Issue link: https://www.e-digitaleditions.com/i/1199406
38 January 2020 Tablets & Capsules I N D U S T R Y a p p l i c a t i o n CDMO turns to rotary granulation process to solve complex reformulation challenge Recro Gainesville is a contract development and manufact ur ing organization (CDMO) that provides oral solid dosage (OSD) form devel- opment, regulatory support, clini- cal and commercial manufacturing, and packaging and logistics services to the global pharmaceutical mar- ket. Based in Gainesville, GA, the company operates facilities totaling 120,000 square feet and specializes in modified-release OSD products and DEA-controlled substances. Recently, a new customer asked the CDMO to reformulate an imme- diate-release OSD with a dosing reg- imen of 3 times per day to create an extended-release product with a complex release profile and a dos- ing regimen of twice per day. Drug product manufacturers often want to reformulate multidose products into once- or twice-daily dosage forms because reducing the dosing regimen can increase patient convenience and adherence and may also reduce potential side effects. A complex reformulation T he c ustomer 's refor mulation presented a challenge, because the product carried a high drug load a n d c ont a in e d t wo ch e m i c a ll y incompatible active pharmaceuti- cal ingredients (APIs), each requir- ing both immediate- and modified- files, they would need to be isolated from each other in the dosage form. The reformulation team quickly determined that matrix and bilayer tablets would be difficult to fine-tune, and a mini-tablet format would be impractical, so they decided to pur- sue a multiparticulate capsule dosage form. Multiparticulate capsules are a common solution for products with complex PK profiles because they can be filled with multiple popula- tions of pellets, allowing formulators to easily adjust the API content and release rates. release components. Because of the specific and elaborate pharmacoki- netics (PK) requirements, the refor- mulation team conducted multiple feasibility PK studies. To allow formulators to easily adjust the dosage strength and the ratio between immediate and mod- ified API release, the product's dis- solution profile needed to be tun- able and the dosage form needed to be modular. Also, because the APIs were chemically incompatible and required different dissolution pro-