Development of a sterile morphine hydrogel for the local treatment of painful skin ulcers.

Objectives: It is often difficult to relieve the pain from skin ulcers. In several patients, topical morphine, applied as a hydrogel, has been described as useful. There is no such product commercially available. We present a solution for compounding, packaging, sterilisation and chemical stability of a morphine containing hydrogel.

Methods: We developed a morphine containing poloxamer 407 thermoreversible hydrogel with a concentration of 5 mg/g (0.5% w/w) morphine hydrochloride. The hydrogel was packaged into a plastic prefillable syringe system: BD Sterifill SCF. This syringe can be steam sterilised after it has been filled.

Results: Sterility tests according to the European Pharmacopoeia showed the product to be sterile directly after production and sterilisation and after 20 months of storage. The stability of the morphine hydrochloride was assessed by monthly analysis of the concentration with a stability indicating HPLC-UV method. Morphine hydrochloride concentrations remained between 90% and 110% of the theoretical concentration for a period of 36 months, when stored at room temperature outside the influence of light.

Conclusion: With the described formulation, packaging, sterilisation and stability data, together with the previously reported biopharmaceutical dissolution profile, we present a complete solution for a morphine containing poloxamer 407 hydrogel that can be compounded in any pharmacy with a steam or hot water steriliser at their disposal. This might improve the availability of a sterile morphine hydrogel for the treatment of painful skin ulcers.