Membrane Formation and Drug Loading Effects in High Amylose Starch Tablets Studied by NMR Imaging

Abstract

Cross-linked high amylose starch is used as an excipient in the preparation of pharmaceutical tablets for the sustained release of drugs. NMR imaging with contrast enhanced by proton density and by self-diffusion coefficient was used to follow the water uptake and swelling, two critical parameters controlling the drug release of the cross-linked starch tablets containing 10 wt % of ciprofloxacin and of acetaminophen, respectively. The drug-loaded tablets were studied in a H2O/D2O mixture at 37 degrees C in comparison to the tablets without any drug loading. The diffusion of water in the tablets all showed a Fickian behavior, but the kinetics of water uptake was faster in the case of the drug-loaded tablets. The formation of a membrane at the water/tablet interface was observed.

Recent advances of starch-based excipients used in extended-release tablets: a review

“…Zhu, X. 's research group innovatively used nuclear magnetic resonance imaging in the study of internal properties of hydrating CLHAS tablets (Thérien-Aubin et al, 2008;Wang et al, 2010;Thérien-Aubin & Zhu, 2009). X-ray microtomography has been used to investigate the dynamic behavior of swelling tablets .…”

NMR spectroscopy and imaging studies of pharmaceutical tablets made of starch

“…In the study of solvent uptake, only the molecules of solvent contribute to the signal. However, contrast of the image could be adjusted by any factors measurable by NMR, such as changes in concentration Chowdhury, Hill, & Whittaker, 2004a;Chowdhury, Hill, Whittaker, Braden, & Patel, 2004b;Fyfe & Blazek, 1997;Thérien-Aubin, Baille, Zhu, & Marchessault, 2005;Thérien-Aubin & Zhu, 2006;Thérien-Aubin, Zhu, Ravenelle, & Marchessault, 2008), relaxation times (Chowdhury et al, 2004b;Fyfe & Blazek, 1997;Rajabi-Siahboomi, Bowtell, Mansfield, Davies, & Melia, 1996), or self-diffusion coefficients Kojima & Nakagami, 2002;Rajabi-Siahboomi et al, 1996;Thérien-Aubin et al, 2008;Tritt-Goc, Kowalczuk, & Pislewski, 2003). NMR imaging is widely used to follow water uptake and moisture diffusion and to assess the water distribution in a system in different polymeric and starch-based systems (Hopkinson, Jones, Black, Lane, & McDonald, 1997;Horigane, Takahashi, Maruyama, Ohtsubo, & Yoshida, 2006b;Horigane et al, 2006a;Kasai, Lewis, Ayabe, Hatae, & Fyfe, 2007;Russo et al, 2007;Ziegler, MacMillan, & Balcom, 2003).…”

“…In this case, the echo time, which is equal to the diffusion time (D), was set to 10 ms in order to achieve enough attenuation of the signal in the self-diffusion experiment. The length of the gradient pulse (d) used in the PGSE sequence was 2 ms, and the gradient strength varied from 5 to 100 G/cm (Thérien-Aubin et al, 2008). For the study of the temperature effect, the experiments were carried on a Bruker DSX300 NMR spectrometer operating at 300.13 MHz, also equipped with similar orthogonal field gradient coils on CHAS I and CHAS II tablets (Table 1) without drug molecules.…”

“…NMR imaging studies can bypass this problem and allow the measurement of the average diffusion coefficient of water in unperturbed systems as the gravimetric studies and also the 'instantaneous' diffusion coefficient (Thérien-Aubin et al, 2005. Furthermore, NMR imaging with contrast resolved by selfdiffusion coefficient can be used to follow the mobility of the water molecules according to their location in the tablet (Thérien-Aubin et al, 2008). The average diffusion coefficient is measured from the pseudogravimetric measurements (Fig.…”

High-amylose carboxymethyl starch matrices for oral sustained drug-release: In vitro and in vivo evaluation

“…The technique can be easily used to monitor simultaneously different areas of interest in the tablet and qualitative/quantitative results can be obtained . The effect of factors such as pH and ionic strength , tablet size , temperature (Therien-Aubin, Baille et al 2005) and drug-loading on solvent uptake and tablet swelling, as well as on gel layer formation at the water/tablet interface (Therien-Aubin, Zhu et al 2008) in the case of cross-linked high-amylose starch tablets has been evaluated using this technique.…”