In electronic cigarette users, nicotine delivery to lungs depends on various factors. One of the important factors is e-liquid nicotine concentration. Nicotine concentration in e-liquids ranges from 0 to >50 mg/mL. Furthermore, nicotine exists in protonated and unprotonated (“free base”) forms. The two forms are believed to affect the nicotine absorption in body. Therefore, in addition to total nicotine concentration, e-liquids should be characterized for their free base nicotine yield. Two approaches are being used for the determination of free base nicotine in e-liquids. The first is applying a dilution to e-liquids followed by two methods: Henderson–Hasselbalch theory application or a Liquid-Liquid Extraction. The second is the without-dilution approach followed by ¹H NMR method. Here, we carried out controlled experiments using five e-liquids of different flavors using these two approaches. In the dilution approach, the Henderson–Hasselbalch method was tested using potentiometric titration. The accuracy was found to be >98% for all five e-liquid samples (n = 3). A Liquid-Liquid Extraction was carried out using toluene or hexane as extraction solvent. The Liquid-Liquid Extraction technique was found to be limited by solvent interactions with flavors. Solvent extractions resulted in flavor dependent inaccuracies in free base nicotine determination (5 to 277% of calculated values). The without-dilution approach was carried out using ¹H NMR as described by Duell et al. This approach is proposed to offer an independent and alternative scale. None of the methods have established a strong correlation between pre- and postvaporization free base nicotine yield. Here we present comparative results of two approaches using analytical techniques. Such a comparison would be helpful in establishing a standardized method for free base nicotine determination of e-liquids.

In inhalation drug products, nanomaterials can be either the active pharmaceutical ingredients, the carriers for the drug, or they may function as excipients. Approximately 4% of all investigational new drugs are applications related to inhalation drug products containing nanomaterials (IDPNCs), at par with the 3% market share of inhalation drug products in the drug delivery market. Liposomal formulations delivered with nebulisers have been used in most clinical trials of IDPCNs reported to date, and their safety profile firmly demonstrated. The most common drug classes investigated in IDPCNs have been antibiotics and antifungal, with other (few) applications in areas including chemotherapeutics. These studies have shown not only ability of the liposomal IDPCNs to decrease toxicity of the therapeutics, but also to improve their efficacy, and the ability to target distant tissues upon pulmonary administration. These initial studies point to the fact that IDPCNs are here to stay, and the tremendous opportunities for: (i) applying IDPCNs for different classes of drugs, (ii) the use of second generation nanocarriers as IDPNCs, (iii) the use of alternative inhalation devices for the treatment of pulmonary disorders, and (iv) also as the delivery of drugs through the lungs.

Pressurized Metered-dose Inhalers (pMDIs) are complex drug-device combination products that are widely used to treat lung diseases, and may also be advantageously employed to deliver active pharmaceutical ingredients (APIs) to the systemic circulation through the lungs. pMDIs occupy ca. 70% of the respiratory inhaler device market share and are expected to continue their dominance in the foreseeable future. The transition from CFCs to hydrofluoroalkane (HFA) propellants has stimulated significant advances in this field, and the proposed phase out of HFAs as indicated in the Kigali amendment to the Montreal Protocol (starting in 2019) is expected to generate renewed interest in the design of alternative propellant systems and subsequently device components and formulations compatible with the more environmentally acceptable propellant alternatives to be used in the future medicinal aerosol formulations. Development of new technologies enabling: (i) the delivery of a broader class of APIs with pMDIs including biologics; (ii) the development of orally inhaled drug products containing nanomaterials; and (iii) the delivery of higher drug doses are some of the areas that are expected to help further the use of pMDIs and thus secure a larger share for orally inhaled products in the global drug delivery market.