Ethyl Lactate as a Pharmaceutical-Grade Excipient and Development of a Sensitive Peroxide Assay - Pharmaceutical Technology

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Ethyl Lactate as a Pharmaceutical-Grade Excipient and Development of a Sensitive Peroxide Assay
The authors investigate whether the addition of an antioxidant could be used to stabilize the solvent ethyl lactate by preventing the formation of peroxides.

Pharmaceutical Technology
Volume 33, Issue 5, pp. 74-84

Table I. Construction of a reverse-absorption calibration curve for hydrogen peroxide (H202) and iron (II)-tris-1,10-phenanthroline (I2PC).
Solubility of BHT in ELPG. To determine an absorption wavelength, a 10 mg/mL solution of BHT in a mixture of IPA and deionized water (1:1) was prepared, and a UV–vis scan revealed a λ max of 280 nm. Following this step, a stock solution of BHT (100 mg) in a 100-mL mixture of IPA and deionized water (1:1) was prepared. A calibration curve was constructed at concentrations of 100, 90, 80, 70, 60, 50, 40, 30, 20, and 10 mg/L. BHT (9 g) was weighed into 10 separate brown-glass scintillation vials, and ELPG was added (5 mL). The vials were sealed and shaken at 25 C (five vials) and 37 C (five vials) for 48 h. An aliquot (1 mL) of each vial was dispensed into a 1.5-mL centrifuge tube, and the ELPG was evaporated to dryness in a vacuum desiccator for 24 h. An 18-gauge needle was inserted into the top of each sample during the drying period with a stainless-steel wire to prevent the formation of a BHT crust layer. A crust layer of BHT, which would prevent further evaporation of the ELPG, could form at the interface of the solvent and air. Each dried sample was washed with 3 mL of IPA into a scintillation vial before adding 3 mL of deionized water. An aliquot (1 mL) from each reconstituted vial was diluted into 100 mL of the mixture of IPA and deionized water (1:1). The unknown concentration was determined by analysis at 280 nm. It was necessary to reconstitute in the IPA because interference at 280 nm was observed with pure ELPG.

Figure 2: Results of a stability study of ethyl lactate of pharmaceutical grade (ELPG) performed at 25 C. Each antioxidant was added at 3% w/v into ELPG. The antioxidants studied were acorbic acid (AA), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), citric acid (CA), methionine (METH), sodium ascorbate (SA), sucrose (SU), and tocopherol (vitamin E [VE]). C1 and N2 represent the control groups. (ALL FIGURES ARE COURTESY OF THE AUTHORS)
Accurate determination of peroxide concentration in ELPG . A method was developed using a reverse UV–vis absorbance technique based on the oxidation of a I2PC to I3PC (as opposed to the reduction of I3PC to I2PC as previously described). A 2% w/v stock solution of I2PC was prepared. Iron (II) ammonium sulfate (1.3635 g) and 1,10-phenanthroline (0.9717 g) was weighed into a 1-L volumetric flask, and 1.0 N hydrochloric acid (10 mL) was added. The solution was made with deionized water to form a 2% w/v blood-red complex in solution. A 1% w/v hydrogen peroxide solution was prepared by adding an aliquot of 3% w/v hydrogen peroxide (1 mL) to deionized water (2 mL). The freshly prepared 1% w/v hydrogen peroxide solution was diluted with deionized water (1:10) to give a stock solution of hydrogen peroxide (1000 mg/L). The stock solution was diluted to obtain the standard concentrations of peroxide as indicated (see Table I), and a calibration curve was constructed. Five aliquots of ELPG (each 200 μL) were added to 2% I2PC (1.5 mL) and deionized water (2.3 mL) to determine the unknown concentration of the peroxides in the sample.


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