Improving cabazitaxel chemical stability in parenteral lipid emulsions using cholesterol

Shao, Yanjie; Zhang, Chungang; Yao, Qing; Wang, Yueqi; Tian, Bin; Tang, Xing; Wang, Yanjiao

doi:10.1016/j.ejps.2013.09.024

Cited by 29 publications

(19 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In particular, the cabazitaxel concentration ranged around the day 0 value in accordance with the accuracy of the analytical method, which in this case was characterised by a relative error ranging in absolute value from about 3.5% to 6% for inter-day dilutions. This error was due to difficulties in handling the premix solution, which was characterised by high viscosity and a tendency to foam, caused by the presence of polysorbate 80, which is a necessary ingredient to increase solubility of the drug in water 15. The stability results for the cabazitaxel premix solution are in accordance with those found by Thiesen and Krämer for docetaxel premix solutions stored both refrigerated and at room temperature.…”

Section: Discussionsupporting

confidence: 79%

“…Interestingly, this behaviour was also observed for cabazitaxel diluted in infusion solution saturated with O 2 and stored at 25°C, indicating the high stability of this drug under the weak acidic conditions of the diluted infusion. In agreement with this result, it has been reported that the rate of degradation of cabazitaxel in buffers at high temperatures (60–80°C) is minimal at near-neutral pH values (4.41<pH<6.20) 15. On the other hand, it has recently been reported that unpredictable precipitation may occur in diluted cabazitaxel infusion solutions, so accurate visual checks are necessary before their use 20…”

Section: Discussionmentioning

confidence: 53%

See 1 more Smart Citation

Physicochemical stability of cabazitaxel and docetaxel solutions

et al. 2014

View full text Add to dashboard Cite

Objectives: It is recommended that the Jevtana (current parenteral cabazitaxel formulation) final infusion solution should be used within 8 h when stored at ambient temperature or within 24 h if refrigerated. We determined the physical and chemical stability of cabazitaxel and docetaxel over prolonged periods after dilution in infusion solutions from their Jevtana and Hospira, respectively, parenteral formulations. \ud \ud Methods: The stability of these antineoplastic drugs was determined after (i) reconstitution of the injection concentrate and (ii) further dilution in 0.9% NaCl solution contained in PVC-free infusion bags. Chemical stability was determined using both high-performance liquid chromatography (HPLC) with ultraviolet detection and high-resolution (HR)-HPLC–mass spectrometry (MS) techniques. Physical stability was determined by visual inspection. \ud \ud Results: The stability tests revealed that reconstituted cabazitaxel solutions (premix solutions) stored at 4°C were physicochemically stable (at a level of ≥95% cabazitaxel) for a minimum of 4 weeks. Diluted infusion solutions in PVC-free infusion bags (docetaxel concentration 0.30 mg/mL; cabazitaxel concentration 0.15 mg/mL) were physicochemically stable (at a level of ≥95% cabazitaxel or docetaxel) for a minimum of 4 weeks, independently of storage temperature (4°C or 25°C). Diluted cabazitaxel infusion solutions appeared stable (at a level of ≥95% cabazitaxel) for a minimum of 4 weeks when stored in the presence of saturated oxygen at 25°C. \ud \ud Conclusions: Cabazitaxel and docetaxel are characterised by high stability in customary infusion fluids for at least 4 weeks

show abstract

Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 53%

Physicochemical stability of cabazitaxel and docetaxel solutions

et al. 2014

View full text Add to dashboard Cite

show abstract

“…A slight decrease in the level of CTX in emulsions, following a long storage period was observed, but this was within acceptable limits. The CTX level showed no significant difference when compared with the predicated values derived from classical homothermal acceleration reported by our team [9]. In a word, the CTX-LM appeared to be physicochemically stable during a 3-month storage period at 25 AE 2°C and a 9-month…”

Section: Storage Stabilitycontrasting

confidence: 47%

“…Therefore, the development of CTX‐loaded intravenous lipid microspheres is an attractive and promising strategy. The systematic development of chemically stable intravenous lipid emulsions containing CTX has already been studied by our research team . Lipid microspheres are disperse systems composed of two immiscible liquids.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the stability and pharmacokinetics of cabazitaxel‐loaded intravenous lipid microspheres: Beneficial effect of cholesterol

Shao

Tian

et al. 2014

Euro J Lipid Sci & Tech

Self Cite

View full text Add to dashboard Cite

In this work, we describe the evaluation of the stability and pharmacokinetics of cabazitaxel‐loaded lipid microspheres (CTX‐LM) prepared by high‐pressure homogenization. Investigation of the physicochemical stability under different homogenization cycles and diverse sterilization times confirmed that 8 cycles at 800 bar and 121°C for 8 min were the optimal technological parameters. The beneficial effect of cholesterol on the physical stability of CTX‐LM was confirmed and its mechanism of action was identified. The stability of CTX‐LM using an aqueous isotonic glucose solution as a diluting agent was greater compared with using 0.9% NaCl solution as a result of an electric charge effect. CTX‐LM are stable under freeze‐thaw conditions and should not be exposed to high temperatures and protected from light during storage. Furthermore, all the changes in parameters were within an acceptable range at 4°C within 9 months, which supported the good long‐term stability of CTX‐LM. Finally, to compare the pharmacokinetics of CTX‐LM with cabazitaxel‐solution in vivo, a rapid, accurate UPLC‐MS/MS method was developed and used to determine cabazitaxel in rat plasma after a single intravenous administration of 4 mg/kg. An obviously larger area under the curve (AUC) of CTX‐LM was observed than that of CTX‐solution, which will improve the antitumor efficacy of cabazitaxel. Practical applications: As a novel semisynthetic taxane, cabazitaxel has shown antitumour activity in a broad range of cell‐lines and tumor models and has been approved in combination with prednisone for the treatment of patients with castration‐resistant metastatic prostate cancer. However, serious undesirable effects in humans, such as anaphylactoid hypersensitivity reactions and peripheral neuropathy were produced by the addition of polysorbate 80 to commercial products. In this paper, CTX‐LM was prepared by high‐pressure homogenization in order to overcome the above drawbacks. The good stability and markedly higher AUC of CTX‐LM may hasten their passage from a pre‐clinical phase to a clinical trial phase and allow their production on a large scale. In this paper, cabazitaxel lipid microspheres exhibited a great stability and had a higher AUC than cabazitaxel solution.

show abstract

“…Interestingly, it had been reported that well-prepared lipid emulsions stabilized by phospholipids are Bautoclavable^(121°C, 10 min or longer) (24)(25)(26), while other nanoparticles like liposomes or phospholipid micelles were generally recognized as Bnonautoclavable^and autoclaving of these formulations was reported decades ago with nearly no follow-up studies (27,28). So it was hypothesized that oil might be a key factor in protecting nanoparticles under conditions like autoclaving.…”

Section: Introductionmentioning

confidence: 97%