uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Influence of water-cellulose binding energy on stability of acetylsalicylic acid
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.ORCID iD: 0000-0002-5496-9664
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
2006 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 323, no 1-2, 139-145 p.Article in journal (Refereed) Published
Abstract [en]

The aim of the present study was to investigate how the energies of water binding in cellulose tabletting excipients influence the availability of moisture to induce hydrolysis of acetylsalisylic acid (ASA). Cellulose powders of varying degree of order, denoted as low-crystallinity cellulose (LCC) and high-crystallinity cellulose (HCC), were produced by treating ordinary microcrystalline cellulose (MCC) in ZnCl2 solutions of varying concentrations. Microcrystalline cellulose (MCC) and lactose monohydrate were used as reference excipients. The samples were then studied by X-ray diffraction, scanning electron microscopy, and differential scanning calorimetry (DSC). Different ratios of each excipient mixed with ASA were stored at 40% RH and 50 degrees C for 35 days to investigate the hydrolytic stability of the mixtures. Stability studies indicated that as concentration of HCC and MCC in binary mixtures with ASA was raised from 1 to 50% (w/w), ASA became increasingly unstable with respect to hydrolysis. Although LCC contained more moisture than the other celluloses, no such trend was observed in the LCC and lactose samples. DSC analysis revealed that each water molecule on the average was bound by more than three hydrogen bonds in the LCC and lactose structures and therefore remained predominantly unavailable to induce hydrolysis. The current study elucidates the necessity of evaluating the energy of water bindings in a pharmaceutical excipient when predicting the excipient's performance in mixtures comprising moisture-sensitive drugs.

Place, publisher, year, edition, pages
2006. Vol. 323, no 1-2, 139-145 p.
Keyword [en]
microcrystalline cellulose, lactose, crystallinity, moisture content, water interactions, stability of moisture-sensitive drug
National Category
Pharmaceutical Sciences Engineering and Technology
Identifiers
URN: urn:nbn:se:uu:diva-83335DOI: 10.1016/j.ijpharm.2006.05.058ISI: 000241346400018PubMedID: 16854539OAI: oai:DiVA.org:uu-83335DiVA: diva2:111243
Available from: 2007-01-17 Created: 2007-01-17 Last updated: 2016-11-30Bibliographically approved
In thesis
1. On the chemical and processing stability of pharmaceutical solids: Solid form dependent water presenting capacity and process induced solid form transformation
Open this publication in new window or tab >>On the chemical and processing stability of pharmaceutical solids: Solid form dependent water presenting capacity and process induced solid form transformation
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

There is a need for improving our knowledge and understanding about formation mechanisms and nature of amorphous state in order to prevent the unintended presence of disorder in solid pharmaceutical products and reduce the related stability issues. The suggested theory that water binding capacity of amorphous cellulose affects the chemical stability of hydrolysis sensitive drugs in formulations with cellulose based excipients needs a clarification and water-cellulose interaction profiles need to be examined.  This thesis has addressed these questions.

Chemical, mechanical and thermal methods have been used to create partially or predominantly amorphous solids. Mechanisms and the pathways for transformation to amorphous phase and the characteristic qualities of this phase is studied in order to give some tools to predict, to control or prevent the creation of disorder in a crystalline structure. The water interaction with amorphous pharmaceutical materials has been studied to improve stability of hydrolysis sensitive drugs. 

 

The transition to amorphous state during handling of pharmaceutical material, referred to as mechanical activation in processes like blending, mixing and compression is substantially a consequence of vitrification. The process is described as creation of hot spots where friction caused by particle sliding raise the temperature above the melting point of the material. The fast cooling process promotes creation of a local disordered molecular arrangement. It is possible to decrease the degree of amorphisation and undesired stability problems by reducing the friction and inhibit the creation of crystal defects during processing.

 

The glass-forming propensity is an inherent material characteristic related to molecular size and structure and is not process dependent. Molecules with a couple of aromatic rings are often poor glass-formers. Less symmetrical, branched molecular structures with presence of electronegative atoms are more readily transformed to and exist in amorphous state when handled and stored at temperatures below their glass transition temperature.

 

The interaction profile of cellulose with water is strongly dependent on solid state structure of cellulose. Crystallinity is the key parameter in water presenting capacity of cellulose. Amorphous regions have a capacity to bind the water and decrease water mobility and in that way reduce cellulose water presenting capacity despite higher moisture content in partially amorphous cellulose compared to crystalline cellulose. The fact that higher amorphous content decreases cellulose water presenting capacity is a promising lead to improve stability of hydrolysis sensitive drugs in compositions with cellulose. This knowledge could be applicable to other pharmaceutical materials as the differences between crystalline and amorphous states of material are generally the same for different kind of materials.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 57 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 203
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-261785 (URN)978-91-554-9325-7 (ISBN)
Public defence
2015-10-23, B22 Biomedicum, Daghammarsköldsväg, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2015-11-26 Created: 2015-09-04 Last updated: 2016-01-13Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Heidarian, MinaMihranyan, AlbertStrömme, MariaEk, Ragnar

Search in DiVA

By author/editor
Heidarian, MinaMihranyan, AlbertStrömme, MariaEk, Ragnar
By organisation
Department of PharmacyNanotechnology and Functional Materials
In the same journal
International Journal of Pharmaceutics
Pharmaceutical SciencesEngineering and Technology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 898 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf