Preservatives In Pharmaceutical Preparations Research Articles

Evaluation of new formulations for neutralizing antimicrobial preservatives in pharmaceutical preparations

BackgroundNeutralization of preservative systems is essential to obtain reliable results when testing samples containing preservatives such as nutritional, cosmetic and pharmaceutical products. Therefore, the aim of this study was to prepare and investigate the neutralization ability of in-house neutralizing systems made of available cost-effective materials in the inactivation of preserved pharmaceutical suspensions. Ibuprofen and Cefpodoxime proxetil preserved suspensions were chosen as the quenching model since subsequent microbiological studies will be conducted on their local pharmaceutical formulations available in the Syrian market. MethodsWe reported toxicity and efficacy ratios of ten neutralizing systems (No.1 to No.10) containing polysorbate 80, cetomacrogol 1000 and polyoxyl 40 hydrogenated castor oil with various concentrations dedicated to the inactivation of Ibuprofen and Cefpodoxime proxetil preserved suspensions, methyl paraben/propyl paraben mixture and sodium benzoate controls against low inoculum ranging between 1 × 102–1.2 × 103 CFU of five challenged bacteria and fungi; Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans and another environmental isolate of Aspergillus niger. Neutralizing systems validation was conducted according to USP chapter 1227 criteria to assess the acceptance of recovery comparisons for both “Neutralizing systems toxicity test” and “Neutralizing systems efficacy test” which enabled determining the appropriate neutralizing formula for both neutralization of preservative system of a specified product and being non-toxic towards the challenged microorganism additions. ResultsMost neutralizing formulas used in the study were non-toxic for all tested microorganisms. According to “Neutralizing systems efficacy test”, No. 3 (polysorbate 80 (3%)) and No. 10 (polysorbate 80 (1%), cetomacrogol 1000 (1%) and polyoxyl 40 hydrogenated castor oil (1%)) effectively recovered at least three microorganisms when used in the neutralization of samples. Most limitations were observed when neutralizing ibuprofen suspension. However, we found neutralizing system No. 10 against Pseudomonas aeruginosa, No. 3 and No. 5 against Escherichia coli and No. 8 and No. 10 against Candida albicans were effective in the neutralization of ibuprofen suspension. All neutralizing systems effectively inactivated the preservative system of cefpodoxime proxetil suspension using all microorganisms while several neutralizing systems failed in quenching cefpodoxime proxetil suspension against Staphylococcus aureus. ConclusionDue to the variation in the neutralization efficacy relative to the product sample and challenged microorganism, neutralization validation procedure must be undertaken before microbiological testing of pharmaceuticals which makes the development and validation of neutralizing systems an essential procedure.

Electrochemical and sonoelectrochemical processes applied to the degradation of the endocrine disruptor methyl paraben

Methyl paraben is commonly employed as a preservative in pharmaceutical preparations, personal care products and some processed foods. However, the ester constitutes a potential pollutant in aquatic environments and has been classified as an endocrine disruptor. This study describes the degradation of methyl paraben (100 mg L−1 in 0.05 mol L−1 aqueous potassium sulfate at pH 5.7) by means of an electrochemical process (employing a boron-doped diamond anode) either alone or coupled with sonolysis. Electrolyses were performed at 25, 30 and 35 ± 1 °C during 120 min using applied constant current densities of 10.8 and 21.6 mA cm−2. The hybrid sonoelectrochemical processes were conducted under similar conditions with the application of ultrasound at a frequency of 20 kHz and a power intensity of 523 W cm−2. Although mineralization of methyl paraben could be achieved using either process, in comparison with the electrochemical method, the hybrid technique showed a higher mineralization efficiency (around 60 %) with approximately 50 % removal of total organic carbon, thereby confirming the synergistic effect of sonolysis.

