title: Relevant Aspects of Roller Compaction covering the Impact of Excipients, Milling Devices, Fines and Feasibility Prediction
creator: Farrenkopf, Jochen
subject: ddc-570
subject: 570 Life sciences
description: Roller compaction is a dry granulation technology, used to overcome unfavorable physical properties of powders and APIs, such as poor flow, low and/or inhomogeneous bulk density or segregation/floating of powder blends. Associated with many advantageous properties, one of the major roller compaction drawbacks is the potential for relatively high amounts of fine particles < 0.1 mm after milling of the ribbons – they can partially disintegrate into their primary particles.  For eight blends with different amounts of fine, medium and coarse granules fractions it could be shown that the flow properties of the blends as well as the tablets tensile strength significantly suffered from the presence of roller compacted fines. Higher amounts of fines (45% and 60%) surprisingly over-compensated this effect: now the high number of particles and their large surface area appears to be predominant – despite the poor flow. The best tensile strength data derived from the medium fraction 0.1 - 1.0 mm: the wide variety of smaller and larger particles with good flow properties easily aligns during filling and compression phase. For the coarse particles 1.0 - 1.25 mm, their limited specific surface area and therefore reduced ability to establish interparticular bindings has minor negative impact on the blends compressibility. For gentle milling of the ribbons, four different milling devices as well as their settings (different sieve screen sizes and types, rotors, rotor speeds, rotor/sieve distances, etc) were evaluated: the integrated Gerteis granulator with newly modified sieve housing delivered the best results, whereas for smaller ribbons quantities also the independently driven Frewitt mill GLA_ORV prove to be a viable option. Low amounts of dry binders (PEG 1500 and 4000, PVP K30, PVP/VA copolymer, HPC) were added to the standard formulation MCC to reduce fines after milling: for this purpose and for batch variability during milling already 3% PEG 1500 had a positive impact, but tablets crushing strength dropped by 20%. 9% PVP K30 is required for fines reduction by 6.1%, the best overall result; however, tablets disintegration time is higher. To learn more about excipients for roller compaction, compression trials were performed with pure excipients and rather formulation-like 1:1 blends with MCC. The objective was to get information about the manufacturing methods comparability (direct tabletting vs. roller compaction/tabletting vs. texture analyzer, TA) and the extend of their predictability. The tablet’s crushing strength of each formulation is calculated by using the slope’s formula for data standardization and direct comparison in a metric ranking order, like for the three different sets of TA data. The direct tabletting data prove to be predictable with a relatively high probability from TA compression of powders. To a limited extend this is also valid for prediction of roller compaction feasibility, using direct tabletting trials as well as the three TA characterization systems. Here the TA compression of powders is preferred if only a limited amount of material is available. If time is more critical than material availability, a roller compaction trial should be considered in order to manufacture a few intact ribbons at different compaction force levels: milling and tabletting of the ribbons can be skipped by assessing the ribbons properties with the TA. Looking into the excipients, MCC of adequately small d50 (type Avicel PH 101) reaches the best scores for direct tabletting and roller compaction / tabletting and justifies being the basic ingredient of roller compaction formulations. In contrast to that, the much larger particles of Avicel PH 200 are not appropriate for this process. Despite its poor performance as pure excipient in direct tabletting and roller compaction / tabletting, Tablettose 70 shows unexpectedly good results in the 1:1 blend with Avicel PH 101, so this combination can be considered for formulation development. Less suited are, mannitol (type Pearlitol SD 200) and pregelatinized starch (type Cerestar 93000) do not seem to be well suited for roller compaction purposes, but the latter can help as tablet disintegration aid in low proportions.
date: 2009
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/10124/1/Dissertation_JFarrenkopf_v30Mar2009u.pdf
identifier: DOI:10.11588/heidok.00010124
identifier: urn:nbn:de:bsz:16-opus-101247
identifier:   Farrenkopf, Jochen  (2009) Relevant Aspects of Roller Compaction covering the Impact of Excipients, Milling Devices, Fines and Feasibility Prediction.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/10124/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng