Applications of an Electrochemical Sensory Array Coupled with Chemometric Modeling for Electronic Cigarettes.

This study investigates the application of an eNose (electrochemical sensory array) device as a rapid and cost-effective screening tool to detect increasingly prevalent counterfeit electronic cigarettes, and those to which potentially hazardous excipients such as vitamin E acetate (VEA) have been added, without the need to generate and test the aerosol such products are intended to emit. A portable, in-field screening tool would also allow government officials to swiftly identify adulterated electronic cigarette e-liquids containing illicit flavorings such as menthol. Our approach involved developing canonical discriminant analysis (CDA) models to differentiate formulation components, including e-liquid bases and nicotine, which the eNose accurately identified.

Aerosolized e-liquid base constituents induce cytotoxicity and genotoxicity in oral keratinocytes.

Objective: Electronic cigarette (e-cigarette) use among adults in the United States continues to rise. Particularly concerning is the impact of e-cigarette aerosol inhalation on the oral mucosa. Aerosols are derived from a heated e-liquid base of propylene glycol/glycerin (PG/G) often mixed with nicotine and chemical flavors.

Can extraoral suction units minimize droplet spatter during a simulated dental procedure?

Background: Aerosol and droplet production is inherent to dentistry. Potential for COVID-19 spread through aerosols and droplets characterizes dentistry as having a high risk of experiencing viral transmission, with necessity for aerosol and droplet mitigation.

Methods: Simulations of restorative treatment were completed on a dental manikin with a high-speed handpiece and high-volume evacuation suction.

Cigalike electronic nicotine delivery systems e-liquids contain variable levels of metals.

Electronic nicotine delivery systems (ENDS) are prefilled, battery-operated products intended to deliver nicotine to the user via an inhaled complex aerosol formed by heating a liquid composed of propylene glycol and glycerol, also referred to as vegetable glycerin and collectively called e-liquid, that contains nicotine and various flavor ingredients. Since their introduction in 2006, the number of ENDS on the market has increased exponentially. Despite their growing ubiquity, the possible health risks associated with ENDS use remain poorly understood.

Clinical implications of the tiotropium/olodaterol inhaler for patients with chronic obstructive pulmonary disease.

Oral inhalation is the recommended delivery method of medications for the treatment of patients with chronic obstructive pulmonary disease (COPD). However, patients may struggle when using the various available inhaler platforms, and, as a result, may fail to achieve the benefit of the prescribed medication. Propellant-based, pressurized metered-dose inhaler and powder-based, dry powder inhaler devices are currently the most commonly prescribed delivery systems.

Methodology for the in vitro evaluation of the delivery efficiency from valved holding chambers with facemasks.

Background: In vitro performance studies of valved holding chamber (VHC)-facemask systems are a cost-effective means of circumventing potentially confounding clinical variables. This article reports results of an in vitro investigation into VHC-facemask performance, using three age-specific soft anatomical model (SAM) faces, under clinically relevant conditions.

Methods: A potentially standardized method was developed to assess VHC-facemask seal leakage, and evaluate the in vitro delivery efficiency of conventional and antistatic VHC-facemask systems.

Automated actuation of nasal spray products: effect of hand-related variability on the in vitro performance of Flonase nasal spray.

Objective: To determine if patient-related variability for adults and children recorded during hand spraying of Flonase with an instrumented nasal spray results in significant differences in spray weight, droplet size or spray pattern.

Methods: Settings derived from adult and pediatric participants hand-spraying nasal sprays were implemented into force and velocity-controlled automated actuators. Spray weight, droplet size distribution and spray pattern tests were performed using iterations of actuation force (AF) and force rise, hold and fall times.

Effect of formulation- and administration-related variables on deposition pattern of nasal spray pumps evaluated using a nasal cast.

Purpose: To systematically evaluate the effect of formulation- and administration-related variables on nasal spray deposition using a nasal cast.

Methods: Deposition pattern was assessed by uniformly coating a transparent nose model with Sar-Gel®, which changes from white to purple on contact with water. Sprays were subsequently discharged into the cast, which was then digitally photographed.

Development of Respimat(®) Soft Mist™ Inhaler and its clinical utility in respiratory disorders.

