The study of delivery medicine using ends device: a bromhexine case study

Cipto Kokadir; Ervina Kalinda; Kamarza Mulia

doi:10.35814/jifi.v24i2.2148

Authors

Cipto Kokadir PT Natura Nuswantara Nirmala (Nucleus Farma), Banten 15229, Indonesia
Ervina Kalinda Department of Chemical Engineering, Faculty of Engineering, Universitas Indonesia, Depok 16424, Indonesia
Kamarza Mulia Department of Chemical Engineering, Faculty of Engineering, Universitas Indonesia, Depok 16424, Indonesia

DOI:

https://doi.org/10.35814/jifi.v24i2.2148

Keywords:

Bromhexine hydrochloride, Computational Simulations, electronic nicotine delivery system, inhalation delivery

Abstract

Electronic Nicotine Delivery System (ENDS) has been used over the last decade to substitute conventional cigarettes. Active pharmaceutical ingredient (API) delivery using these devices has been reported in the literature, mainly for bronchodilators and nicotine; however, mucolytic agents have not previously been evaluated through this route, and many puffs were required to achieve the therapeutic dose in existing formulations. This study aimed to deliver and measure bromhexine hydrochloride (BRM) as API via inhalation using an e-liquid formulation. The e-liquid was obtained by trapping the aerosol and measuring the concentration using high-performance liquid chromatography-mass spectrometry (HPLC-MS) in multiple reaction monitoring (MRM) modes. Our study demonstrated that five puffs accumulated 3.3156 ng/mL of BRM, and the efficiency of the ENDS device was calculated to be 99.8%. In addition, computational simulations were performed, resulting in a binding affinity of BRM of -7.3 kcal.mol-1 compared to salbutamol with -8.1 kcal.mol-1. Nevertheless, BRM has a hydrogen bond between the amine group and Ser204, Pi-Alkyl bonds with Ala200 and Val114, also alkyl interactions with Phe289 and Phe290. However, the BRM interaction with the protein does not form a stable complex in the dynamics simulation, but it may act as an allosteric modulator or partial agonist. The results of this study corroborate previous results that ENDS technology may have wide innovations for inhalation medicines.

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