scholarly journals Physicochemical Stability of a Novel Tacrolimus Ophthalmic Formulation for the Treatment of Ophthalmic Inflammatory Diseases

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 118
Author(s):  
Marion Barrieu ◽  
Philip Chennell ◽  
Mouloud Yessaad ◽  
Yassine Bouattour ◽  
Mathieu Wasiak ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Breakdown Product ◽  
Ph Measurements ◽  
Chromatography Method ◽  
Physicochemical Stability ◽  
Liquid Chromatography Method ◽  
Ophthalmic Solutions ◽  
Preservative Free ◽  
Storage Temperatures ◽  
Ophthalmic Formulation

Tacrolimus is an immunosuppressant used to treat a large variety of inflammatory or immunity-mediated ophthalmic diseases. However, there are currently no commercial industrial forms available that can provide relief to patients. Various ophthalmic formulations have been reported in the literature, but their stability has only been tested over short periods. The objective of this study was to evaluate the physicochemical stability of a preservative-free tacrolimus formulation (0.2 and 1 mg/mL) at three storage temperatures (5 °C, 25 °C and 35 °C) for up to nine months in a multidose eyedropper. Analyses performed were the following: visual inspection and chromaticity, turbidity, viscosity, size of micelles, osmolality and pH measurements, tacrolimus quantification by a stability-indicating liquid chromatography method, breakdown product research, and sterility assay. In an in-use study, tacrolimus quantification was also performed on the drops emitted from the eyedroppers. All tested parameters remained stable during the nine month period when the eyedrops were stored at 5 °C. However, during storage at 25 °C and 35 °C, several signs of chemical instability were detected. Furthermore, a leachable compound originating from a silicone part of the eyedropper was detected during the in-use assay. Overall, the 0.2 mg/mL and 1 mg/mL tacrolimus ophthalmic solutions were physicochemically stable for up to nine months when stored at 5 °C.

scholarly journals Stability of Ophthalmic Atropine Solutions for Child Myopia Control

Pharmaceutics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 781
Author(s):  
Baptiste Berton ◽  
Philip Chennell ◽  
Mouloud Yessaad ◽  
Yassine Bouattour ◽  
Mireille Jouannet ◽  
...  
Keyword(s):  
Visual Inspection ◽  
Low Dose ◽  
Breakdown Product ◽  
World Population ◽  
Ph Measurements ◽  
Chromatography Method ◽  
Liquid Chromatography Method ◽  
The Stability ◽  
Chromaticity Measurements ◽  
Myopia Control

Myopia is an ophthalmic condition affecting more than 1/5th of the world population, especially children. Low-dose atropine eyedrops have been shown to limit myopia evolution during treatment. However, there are currently no commercial industrial forms available and there is little data published concerning the stability of medications prepared by compounding pharmacies. The objective of this study was to evaluate the stability of two 0.1 mg/mL atropine formulations (with and without antimicrobiobial preservatives) for 6 months in two different low-density polyethylene (LDPE) multidose eyedroppers. Analyses used were the following: visual inspection, turbidity, chromaticity measurements, osmolality and pH measurements, atropine quantification by a stability-indicating liquid chromatography method, breakdown product research, and sterility assay. In an in-use study, atropine quantification was also performed on the drops emitted from the multidose eyedroppers. All tested parameters remained stable during the 6 months period, with atropine concentrations above 94.7% of initial concentration. A breakdown product (tropic acid) did increase slowly over time but remained well below usually admitted concentrations. Atropine concentrations remained stable during the in-use study. Both formulations of 0.1 mg/mL of atropine (with and without antimicrobial preservative) were proved to be physicochemically stable for 6 months at 25 °C when stored in LDPE bottles, with an identical microbial shelf-life.

scholarly journals Do Ophthalmic Solutions of Amphotericin B Solubilised in 2-Hydroxypropyl-γ-Cyclodextrins Possess an Extended Physicochemical Stability?