The Respimat(®) Soft Mist™ Inhaler (SMI) (Boehringer Ingelheim International GmbH, Ingelheim, Germany) was developed in response to the need for a pocket-sized device that can generate a single-breath, inhalable aerosol from a drug solution using a patient-independent, reproducible, and environmentally friendly energy supply. This paper describes the design and evolution of this innovative device from a laboratory concept model and the challenges that were overcome during its development and scaleup to mass production. A key technical breakthrough was the uniblock, a component combining filters and nozzles and made of silicon and glass, through which drug solution is forced using mechanical power.

Deposition, imaging, and clearance: what remains to be done?

Deposition and clearance studies are used during product development and in fundamental research. These studies mostly involve radionuclide imaging, but pharmacokinetic methods are also used to assess the amount of drug absorbed through the lungs, which is closely related to lung deposition. Radionuclide imaging may be two-dimensional (gamma scintigraphy or planar imaging), or three-dimensional (single photon emission computed tomography and positron emission tomography).

Automated actuation of nasal spray products: determination and comparison of adult and pediatric settings.

Objective: To determine and compare patient-relevant settings for automated nasal spray actuation stations from adult and pediatric hand data.

Methods: Twenty adults and 20 pediatric participants were asked to spray Flonase(®) Nasal Spray six times in a Hand Actuation Monitor, which records force and displacement data in 5-ms increments. Settings for force- and velocity-controlled actuation stations were determined from the data using a predefined set of calculations.

Assessment of facial and ocular deposition of nebulized aerosol using a color-based method.

Purpose: The objective of this investigation was to develop an inexpensive and uncomplicated color-based method to rapidly assess undesirable facial and ocular deposition of aerosolized droplets on the surface of a 3D rigid replica of a 4-year-old child's face.

Methods: Sar-Gel(®), which changes color on contact with water, was evenly coated on the face model through which air was drawn using two breathing patterns (representing moderate and shallow inhalations) or a constant rate of 0, 10, and 20 L/min. A standard and two proprietary (one shaped to resemble a fish face, the other shaped to resemble a dragon face) pediatric facemasks were evaluated.

Demonstrating Bioequivalence of Locally Acting Orally Inhaled Drug Products (OIPs): Workshop Summary Report.

This March 2009 Workshop Summary Report was sponsored by Product Quality Research Institute (PQRI) based on a proposal by the Inhalation and Nasal Technology Focus Group (INTFG) of the American Association of Pharmaceutical Scientists (AAPS). Participants from the pharmaceutical industry, academia and regulatory bodies from the United States, Europe, India, and Brazil attended the workshop with the objective of presenting, reviewing, and discussing recommendations for demonstrating bioequivalence (BE) that may be considered in the development of orally inhaled drug products and regulatory guidances for new drug applications (NDAs), abbreviated NDAs (ANDAs), and postapproval changes. The workshop addressed areas related to in vitro approaches to demonstrating BE, biomarker strategies, imaging techniques, in vivo approaches to establishing local delivery equivalence and device design similarity.

Assessment of nasal spray deposition pattern in a silicone human nose model using a color-based method.

Purpose: To develop a simple and inexpensive method to visualize and quantify droplet deposition patterns.

Methods: Deposition pattern was determined by uniformly coating the nose model with Sar-Gel (a paste that changes from white to purple on contact with water) and subsequently discharging sprays into the nose model. The color change was captured using a digital camera and analyzed using Adobe Photoshop.

Use of flexible weighted nasal spray dip tubes to improve product performance.

Background: Nasal spray performance attributes are related to the formulation, device, and patient, with the delivery of precise doses with minimal waste being key goals during product development, especially for potent and high cost drugs.

Methods: We investigated the influence of replacing the traditional rigid dip tube with a weighted, flexible dip tube on spray weight and tail-off characteristics in five over-the-counter nasal sprays representing varying viscosities, metering chamber volumes, formulation volumes, and active ingredients. Nasal sprays were actuated in ways representative of patient use.

Phospholipid-induced in vivo particle migration to enhance pulmonary deposition.

Amount of drug actually reaching the target region in the lung following pulmonary inhalation is often estimated at less than 10% for older devices. Current particle and device engineering technologies have improved on this but still fail to recover the "wasted" fraction of the drug and deliver it deeper into the lungs, which is generally desirable. FDA has approved several exogenous surfactants for prophylaxis and rescue treatment of respiratory distress syndrome (RDS).

