Development of an intravenously injectable chemically stable aqueous omeprazole formulation using nanosuspension technology

Möschwitzer, Jan P.; Achleitner, Georg; Pomper, Herbert; Müller, Rainer H.

doi:10.1016/j.ejpb.2004.03.022

Cited by 167 publications

(62 citation statements)

References 1 publication

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“…They are suitable for intravenous injection. 29 The PDI values were 0.141±0.015 for SN-38/NCs-A and 0.202±0.067 for SN-38/NCs-B. PDI values 0.3 indicate a narrow size distribution .…”

Section: Particle Size and Morphological Analysismentioning

confidence: 92%

In vitro and in vivo evaluation of SN-38 nanocrystals with different particle sizes

Chen¹,

Li²,

Zhang³

et al. 2017

IJN

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7-Ethyl-10-hydroxycamptothecin (SN-38) is a potent broad-spectrum antitumor drug derived from irinotecan hydrochloride (CPT-11). Due to its poor solubility and instability of the active lactone ring, its clinical use is significantly limited. As one of the most promising formulations for poorly water-soluble drugs, nanocrystals have attracted increasing attention. In order to solve these problems and evaluate the antitumor effect of SN-38 in vitro and in vivo, two nanocrystals with markedly different particle sizes were prepared. Dynamic light scattering and transmission electron microscopy were used to investigate the two nanocrystals. The particle sizes of SN-38 nanocrystals A (SN-38/NCs-A) and SN-38 nanocrystals B (SN-38/NCs-B) were 229.5±1.99 and 799.2±14.44 nm, respectively. X-ray powder diffraction analysis showed that the crystalline state of SN-38 did not change in the size reduction process. An accelerated dissolution velocity of SN-38 was achieved by nanocrystals, and release rate of SN-38/NCs-A was significantly faster than that of SN-38/NCs-B. Cellular uptake, cellular cytotoxicity, pharmacokinetics, animal antitumor efficacy, and tissue distribution were subsequently examined. As a result, enhanced intracellular accumulation in HT1080 cells and cytotoxicity on different tumor cells were observed for SN-38/NCs-A compared to that for SN-38/NCs-B and solution. Besides, compared to the SN-38 solution, SN-38/NCs-A had a higher bioavailability after intravenous injection; while the bioavailability of SN-38/NCs-B was even lower than that of the SN-38 solution. SN-38/NCs-A exhibited a significant inhibition of tumor growth compared to SN-38 solution and SN-38/NCs-B in vivo. The antitumor effect of SN-38/NCs-B was stronger than SN-38 solution. The tissue distribution study in tumor-bearing mice showed that nanocrystals could markedly improve the drug accumulation in tumor tissue by the enhanced permeability and retention effect compared to SN-38 solution, and the amount of SN-38 in tumors of SN-38/NCs-A group was much more than that of SN-38/NCs-B group. In conclusion, nanocrystals dramatically enhanced the anticancer efficacy of SN-38 in vitro and in vivo, and the particle size had a significant influence on the dissolution behavior, pharmacokinetic properties, and tumor inhibition of nanocrystals.

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“…They are suitable for intravenous injection. 29 The PDI values were 0.141±0.015 for SN-38/NCs-A and 0.202±0.067 for SN-38/NCs-B. PDI values 0.3 indicate a narrow size distribution .…”

Section: Particle Size and Morphological Analysismentioning

confidence: 92%

In vitro and in vivo evaluation of SN-38 nanocrystals with different particle sizes

Chen¹,

Li²,

Zhang³

et al. 2017

IJN

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“…Common processes, such as hydrolytic/oxidative degradation, particle growth, aggregation/agglomeration, change in crystallinity state, and sedimentation or creaming, may occur. [8][9][10] Moreover, nanosuspensions are always diluted, and have to be administered in large volumes to achieve therapeutic levels in the circulation. 11 To overcome these problems, it is desirable to formulate nanosuspensions into solid dose forms.…”

