With the continuous trend in the pharmaceutical industry to outsource the production of active pharma ingredients (APIs) to reduce costs, the manufacturing process has been split and more players are part of the process chain until the final dosage form is produced and ready for the patient to take against their ailments. Even more, keeping the stability and purity of an API increases in importance.
To fully utilize the cost saving potential of this split process, the API manufacturer needs to deliver the substances ready to use by the drug manufacturer in a form or state suitable for the respective drug dosage form, be it solid or liquid for oral, intravenous or topical administration. The drug manufacturer on the other side needs to be able to ensure a continuous process, reducing cleaning time in his systems and avoiding reprocessing. For this purpose, he needs APIs allowing compliance with final product specifications.
THE HIPERING PROCESS AGGREGATES AND DENSIFIES DRY POWDERS
To meet the needs of both sides Tradichem in Spain has developed a pharmaceutical process for the transformation of raw materials based on a sequence of processes that modify the physical properties of the starting material while keeping its purity and chemical specification. This process was named Hipering and enables aggregation and densification of dry powders into a uniform solid mass that is broken down into specific granule size via a milling system and is offered as a service to API manufacturers by Tradichem. The Hipering technology set-up consists of a roller compactor with one smooth and one knurled surfaced roll fed by a screw feeding system, which is filled through Piab’s piFLOWp vacuum conveyor directly from the bin using a feed adapter. The compactor is connected to a rotor granulator for milling the outcoming compacted plaques into granules.
PIAB’S VACUUM CONVEYOR PROTECTS APIS FROM CONTAMINATION AND SUPPORTS COMPACTING BY CONSTANT FEEDING OF THE PROCESS
Cristina Lozano, Chemical Engineer and Site Manager at Tradichem explains “The advantage of using the piFLOWp vacuum conveyor for feeding the Hipering system lies in its closed system, which prevents the API from taking on moisture and from being contaminated from outside sources. The ingredient does not need any manual handling as it is sucked in from the bin it is delivered in through the vacuum created by the conveyor, allowing it to run automatically through the system until the final granules are derived.”
The system is set-up upright, as the vertical pressure is an important factor in achieving the compactness required. The vertical pressure is further enhanced by ensuring a continuous feeding of the hopper, which is equipped with a sensor measuring the filling level. It automatically activates Piab’s piFLOWp vacuum conveyor when the level drops below a certain point. Thanks to the homogenous load of the hopper achieved through the continuous feeding by the conveyor, a consistent product with the same density within the whole production batch is achieved.
UNCOMPLICATED CLEANING OF THE PIFLOWP ALLOWS FAST CHANGES BETWEEN DIFFERENT APIS
“Being able to conduct rapid product changes to process the APIs depending on the demand coming in from drug manufacturers was another important factor”, adds Cristina Lozano “The simple and uncomplicated cleaning of the Piab vacuum conveyors convinced us further. Thanks to the quick-release system with filters and gaskets, the entire conveyor can be disassembled, cleaned and reassembled for the next production in just a few steps, and it is important to us that the conveyor can be cleaned not only in the shortest possible time, but also thoroughly so that no residues of the previous production could possibly contaminate the next.”
David Sanchez, Sales Director Vacuum Conveying for Southern Europe at Piab asserts. “The vacuum is generated by the COAX® technology by the discharge of compressed air from a multi-stage nozzle system. This allows both a high efficiency of the system and an absolute vacuum level of 250 mbar maximum. Blockages in the delivery line are almost impossible. Since no mechanically moving parts are present in the vacuum pump, the system works maintenance-free. The vacuum pump is mounted directly on the conveyor. The collection volume of the conveyor can be adapted to different requirements depending on, for example, the product density.”
PURE API COMPACTING
While compacting powders in the pharmaceutical industry is possible in general with other dry granulation processes, the compaction of active ingredients alone, without the aid of adequate excipients reaching a quality level to prepare final pharmaceutical formulations was so far not possible.
Compacting the APIs alone, however, has numerous advantages. The major one is the creation of multiple new surface sites, additional contact points, and potential binding sites as these allow excipients that support the activation of the substance in the body to better interact with the API. This leads to a lower use of excipients and, hence, a smaller product size – a tinier capsule to swallow. Continuing the material and thereby cost reduction, a smaller capsule uses less gelatine for its shell. With less product volume packaging material can be reduced, which ultimately affects logistics costs. From a drug manufacturers point of view, it further increases productivity and finished product production by 30 to 50 percent. The more free-flowing powder with its higher particle density coming out of the Hipering process diminishes cleaning times, while the improved particle size distribution increases the overall product quality. All the while, the API stability is further extended as the granulated product is less volatile, and purity maintained.
VACUUM CONVEYING IN COMPLIANCE WITH PHARMA AND FOOD STANDARDS
Piab’s piFLOWp conveyors for powders and bulk solids recommended to Tradichem by the manufacturer of the compactor are perfectly matched to the high standards of operational safety and hygiene in the pharmaceutical and food industries. They are made of electropolished stainless steel and materials that comply with US FDA and EU 1935/2004 regulations. As a conveying line, a suction hose made of PU is used. An internal steel spiral helps to minimize the electrostatic charge of the product or diverts it to equipotential bonding. The filter in the upper part of the conveyor is cleaned with a filter shock after each conveying cycle. The device control is in a separate control cabinet. The piFLOWp conveyors are ATEX Dust and Gas certified. Typical applications are powder and granules transfer, form-fill-seal machines, big bag loading and unloading, drum/bag filling and emptying, mill/sieve/mixer/blender filling, tablet/fragile products transfer, applications in explosive atmosphere, hygienic applications or places where space is at a premium.