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Physico-chemical characterization of the active pharmaceutical ingredient Mesalazine - An investigation of previously not specified properties at QPharma AB

Englund, Isabell LU (2016) KLG920 20161
Food Technology and Nutrition (M.Sc.)
Abstract
This study was done due to observed differences during production, involving the active pharmaceutical ingredient mesalazine, obtained from different suppliers. The aim of the present thesis was to make an investigation of previously not specified properties of mesalazine. This was done to enable adjustment of different parameters during production to account for differences in the raw material.

Mesalazine from two suppliers, A and B, were included in this study. The melting profile and interactions between mesalazine from both suppliers and some of the excipients included in the tablet (microcrystalline cellulose, polyvinylpyrrolidone and magnesium stearate) were investigated by differential scanning calorimetry. The melting profiles... (More)
This study was done due to observed differences during production, involving the active pharmaceutical ingredient mesalazine, obtained from different suppliers. The aim of the present thesis was to make an investigation of previously not specified properties of mesalazine. This was done to enable adjustment of different parameters during production to account for differences in the raw material.

Mesalazine from two suppliers, A and B, were included in this study. The melting profile and interactions between mesalazine from both suppliers and some of the excipients included in the tablet (microcrystalline cellulose, polyvinylpyrrolidone and magnesium stearate) were investigated by differential scanning calorimetry. The melting profiles of pure mesalazine from supplier A and B were comparable. The profiles indicated presence of an unstable polymorph. This polymorph was not observed when scanning binary mixtures containing mesalazine and microcrystalline cellulose or PVP. However, interactions were observed between mesalazine and all excipients examined. Both similarities and differences were observed in the interactions when comparing mesalazine from the two suppliers.

The particle size and particle shape of mesalazine were investigated by QicPic. The results were compared with results from previously performed analysis using laser diffraction. The values of D50 obtained from QicPic and laser diffraction was similar, while the values of D90 differed. According to QicPic, mesalazine from supplier B seem to contain smaller particles that are more spherical than the particles in mesalazine from supplier A.

The water uptake and water activity of samples stored at different conditions of temperature and relative humidity was determined. No clear pattern was observed for the water uptake. The water activity seemed to increase with increased temperature and/or relative humidity. No clear difference of the water activity of mesalazine from different suppliers was observed.

Granulation was performed for three batches of mesalazine from supplier A and one batch for mesalazine from supplier B. The optimal amount of granulation liquid was investigated by varying the amount added during granulation of mesalazine from supplier A. Results from sieve analysis of granulates of mesalazine from supplier A and B with the standard value of granulation liquid differed, meaning different particle size distribution was obtained. 15% extra granulation liquid had to be added when performing granulation of mesalazine from supplier A compared to supplier B to get granulates with equal properties. However, the texture of granulates containing mesalazine from supplier A, where the currently used amount of granulation liquid during production was added, and when 10% extra granulation liquid was added were preferable. (Less)
Popular Abstract (Undetermined)
Denna studie har gjorts för att möjliggöra anpassning av olika parametrar vid tillverkning av tabletter innehållande mesalazine. Mesalazine används vid behandling av Ulcerös kolit och Crohns sjukdom, sjukdomar som drabbar mag- och/eller tarmkanalen.
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author
Englund, Isabell LU
supervisor
organization
course
KLG920 20161
year
type
H2 - Master's Degree (Two Years)
subject
keywords
mesalazine, DSC, QicPic, pharmaceutical technology, läkemedelsteknologi
language
English
id
8882292
date added to LUP
2016-06-29 11:19:15
date last changed
2016-06-29 11:32:08
@misc{8882292,
  abstract     = {This study was done due to observed differences during production, involving the active pharmaceutical ingredient mesalazine, obtained from different suppliers. The aim of the present thesis was to make an investigation of previously not specified properties of mesalazine. This was done to enable adjustment of different parameters during production to account for differences in the raw material. 

Mesalazine from two suppliers, A and B, were included in this study. The melting profile and interactions between mesalazine from both suppliers and some of the excipients included in the tablet (microcrystalline cellulose, polyvinylpyrrolidone and magnesium stearate) were investigated by differential scanning calorimetry. The melting profiles of pure mesalazine from supplier A and B were comparable. The profiles indicated presence of an unstable polymorph. This polymorph was not observed when scanning binary mixtures containing mesalazine and microcrystalline cellulose or PVP. However, interactions were observed between mesalazine and all excipients examined. Both similarities and differences were observed in the interactions when comparing mesalazine from the two suppliers.

The particle size and particle shape of mesalazine were investigated by QicPic. The results were compared with results from previously performed analysis using laser diffraction. The values of D50 obtained from QicPic and laser diffraction was similar, while the values of D90 differed. According to QicPic, mesalazine from supplier B seem to contain smaller particles that are more spherical than the particles in mesalazine from supplier A.

The water uptake and water activity of samples stored at different conditions of temperature and relative humidity was determined. No clear pattern was observed for the water uptake. The water activity seemed to increase with increased temperature and/or relative humidity. No clear difference of the water activity of mesalazine from different suppliers was observed.

Granulation was performed for three batches of mesalazine from supplier A and one batch for mesalazine from supplier B. The optimal amount of granulation liquid was investigated by varying the amount added during granulation of mesalazine from supplier A. Results from sieve analysis of granulates of mesalazine from supplier A and B with the standard value of granulation liquid differed, meaning different particle size distribution was obtained. 15% extra granulation liquid had to be added when performing granulation of mesalazine from supplier A compared to supplier B to get granulates with equal properties. However, the texture of granulates containing mesalazine from supplier A, where the currently used amount of granulation liquid during production was added, and when 10% extra granulation liquid was added were preferable.},
  author       = {Englund, Isabell},
  keyword      = {mesalazine,DSC,QicPic,pharmaceutical technology,läkemedelsteknologi},
  language     = {eng},
  note         = {Student Paper},
  title        = {Physico-chemical characterization of the active pharmaceutical ingredient Mesalazine - An investigation of previously not specified properties at QPharma AB},
  year         = {2016},
}