Optimization of Very Low-Dose Formulation of Vitamin D3 with Lyophilizate for Dry Powder Inhalation System by Simple Method Based on Time-of-Flight Theory

It has been previously reported that active vitamin D3 (VD3) is a candidate drug that can repair alveolar damage in chronic obstructive pulmonary disease at a very low dose. We herein report the optimization of a very low-dose formulation of VD3 for dry powder inhalation by a simple method based on time-of-flight (TOF) theory. As the preparation content of VD3 is very low, aerodynamic particle size distribution cannot be measured by pharmacopeial methods that require quantification of the main drug. Thus, a simple method based on TOF theory, which can measure aerodynamic particle size distribution without quantification, was used. The optimized formulation for an inhalation system using a lyophilized cake contained phenylalanine as the excipient (VD3 1 μg/vial + phenylalanine 0.3 mg/vial) and showed high performance with fine particle fraction ≤ 3 μm = 47.2 ± 4.4%. The difference between the results of pharmacopeial methods and simple method was examined using the formulation containing 10 µg/vial of VD3 and was within 5.0%. The preparation is expected to efficiently deliver VD3 to the lungs. Our simple method can optimize dry powder inhalation formulations more easily and rapidly even when the content of the main drug in a preparation is very low.

Simple Method to Measure the Aerodynamic Size Distribution of Porous Particles Generated on Lyophilizate for Dry Powder Inhalation

Recently, statistical techniques such as design of experiments are being applied for efficient optimization of oral formulations. To use these statistical techniques for inhalation formulations, efficient methods for rapid determination of the aerodynamic particle size distribution of many samples are needed. Therefore, we aimed to develop a simple method to measure aerodynamic particle size distribution that closely agrees with the results of inhalation characteristic tests. We added attachments for dispersion to the aerodynamic particle sizer (APS) so that formulations could be dispersed under the same condition as for multi-stage liquid impinger (MSLI) measurement. Then, we examined the correlation between MSLI and APS using lyophilizate for dry powder inhalation formulations that generate porous particles just on inhalation. It is difficult to obtain the accurate aerodynamic particle size distribution of porous particles by APS because the particle density is difficult to estimate accurately. However, there was a significant correlation between MSLI and APS when the particle density settings for APS measurement was calculated by a conversion factor based on the result of MSLI. The APS with dispersion attachments and this conversion factor can measure a number of samples in a short time, thereby enabling more efficient optimization of dry powder inhalers.

EVALUATION OF AERODYNAMIC PARTICLE SIZE DISTRIBUTION OF DRUGS USED IN INHALATION THERAPY: A CONCISE REVIEW

Most of the inhalation products in the market use metered dose inhaler (MDI) technology or dry powder inhaler (DPI) technology. MDIs use propellant to deliver desired dose of liquid formulation in aerosol form. DPI contains active in fine particulate form embedded onto an inert carrier. In both cases, amount of drug dispensed from the device reaching the lungs is dependent upon drug product characteristics as well as formulation-device relationship. Hence, in addition to particle size, aerodynamic distribution of the drug upon delivery by the device plays an important role in determining amount of drug reaching the lungs. Therefore particle size characterization is an important tool in determining the extent of drug delivery from the metered dose inhaler. Aerodynamic particle size distribution is frequently determined by use of cascade impactors and data so generated is accepted by regulatory agencies as a tool for predicting efficacy of MDIs and DPIs. This review discusses principle and working of cascade impactors. Additionally, the review also examines the role of laser diffraction technique in estimating size of dispersed particles.

Bioaerosol Size Effect in COVID-19 Transmission

The fast spread of COVID-19 constitutes a worldwide challenge to the public health, educational, and trade systems, affecting the overall wellbeing of human societies. The high transmission and mortality rates of this virus, and the unavailability of a vaccine and antidote, resulted in the decision of multiple governments to force measurements of social distancing. Thus, it is of general interest to consider the validity of the proposal for keeping a social distancing of at least 6.0 ft (1.8 m) from persons with COVID-19. The eventual exposure to the bioaerosol can result in the deposition o the pathogen in the respiratory track of the host causing disease and an immunological response. In the atmospheric context, the work evaluates the effect of aerodynamic particle size in carrying RNA copies of the novel coronavirus. A COVID-19 carrier person talking, sneezing, or coughing at distance of 1.8 m can still provide a pathogenic bioaerosol load with submicron particles that remain viable in air for up to 3 hours for exposure of healthy persons near and far the source in a stagnant environment. The deposited bioaerosol creates contaminated surfaces, which if touched can act as a path to introduce the pathogen by mouth, nose, or eyes and cause disease.