Real-time image-based investigation of spheronization and drying phenomena using different pellet formulations

Abstract

Extrusion-spheronization (ES) is a frequently used agglomeration process in the pharmaceutical industry to manufacture spherical solid units or pellets with a narrow size and shape distribution. In this study, photometric stereo imaging was applied in real-time during the final steps of the ES process, being spheronization and drying. In addition to the pellet size distribution of undispersed (wet) samples, the imaging technique captures visual information on pellet shape and surface brightness. Pellet samples were taken at 20 time points during spheronization and were imaged atline (during spheronization) and off-line (after spheronization). Particle size distributions and visual image information were both used to characterize the spheronization behaviour of different formulations. Next, particle size distributions and surface brightness values calculated from the atline obtained images during fluid bed drying of pellets were analysed. The particle size distribution and brightness value changes occurring during pellet drying were explained both by the reduction in residual moisture content and drug solid-state transition. Due to the rapidness of the technique with regard to sample preparation, sample measurement and the acquisition of results in combination with the possibility to measure undispersed (wet) samples, valuable information on spheronization and drying characteristics of different formulations was obtained in real-time. KeywordsPhotometric stereo imaging -extrusion-spheronization -fluid bed drying -particle size and shape (distribution) -brightness -visualization

Impact of Drying on Solid State Modifications and Drug Distribution in Ibuprofen-Loaded Calcium Stearate Pellets

“…In products prepared by wet granulation and wet extrusion, drying is a key process, as it allows the formation of permanent bonds (so-called solid bridges) between primary particles . However, drying not only removes the liquid from wet granules/pellets but also may impact the physicochemical properties of both the active pharmaceutical ingredient (API) − and the excipient(s). , Thereby, the performance of the dried pellets may be modified with respect to their in vitro dissolution characteristics − and compaction behavior. ,,− Physicochemical properties are likely to change where there are interactions between the API, excipient(s), and granulation liquid . In general, interactions with the granulation liquid include swelling and dissolution of excipient and/or API particles in the granulation liquid.…”

Recent Developments in Smart Drying Technology

“…This problem can be overcome with statistical treatment of data to extract relevant information and decrease irrelevant information. On the other hand, ultrasound signals are not usually strong and the sensitivity of the technique may be affected by the fluidizing air flow rate, construction material, and external uncontrollable and unintended interferences in the dryer [97] , necessitating the preprocessing of the spectra before the actual analysis. The ultrasound technique relies on highly specialized sensors and requires calibration with a reference technique.…”

Assessment of Recent Process Analytical Technology (PAT) Trends: A Multiauthor Review

“…Particle sizing using the photometric stereo approach was also successfully done on a set of roller compacted granules produced by pneumatic dry granulation. 160 Burggraeve et al 161 studied photometric stereo imaging in real-time during the final steps of the extrusion−spheronization pelletisation process (spheronization and drying). Pellet samples were taken at 20 time points during spheronization and were imaged at-line (during spheronization) and off-line (after spheronization).…”

“…Burggraeve et al studied photometric stereo imaging in real-time during the final steps of the extrusion–spheronization pelletisation process (spheronization and drying). Pellet samples were taken at 20 time points during spheronization and were imaged at-line (during spheronization) and off-line (after spheronization).…”