Use of supercritical CO2 for the sterilization of liposomes: Study of the influence of sterilization conditions on the chemical and physical stability of phospholipids and liposomes.

The effects of four potential supercritical carbon dioxide (ScCO2) sterilization conditions on the chemical stability of 9 phospholipids and on the physicochemical characteristics of liposomes consisting of stable phospholipids, as well as their sterilization efficiency were evaluated. These conditions were : C1 (ScCO2/70 °C/150 bar/240 min), C2 (ScCO2/0.25 % water/ 0.15% H2O2/ 0.5% acetic anhydride/38° C/85 bar/45 min), C3 (ScCO2/0.08 % peracetic acid/35° C/104 bar/180 min) and C4 (ScCO2/200 ppm H2O2/40 °C/270 bar/90 min). The results showed for phospholipids, a significant increase in hydrolysis products of 3.77 to 14.50 % and an increase in oxidation index of 6.10 to 430.50 % with unsaturated phospholipids for all tested conditions while with saturated phospholipids, no significant degradation was observed. Concerning the liposome formulation, no change in dispersion color and no phospholipid degradation were observed. However, a decrease in liposome size from 126.90 nm to 111.80 nm, 96.27 nm, 99.60 nm and 109.13 nm and an increase in the PdI from 0.208 to 0.271, 0.233, 0.285, and 0.298 were found with conditions C1, C2, C3 and C4 respectively. For the sterilization efficiency, conditions C1, C2 and C3 achieved the required sterility assurance level (SAL) of 10-6 for liposomes.

Detection of Falsified Antimalarial Sulfadoxine-Pyrimethamine and Dihydroartemisinin-Piperaquine Drugs Using a Low-Cost Handheld Near-Infrared Spectrometer.

Falsified drugs are of serious concern to public health worldwide, particularly for developing countries where quality control of drugs is inefficient. In law enforcement against such fake medicines, there is a need to develop reliable, fast, and inexpensive screening methods. In this work, the ability of an innovative low-cost handheld near-infrared spectrometer to identify falsifications among two antimalarial fixed dose combination tablets, dihydroartemisinin/piperaquine and sulfadoxine/pyrimethamine, has been investigated. Analyzed samples were collected in Burkina Faso mainly in rural transborder areas that could be infiltrated by illicit drugs. A principal component analysis was applied on the acquired near-infrared spectra to identify trends, similarities, and differences between collected samples. This allowed to detect some samples of dihydroartemisinin/piperaquine and sulfadoxine/pyrimethamine which seemed to be falsified. These suspicious samples were semiquantitatively analyzed by thin-layer chromatography using Minalab® kits. Obtained results allowed to confirm the falsifications since the suspected samples did not contain any of the expected active pharmaceutical ingredients. The capacity of the low-cost near-infrared device to identify specifically a brand name of dihydroartemisinin/piperaquine or sulfadoxine/pyrimethamine has been also studied using soft independent modelling of class analogy (SIMCA) in the classical and data driven versions. The built models allowed a clear brand identification with 100% of both sensitivity and specificity in the studied cases. All these results demonstrate the potential of these low-cost near-infrared spectrometers to be used as first line screening tools, particularly in resource limited laboratories, for the detection of falsified antimalarial drugs.

Contribution to the Detection of Poor Quality Sildenafil Drugs in Burkina Faso Using High-Performance Thin-Layer Chromatography.

In substandard drugs enforcement, there is a need to develop reliable, fast, and inexpensive analytical methods. Due to its very characteristics, HPTLC offers opportunities for the development of methods that meet these requirements. This technique was used to develop and validate a method for the determination of sildenafil in pharmaceutical formulations from the licit and illicit supply chain in Burkina Faso. Taking into account optimization parameters such as measurement wavelength and mobile phase composition, the best elution quality is found at the maximum signals of spots on silica plates at 305 nm, using a mixture of dichloromethane-methanol mixture 9 : 1 (v/v) proportions. The method developed under these conditions was validated using the accuracy profile as a decision tool. The establishment of the response function curves allowed the choice of the polynomial function applied to the peak areas. This mathematical model provides a validity range between 0.4 and 0.6 mg/mL. The application of the developed and validated method to collected samples allowed the detection of two substandard drugs and confirmed the poor quality of drugs in the illicit market. More data using this approach in a variety of drug molecules could lead to the establishment of databases of counterfeit drugs in Burkina Faso.

Green Analytical Methods of Antimalarial Artemether-Lumefantrine Analysis for Falsification Detection Using a Low-Cost Handled NIR Spectrometer with DD-SIMCA and Drug Quantification by HPLC.

Two green analytical approaches have been developed for the analysis of antimalarial fixed dose tablets of artemether and lumefantrine for quality control. The first approach consisted of investigating the qualitative performance of a low-cost handheld near-infrared spectrometer in combination with the principal component analysis as an exploratory tool to identify trends, similarities, and differences between pharmaceutical samples, before applying the data driven soft independent modeling of class analogy (DD-SIMCA) as a one-class classifier for proper drug falsification detection with 100% of both sensitivity and specificity in the studied cases. Despite its limited spectral range and low resolution, the handheld device allowed detecting falsified drugs with no active pharmaceutical ingredient and identifying specifically a pharmaceutical tablet brand name. The second approach was the quantitative analysis based on the green and fast RP-HPLC technique using ethanol as a green organic solvent and acetic acid as a green pH modifier. The optimal separation was achieved in 7 min using a mobile phase composed of ethanol 96% and 10 mM of acetic acid pH 3.35 (63:37, v/v). The developed method was validated according to the total error approach based on an accuracy profile, was applied to the analysis of tablets, and allowed confirming falsified drugs detected by spectroscopy.

Comparison of hyperspectral imaging techniques for the elucidation of falsified medicines composition.

Hyperspectral imaging has shown a high potential to analyze falsifications of solid pharmaceutical products since the last decade. Thanks to the non-destructive, ecological and non-invasive properties, it is a preferred technique for these kinds of applications. Moreover, thanks to the spectroscopic properties, it is possible to detect as well organic compounds as inorganic compounds in a single analysis. Therefore, we recommend using it as second-line laboratory analysis technique. Raman microscopy and Fourier Transform Infrared (FT-IR) microscopy are two interesting techniques that are complementary. In this study, the potential of the two hyperspectral imaging techniques is evaluated to elucidate the composition of falsified antimalarial tablets. Hyperspectral data are analyzed by Multivariate Curve Resolution-Alternating Least Square (MCR-ALS). The results obtained from this study show that Raman hyperspectral imaging seems to be more suited to detect low dosed compounds possibly due to a smallest sampling volume. It has been also possible to link formulations of falsified samples of two different brands.

Determination of groundwater mercury (II) content using a disposable gold modified screen printed carbon electrode.

Mercury (II) measurements were performed thanks to a newly developed electrochemical method using a disposable gold modified screen printed carbon electrode. The method has a wide dynamic range (1-100 µg/L), a good accuracy and a limit of detection in compliance with WHO standards. The application of the method to several groundwater samples made it possible to identify, for the first time, mercury content higher than the recommended WHO standard value in a gold mining activity area in the northern part of Burkina Faso. The accuracy of the assay was checked by ICP/MS.