Marie-Hélène Langlois

Simultaneous Determination of Irbesartan and Hydrochlorothiazide in Tablets by Derivative Spectrophotometry

Abstract A second-derivative spectrophotometric method for the simultaneous determination of irbesartan (IRB) and hydrochlorothiazide (HCT) in tablets is described. Measurements were made at the zero-crossing wavelengths at 230.1 nm for IRB and 232.7 nm for HCT. The calibration graphs were linear in the range of 14.4–33.6 mg L−1 for IRB and 1.2–2.8 mg L−1 for HCT. The limits of quantitation were 5.0 and 1.1 mg L−1. The proposed method was successfully applied to the simultaneous determination of IRB and HCT in commercial tablets with a high percentage of recovery, good accuracy, and precision.

Simultaneous determination of rutin and benzocaine in suppositories by reversed-phase high-performance liquid chromatography

A simple and precise reversed-phase HPLC procedure for the simultaneous determination of rutin and benzocaine in suppositories is proposed. The chromatographic conditions were: Apex ODS column; methanol-10 mM triethylamine aqueous solution pH 3.0 (57 : 43, v/v) as the mobile phase; detection wavelength, 270 nm. Calibration curves were linear at concentration ranges 6.0 μg ml−1–14.0 μg ml−1 and 1.5 μg ml−1– 3.5 μg ml−1 for rutin and benzocaine, respectively. The reproductibility was 1.05% and 0.95% for rutin and benzocaine, respectively.

Simultaneous Determination of Two Synthetic Dyes Erytrosine and Sunset Yellow in a Pharmaceutical Syrup By First Derivative Visible Spectrophotometry

ABSTRACT. A rapid first derivative spectrophotometric method for simultaneous determination of two synthetic dyes, erytrosine (E 127) and sunset yellow (E 110), in a mixture is proposed. The procedure does not require any separation step. The method was applied for determining the two compounds in a pharmaceutical syrup. Good linearity, accuracy, precision and selectivity were found, and the method is proposed for routine quality control purposes.

Development of a solvent-free analytical method for paracetamol quantitative determination in Blood Brain Barrier in vitro model.

A Reversed Phase-High Performance Liquid Chromatography/Diode Array Detection method was developed and validated for paracetamol quantification in cell culture fluid from an in vitro Blood Brain Barrier model. The chromatographic method and sample preparation were developed using only aqueous solvents. The column was a XTerra RP18 150 × 4.6mm, 3.5 μm with a guard column XTerra RP18 20 × 4.6 mm, 3.5 μm at 35 °C and the mobile phase was composed by 100% formate buffer 20 mM at pH 4 and flow rate was set at 1 mL/min. The detection was at 242 nm. The sample was injected at 10 μL. Validation was performed using the accuracy profile approach. The analytical procedure was validated with the acceptance limits at ± 10% over a range of concentration from 1 to 58 mg L(-1). The procedure was then used in routine to determine paracetamol concentration in a brain blood barrier in vitro model. Application of the Unither paracetamol formulation in Blood Brain Barrier model allowed the determination and comparison of the transcellular passage of paracetamol at 37 °C and 4 °C, that excludes paracellular or non specific leakage.

In Vitro Ceftriaxone Stability at New-borns Rectal PH Assessed by UV and HPLC Methods

This study showed the comparison of UV spectroscopy and High Performance Liquid Chromatography (HPLC) for ceftriaxone stability. UV spectroscopy using wavelength ratio between 241 and 271 nm absorbance values can be used successfully as a screening technique in ceftriaxone stability investigations. Ion paring reversed phase – High Performance Liquid Chromatography provided more precise stability characterization. The HPLC conditions developed were in isocratic mode using an YMC ODS H80, 150 x 4.6 mm, 4 μm with a mobile phase composed by 40% of methanol and 60% of phosphate buffer (10 mM; pH 7.5) where tetrabutylammonium bromide was solubilized at 18 mM. Detection was performed with a diode array detector from 200 to 400 nm. Sample injection volume was at 5 μL. Methanol was selected because better symmetry of ceftriaxone peak than acetonitrile was obtained. Both methods were validated. The calibration curve and stability study was performed over a concentration range of 7.5 to 16.5 mg.L-1. 100% corresponded to the concentration of 15 mg.L-1. Intermediate precision was tested on 6 independent samples at concentrations corresponding to 100% (15 mg.L-1) on 6 consecutive days. These values were within the acceptance criteria of 2% and showed that both methods were precise. Accuracy of the method was evaluated analyzing three independent samples at concentrations corresponding to 100%. Recovery percentage calculated between the known concentration and the calculated concentration of ceftriaxone showed that the methods were accurate. Thus both methods were linear. The stability study was performed at 40°C as infants with sepsis are generally febrile. Over the rectal pH range recorded in sick infants, the stability of ceftriaxone was maximal at pH 7.5. Over 6 hours in a pH range of 6.5 to 8.5 less than 10% of ceftriaxone is degraded. However at pH 5.5, degradation occurred more rapidly and loss of drug was significant.