Section: Introductionmentioning

confidence: 99%

Formulating food protein-stabilized indomethacin nanosuspensions into pellets by fluid-bed coating technology: physical characterization, redispersibility, and dissolution

Lü²,

Qi³

et al. 2013

IJN

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Background: Drug nanosuspensions are very promising for enhancing the dissolution and bioavailability of drugs that are poorly soluble in water. However, the poor stability of nanosuspensions, reflected in particle growth, aggregation/agglomeration, and change in crystallinity state greatly limits their applications. Solidification of nanosuspensions is an ideal strategy for addressing this problem. Hence, the present work aimed to convert drug nanosuspensions into pellets using fluid-bed coating technology. Methods: Indomethacin nanosuspensions were prepared by the precipitation-ultrasonication method using food proteins (soybean protein isolate, whey protein isolate, β-lactoglobulin) as stabilizers. Dried nanosuspensions were prepared by coating the nanosuspensions onto pellets. The redispersibility, drug dissolution, solid-state forms, and morphology of the dried nanosuspensions were evaluated. Results: The mean particle size for the nanosuspensions stabilized using soybean protein isolate, whey protein isolate, and β-lactoglobulin was 588 nm, 320 nm, and 243 nm, respectively. The nanosuspensions could be successfully layered onto pellets with high coating efficiency. Both the dried nanosuspensions and nanosuspensions in their original amorphous state and not influenced by the fluid-bed coating drying process could be redispersed in water, maintaining their original particle size and size distribution. Both the dried nanosuspensions and the original drug nanosuspensions showed similar dissolution profiles, which were both much faster than that of the raw crystals. Conclusion: Fluid-bed coating technology has potential for use in the solidification of drug nanosuspensions.

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“…The highpressure homogenization (HPH) method is one of the bestestablished processes (14)(15)(16)(17)(18). It is reported that the diameters of the resulting nanocrystals can be controlled by adjusting the pressure and number of cycles used (19,20).…”

Section: Introductionmentioning

confidence: 99%

Nitrendipine Nanocrystals: Its Preparation, Characterization, and In Vitro–In Vivo Evaluation

et al. 2011

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Abstract. The present investigation was undertaken with the objective of developing a solid formulation containing nitrendipine nanocrystals for oral delivery. Nitrendipine nanocrystals were prepared using a tandem precipitation-homogenization process. Then, spray drying, a cost-effective method very popular in industrial situations, was employed to convert the nanocrystals into a solid form. The parameters of the preparation process were investigated and optimized. The optimal process was as follows: firstly, nitrendipine/acetone solution (100 mg/ml) was added to a polyvinyl alcohol solution (1 mg/ml) at 10°C, then the pre-suspension was homogenized for 20 cycles at 1,000 bar. Both differential scanning calorimetry and X-ray diffraction analysis indicated that nitrendipine was present in crystalline form. The in vitro dissolution rate of the nanocrystals was significantly increased compared with the physical mixture and commercial tablet. The in vivo testing demonstrated that the C max of the nanocrystals was approximately 15-fold and 10-fold greater than that of physical mixture and commercial tablet, respectively. In addition, the AUC 0→24 of the nanocrystals was approximately 41-fold and 10-fold greater than that of physical mixture and commercial tablet, respectively.

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Development of an intravenously injectable chemically stable aqueous omeprazole formulation using nanosuspension technology

Cited by 167 publications

References 1 publication

In vitro and in vivo evaluation of SN-38 nanocrystals with different particle sizes

In vitro and in vivo evaluation of SN-38 nanocrystals with different particle sizes

Formulating food protein-stabilized indomethacin nanosuspensions into pellets by fluid-bed coating technology: physical characterization, redispersibility, and dissolution

Nitrendipine Nanocrystals: Its Preparation, Characterization, and In Vitro–In Vivo Evaluation

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