Micro-mechanical modeling of the paper compaction process

Double-roll compaction is a process to create extensible paper and paperboard suitable for replacing plastic in 3D forming applications. Understanding the macro- and micro-mechanisms governing the compaction process allows increasing the stretch potential while maintaining sufficient strength and bending stiffness. In this work, we approach the compaction process of paperboard with micro-mechanical methods featuring the unprecedented level of details otherwise inaccessible with currently available experimental tools. The loading scheme is based on experiments and continuum level simulations. The different levels of compaction and their continuous impact on the fibers’ geometry, void closures, and irreversible deformation of the fibers are thoroughly characterized. We find that the structural changes are concentrated in the fibers oriented within 30 degrees of the direction of compaction. The deformation accumulates primarily in the wall of the fibers in the form of irreversible strains. The spring-back effect beyond the compaction is negligible. For the first time, the role of normal and frictional fiber-to-fiber interactions in the compaction process is investigated and quantified. The frictional interaction between the fibers has a surprisingly low impact on the outcome of the compaction process, and the normal interaction between the fibers has a dominant response. The consequence of this finding is potentially limited impact of the surface modifications targeting the friction.

Implementing Feedback Granule Size Control in a Continuous Dry Granulation Line Using Controlled Impeller Speed of the Granulation Unit, Compaction Force and Gap Width

Purpose In continuous manufacturing of pharmaceuticals, dry granulation is of interest because of its large throughput capacity and energy efficiency. In order to manufacture solid oral dosage forms continuously, valid control strategies for critical quality attributes should be established. To this date, there are no published control strategies for granule size distribution in continuous dry granulation. Methods In-line laser diffraction was used to determine the size of granules in a continuous roll compaction/dry granulation line (QbCon® dry). Different process parameters were evaluated regarding their influences on granule size. The identified critical process parameters were then incorporated into control strategies. The uncontrolled and the controlled processes were compared based on the resulting granule size. In both processes, a process parameter was changed to induce a shift in median particle size and the controller had to counteract this shift. Results In principle, all process parameters that affect the median particle size could also be used to control the particle size in a dry granulation process. The sieve impeller speed was found to be well suited to control the median particle size as it reacts fast and can be controlled independently of the throughput or material. Conclusion The median particle size in continuous roll compaction can be controlled by adjusting process parameters depending on real-time granule size measurements. The method has to be validated and explored further to identify critical requirements to the material and environmental conditions.

Application of response surface methodology (RSM) in statistical optimization and pharmaceutical characterization of a patient compliance effervescent tablet formulation of an antiepileptic drug levetiracetam

Background The main objective of the present study was to develop and optimize an effervescent tablet of levetiracetam, an antiepileptic drug, using central composite design with response surface methodology (RSM).The present investigation helps to overcome the problem associated with levetiracetam tablets and liquid dosage forms with children and elderly people like bad taste and swallowing difficulties. It also facilitates as an alternative manufacturing process for advanced patented technology like 3D printing process employed in SPRITAM® tablet. Levetiracetam effervescent tablets were prepared by dry granulation (roll compaction) method using water-soluble excipients and optimized by central composite rotatable design (CCRD) using two variables (citric acid and effersoda) at two levels (high and low). Overall, fourteen formulation trials were generated through statistical software Minitab 17.3.0 placing 6 center points, 4 cube points, and 4 axial points. All formulations were subjected to compression using single punch machine. Results Quality attributes of compressed tablets were evaluated using various compendial and non-compendial tests. RSM was used to observe the responses like effervescent time, hardness, and friability of the prepared tablet batches for different levels of all the variables. Polynomial equations were developed, and model plots (contour plot and 3-dimensional model surface plots) were generated to study the impact of acid-base couple on the responses. Finally, the optimized formulation was selected on the basis of desired effervescent time, hardness, friability, percent drug release, and drug content. From the studied RSM design, it was observed that small changes in the independent variables (citric acid and effersoda) correlate with shifts in the dependent variables, i.e., the desired responses. The study reveals that all the independent variables (citric acid and effersoda) and dependent variables (effervescent time, hardness, and friability) have a good correlation as indicated by good linear regression coefficient of 0.9808, 0.9939, and 0.9892 for effervescent time, hardness, and friability respectively. Conclusion Levetiracetam effervescent tablets are satisfactorily prepared by dry granulation (roll compaction) approach. All desired critical quality attributes were found to be satisfactory. The applicability of RSM with desirability function in optimizing the levetiracetam formulation has made it possible to identify the impact of various independent variables and explore their effect on required responses.