The comparison of seven different methods to quantify the amorphous content of spray dried lactose

Vesa-Pekka Lehto (Corresponding Author), Mikko Tenho, Kalle Vähä-Heikkilä, Päivi Harjunen, Maarit Päällysaho, Jouni Välisaari, Pentti Niemelä, Kristiina Järvinen

Research output: Contribution to journalArticleScientificpeer-review

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Abstract

The purpose of this work was to verify the usefulness, advantages and disadvantages of seven methods that are widely used to detect, and quantify the amorphous contents in pharmaceutical solids. Here, StepScan DSC, a type of modulated temperature calorimetry method, was applied for the first time to quantify amorphicity. The comparison of the analytical methods was undertaken with real (non-artificial) test samples, i.e. spray-dried lactose samples with various degrees of crystallinity. In these samples, it was essential that the amorphous and the crystalline portions are not present as separate particles, which is the case when physical (artificial) mixtures of totally amorphous and totally crystalline materials are used to produce the calibration curves. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), StepScan DSC (SS-DSC), isothermal microcalorimetry (IMC), solution calorimetry (SC), Raman spectrometry and gravimetric moisture sorption (GMS) were utilized to quantify the amorphous contents. The results obtained with IMC, SC, Raman, SS-DSC and GMS were in good agreement with each other. Generally, XRPD is the only method that reveals the disordered/amorphous nature of the samples in the crystallographic sense and, in the present study, it also provided consistent results. The conventional DSC method resulted in great variations for the mean amorphicity values since the method is not suitable for lactose where the dehydration of the hydrate and recrystallization of the amorphate overlap during the measurement of the partially amorphous samples. The recrystallized products of totally and partially amorphous lactose samples were found to be different, the former also including crystalline anhydrate. This complicated the interpretation of the IMC and GMS results, where the recrystallization process was monitored and analyzed. Thus, caution is warranted when the amorphicity of real samples is quantified by means of the calibration curves obtained with the physical mixtures of amorphous and crystalline lactose. With SS-DSC, where the quantification was based on the measurement of the heat capacity change associated with glass transition, this problem was not encountered. Utilizing only one method may lead to erroneous conclusions and hence, on the basis the present results, it is advisable to employ a combination of spectroscopic (Raman) and calorimetric (IMC) or gravimetric (GMS) methods.
Original languageEnglish
Pages (from-to)85-93
Number of pages9
JournalPowder Technology
Volume167
Issue number2
DOIs
Publication statusPublished - 2006
MoE publication typeA1 Journal article-refereed

Fingerprint

Lactose
Sorption
Differential scanning calorimetry
Calorimetry
Moisture
Crystalline materials
X ray powder diffraction
Crystallization
Calibration
Hydrates
Dehydration
Drug products
Spectrometry
Specific heat
Glass transition
Pharmaceutical Preparations

Keywords

  • amorphicity
  • calorimetric methods
  • lactose
  • moisture sorption
  • recrystallization
  • spectroscopic methods
  • x-ray powder diffraction
  • pharmaceutical compounds

Cite this

Lehto, V-P., Tenho, M., Vähä-Heikkilä, K., Harjunen, P., Päällysaho, M., Välisaari, J., ... Järvinen, K. (2006). The comparison of seven different methods to quantify the amorphous content of spray dried lactose. Powder Technology, 167(2), 85-93. https://doi.org/10.1016/j.powtec.2006.05.019
Lehto, Vesa-Pekka ; Tenho, Mikko ; Vähä-Heikkilä, Kalle ; Harjunen, Päivi ; Päällysaho, Maarit ; Välisaari, Jouni ; Niemelä, Pentti ; Järvinen, Kristiina. / The comparison of seven different methods to quantify the amorphous content of spray dried lactose. In: Powder Technology. 2006 ; Vol. 167, No. 2. pp. 85-93.
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Lehto, V-P, Tenho, M, Vähä-Heikkilä, K, Harjunen, P, Päällysaho, M, Välisaari, J, Niemelä, P & Järvinen, K 2006, 'The comparison of seven different methods to quantify the amorphous content of spray dried lactose', Powder Technology, vol. 167, no. 2, pp. 85-93. https://doi.org/10.1016/j.powtec.2006.05.019

The comparison of seven different methods to quantify the amorphous content of spray dried lactose. / Lehto, Vesa-Pekka (Corresponding Author); Tenho, Mikko; Vähä-Heikkilä, Kalle; Harjunen, Päivi; Päällysaho, Maarit; Välisaari, Jouni; Niemelä, Pentti; Järvinen, Kristiina.

