Development of a Stability-Indicating, Predictive, and Prospective Study of a Semi-Solid Formulation of Butylscopolamine Bromide (BBS)

Introduction
The hospital pharmacy unit was requested to develop a semi-solid formulation of BBS 1% to address the shortage of Scopoderm^® TTS 1 mg/72 hours. The aim of our study is to develop and validate a stability-indicating HPLC-DAD assay method for routine controls and stability studies.

Materials and Methods
The calibration curve was established using three calibration standard solutions: 50, 100, and 150 µg/mL, and three validation standards : 60, 100, and 140 µg/mL. A Luna® Omega C18 100 mm x 2.1 mm, 1.6 µm and thermostated column (50 °C) was used as the stationary phase. The mobile phase consisted of a gradient of an aqueous phase A (acetonitrile/perchloric acid 0.2% 5/95 v/v) and an organic phase B (acetonitrile/perchloric acid 0.2% 70/30 v/v). The injection volume was 2 µL, the flow rate was 0.4 mL/min, and the detection wavelength was set at 210 nm. Specificity, selectivity, linearity, limit of detection (LOD) and quantification (LOQ), precision, accuracy, and accuracy profile were evaluated according to GERPAC and SFSTP guidelines. Forced degradation (FD) studies were conducted on BBS under the following conditions: acidic (1 M HCl, 51 h), alkaline (0.01 and 0.1 M NaOH, 3 h), photo-oxidative (265 nm, 16 days), thermal (80°C, 24 h), and oxidative (3% H2O2, 80°C, 24 h) to identify degradation products.

The predictive stability study was performed by storing samples at 32°C (up to 12 months), 40°C (up to 12 months), and 60°C (2 months). The prospective stability study was conducted by storing samples at 5°C and 25°C for 24 months. The physicochemical properties analyzed were: macroscopic appearance, BBS and its impurities content, pH, and IR spectrum.

Results
The retention time of BBS was 7 ± 0.6 min. FD under acidic, alkaline, heat, and photo-oxidative conditions identified impurity B. Under oxidative conditions at 80°C, several unspecified impurities appeared. All validation parameters met the specifications: linearity (R² > 0.99), repeatability and reproducibility (CV < 5% and CV < 8% by ANOVA), and accuracy (CV < 10%). The tolerance interval limits were all within the predefined acceptability range (10%).

After 2 months of the stability study, the macroscopic appearance, IR spectra, BBS content variations, and pH remained within acceptable limits at 5°C, 25°C, 32°C, and 40°C. Impurity B exceeded 0.10% after 15 days at 60°C, 1 month at 40°C, and 2 months at 32°C. The BBS content at 60°C increased up to 146% at M1 due to water loss in the cream related to the syringes’ loss of seal integrity.

Discussion/Conclusion
The HPLC assay method is validated. The BBS 1% cream is stable after 2 months of storage at 5°C and 25°C. The predictive stability study will be performed at M3 based on the stability data at 32°C, 40°C, and 60°C.