Phase I clinical trial of repeat dose terameprocol vaginal ointment in healthy female volunteers.

Objectives: This safety study of terameprocol (also called M4N, EM-1421) daily vaginal application in healthy women explores its potential application as a microbicide in interrupting human immunodeficiency virus sexual transmission and additional interruption of human papillomavirus and herpes simplex virus transmission.

Methods: A double-blind placebo controlled phase I repeat dose tolerability and pharmacokinetic, crossover study of 90 mg terameprocol (2% w/w ointment) administered intravaginally for 7 consecutive days in healthy female subjects. The pharmacokinetics after administration was examined on days 1 and 7 of dosing.

Phase I/II clinical safety studies of terameprocol vaginal ointment.

Objectives: Terameprocol (M4N, EM-1421) is a novel transcription inhibitor that selectively interferes with HPV viral genes E6/E7 with Sp1-dependent promoters, and induces apoptosis by inactivation of the CDC2/cyclin B complex (maturation promoting factor) and production and phosphorylation of survivin. This trial was designed to define the maximum tolerated dose (MTD), dose-limiting toxicity and determine the pharmacokinetic profiles of intravaginal terameprocol in women with HPV-linked cervical squamous intraepithelial neoplasia.

Methods: An open label, dose escalation Phase I/II clinical trial enrolled women with biopsy confirmed CIN 1, 2 or 3.

The analysis and prediction of functional robustness of inhaler devices.

The studies described in this paper were undertaken to develop a method for the quick analysis and prediction of robustness of inhaler devices, and to define a standard among inhaler devices against which the structural integrity of new innovations could be judged. In addition, an effort was made to correlate mechanical properties with product performance metrics. The effect of mechanical stresses, alone and in combination with elevated temperatures, on the in vitro performance of pressurized metered dose inhalers (pMDIs) was investigated.

Validity of in vitro tests on aqueous spray pumps as surrogates for nasal deposition, absorption, and biologic response.

This research investigated the impact of the full range of in vitro spray characterization tests described in the FDA Draft Bioequivalence Guidance on nasal deposition pattern, pharmacokinetics, and biological response to nicotine administered by two aqueous nasal spray pumps in human volunteers. Nicotine was selected as a model drug (even though it is not locally acting) based on its ability to alter cardiac function and available plasma assay. Significant differences in pump performance-including mean volume diameters, spray angle, spray width, and ovality ratios-were observed between the two pumps.

Positive expiratory pressure changes aerosol distribution in patients with cystic fibrosis.

Hypothesis: We hypothesized that aerosol distribution in the lungs of patients with cystic fibrosis changes with positive expiratory pressure (PEP).

Methods: Eight patients were randomized to one of 2 conditions. On one study day, patients inhaled saline aerosol containing 99mtechnetium generated by a Pari LC Plus nebulizer and exhaled through a Pari PEP device.

The effect of formulation variables and breathing patterns on the site of nasal deposition in an anatomically correct model.

Purpose: This study was conducted to evaluate the effect of formulation variables and breathing patterns on aerosol distribution in the nasal cavity.

Methods: Placebo nasal spray formulations containing 0.25% w/v Avicel CL611 (viscosity = 4 cP) and 2% w/v methylcellulose (MC; viscosity = 18.

Drug delivery to the nasal cavity: in vitro and in vivo assessment.

Drugs are given intranasally for both local and systemic applications, and the use of the intranasal route is predicted to rise dramatically in the next 10 years. Nasal drug delivery may be assessed by a variety of means, but high reliance is often placed upon in vitro testing methodology (emitted dose, droplet or particle size distribution, spray pattern, and plume geometry). Spray pattern and plume geometry define the shape of the expanding aerosol cloud, while droplet size determines the likelihood of deposition within the nasal cavity by inertial impaction.

Inhalation therapy: technological milestones in asthma treatment.

The humble origins of the propellant driven metered dose inhaler, as a response to a child's enquiry, initiated an industry which supplies approximately a half billion inhalers globally for the treatment of asthma. These inhalers fall into three major groups: nebulizers; propellant driven metered dose inhalers and dry powder inhalers. Each requires drug formulation, metering and device technology to be successful.