Objectives Several studies have investigated the effectiveness of high-dose ambroxol in treating patients with Gaucher disease type 3. Since there are no registered high-dose ambroxol preparations available, information on the development of this preparation can be important to improve access. The pharmacy and clinical pharmacology department of Amsterdam University Medical Center has developed a simple 75 mg ambroxol hydrochloride (HCl) capsule formulation for this purpose. The aim of this study was to investigate the stability of 75 mg ambroxol capsules. Methods Three batches (n=1000) of 75 mg ambroxol HCl capsules were produced and stored in climate chambers for 6 months under accelerated (40±2°C and 75% relative humidity (RH)±5% RH) and long-term (25±2°C and 60% RH±5% RH) conditions. At 0, 3 and 6 months, appearance, identity, related substances, assay, uniformity of dosage units (content uniformity (CU)), dissolution and microbiology were evaluated. The specifications and acceptance criteria were derived from the European Pharmacopoeia and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines. Results All parameters met the predefined specifications from t=0 to t=6 months for both the accelerated and long-term stability studies. There were no visible changes in appearance of the capsule content, no degradation products above 0.05%, and no decrease in ambroxol content. Furthermore, the capsules met the criteria for CU with an acceptance value ≤15.0. The dissolution was rapid, with ≥80% of ambroxol released from the capsules within 30 min, and no microbiological growth was observed. Conclusions The 75 mg ambroxol HCl capsules are stable for at least 6 months at room temperature. This paper provides guidance to pharmacies for compounding of high-dose ambroxol HCl capsules to ensure the availability of ambroxol for patients in need.
Le et al. (Thu,) studied this question.