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Investigation of the relationship between physical properties of mesalazine and its behavior during dry mixing

Edvinsson, Johannes LU (2019) KLGM15 20191
Food Technology and Nutrition (M.Sc.)
Abstract
The master thesis was done at QPharma to investigate a processing problem during production of tablets, where an excessive volume expansion during dry mixing of three ingredients occurred from time to time. A volume expansion (dilation) is needed for particles, within a powder, to become mixed with other particles. However, the extent of the dilation is dependent on intermolecular forces between particles which in turn is dependent on physical properties such as size, size distribution and shape. During the project, batches with excessive dilation were compared to batches with normal expansion, considering the physical properties. It was found out that the problematic batches contained more small particles called fines and less coarse... (More)
The master thesis was done at QPharma to investigate a processing problem during production of tablets, where an excessive volume expansion during dry mixing of three ingredients occurred from time to time. A volume expansion (dilation) is needed for particles, within a powder, to become mixed with other particles. However, the extent of the dilation is dependent on intermolecular forces between particles which in turn is dependent on physical properties such as size, size distribution and shape. During the project, batches with excessive dilation were compared to batches with normal expansion, considering the physical properties. It was found out that the problematic batches contained more small particles called fines and less coarse particles, compared to the unproblematic batches. No difference could be seen when comparing the shapes of the particles.

The difference in size distribution for problematic and unproblematic batches resulted in a large difference in surface area. One of the three ingredients is added as a glidant, that exists of very small particles that adhere to the already small API (active pharmaceutical ingredient) particles, acting as a spacer between the API particles and thus reduces the intermolecular forces (cohesion) and increases the flowability.
It was found out that due to the difference in surface area, a consequence was that the surface area coverage by the glidant was lower for the problematic batches resulting in less reduction of the intermolecular forces. Experiments were done to try to relate the surface area coverage to the dilation difference, but no robust method could be developed that showed any differences.

In conclusion, it was found out that dilation and higher percentage of fines correlated. However, the exact mechanism behind the volume expansion due to the fines could not be identified. Despite this, the master thesis laid a foundation for further investigation, and proposed solutions to the problem. (Less)
Popular Abstract (Swedish)
Examensarbetet undersöker om det i en viss process går att förutsäga hur ett läkemedelspulver och dess
partiklar kommer att bete sig utifrån att undersöka fysikaliska egenskaper hos partiklarna.
Att hantera pulver inom läkemedelsindustrin är en väldigt stor utmaning. På grund av att de flesta läkemedel idag säljs som
tabletter som tillverkats från pulver, så är utmaningen av mycket stor betydelse, vilket ökar intresset för att undersöka
problemet vidare. Dessa pulver består av partiklar som är så extremt små att de beter sig på ett ganska oväntat och annorlunda
sätt. På grund av att de är så små, så sitter de ofta hellre ihop med andra liknande partiklar än att bete sig som individuella
partiklar vilket leder till ett... (More)
Examensarbetet undersöker om det i en viss process går att förutsäga hur ett läkemedelspulver och dess
partiklar kommer att bete sig utifrån att undersöka fysikaliska egenskaper hos partiklarna.
Att hantera pulver inom läkemedelsindustrin är en väldigt stor utmaning. På grund av att de flesta läkemedel idag säljs som
tabletter som tillverkats från pulver, så är utmaningen av mycket stor betydelse, vilket ökar intresset för att undersöka
problemet vidare. Dessa pulver består av partiklar som är så extremt små att de beter sig på ett ganska oväntat och annorlunda
sätt. På grund av att de är så små, så sitter de ofta hellre ihop med andra liknande partiklar än att bete sig som individuella
partiklar vilket leder till ett blandningsmotstånd. (Less)
Please use this url to cite or link to this publication:
author
Edvinsson, Johannes LU
supervisor
organization
course
KLGM15 20191
year
type
H2 - Master's Degree (Two Years)
subject
keywords
Pharmaceutical technology, Läkemedelsteknologi
language
English
id
8980365
date added to LUP
2019-07-04 14:55:05
date last changed
2019-07-04 14:55:05
@misc{8980365,
  abstract     = {The master thesis was done at QPharma to investigate a processing problem during production of tablets, where an excessive volume expansion during dry mixing of three ingredients occurred from time to time. A volume expansion (dilation) is needed for particles, within a powder, to become mixed with other particles. However, the extent of the dilation is dependent on intermolecular forces between particles which in turn is dependent on physical properties such as size, size distribution and shape. During the project, batches with excessive dilation were compared to batches with normal expansion, considering the physical properties. It was found out that the problematic batches contained more small particles called fines and less coarse particles, compared to the unproblematic batches. No difference could be seen when comparing the shapes of the particles.

The difference in size distribution for problematic and unproblematic batches resulted in a large difference in surface area. One of the three ingredients is added as a glidant, that exists of very small particles that adhere to the already small API (active pharmaceutical ingredient) particles, acting as a spacer between the API particles and thus reduces the intermolecular forces (cohesion) and increases the flowability. 
It was found out that due to the difference in surface area, a consequence was that the surface area coverage by the glidant was lower for the problematic batches resulting in less reduction of the intermolecular forces. Experiments were done to try to relate the surface area coverage to the dilation difference, but no robust method could be developed that showed any differences. 

In conclusion, it was found out that dilation and higher percentage of fines correlated. However, the exact mechanism behind the volume expansion due to the fines could not be identified. Despite this, the master thesis laid a foundation for further investigation, and proposed solutions to the problem.},
  author       = {Edvinsson, Johannes},
  keyword      = {Pharmaceutical technology,Läkemedelsteknologi},
  language     = {eng},
  note         = {Student Paper},
  title        = {Investigation of the relationship between physical properties of mesalazine and its behavior during dry mixing},
  year         = {2019},
}