When Brazilian pharmaceutical company Libbs wanted to expand production, it quickly became clear it also needed to modernize its granulation process. Libbs selected a reliable provider of a high-quality granulation line that helped it perform a smooth technology transfer for nearly a dozen products. Libbs also found an inventive solution to an unusual problem concerning a corrosive product.
Libbs Farmaceutica, based in Barra Funda, Brazil, was founded in 1958. The company has roughly 2,500 employees and produces medicines for areas such as cardiology, gynecology, oncology, transplantation and the central nervous system. Libbs markets more than 90 different brands at drugstores in the Brazilian market. In 2014, Libbs was the first Brazilian company to implement a traceability system that allows medications to be traced, fulfilling the regulations of the National Health Surveillance Agency (Anvisa) that will become binding in 2022. Two years later, Libbs installed a modern biotech unit in Embu das Artes near São Paulo for the production of biological pharmaceuticals to fight cancer and autoimmune diseases, which is currently the largest single-use factory in South America.
When the number of customer requests rapidly increased, Libbs engineers decided to expand their production capacities with a new granulation line, and simultaneously modernize their granulation process.
"We knew that the process was about to change fundamentally," said Diogo Fonseca, project engineer at Libbs. "That was why we were looking for a partner who could reliably support us with the necessary technology transfer and provide us with the machine quality we wanted."
Libbs had previously purchased a fluid bed from the Bosch subsidiary Hüttlin, so it looked to this provider again for a solution.
An unusual challenge
It was crucial the technology provider could solve a vital problem: one of Libbs’ products, which is used to treat respiratory diseases, contains corrosive active pharmaceutical ingredients (API). Whenever the API touched water, the stainless steel of the machine parts that came into contact with the product began to corrode. "When Libbs described their problem, we were intrigued," said Claudio Zan, project manager at Bosch Packaging Technology in Brazil. "We had never had to address this type of issue before. But we accepted the challenge and immediately began a series of tests at our customer’s site."
The first approach to solving the problem, which consisted of coating the surface of the machine equipment with silicone, turned out to be unsatisfactory.
The second attempt, which involved switching the type of stainless steel, was successful. "The German colleagues from Hüttlin sent us samples of different materials that are resistant against corrosion," Zan said. "After waiting for two days to verify the reaction of the material in contact with the product, we knew we finally had the groundbreaking solution."
Hastelloy, a nickel-based alloy that is particularly resistant to aggressive corrosive media, provided optimal results and showed no adverse reactions at all during the tests.
An efficient new production process
As a result, Hüttlin built the new granulation line that includes the high-shear bottom drive mixer and granulator HBG 600 and the fluid bed system HDGC 200 — using Hastelloy. Until then, Libbs had worked with a planetary mixing system. The new mixer and granulator uses the Gentlewing system instead. The shape of the impeller matches the contours of the mixing container, and its angled plate ensures maximum mixing quality with minimum mechanical stress on the product. "Due to the tight clearances between the product vessel and the impeller, wall caking is minimized," Fonseca said. "Since the impeller’s Z-design also ensures thorough discharge, the new system helps us reduce product loss."
In turn, Libbs’ drying oven was replaced with the new fluid bed system with a patented process gas distributor plate that delivers uniform fluidization for the entire batch, regardless of the drying conditions. In addition to significantly reducing process times, the high exit speed of the process air prevents the product from sticking to and clogging up the bed, resulting in a product with uniform residual moisture and improved process reproducibility. A three-component nozzle provides a fast-drying, thin coating layer of particles.
Technology transfer from old to new
"The uniformity of the granules and their homogenous size distribution produce optimal flow and pelletizing characteristics," said Zan. "The particles are spherical instead of square improving the flow properties. This prevents large agglomerates from forming and leads to good dosing accuracy while reducing process times for tablet compression or the capsule filling process." By physically attaching the high-shear mixer to the fluid bed system, a safe inline process with minimum transfer times is ensured.
To achieve a smooth technology transfer from the former to the new granulation and drying process, the experts from the Bosch Pharma Service at Hüttlin worked closely together with the colleagues from Libbs. Together, they successfully implemented the new granulation system for 10 products. Experts also helped Libbs register the new process with the regulation authorities. With reliable provider support from development to installation and validation, Libbs carried out the large project successfully and safely.
Claudio Zan is sales manager at Bosch Packaging Technology and is responsible for developing new markets in Latin America. He is an industrial pharmacist and holds an MBA in marketing. Zan looks back on more than 20 years of experience in sales, production and marketing, working with Brazilian and multinational companies all over the world.