A Method for the Colorimetric Quantification of Sodium Lauryl Sulphate in Tablets: A Proof of Concept

Introduction

The industry of generic drug manufacturing plays an essential role in the national healthcare systems. It allows for an increase in the availability of medication for a wider population to decreases the financial burden and simultaneously retains the same level of safety and efficacy as an original drug product. To claim the same indications as an original drug product, the generic (test) product should prove and justify the similarity to the original one [1]. Based on the drug solubility and permeability, as well as drug release kinetics from the reference product, the justification of test-to-reference product similarity can include or exclude very expensive and resourceful bioequivalence studies involving healthy volunteers [1].

Sodium lauryl sulphate (SLS), also known as sodium dodecyl sulphate, can be found in different forms but mostly in oral dosage forms [2] (Supplementary Table S1). SLS is used in tablet formulations in the concentration range of 0.1–1.5 wt.% [3] to improve the tablet wettability and apparent solubility of drug substances. Additionally, it can act as a lubricant to reduce friction and adhesion within the die during tablet pressing [4]. According to the U.S. Food and Drug Administration, SLS was claimed as a lubricant twenty times in Abbreviated New Drug Application [5]. Importantly, SLS can change oral bioavailability by increasing the apparent solubility of the drug and influencing transepithelial transport [6,7]. SLS, at a concentration range of 0.025–1.0%, showed an ex vivo dose-related permeability increase through the canine oral mucosa for twelve organic compounds [8]. The underlying mechanism of the SLS-mediated enhanced permeability was explained by the reversible opening of tight junctions [7]. SLS can increase the paracellular transport of metformin via human colorectal adenocarcinoma (Caco-2) cells which mimic the intestinal epithelium: the initial permeability of metformin (1.36 × 10−5 ± 1.25 × 10−6 cm/s) was increased 1.9-fold at an SLS concentration of 0.012% (w/v) [9].

To achieve test-to-reference product composition and property similarity, the development of the generic product often includes a deformulation stage of the original product. This stage includes the quantification of critical excipients such as SLS. This allows for shortening of the formulation development based on the in vitro property’s similarity (such as disintegration time and dissolution profile). Additionally, deformulation increases the success rate of bioequivalence studies because the in vitro property’s similarity cannot guarantee the in vivo similarity.

Very often, tablets are manufactured with a coating to provide visual differentiation, to improve stability, or to mask the taste. Coatings contain several excipients, such as sugars, polymers, plasticizers, surfactants, antifoaming agents, organic dyes, and inorganic pigments. If a scientist is interested in the composition of a tablet core, it is highly recommended that they remove the coating from the tablet’s surface. If the component of interest is distributed evenly in the core, a part of the core (without coating) with a known mass can be used. Otherwise, if the distribution is unknown, careful removal of the coating and the use of the whole core is recommended. The removal of the coating will decrease the chemical complexity of the tested object, uncertainty, and the probability of undesirable chemical interactions upon quantification.

In order to determine the SLS content in a tablet, several methods have been proposed. These include gas chromatography (GC) methods which require a derivatization step to convert SLS to lauryl alcohol, which then can be used to determine directly [10,11,12] or derivatize further with silylating agents [13]. These methods involve tedious sample preparations, where the sample is heated to 80 °C within acidic conditions for up to several hours to achieve SLS conversion. Also, not all laboratories are equipped with the required equipment for sample preparation or GC itself. Methods using high-performance liquid chromatography (HPLC) with ultra-violet (UV) spectroscopy detection were not found, which is likely due to the lack of chromophores within the SLS molecules. While it is possible to use liquid chromatography-mass spectrometry (LC-MS) to determine SLS [14], it being more selective would require expensive equipment. Alternatively, chromogenic [15,16], fluorescence [17], and some electrochemical methods are also proposed [18].

SLS is a critical excipient that can influence the bioavailability of drugs (such as metformin). Thus, precisely determining its concentration is tremendously important in generic product development. This study aims to undertake a feasibility study in order to develop a simple, economical, and robust analytical method for the quantification of SLS in tablets containing metformin.

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Chemicals and Materials

Chloroform was obtained from Fisher Chemical, ≥99.8%, stabilised with amylene. Purified water was obtained from a StakPure Omnia Tap 6 water purifier (Stakpure, Berlin, Germany), with a conductivity of 18.2 MΩ × m. Sodium sulphate (ACS reagent, ≥99.0%, anhydrous, powder) and sulfuric acid (ACS reagent, 95.0–98.0%) were obtained from Sigma-Aldrich (Merck KGaA, Darmstadt, Germany). Methylene blue (98.0%) was obtained from Tokyo Chemical Industry Co., Ltd. (Tokyo, Japan). Sodium lauryl sulphate (SLS) was provided by BASF SE (Ludwigshafen am Rhein, Germany). The methylene blue reagent contained 12 mg methylene blue, 2.5 g sodium sulphate anhydrous, and 0.5 mL sulfuric acid in 50 mL of purified water, prepared in our laboratory using the above-mentioned ingredients. In the same laboratory, an acidified sodium sulphate solution was prepared by mixing 25 mL of saturated sodium sulphate solution in purified water and 25 mL of sulfuric acid. JANUMET^® tablets (Merck Sharp & Dohme Idea Inc., Haarlem, The Netherlands; Table 1) contained SLS and metformin.

Table 1. Expected tablet cores composition.

Paulausks, A.; Mazurs, A.; Mohylyuk, V. A Method for the Colorimetric Quantification of Sodium Lauryl Sulphate in Tablets: A Proof of Concept. Pharmaceutics 2024, 16, 1100. https://doi.org/10.3390/pharmaceutics16081100

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