ABSTRACT
For a solid understanding of drug characteristics, in vitro measurement of the intrinsic dissolution rate is important. Hydrodynamics are often emphasized as the decisive parameter influencing the dissolution. In this study, experiments and computational fluid dynamic (CFD) simulations showed that the mixing behavior in the rotating disc apparatus causes an inhomogeneous flow field and a systematic error in the calculation of the intrinsic dissolution rate. This error is affected by both the experimental time and the velocity. Due to the rotational movement around the tablet center, commonly utilized in pharmacopeia methods, a broad variance is present with regard to the impact of fluid velocity on individual particles of the specimen surface. As this is significantly reduced in the case of uniform overflow, the flow channel is recommended for investigating the dissolution behavior. It is shown that rotating disc measurements can be compared with flow channel measurements after adjusting the measured data for the rotating disc based on a proposed, representative Reynolds number and a suggested apparatus-dependent correction factor. Additionally, modeling the apparatus-independent intrinsic dissolution rate for different temperatures in the rotating disc apparatus is possible using the adapted Levich's equation.
Subject(s)
Hydrodynamics , Solubility , Tablets/chemistry , Drug Liberation , Pharmacopoeias as Topic , Computer Simulation , Chemistry, Pharmaceutical/methods , TemperatureABSTRACT
Continuous manufacturing provides advantages compared to batch manufacturing and is increasingly gaining importance in the pharmaceutical industry. In particular, the implementation of tablet processes in continuous plants is an important part of current research. For this, in-line real-time monitoring of product quality through process analytical technology (PAT) tools is crucial. This study focuses on an in-line UV/Vis spectroscopy method for monitoring the active pharmaceutical ingredient (API) content in tablets. UV/Vis spectroscopy is particularly advantageous here, because it allows univariate data analysis without complex data processing. Experiments were conducted on a rotary tablet press. The tablets consisted of 7- 13 wt% theophylline monohydrate as API, lactose monohydrate and magnesium stearate. Two tablet production rates were investigated, 7200 and 20000 tablets per hour. The UV/Vis probe was mounted at the ejection position and measurements were taken on the tablet sidewall. Validation was according to ICH Q2 with respect to specificity, linearity, precision, accuracy and range. The specificity for this formulation was proven and linearity was sufficient with coefficients of determination of 0.9891 for the low throughput and 0.9936 for the high throughput. Repeatability and intermediate precision were investigated. Both were sufficient, indicated by coefficients of variations with a maximum of 6.46% and 6.34%, respectively. The accuracy was evaluated by mean percent recovery. This showed a higher accuracy at 20000 tablets per hour than 7200 tablets per hour. However, both throughputs demonstrate sufficient accuracy. Finally, UV/Vis spectroscopy is a promising alternative to the common NIR and Raman Spectroscopy.
ABSTRACT
Melt granulation for improving material handling by modifying particle size distribution offers significant advantages compared to the standard methods of dry and wet granulation in dust reduction, obviating a subsequent drying step. Furthermore, current research in pharmaceutical technology aims for continuous methods, as these have an enhanced potential to reduce product quality fluctuations. Concerning both aspects, the use of a planetary roller granulator is consequential. The process control with these machines benefits from the enhanced ratio of heated surface to processed volume, compared to the usually-applied twin-screw systems. This is related to the unique concept of planetary spindles flowing around a central spindle in a roller cylinder. Herein, the movement pattern defines the transport characteristics, which determine the energy input and overall processing conditions. The aim of this study is to investigate the residence time distribution in planetary roller melt granulation (PRMG) as an indicator for the material transport. By altering feed rate and rotation speed, the fill level in the granulator is adjusted, which directly affects the average transport velocity and mixing volume. The two-compartment model was utilized to reflect these coherences, as the model parameters symbolize the sub-processes of axial material transport and mixing.
ABSTRACT
PURPOSE: In powder compaction on rotary tablet presses, the addition of a lubricant is normally mandatory. However, the typical internal lubrication method tends toward overlubrication, resulting in an alteration of the critical quality attributes of the product. In this study, the feasibility of an external lubrication system only using electrostatics for the application was investigated. METHODS: Three well-established lubricants were analyzed regarding their ability to accumulate and retain charge. In subsequent tableting experiments, the impact of different lubrication methods on critical quality attributes and process parameters was investigated. RESULTS: Due to material characteristics, the charge on magnesium stearate particles was most stable over time. The application of this lubricant on the punches via external lubrication with electrostatic forces resulted in a significant reduction of the ejection forces. Furthermore, the tensile strength of the tablets produced in these trials was significantly higher compared to tablets that were produced with internal lubrication. CONCLUSION: The external lubrication method with an electrostatically charged lubricant is a promising method for reducing both the necessary amount of lubricant and the impact of the lubricant on the product.