The Potential Use of Cyclosporine Ultrafine Solution Pressurised Metered-Dose Inhaler in the Treatment of COVID-19 Patients

Introduction: Serious COVID-19 respiratory problems start when the virus reaches the alveolar level, where type II cells get infected and die. Therefore, virus inhibition at the alveolar level would help prevent these respiratory complications. Method: A literature search was conducted to collect physicochemical properties of small molecule compounds that could be used for the COVID-19 treatment. Compounds with a low melting point were selected along with those soluble in ethanol, hydrogen-bond donors, and acceptors. Results : There are severe acute respiratory syndrome coronavirus inhibitors with physicochemical properties suitable for the formulation as an ultrafine pressurised metered-dose inhaler (pMDI). Mycophenolic acid, Debio 025, and cyclosporine A are prime candidates among these compounds. Cyclosporine A (hereafter cyclosporine) is a potent SARS-CoV-2 inhibitor, and it has been used for the treatment of COVID-19 patients, demonstrating an improved survival rate. Also, inhalation therapy of nebulised cyclosporine was tolerated, which was used for patients with lung transplants. Finally, cyclosporine has been formulated as a solution ultrafine pMDI. Although vaccine therapy has been started in most countries, inhalation therapies with non-immunological activities could minimise the spread of the disease and be used in vaccine-hesitant individuals. Conclusion: Ultrafine pMDI formulation of cyclosporine or Debio 025 should be investigated for the inhalation therapy of COVID-19.

Comparing weight method and float method for pressurised metered dose inhaler as dose counting method.

INTRODUCTION Pressurised metered-dose inhalers (pMDIs) are not equipped with dose counters, so estimating the actuation remaining is difficult. We compared weight method and float method in estimating the actuation remaining in discarded pMDIs.METHODOLOGY Used non-metered pMDIs were collected from Pharmacy department Hospital Seri Manjung from June to Dec 2018. Each of the returned canister was evaluated using float and weight method to predict the balance actuation in the canister. For the float test, the canister was placed in a container of water. Based on its position in the water, the pMDI was categorised as 1=empty, 2=¼ full, 3=½ full, 4=¾ full, or 5=full. For the weight method, canisters were weighed, and actuation remaining were calculated using a linear regression equation where the general equation is: Actuation remaining = Constant + β*pMDI weight, and further categorised as above. The percentage of empty pMDIs between the two methods were compared.RESULTS A total of 4517 pMDIs were returned to the pharmacy, of which 2131 (47%) were salbutamol, 1149 (25%) budesonide, 685 (15%) ipratropium/fenoterol, 340 (8%) innovator fluticasone, 182 (4%) generic fluticasone, and 30 (1%) beclomethasone. Overall, the float method classified 75% pMDIs as empty, compared to 71% by the weight method. The percentage of empty salbutamol, generic fluticasone, and beclomethasone pMDIs were similar between both methods. A higher percentage of budesonide pMDIs were classified as empty by the float method compared to the weight method (62% vs 37%). For ipratropium/fenoterol pMDIs, the float method did not identify any empty canisters, but 82% were classified as empty by the weight method. CONCLUSION This study produced a prediction equation that can be used to estimate remaining actuation in a pMDI based on its weight. There were differences in the identification of empty pMDIs between the float test and the weight method, which varied by drug. The weight method may be a convenience method to be used to measure actuation remaining in pMDIs returned to the pharmacy, as well as patients’ adherence to pMDIs.

Spacer devices for inhaled therapy: why use them, and how?

We present an extensive review of the literature to date pertaining to the rationale for using a spacer/valved holding chamber (VHC) to deliver inhaled therapy from a pressurised, metered-dose inhaler, a discussion of how the properties of individual devices may vary according to their physical characteristics and materials of manufacture, the potential risks and benefits of ancillaries such as valves, and the evidence that they contribute tangibly to the delivery of therapy.We also reiterate practical recommendations for the correct usage and maintenance of spacers/VHCs, which we trust offer practical help and advice to patients and healthcare professionals alike.