Preservatives In Pharmaceutical Formulations Research Articles

Development and validation of liquid chromatographic methods for the estimation of the acceptance values of some hazardous preservatives in pharmaceutical formulations. A comparative study

Gradient and isocratic liquid chromatography were applied for the simultaneous determination of three preservatives, namely; benzyl alcohol (BA), methyl paraben (MP) and propyl paraben (PP). Separation for both elution modes was carried out using a C18 column kept at 60°C throughout the analysis, accompanied with a flow rate of 2 mL/min and UV detection at 254 nm. Gradient liquid chromatography used a time programme with two solvents (0.1% formic acid and acetonitril), while isocratic elution was performed with 0.1% formic acid: 2-propanol in a ratio of 70:30, v/v. Full validation study was conducted for both separation modes, where both of them were linear over the concentration ranges of 100.0–2000.0, 2.5–100.0, and 2.0–200.0 µg/mL for BA, MP and PP respectively. Using gradient elution, the detection limits for BA, MP, and PP were found to be 50.0, 1.8, and 1.5 µg/mL respectively. The corresponding values in isocratic elution were 60.0, 1.5, and 1.3 µg/mL. On the other hand, the limit of quantification for BA, MP, and PP using gradient mode are 70.0, 2.0, and 1.8 µg/mL respectively. While isocratic elution resulted in corresponding values of: 80.0, 2.3, and 1.7 µg/mL. The accuracy of the proposed method was illustrated from the high percentage recoveries values which were 99.67%, 100.42%, and 99.85% for BA, MP, and PP respectively using gradient mode, with corresponding values of 99.79%, 100.39%, and 99.87% for the isocratic elution mode. In addition, gradient elution was further applied to detect and assay the selected preservatives in different pharmaceutical formulations demonstrating that their quantities are within the stated ranges, and eventually, a comparative overview was introduced.

Degradation of parabens by Pseudomonas beteli and Burkholderia latens

p-Hydroxybenzoic acid esters (parabens) are commonly used antimicrobial preservatives in pharmaceutical formulations. Two microorganisms, isolated from non-sterile methyl paraben (MP) and propyl paraben (PP) solutions, were found to degrade the respective parabens. Identification by 16S rRNA partial gene sequencing revealed them to be Pseudomonas beteli and Burkholderia latens, respectively. The present work describes a previously unreported interaction of the parabens with P. beteli and B. latens. Degradation of MP at various concentrations by P. beteli, followed a logarithmic pattern, while that of PP by B. latens was found to be linear. It was subsequently observed that P. beteli could degrade only MP, while B. latens could degrade both the parabens. Absence of HPLC chromatogram peaks of expected degradation products indicated that the parabens were used up as a carbon source. The behaviour of pathogens ( Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans and Aspergillus niger) of the pharmacopoeial preservative effectiveness test (PET), towards MP, showed that none had the ability to degrade the paraben. It was concluded that, for a paraben-preserved multi-dose ophthalmic formulation, the sole use of the four pathogens that are recommended by the pharmacopoeia for PET can falsely indicate the formulation to be effective against ‘in-use’ contamination.

Application of a capillary electrophoresis method for simultaneous determination of preservatives in pharmaceutical formulations

Preservatives are used to protect pharmaceutical formulations from microbial attack during the period of administration to the patient. Because of their biological activity, preservatives have to be identified and assayed according to the same rules as apply to active components. A number of methods for separation of preservatives are reported, to account for the heterogeneity of their chemical structures. A capillary electrophoretic method was devised for simple and simultaneous qualification and quantification of the preservatives most often included in pharmaceuticals, such as benzyl alcohol, parabens, phenol, m-cresol, chlorobutanol, thimerosal. After systematic method development, the electrophoretic conditions were defined as: 50 mM borate buffer pH 9.0 containing 20 mM SDS. Separations were performed at a temperature of 20 degrees C and with detection at 214 nm. Preservatives under examination can be analyzed within a 10 min run. The method was successfully validated and applied to the determination of preservatives in a number of pharmaceuticals. Results from the CE method were compared with those from reference methods.

High performance liquid chromatographic determination of ambroxol in the presence of different preservatives in pharmaceutical formulations

A high-performance chromatographic method is described for simultaneous determination of ambroxol in the presence of different preservatives in syrups. The method separates ambroxol from methyl- ethyl-, propyl- and butyl paraben and from other multi-component mixtures. The retention behaviour of ambroxol and parabens as a function of both pH and mobile phase composition was investigated. The eluents were monitored with a UV detector at 247 nm. Linear relationships between the amount of pharmaceutical compounds and peak heights were confirmed at the concentrations of 0.74–14.08 μg ml −1. The high recovery (no extraction of the samples is required) and the low %RSD confirm the suitability of the proposed method for the determination of ambroxol in different pharmaceutical preparations.

Reversed-phase determination of famotidine, potential degradates, and preservatives in pharmaceutical formulations by high-performance liquid chromatography using silica as a stationary phase

An analytical method was developed for the determination of famotidine, potential degradates, and preservatives in several pharmaceutical formulations. The method employs reversed-phase chromatography on a silica column with a methanol—phosphate solution as the mobile phase. The influence of the concentration of phosphate and organic modifier are discussed. Accuracy and precision for this method along with assay data from different formulations of famotidine are presented. Two different commercial silica columns were tested with this method. Chromatographic differences related to the surface area and pore size of the silica are discussed.

Quantitative analysis of some preservatives in pharmaceutical formulations by different chromatographic methods

AbstractDifferent chromatographic methods for determination of methyl hydroxybenzoate and propyl hydroxybenzoate in pharmaceutical formulations are compared. Procedures for HPTLC, HPLC and GC/MS are given.