as enhancement of bioavailability, lowering of dose requirement, and facilitating sustained release of the drug. This effect is dependent on the various characteristics of nanocrystals (particle size, saturation solubility, dissolution velocity), which have an impact on the improved performance of the nanocrystals. Various sophisticated techniques have been developed to evaluate these characteristics. This article describes in detail the various characterization techniques along with a brief review of the significance of the various parameters on the performance of nanocrystals.

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“…For example, Huang et al conducted a pharmacokinetic study in rats to evaluate the bioavailability of a nanosuspension formulation of SKLB610, a potent inhibitor of vascular endothelial growth factor receptor 2 12. In that study, the nanosuspension formulation resulted in a 3.8-fold and 2.6-fold higher C max and AUC last , respectively, than the coarse suspension.…”

Section: Discussionmentioning

confidence: 99%

Novel nanocrystal formulation of megestrol acetate has improved bioavailability compared with the conventional micronized formulation in the fasting state

Jang¹,

Yoon²,

Kim³

et al. 2014

DDDT

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BackgroundMegestrol acetate is an effective treatment for improving appetite and increasing body weight in patients with cancer-associated anorexia. However, Megace® oral suspension (OS), a micronized formulation of megestrol acetate, has low bioavailability in the fasting state. To overcome this limitation, a nanocrystal formulation has been developed. This study was performed to evaluate the pharmacokinetics and tolerability of the nanocrystal formulation and to compare them with those of Megace® OS in the fed and fasting states.MethodsA randomized, open-label, two-treatment, two-period, two-sequence, crossover study was performed in three parts in 93 healthy subjects. A single 625 mg/5 mL oral dose of a nanocrystal formulation was administered in the fasting and fed states (part I). In parts II and III, a single 625 mg/5 mL oral dose of the nanocrystal formulation or Megace® OS 800 mg/20 mL was given in the fed and fasting states, respectively. Blood samples were collected for up to 120 hours post dose for pharmacokinetic analysis. Tolerability was evaluated throughout the entire study period.ResultsThe nanocrystal formulation of megestrol acetate was rapidly absorbed in both the fed and fasting states. In the fed state, systemic exposure was comparable between the nanocrystal formulation of megestrol acetate and Megace® OS. In the fasting state, however, the peak plasma concentration and area under the plasma concentration-time curve to the last measurable concentration of megestrol acetate was 6.7-fold and 1.9-fold higher, respectively, for the nanocrystal formulation than for Megace® OS. No serious adverse events were reported.ConclusionSystemic exposure to megestrol acetate is less affected by lack of concomitant food intake when it is administered using the nanocrystal formulation. The nanocrystal formulation of megestrol acetate could be more effective in treating patients with cachexia or anorexia.

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The Preparation and Evaluation of Water-Soluble SKLB610 Nanosuspensions with Improved Bioavailability

Cited by 18 publications

References 26 publications

Effects of stabilizing agents on the development of myricetin nanosuspension and its characterization: An in vitro and in vivo evaluation

Effects of stabilizing agents on the development of myricetin nanosuspension and its characterization: An in vitro and in vivo evaluation

Performance Parameters and Characterizations of Nanocrystals: A Brief Review

Novel nanocrystal formulation of megestrol acetate has improved bioavailability compared with the conventional micronized formulation in the fasting state

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