SUBMISSION

Synthesis and solubility studies of dual active asthma drugs in liquid state

Devon Cotter

Jacob Thorn

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Presented at
ACS Spring Meeting 2021

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Abstract

Patients suffering from asthma and COPD receive treatment in the form of solid-state ingestible tablets or inhalants. Such forms of treatment are not a pervasive solution to those suffering from long term asthma and severe COPD due to the delivery effectiveness of most beta-agonists and corticosteroids such as albuterol and fluticasone (common drugs prescribed for dealing with asthma exacerbation with worsening conditions). Effectiveness of delivery derives from administration (i.e. inhaled medications hardly reach below the larynx of the human body). Thus, the intended effect of the drug is lost amid delivery complications. An alternative method to inhalants that contiguously resolves complications with delivery and effect while mitigating the use of corticosteroids is to administer these drugs in an ionic liquid form. An ionic liquid approach would be especially useful against standard dry powder inhalants (DPIs) as these solid state drugs can exist in multiple crystalline forms (i.e., polymorphism). Polymorphism declines the drug solvation ultimately decimating its bioavailability while converting the drug to less or nonactive forms. Ionic liquids with multiple cations and anions of varying molar ratios balanced by a neutral charge (e.g., one cation and multiple anions, multiple cations and one anion, or multiple cations and anions) are known as double salt ionic liquids (DSILs). When applied to pharmaceuticals, the DSIL approach should increase drug bioavailability (higher aqueous solubility), remove the existence of polymorphic forms, and add multifunctionality to the final drugs (i.e., the pharmaceutical activity of the parent ions is retained). This study investigates the DSIL forming properties of albuterol when combined with ionic forms of over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs) and docusate anion (a known penetration enhancer), as well as the aqueous solubility of the synthesized compounds

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