Simultaneous Determination of Ibuprofen and Pseudoephedrine Hydrochloride in Pharmaceutical Tablets by Reversed-Phase HPLC

Abstract An isocratic HPLC method was developed and validated for the simultaneous determination of ibuprofen (IBU) and pseudoephedrine hydrochloride (PSE). Chromatography was carried out on an Apex phenyl column using 0.025 M acetic acid, triethylamine solution (pH 4.5) – acetonitrile (80:20, v/v) as mobile phase at a flow rate of 1 mL · min−1. UV detection was performed at a wavelength of 210 nm. The method was validated for specificity, linearity, accuracy, precision, and was successfully applied to pharmaceutical tablets of Rhinadvil®.

Preformulation studies of ceftriaxone for pediatric non-parenteral administration as an alternative to existing injectable formulations

Abstract Ceftriaxone, a third generation cephalosporin, has a wide antibacterial spectrum that has good CNS penetration, which makes it potentially suitable for initial treatment of severe neonatal pediatric infections providing suitable formulation. We evaluated its physicochemical and technical characteristics to assess its potential for development as a non‐parenteral dosage form. As ceftriaxone is marked only for injectable use, these data are not available. Using HPLC and Karl Fischer titration, sensitivity of ceftriaxone to water, feasibility and impact of pharmaceutical processes and compatibility with common pharmaceutical excipients were assessed. X‐ray diffraction studies gave deeper insight into the mechanisms involved in degradation. Chemometrical analysis of near infrared spectra enabled classification of ceftriaxone powder according to exposure conditions or processes applied. The results showed that ceftriaxone was not highly hygroscopic, could be processed in all climatic zones, but should be packaged protected against humidity. Controlling water presence in formulation was shown critical, as ceftriaxone degraded in the presence of water content above 2.4% w/w. To improve flowability, a critical parameter for dry dosage form development, granulation (wet and dry techniques, providing complete drying and moderate force compaction respectively) was shown feasible. Compression with moderate forces was possible, but grinding and high compression forces significantly affected long term ceftriaxone stability and should be avoided. Based on these results, development of ceftriaxone non‐parenteral solid or liquid non‐aqueous forms appears feasible. Graphical abstract Figure. No Caption available.

Development of rectal self-emulsifying suspension of a moisture-labile water-soluble drug

Self-emulsifying drug delivery systems, commonly used for oral delivery of poorly soluble compounds, were used to formulate water soluble but moisture labile compounds for rectal application. The objective was to use the oily phase of the system to formulate a liquid, non-aqueous product while obtaining the advantages of self-emulsification, rapid contact with the rectal mucosa and rapid absorption post-administration. Ceftriaxone was used as a model drug and the human bile salt sodium chenodeoxycholate was used as an absorption enhancer. After preliminary screening of 23 excipients, based on their emulsification ability and emulsion fineness in binary and ternary mixtures, a full factorial design was used to screen different formulations of three preselected excipients. The optimal formulation contained 60% of excipients, namely Capryol 90, Kolliphor EL and Kolliphor PS20 in 4 : 6 : 6 ratio and 40% of a powder blend that included 500 mg of ceftriaxone. Characterization of the system showed that it complied with the requirements for rectal administration, in particular rapid emulsification in a small quantity of liquid. Rabbit bioavailability showed rapid absorption of ceftriaxone, achieving 128% bioavailability compared to powder control formulation. These results demonstrated the potential of self-emulsifying formulations for rectal administration of Class 3 BCS drugs.