Dilip M. Parikh
|Dilip M. Parikh|
Granulation is an integral part of solid dosage manufacturing in the pharmaceutical industry. The majority of the granulation process uses a liquid binder to granulate the product in the mixer and then a tray dryer or a fluid bed dryer. A number of products that received FDA approval in the early days use tray dryers and are considering transferring to fluid bed. Besides FDA requirements and other financial and engineering considerations, maintaining the final product attributes is most crucial. We must understand the differences in the two types of dryers and the impact it may have on the quality of our product after such a transfer.
Solids drying involves two fundamental processes. Heat is transferred to the granule to evaporate liquid, and mass is transferred as a liquid or vapor within the solid and as vapor from the surface into the surrounding gas phase. The factors that influence the rates of these processes determine the drying rates.
For tray drying, the wet mass is spread on to trays and the tray rack is then placed in the oven. The heat transfer is accomplished by direct contact between the wet solids and hot gases. The vaporized liquid is carried away by the drying gases. There is no relative motion among solid particles. The solids bed exists as a dense bed, with particles resting upon one another, and experiencing no relative motion among them. Depending on the quantity and the type of solvent used, it may take anywhere from a few hours to 24 hours to dry the product.
In the case of fluid bed drying, the particles are suspended in a hot gas/air stream. The heat transfer is accomplished by direct contact between the wet solids and hot gases. The vaporized liquid is carried away by the drying gases. The solids are in expanded condition, with the particles supported by drag forces caused by the gas phase. The solids and gases intermix and behave like a boiling liquid. The drying time could be 30-90 minutes.
The possibility of having color migration and case-hardening of tray dried is quite common. The processing of dried granules by milling and subsequent compression should be investigated to make sure the critical product attributes are identified and monitored during the transfer of product from tray drying to fluid bed drying. While using a fluid bed dryer, it is advisable to pass the wet mass through a coarse screen, so cohesive chunks of product can be subdivided into free-flowing granules that will improve process efficiency.
The combination of the granulating solvent and drying conditions could result in the conversion of some of the products to alternate crystalline forms during the drying process as presented in a case study, Drying of Glycine and Microcrystalline Cellulose (1:1 - one part of glycine and one part of microcrystalline cellulose - i.e. 50% of each ingredient). The study compared aqueous granulation in a fluid bed unit as well as in a tray dryer. Using near infra red, the researcher concluded that the slower drying techniques, such as tray drying, resulted in significantly less formation of Alpha-glycine - a polymorph. The drying rate determined the overall polymorph content. The faster the granulation was dried, the more rapid the increase in super saturation with respect to the metastable form and the greater thermodynamic driving force for the nucleation and crystallization of the metastable form. The granulation rapidly dried by fluidized bed drying, resulted in more crystallization of Alpha-glycine than the granulations that were tray dried.
In summary, while considering product transfer from tray drying to fluid bed one needs to understand the equipment differences, drying kinetics, capital cost, and space requirements, while assuring that the product attributes have not changed.
Dilip M, Parikh is president of DPharma Group Inc., Ellicott City, MD, a pharmaceutical technology consulting firm. He is an industrial pharmacist with more than 35 years of industrial experience in R&D, manufacturing, cGMP compliant facility planning, and operational management at various pharmaceutical companies in Canada and the U.S. The editor of the “Handbook of Pharmaceutical Granulation Technology”, 3rd Edition, Parikh has authored three other book chapters and a number of scientific publications, and has spoken worldwide at scientific conferences on solid dosage technology development and manufacturing.