Issue link: https://www.e-digitaleditions.com/i/1199406
Tablets & Capsules January 2020 39 To finish the multiparticulates, the company uses the system's solu- tion/suspension coating mode to add a high-quality functional polymer coating to the pellets and achieve the modified-release profile. The team could have completed this step as a separate Wurster coating process, but the one-pot method was much more efficient than transferring the pellets to a different type of equip- ment and having to develop another set of processing parameters. A successful outcome The reformulation required effi- cient production of a dosage form with high drug loads, complex disso- lution profiles, and incompatible APIs. The conical rotor powder layering process enabled significantly higher API loading than a typical Wurster process, achieving a 400 percent weight gain in 8 hours at commercial scale. The ability to coat the pellets in the same vessel further increased production efficiency. The uniformity of the resulting particulate pellets was evident by the narrow particle size distribution after processing. The result was a high-quality, modular, and tunable OSD that exceeded the client's expectations. " Working with Freund-Vector has contributed to a more seam- less development cycle, helping us to keep the project on track with customer expectations," said Scog- gins. "The Granurex rotor processing equipment is very useful for repro- ducible production and coating of high-drug-load pellets. Recro will use this process and equipment for other client projects." T&C Recro Gainesville Gainesville, GA 770 534 8239 info@recrocdmo.com recrogainesville.com Freund-Vector Marion, IA 319 377 8263 sales@freund-vector.com www.freund-vector.com layering, and Wurster-like coating, either separately or in combination for fast, efficient processing. " W hen the Granurex was first introduced to the market, it was designed as a stand-alone system," said Ryan Crawford, process devel- opment scientist at Freund-Vector. "Later, its design was modified to be an insert into the VFC Flo-Coater product line. This allows the Granu- rex to be interchanged with Wurster and top-spray granulation process- ing." While the system used for this project is one of the original, stand- alone designs, Recro also has VFC Flo-Coater technology available for projects where these additional pro- cessing applications would be useful. The system uses a conical rotor to spin a core substrate material—in this case 30/35-mesh sugar spheres— inside a chamber. The system then sprays powdered API into the cham- ber via a powder spray gun on one side of the chamber, while spraying a binder solution from a spray gun on the other side of the chamber. Both spray guns are completely sub- merged in the rotating material bed. This process simultaneously layers and adheres the API powder directly onto the cores. The benefits of this method are that it typically requires little binder, quickly applies a large amount of API to each sphere, and produces reli- ably uniform pellets. In this case, the system's powder layering function greatly simplified and accelerated the production of the four high-drug- load pellet populations required. The pellets can achieve a 500 percent weight gain in a relatively short time, while maintaining a ver y nar row particle-size distribution. "The Granurex system provides the ability to apply a powder coat- ing to multiparticulates instead of dissolving or suspending the coating material in a liquid," says Crawford. "This allows for the coating material to be applied at a 100 percent con- centration as opposed to a typical 10 to 30 percent when applying the coating using a liquid carrier. As a result, the coating process is com- pleted more rapidly." The team needed to develop four pellet types using different amounts of various polymers to produce the release rates required for the speci- fied PK. The formulators could then vary the type and amount of poly- mer and the quantities of each pellet population in each capsule, making the dosage strength and release rates modular and tunable. With the dosage form selected, the next step was to determine how to form pellets with large API loads. To create multiparticulate pellets, companies often use Wurster coat- ing, in which a solution or suspension containing the API and a film-form- ing agent is sprayed onto a substrate such as sugar spheres, creating pellets with a high-quality coating. The Wurster coating process is relatively slow, however, and the pellets may require multiple coat- ings to achieve a high enough drug load. Multiple coating steps create larger pellets, which can increase the size of the final dosage form, mak- ing it too large for patients to easily swallow. Also, because this product required four separate populations of high-drug-load pellets, the formula- tors would need to split each batch into sub-lots for additional coating, and the process would have been prohibitively time consuming. An efficient solution For a more efficient method of creating the multiparticulate pel- lets, Recro turned to the Granurex GX-40 rotar y granulation system from Freund-Vector, a global supplier of processing equipment and services to the pharmaceutical, nutraceutical, and other industries. "Recro's ongoing relationship with Freund-Vector is very collaborative," said Myke Scoggins, director, prod- uct development at Recro Gaines- ville. "Freund-Vector provides spe- cific equipment recommendations and troubleshooting assistance during formulation and process development as well as expert assistance when scal- ing from development-scale batch sizes to commercial volumes." The Granurex system can be used for spherical granulation, dry powder