Study and Development of Reversed-Phase HPLC Systems for the Determination of 2-Imidazolines in the Presence of Preservatives in Pharmaceutical Preparations

Different HPLC chromatographic systems were investigated on a C18 ACE 5 pm, 150 x 4.6 mm id column for the determination of tymazoline, tramazoline, and antazoline, with either naphazoline or xylometazoline, in commercial preparations. For the development and optimization of the systems, a Response Surface Method (r=0.925-0.980) was used to illustrate the changes in k as a function of pH values and different salt concentrations. The simultaneous separation of 2-imidazolines was accomplished at 40 degrees C with 0.01 M ammonium acetate-methanol (50+50, v/v, pH 6.0) mobile phase at a flow rate of 1.2 mL/min. In order to deal with the usual coexistence of 2-imidazolines with benzethonium and benzalkonium chloride preservatives, it was necessary to use another chromatographic system, 0.01 M ammonium acetate-methanol (50+50, v/v) mobile phase on a cyano ACE 5 pm, 150 x 4.6 mm id column. As part of a more thorough theoretical investigation, a partial least-squares (PLS) technique was used for modeling the RP-HPLC retention data. The model was based on molecular structure descriptors of the analytes' X variables and on their retention time (Log K) Y. The goodness of fit was estimated by the PLS correlation coefficient (r2) and root mean square error of estimation values, which were 0.994 and 0.0479, respectively.

Distinct Effect of Benzalkonium Chloride on the Esterase and Aryl Acylamidase Activities of Butyrylcholinesterase

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) from vertebrates, other than their predominant acylcholine hydrolase (esterase) activity, display a genuine aryl acylamidase activity (AAA) capable of hydrolyzing the synthetic substrate o-nitroacetanilide to o-nitroaniline. This AAA activity is strongly inhibited by classical cholinesterase (ChE) inhibitors. In the present study, benzalkonium chloride (BAC), a cationic detergent widely used as a preservative in pharmaceutical preparations, has been shown to distinctly modulate the esterase and AAA activities of BChEs. The detergent BAC was able to inhibit the esterase activity of human serum and horse serum BChEs and AChEs from electric eel and human erythrocyte. The remarkable property of BAC was its ability to profoundly activate the AAA activity of human serum and horse serum BChEs but not the AAA activity of AChEs. Thus BAC seem to preferentially activate the AAA activity of BChEs alone. Results of the study using the ChE active site-specific inhibitor diisopropyl phosphorofluoridate indicated that BAC binds to the active site of ChEs. Furthermore, studies using a structural homolog of BAC indicated that the alkyl group of BAC is essential not only for its interaction with ChEs but also for its distinct effect on the esterase and AAA activities of BChEs. This is the first report of a compound that inhibits the esterase activity, while simultaneously activating the AAA activity, of BChEs.

Removal of toxic preservatives in pharmaceutical preparations of insulin by the use of ultra-stable zeolite Y

Ultra-stable zeolite Y and mordenite with pore sizes of 0.75 and 0.70 nm, respectively, showed the capacity to bind phenol and m-cresol rapidly. Phenol and m-cresol are used as preservatives in pharmaceutical preparations for humans and, with the use of a 15 mg filter of ultra-stable zeolite Y, 98 % of the preservative in a 200 μl pharmaceutical insulin preparation, Actrapid®, was removed after 5 s of passage through the filter. The insulin content in the filtrate was not disminished. © Rapid Science Ltd. 1998

Manometric Method for the Evaluation of Preservatives

A manometric method using the Warburg apparatus has been investigated as a possible screening technique for the evaluation of agents used as preservatives in pharmaceutical preparations. This procedure also was utilized to determine the relative effectiveness of different preservatives, and preservative-surfactant combinations. The respiratory effects on baker's yeast were determined with methyl-paraben, propylparaben, and sorbic acid, separately, and each in the presence of polysorbate 80. Each of the three preservatives caused a decrease in oxygen consumption by baker's yeast. In general, the order of effectiveness was propylparaben > sorbic acid > methylparaben. Polysorbate 80 decreased the effectiveness of each of the three preservatives. Sorbic acid was the least affected, except at a preservative concentration of 0.025%. These manometric results are rapidly obtained, informative, and in general agreement with results found by more time-consuming procedures.

The Relative Action of Preservatives in Pharmaceutical Preparations

The Relative Action of Preservatives in Pharmaceutical Preparations