Hospital formulation of scopolamine transdermal device for the treatment of agonic rales
6 October 2023
E. Gonnard-Déséchaud1, E. Sournac1, L. Usseglio1, C. Marchand1, C. Paillet1, A. Citterio-Quentin2, C. Merienne1, F. Pirot1, 31 Hospices Civils de Lyon (HCL) - Unité de Préparation et de Contrôle des Médicaments, plateforme FRIPHARM, Pharmacie à usage intérieur, Groupement Hospitalier Edouard Herriot
2 HCL - Service de Biochimie et Biologie Moléculaire UM Pharmaco-Toxicologie, Groupement Hospitalier SUD
3 Université Claude Bernard Lyon-1, Faculté de Pharmacie de Lyon, Laboratoire de Biologie tissulaire et Ingénierie Thérapeutique UMR 5305
Introduction
In anticipation of a supply shortage transdermal system of scopolamine, we report the development of hospital preparations of scopolamine hydrobromide (i) (1,25%, BHS) and scopolamine butylbromide (ii) (1%, BBS) respectively indicated for the treatment of central (nausea, dizziness) and peripheral symptoms (bronchial congestion, agonic rales). Two previous studies have reported the transdermal use of BHS and BBS (1).
Materials and Methods
Two formulations are prepared by supplementing BHS or BBH in a cream (oil-in-water emulsion). Following production, 10 mg/cm² of each emulsion (E-BHS and E-BBS) are applied to the surface of ready-to-use transdermal devices. An in silico prediction study of transcutaneous absorption is carried out, taking into account the physico-chemical parameters of the molecules (2) (molecular weight, octanol/water partition coefficient, concentration of active ingredient) used as determinants in a permeation algorithm (3). A dissolution study of BHS and BBS from E-BHS and E-BBS impregnated on these devices (Ph. Eur. 11.1 : 2.9.4 Patch dissolution test) completes the characterization of transdermal formulations.
Results and discussion
Transcutaneous absorption rates of BHS and BBS, determined from the permeation algorithm, are of the same order of magnitude as excretion rates (5 µg/h), confirming the feasibility of effective percutaneous administration. Further in vitro dissolution and ex vivo skin bioavailability studies will aim to confirm or refute the relevance of such a methodological approach about topical formulations obtained throught ready-to-use transdermal devices.
Conclusion
Limited drug supplies require simple and reproducible production and formulation processes. This work reports on a brief methodology for preparing transdermal medication.
1. Odachi K, Narita Y et al. Efficacy of transdermal scopolamine for sialorrhea in patients with amyotrophic lateral sclerosis. Schumacher U. Cogent Med. 1 janv 2017;4(1):1365401.
2. DrugBank Online [Internet]. 2023. Butylscopolamine. Disponible sur: https://go.drugbank.com/drugs/DB00747
3. Burli A, Law RM, Rodriguez J et al. Organic compounds percutaneous penetration in vivo in man: Relationship to mathematical predictive model. Regul Toxicol Pharmacol. 1 avr 2020;112:104614.