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Capping tendency in Mannitol based tablets: A DoE approach to study effects of filler, binder, binder concentration and compression force by means of instrumented tablet press and X-ray computed tomography

Persson, Emelie LU (2015) KLG920 20151
Food Technology and Nutrition (M.Sc.)
Abstract
Capping and/or lamination occur as a result of low mechanical strength in tablets. The mechanical strength can be enhanced with suitable formulation- and process parameters for the tablet powder in question. The aim of the present thesis was to investigate capping tendencies of mannitol based tablets. More specifically, the effect of varied particle size of mannitol, type and concentration of binder and compression force during tableting. A factorial design of experiments was used. Additionally, the work of compaction was measured and related to tablet strength of the resulting tablets as a mean to derive information regarding capping tendencies at an early stage in the development process of tablets. Three formulations resulted in tablets... (More)
Capping and/or lamination occur as a result of low mechanical strength in tablets. The mechanical strength can be enhanced with suitable formulation- and process parameters for the tablet powder in question. The aim of the present thesis was to investigate capping tendencies of mannitol based tablets. More specifically, the effect of varied particle size of mannitol, type and concentration of binder and compression force during tableting. A factorial design of experiments was used. Additionally, the work of compaction was measured and related to tablet strength of the resulting tablets as a mean to derive information regarding capping tendencies at an early stage in the development process of tablets. Three formulations resulted in tablets without tendencies to cap. The first contained NBD-022 (L-HPC), the second and third contained VA 64 Fine (copovidone) and CLSF (crospovidone) respectively. The three formulations were prepared with a mannitol of small particle size and a low concentration of binder. Additional binders investigated were LH-11 (L-HPC) and PEG 6000 (poly ethylene glycol). Elastic and plastic deformations of powders during compaction were evaluated by relative values of elasticity and plasticity respectively. Tablets providing highest tablet strength had a plasticity of about 88-91%. Tablets, which capped in the crushing strength test, had a plasticity of about 83-87 %. Hence the critical limit of plasticity, in terms of capping phenomena, was 86-87 %. A chemo metric analysis of the data indicates that there is a combination of pressure force and binder concentration that gives preferable values of plasticity, elasticity and elastic recovery in-die. This means that depending on fraction of binder, a suitable pressure force can be chosen to eliminate the risk of capping tendency in the resulting tablet. According to the DoE models, plasticity higher than 87-88 % and elasticity less than 2.4-2.5 % are preferable with respect to binder concentration and compression force. X-ray computed tomography made it possible for interpretation of the relative density variations in the analyzed tablets. Furthermore, capping tendencies could be indicated from the measurements and the indication of capping obtained from the XCT images was in good agreement with results from the crushing strength test. (Less)
Popular Abstract (Swedish)
Studien genomfördes för att undersöka hur den mekaniska hållfastheten i tabletter kunde förbättras för att därmed kunna undvika en av de vanligaste tablettdefekterna, så kallad lockning. Tre formuleringar togs fram vilka resulterade i tabletter utan tendenser till lockning. Utöver det visade det sig möjligt att, genom en kemometrisk metod, förutspå det intervall av presskraft som genererar mekaniskt starka tabletter vid tillverkning av mannitolbaserade tabletter. Röntgentomografi användes för att undersöka tabletters inre struktur samt utvärdera eventuella lockningstendenser.
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author
Persson, Emelie LU
supervisor
organization
course
KLG920 20151
year
type
H2 - Master's Degree (Two Years)
subject
keywords
läkemedelsteknologi, pharmaceutical technology
language
English
id
7440471
date added to LUP
2015-06-24 15:25:44
date last changed
2015-06-24 15:25:44
@misc{7440471,
  abstract     = {Capping and/or lamination occur as a result of low mechanical strength in tablets. The mechanical strength can be enhanced with suitable formulation- and process parameters for the tablet powder in question. The aim of the present thesis was to investigate capping tendencies of mannitol based tablets. More specifically, the effect of varied particle size of mannitol, type and concentration of binder and compression force during tableting. A factorial design of experiments was used. Additionally, the work of compaction was measured and related to tablet strength of the resulting tablets as a mean to derive information regarding capping tendencies at an early stage in the development process of tablets. Three formulations resulted in tablets without tendencies to cap. The first contained NBD-022 (L-HPC), the second and third contained VA 64 Fine (copovidone) and CLSF (crospovidone) respectively. The three formulations were prepared with a mannitol of small particle size and a low concentration of binder. Additional binders investigated were LH-11 (L-HPC) and PEG 6000 (poly ethylene glycol). Elastic and plastic deformations of powders during compaction were evaluated by relative values of elasticity and plasticity respectively. Tablets providing highest tablet strength had a plasticity of about 88-91%. Tablets, which capped in the crushing strength test, had a plasticity of about 83-87 %. Hence the critical limit of plasticity, in terms of capping phenomena, was 86-87 %. A chemo metric analysis of the data indicates that there is a combination of pressure force and binder concentration that gives preferable values of plasticity, elasticity and elastic recovery in-die. This means that depending on fraction of binder, a suitable pressure force can be chosen to eliminate the risk of capping tendency in the resulting tablet. According to the DoE models, plasticity higher than 87-88 % and elasticity less than 2.4-2.5 % are preferable with respect to binder concentration and compression force. X-ray computed tomography made it possible for interpretation of the relative density variations in the analyzed tablets. Furthermore, capping tendencies could be indicated from the measurements and the indication of capping obtained from the XCT images was in good agreement with results from the crushing strength test.},
  author       = {Persson, Emelie},
  keyword      = {läkemedelsteknologi,pharmaceutical technology},
  language     = {eng},
  note         = {Student Paper},
  title        = {Capping tendency in Mannitol based tablets: A DoE approach to study effects of filler, binder, binder concentration and compression force by means of instrumented tablet press and X-ray computed tomography},
  year         = {2015},
}