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40 Pharmaceutical Technology APIs, EXCIPIENTS, AND MANUFACTURING eBOOK 2021 P h a r mTe c h . c o m Manufacturing is a likely outcome so a reservoir device that makes sense for a month's treatment of a regularly taken medicine makes less sense for a therapy that may only be taken once a month whereas a unit dose DPI or a nebulization therapy is entirely suited to this new treatment paradigm. The pMDI definitely has an important role to play in the fight against respiratory disease but this tends to be with long established molecules more than it is with the ther- apies of the future. Berg (Catalent): The real choice when selecting one delivery device over another centers on the type of molecule, type of formulation, molecule stability, and the respirable dose that can be delivered from the device. DPIs provide better physicochemical sta- bility, as MDIs have limitations such as sedimen- tation and crystal growth. Furthermore, MDIs are constrained by high dose requirements, as in the case of inhaled antibiotics with nominal doses up to ~600 mg. As previously mentioned, inhalation drug development is increasingly tackling complex dis- eases and looking to deliver larger molecules such as oligonucleotides, peptides and proteins, antibod- ies, and nanobodies. The structure of these mole- cules, their potencies and formulation parameters, make them candidates for dry powder formulations achieved through spray drying. Heath and Hirst (Recipharm): When selecting an ap- propriate device for a specific drug formulation, several factors must be considered: • pMDIs as a platform are limited by the volume of the formulation in the metering chamber (typically <100 µL), and there are considerations with drug solubility if making a solution. • In terms of protection from the environment, a pMDI formulation is contained within a sealed aluminium cannister, but there are op- portunities for the formulation to interact with the elastomeric components of the valve. Reservoir DPIs contain bulk formulation, which is dispensed in small doses each time the patient actuates the device. The inherent design of this device type potentially leaves it more exposed to the elements, and it can be challenging to dispense doses accurately. • Excipient compatibility is one of the most critical aspects during development for any inhalation platform. Although there are a limited number of approved excipients for in- haled products, they must be managed and screened for early in the process. In addition, if a drug developer wishes to utilize a bespoke delivery device for patent protection purposes, then a DPI will be selected. These de- vices tend to be bespoke, rather than 'off the shelf ', often requiring simultaneous development of the device, the formulation, and the filling and assem- bly process, all of which adds complexity into the product development and approval processes. Conversely, the design of a pMDI is generally more universal and more cost-effective. It does not require the design of a bespoke device, and the device is typically able to be filled using already installed filling equipment. Design and scale-up PharmTech: What are some best practices in design, manufacture, and scale-up? Heath and Hirst (Recipharm): It is important to iden- tify, optimize, and control the parameters that will inf luence the finished product's performance, in terms of dose delivery and therapeutic effect. These include API particle size, device component dimensions, and the formulation. Manufacturing