In: Powder Technology, Vol. 167, No. 2, 2006, p. 85-93.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - The comparison of seven different methods to quantify the amorphous content of spray dried lactose

AU - Lehto, Vesa-Pekka

AU - Tenho, Mikko

AU - Vähä-Heikkilä, Kalle

AU - Harjunen, Päivi

AU - Päällysaho, Maarit

AU - Välisaari, Jouni

AU - Niemelä, Pentti

AU - Järvinen, Kristiina

PY - 2006

Y1 - 2006

N2 - The purpose of this work was to verify the usefulness, advantages and disadvantages of seven methods that are widely used to detect, and quantify the amorphous contents in pharmaceutical solids. Here, StepScan DSC, a type of modulated temperature calorimetry method, was applied for the first time to quantify amorphicity. The comparison of the analytical methods was undertaken with real (non-artificial) test samples, i.e. spray-dried lactose samples with various degrees of crystallinity. In these samples, it was essential that the amorphous and the crystalline portions are not present as separate particles, which is the case when physical (artificial) mixtures of totally amorphous and totally crystalline materials are used to produce the calibration curves. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), StepScan DSC (SS-DSC), isothermal microcalorimetry (IMC), solution calorimetry (SC), Raman spectrometry and gravimetric moisture sorption (GMS) were utilized to quantify the amorphous contents. The results obtained with IMC, SC, Raman, SS-DSC and GMS were in good agreement with each other. Generally, XRPD is the only method that reveals the disordered/amorphous nature of the samples in the crystallographic sense and, in the present study, it also provided consistent results. The conventional DSC method resulted in great variations for the mean amorphicity values since the method is not suitable for lactose where the dehydration of the hydrate and recrystallization of the amorphate overlap during the measurement of the partially amorphous samples. The recrystallized products of totally and partially amorphous lactose samples were found to be different, the former also including crystalline anhydrate. This complicated the interpretation of the IMC and GMS results, where the recrystallization process was monitored and analyzed. Thus, caution is warranted when the amorphicity of real samples is quantified by means of the calibration curves obtained with the physical mixtures of amorphous and crystalline lactose. With SS-DSC, where the quantification was based on the measurement of the heat capacity change associated with glass transition, this problem was not encountered. Utilizing only one method may lead to erroneous conclusions and hence, on the basis the present results, it is advisable to employ a combination of spectroscopic (Raman) and calorimetric (IMC) or gravimetric (GMS) methods.

AB - The purpose of this work was to verify the usefulness, advantages and disadvantages of seven methods that are widely used to detect, and quantify the amorphous contents in pharmaceutical solids. Here, StepScan DSC, a type of modulated temperature calorimetry method, was applied for the first time to quantify amorphicity. The comparison of the analytical methods was undertaken with real (non-artificial) test samples, i.e. spray-dried lactose samples with various degrees of crystallinity. In these samples, it was essential that the amorphous and the crystalline portions are not present as separate particles, which is the case when physical (artificial) mixtures of totally amorphous and totally crystalline materials are used to produce the calibration curves. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), StepScan DSC (SS-DSC), isothermal microcalorimetry (IMC), solution calorimetry (SC), Raman spectrometry and gravimetric moisture sorption (GMS) were utilized to quantify the amorphous contents. The results obtained with IMC, SC, Raman, SS-DSC and GMS were in good agreement with each other. Generally, XRPD is the only method that reveals the disordered/amorphous nature of the samples in the crystallographic sense and, in the present study, it also provided consistent results. The conventional DSC method resulted in great variations for the mean amorphicity values since the method is not suitable for lactose where the dehydration of the hydrate and recrystallization of the amorphate overlap during the measurement of the partially amorphous samples. The recrystallized products of totally and partially amorphous lactose samples were found to be different, the former also including crystalline anhydrate. This complicated the interpretation of the IMC and GMS results, where the recrystallization process was monitored and analyzed. Thus, caution is warranted when the amorphicity of real samples is quantified by means of the calibration curves obtained with the physical mixtures of amorphous and crystalline lactose. With SS-DSC, where the quantification was based on the measurement of the heat capacity change associated with glass transition, this problem was not encountered. Utilizing only one method may lead to erroneous conclusions and hence, on the basis the present results, it is advisable to employ a combination of spectroscopic (Raman) and calorimetric (IMC) or gravimetric (GMS) methods.

KW - amorphicity

KW - calorimetric methods

KW - lactose

KW - moisture sorption

KW - recrystallization

KW - spectroscopic methods

KW - x-ray powder diffraction

KW - pharmaceutical compounds

U2 - 10.1016/j.powtec.2006.05.019

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Lehto V-P, Tenho M, Vähä-Heikkilä K, Harjunen P, Päällysaho M, Välisaari J et al. The comparison of seven different methods to quantify the amorphous content of spray dried lactose. Powder Technology. 2006;167(2):85-93. https://doi.org/10.1016/j.powtec.2006.05.019