Development of a carbocysteine 10% + urea 5% cream for the topical treatment of congenital ichthyosis

Abstract

Objective: Optimization of a topical formula of N-acetylcysteine and urea for the topical treatment of ichthyosis. Method: We reviewed the chemical structure of the N-acetylcysteine molecule and its metabolic processes. A search was conducted of possible alternative molecules with a chemical structure similar to that of N-acetylcysteine that could have improved organoleptic properties. The following databases were used: PubChem®, Botplus®, the Drug Information Centre of the Spanish Agency of Medicines and Medical Devices. The molecule selection criteria were as follows: structural similarity, same therapeutic group, same mechanism of action, same authorized indication, absence of unpleasant smell, and being marketed as raw material in Spain. To complete the pharmaceutical development and validation of the compound, several tests and controls were conducted following the emulsion production procedure of the National Formulary. In order to establish the validity period, we followed the recommendations of the "Guide to Good Drug Preparation Practices in Hospital Pharmacy Services". Results: N-acetylcysteine has a free sulfhydryl group, which is responsible for its smell, and undergoes deacetylation. Its main metabolites are cystine and cysteamine. The following molecules were assessed: cystine, cysteamine, carbocisteine, cysteine and methionine. Carbocisteine was selected because it met all the selection criteria. Carbocisteine is practically insoluble in water and soluble in mineral acids and alkaline hydroxides solutions. Unlike N-acetylcysteine, it does not have a fetid smell. It reaches its maximum stability at pH 5.5 to 7.5. The composition of the compound (100 g) was as follows: carbocisteine (10 g), urea (5 g), glycerine (15 g), water (44 mL), sodium hydroxide (1 g), and Neo PCL® Oil/Water (O/W) (25 g). It has an expiration period of 30 days. The organoleptic characteristics, emulsion type, and pH remained stable within the established expiration period. The carbocisteine compound has been incorporated into the group of topical treatments available for the treatment of patients with ichthyosis in our hospital. Conclusions: The carbocisteine molecule is a good therapeutic alternative that lacks the unpleasant smell of N-acetylcysteine. The carbocisteine compound developed has been included as topical treatment for ichthyosis due to its tolerability, acceptability, and effectiveness in the treatment of patients affected by this genodermatosis.