Stability Study of a Buccal Hydrogel Containing 2% Lidocaine (20mg/g) and 0.05% Clobetasol (500µg/g) Used for the Treatment and Relief of Mucositis

Introduction
Oral mucositis (OM) is one of the most common adverse effects of cancer therapies and radiotherapy, affecting patients’ quality of life and tolerance to treatment. Thus, it is important to relieve OM to continue anticancer therapies. As a first-line approach, local treatment is implemented to provide relief. Clinicians are interested in combining lidocaine and clobetasol in a treatment. In the absence of a marketed drug, developing a buccal hydrogel combining 2% lidocaine and 0.05% clobetasol would address this uncovered medical need. The objective of this study was to evaluate the physicochemical and microbiological stability of this hydrogel.

Material and method
A batch of buccal hydrogel was prepared and then packaged into 6 polypropylene jars and 6 aluminum tubes. These samples were stored in triplicate at two different temperatures: room temperature and between +2°C and +8°C. The chemical stability was determined using a stability-indicating assay method developed by HPLC-UV according to GERPAC guidelines. The linearity, specificity, repeatability, accuracy, and intermediate precision of the method were evaluated, the matrix effect was investigated, and forced degradation tests using HCl, NaOH, and H2O2 were conducted. Concentration was considered stable if its variation was less than 10% of the initial value without any appearance of degradation products. It was planned at days 0, 1, 3, 7, 14, 30, 60, 90, and 180. The pH was measured using a calibrated pH meter and considered stable if the variation was within +/- 1 point. The physical stability was assessed using a Haake Mars III rheometer with a cone-plate geometry. The viscosity was measured at 50 s-1 and considered stable within the range of 4-7 Pa.s. The microbiological stability was determined according to the monograph 5.1.4 of the European Pharmacopoeia (Ph.Eur 5.1.4). The preservation of organoleptic properties (color, odor, taste) was also evaluated.

Results
The assay method was linear, repeatable, reproducible, and accurate (coefficients of variation below 5%). It was specific with no matrix effect detected.
At day 30, the maximum variation in active ingredients content was less than 6% without any appearence of degradation product. The pH was (mean (SD)) 6.30 (0.015) at day 0 and 6.41 (0.033) at day 30. The viscosity was 6.09 Pa.s (0.13) at day 0 and 5.13 Pa.s (0.18) at day 30. At day 30, the microbiological stability was compliant with Ph.Eur.5.1.4 and the organoleptic properties remained unchanged.

Conclusion
The preliminary results at day 30 show a stability of all evaluated parameters for all samples. These datas are encouraging. However, it is necessary to continue the stability study, up to the predefined 6 months.