Pharmaceutics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 786
Author(s):  
Philip Chennell ◽  
Mouloud Yessaad ◽  
Florence Abd El Kader ◽  
Mireille Jouannet ◽  
Mathieu Wasiak ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Breakdown Product ◽  
Eye Drops ◽  
Chromatography Method ◽  
Term Stability ◽  
Long Term Stability ◽  
The Stability ◽  
Ophthalmic Solutions

Fungal keratitis is a sight-threatening disease for which amphotericin B eye drops is one of the front-line treatments. Unfortunately, there are currently no commercial forms available, and there is little data concerning the long-term stability of compounded formulations based on intravenous dosages forms. New formulations of amphotericin B ophthalmic solutions solubilised with γ-cyclodextrins have shown promising in-vitro results, but stability data is also lacking. The objective of this study was therefore to investigate the stability of a formulation of ready-to-use amphotericin B solubilised in 2-hydroxypropyl-γ-cyclodextrins (AB-HP-γ-CD), for 350 days. An amphotericin B deoxycholate (ABDC) formulation was used as a comparator. Analyses used were the following: visual inspection, turbidity, osmolality and pH measurements, amphotericin B quantification by a stability-indicating liquid chromatography method, breakdown product research, and sterility assay. AB-HP-γ-CD formulation showed signs of chemical instability (loss of amphotericin B) after 28 and 56 days at 25 °C and 5 °C. Adding an antioxidant (ascorbic acid) to the formulation did not improve stability. ABDC formulation showed signs of physical instability (increased turbidy and amphotericin B precipitation) after 28 days and 168 days at 25 °C and 5 °C. As such, AB-HP-γ-CD formulation does not provide long-term stability for ophthalmic amphotericin B solutions.

scholarly journals Lipemia in the Plasma Sample Affects Fentanyl Measurements by Means of HPLC-MS2 after Liquid-Liquid Extraction

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4514
Author(s):  
Marta Tikhomirov ◽  
Tomasz Śniegocki ◽  
Błażej Poźniak
Keyword(s):  
Forensic Toxicology ◽  
Liquid Extraction ◽  
Rabbit Plasma ◽  
Chromatography Method ◽  
Method Performance ◽  
Liquid Liquid Extraction ◽  
Normal Plasma ◽  
Validation Procedure ◽  
Liquid Chromatography Method ◽  
The Impact

Examination of fentanyl levels is frequently performed in certain scientific evaluations and forensic toxicology. It often involves the collection of very variable blood samples, including lipemic plasma or serum. To date, many works have reported the methods for fentanyl detection, but none of them have provided information about the impact on the assay performance caused by an excessive amount of lipids. This aspect may be, however, very important for highly lipophilic drugs like fentanyl. To address this issue, we developed the liquid chromatography method with mass spectrometry detection and utilized it to investigate the impact of lipids presence in rabbit plasma on the analytical method performance and validation. The validation procedure, conducted for normal plasma and lipemic plasma separately, resulted in good selectivity, sensitivity and linearity. The limits of detection and quantification were comparable between the two matrices, being slightly lower in normal plasma (0.005 and 0.015 µg/L) than in lipemic plasma (0.008 and 0.020 µg/L). Liquid–liquid extraction provided a low matrix effect regardless of the lipid levels in the samples (<10%), but pronounced differences were found in the recovery and accuracy. In the normal plasma, this parameter was stable and high (around 100%), but in the lipemic matrix, much more variable and less efficient results were obtained. Nevertheless, this difference had no impact on repeatability and reproducibility. In the present work, we provided reliable, convenient and sensitive method for fentanyl detection in the normal and lipemic rabbit plasma. However, construction of two separate validation curves was necessary to provide adequate results since the liquid-liquid extraction was utilized. Therefore, special attention should be paid during fentanyl quantification that involves lipemic plasma samples purified by this technique.

scholarly journals HPLC Quantification of Cytotoxic Compounds fromAspergillus niger

2017 ◽  
Vol 2017 ◽  
pp. 1-7
Author(s):  
Paula Karina S. Uchoa ◽  
Leandro Bezerra de Lima ◽  
Antonia T. A. Pimenta ◽  
Maria da Conceição F. de Oliveira ◽  
Jair Mafezoli ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Standard Deviation ◽  
High Performance ◽  
Chromatography Method ◽  
Relative Standard ◽  
Validation Parameters ◽  
Cytotoxic Compounds ◽  
Liquid Chromatography Method ◽  
Marine Strain

A high-performance liquid chromatography method was developed and validated for the quantification of the cytotoxic compounds produced by a marine strain ofAspergillus niger. The fungus was grown in malt peptone dextrose (MPD), potato dextrose yeast (PDY), and mannitol peptone yeast (MnPY) media during 7, 14, 21, and 28 days, and the natural products were identified by standard compounds. The validation parameters obtained were selectivity, linearity (coefficient of correlation > 0.99), precision (relative standard deviation below 5%), and accuracy (recovery > 96).

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