Manufacturing and Device Options for the Delivery of Biotherapeutics

Abstract

Biotherapeutic aerosol formulations are an intense area of interest for systemic and local drug delivery. This article provides a short overview of typical factors required specifically for biotherapeutic aerosol formulation design, the processing options open for consideration, and the issue of inhalation device selection. Focusing on spray drying, four case studies are used to highlight the relevant issues, describing investigations into: (1) the mechanical stresses occurring in bacteriophage formulations during spray-dryer atomization; (2) modeling of the spray-dryer process and droplet drying kinetics, to assist process design and predictions of formulation stability; (3) a predictive approach to the design and processing of a five-component dry powder aerosol formulation; and (4) the survival of bacteriophages after pressurized metered dose inhaler atomization.

Phage therapy of pulmonary infections

“…This is in terms of reports of phage use to treat infections within clinical settings as well as their application within the context of animal disease models. Though not covered here, there exist two related areas of study, that of phage delivery as aerosols into lungs 12,13 and the use of phages to combat the air sac-associated bacterial disease of poultry, colibacillosis, e.g., 14; see also section 2.2 of 15.…”

Prophylaxis of Mycobacterium tuberculosis H37Rv Infection in a Preclinical Mouse Model via Inhalation of Nebulized Bacteriophage D29

“…The treatment of pulmonary infections in humans using phages has been reviewed elsewhere (22). Advanced research of aerosol phage therapy has become prevalent, including in vitro studies evaluating phage delivery with nebulizers, dry powder inhalers, and pressurized metered-dose inhalers (23)(24)(25)(26)(27)(28)(29)(30)(31). As more than 80% of TB cases originate from M. tuberculosis infections in the lungs, aerosol delivery of phage may be an ideal mechanism for enabling activity at the primary site of M. tuberculosis infection (32).…”

Phage therapy for respiratory infections

“…Due to the affordability and simple operation, pressurized metered dose inhalers (pMDIs) have long been favored by patients and healthcare professionals for asthma and chronic obstructive pulmonary disease management. However, there was only one report on the feasibility of formulating phage into pMDIs [58]. Hoe et al [58] formulated aqueous FKZ/D3 and KS4-M phages ( myoviridae ) suspensions in a reverse emulsion with Tyloxapol surfactant (100 mg/mL) and filled into hydrofluoroalkane 134a pMDI canisters with a 50 μL metering valve.…”