Printing of cutaneous patches loaded with propranolol for the treatment of infantile haemangiomas

Topical propranolol has been used in clinics for treating cutaneous infantile haemangiomas, but frequent applications of semi-solid preparations are required to maintain therapeutic drug concentrations in the skin layers over time. This work aims to study the preparation of cutaneous propranolol patches by hot-melt ram extrusion printing, a novel technique suitable for the personalization of the dosage forms. The preparation steps are: i) mixing of a poly-ammonium methacrylate polymer (Eudragit RL) with a suitable amount of plasticizer [acetyl triethyl citrate (ATEC), triacetin or tributyl citrate, TBC] and the drug (propranolol base, or hydrochloride), ii) the melting in the ram extruder, and iii) the printing on the backing layer foil. All formulations released the loaded drug in a reasonable time and exhibited suitable adhesive properties. The determination of permeation profiles of the drug revealed the patch made of Eudragit RL and TBC and containing 1% propranolol hydrochloride as the most promising formulation for ensuring the drug retention on the human epidermis (Qret/J = 1.32) and, therefore, it can be selected when a superficial haemangioma has to be treated. Conversely, the patch made of Eudragit RL and ATEC and 1% propranolol base can be used in the case of deep haemangiomas.

Automated summary

Topical propranolol has been used for treating cutaneous infantile haemangiomas, but frequent applications are needed. This study developed propranolol patches using hot-melt ram extrusion printing, with formulations releasing the drug in a reasonable time and exhibiting suitable adhesive properties. The patch made of Eudragit RL and TBC with 1% propranolol hydrochloride is the most promising for superficial haemangiomas, while the patch made of Eudragit RL and ATEC with 1% propranolol base can be used for deep haemangiomas.