Extensive electronic investigation of BMBH structure and adsorption locator on graphene with molecular dynamics of human serum albumin interaction

Introduction

The primary goal of scientists and dosage form designers is to improve the safety of a drug molecule while preserving its therapeutic efficacy^{1, 2–3}. Recent advancements in Novel Drug Delivery Systems (NDDS) aim to achieve this by developing dosage forms that are easy to administer, ultimately improving patient compliance. Pharmaceutical technologists have focused their efforts on creating Fast Dissolving Drug Delivery Systems^{4, 5–6}. These tablets, which rapidly disintegrate or dissolve in the mouth, are especially beneficial for children, elderly patients, those with swallowing difficulties, or when drinking liquids may not be feasible. Bambuterol hydrochloride is a long-acting β₂-adrenergic receptor agonist (LABA) used primarily in managing asthma and chronic obstructive pulmonary disease (COPD)^7,8. As a prodrug of terbutaline, it undergoes hepatic metabolism to release the active compound, providing a sustained bronchodilatory effect. Due to its extended half-life, bambuterol offers advantages over short-acting β₂-agonists by reducing dosing frequency and improving patient compliance⁹. This research examines bambuterol hydrochloride in pulmonary medicine. It highlights its potential to improve disease control, patient adherence, and treatment outcomes for asthma and COPD. Bambuterol hydrochloride (BMBH), chemically known as (RS)-5-(2-tert-butylamino-1-hydroxyethyl)-m-phenylene bis(dimethyl carbamate) hydrochloride (Fig. 1), is a long-acting, orally administered sympathomimetic drug with predominant adrenergic activity (β1-agonist). It is widely prescribed for asthma and COPD management^{10, 11–12}. As an ester prodrug of the β2 adrenergic agonist terbutaline^13,14, bambuterol hydrochloride has been analyzed using solid-state NMR spectroscopy, GC–MS, and potentiometric titration. Research suggests that its active enantiomer is more effective in treating asthma than the (S)-bambuterol hydrochloride enantiomer¹⁵. It acts as a directly acting sympathomimetic agent and primarily exhibits adrenergic activity¹⁶. As a dicarbamate ester, it remains stable pre-systemically until it reaches lung tissues, where it undergoes hydrolysis by butyrylcholinesterase to release terbutaline, the active β2 adrenergic agonist¹⁷. Applying NDDS such as SEDDS, SMEDDS, and FDTs for bambuterol hydrochloride has shown promise in addressing its bioavailability challenges, potentially leading to more effective asthma management strategies. SEDDS enhance drug solubility and bioavailability by self emulsifying in gastrointestinal fluids. A study formulated a solid SEDDS for BMBH, showing improved permeability and potential bioavailability. SMEDDS forms microemulsions for better drug absorption. BMBH/ SMEDDS showed stability, rapid emulsification, and...