When you finally arrive at a formulation that meets the target product profile, it is then necessary to devise a process by which it can be manufactured at scale. What started as a concept with beakers, stirring rods, and pipettes must become a process with bulk handling and automated or semi-automated equipment. Steps such as sifting, granulating, blending, and compression conceived at the research lab bench now go to the suite for reproducible and routine processing.
Groups in charge of formulation services should lay the foundation for scale-up in early studies – preformulation and quality by design (QBD) concepts, as discussed in the earlier part of this blog series. However, not all variables can be accounted for. Bulk handling procedures may compromise physicochemical properties. For example, powder/granule particles of defined and suitable size that handle well with manual processing procedures may comminute with shear during bulk processing compromising the target product profile (TPP). Your formulation partner’s equipment capacity is another consideration.
Equipment used at process scale must produce results consistent with the bench-scale procedures. The reverse is also true. Fit-for-purpose development formulation services laboratories generally have suitably small scale equipment for conservation of materials in early development. However, the equipment trains of larger CMOs can mandate the dedication of unacceptably large quantities of precious API. Economic considerations apply with respect to clinical and commercial factors, too. Drugs intended for ubiquitous mass mar-ket patient populations might not tolerate expensive APIs and excipients as well as rare disease drugs or conditions with small patient populations. Not insignificantly, a GMP environment and processes must be established.
Different dosage forms all have unique challenges. Tablets will require consideration of particle homogeneity, flow properties, moisture sensitivity, and polymorphic form. While important from conception these proper-ties require different controls when working at larger scales, as exemplified above. Blend homogeneity, including sampling strategies to measure, requires a different approach again. Sterile products demand much more rigorous handling processes to avoid microbial contamination. Typically, this means working with a formulation organization whose services include ISO-7 suites. Semi-solid drug products require continuity of equipment, for instance, controls for bulk heating or cooling and reproducibility from manual benchtop homogenizers to automated homogenizers in the suite.
Taken together, development of a useful dosage form must bring together a comprehensive set of services that include pre-formulation characterization, formulation design, and process development and, as we shall see in the final installment of this blog series, concurrent analytical characterization every step of the way.
Check out the first installment in this 4-part Pharma Formulation blog series, Solving a Problem.
Respect the Chemistry, the second installment in the Pharma Formulation blog series contemplates API and physicochemical considerations.
Our Unique Formulation Opportunities for Drug Manufacturers Whitepaper discusses drug formulation including
novel drug delivery systems, the pros, and cons of certain drug forms and the challenges of developing a NDDS.