Influence of water-cellulose binding energy on stability of acetylsalicylic acid
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
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.
microcrystalline cellulose, lactose, crystallinity, moisture content, water interactions, stability of moisture-sensitive drug
Pharmaceutical Sciences Engineering and Technology
IdentifiersURN: urn:nbn:se:uu:diva-83335DOI: 10.1016/j.ijpharm.2006.05.058ISI: 000241346400018PubMedID: 16854539OAI: oai:DiVA.org:uu-83335DiVA: diva2:111243