Effects of cyclodextrins on the acid hydrolysis of digoxin

Abstract

The effects of three cyclodextrins (alpha-, beta-, gamma-CyD) on the acid hydrolysis of digoxin were examined. From the high performance liquid chromatographic tracing of each of the four components (digoxin, bisdigitoxoside, monodigitoxoside, digoxigenin) in reaction mixtures, the individual rate constants (K1-K6) were determined by analogue computer simulation. The hydrolysis was suppressed by CyDs in the order of beta-great than gamma-greater than alpha-greater than-CyD, where beta-CyD inhibited the appearance rates of digoxigenin (k3, K5, and K6) significantly. In the dissolution study of digoxin tablets, the increase in dissolution rate and decrease in acid hydrolysis were attained by inclusion complexation. The data are presented suggesting that CyDs are useful for improving the oral bioavailability of digoxin.

An NMR study of cyclodextrin complexes of the steroidal neuromuscular blocker drug Rocuronium Bromide

“…There are almost equal representations from protons on the˛face of the steroid (six) and from theˇface (five), and there is a nearly equal distribution of entries from axial (three) and equatorial steroid protons (four). As noted previously for the other two systems, the 13 C CIS values for the 1 : 4 system were small and there was no discernable pattern when they were mapped onto the steroid skeleton. Hence the 1 H and the 13 C steroid CIS values indicate no preference for edge binding, face binding, or for any particular face of the steroid.…”

“…The protons with large CIS are equally distributed over both sides of the steroid (five on thef ace, and five on theˇface). CIS effects in the 13 C spectrum were significant, but small (typically ca š0.3 ppm, and up to C1.7 ppm) and without an apparent pattern. The CIS in the 1 H spectrum of theˇ-cyclodextrin are listed in Table 3.…”

“…Some reports implicate that ring A of (non-bile) steroids is involved in formation of the complex. 13,16,23,24 Less work has been published on the interactions of steroids with the larger -cyclodextrin.…”

“…1D 1 H NMR spectra for binding studies and Job plots were acquired with a digital resolution of 0.0002 ppm/point and using a small amount of MeOH as an internal chemical shift reference. ROESY experiments were performed in the phasesensitive mode and with presaturation of the water signal, 16 scans, sw D 6.4 ppm, 256 t 1 increments, mixing time 400 ms. 13 C chemical shifts were recorded from the HSQC spectra. HSQC data were obtained with eight scans, sw H D 6.3 ppm, sw C D 180 ppm, and 256 t 1 increments.…”

Design and Evaluation of Cyclodextrin-Based Drug Formulation

“…The possible enhancing mechanisms of CyDs on the bioavailability of drugs in various administration routes are summarized as follows: 1) hydrophilic CyDs increase the solubility, dissolution rate, and wettability of poorly watersoluble drugs, [82][83][84][85][86][87][88][89][90][91][92][93][94][95][96][97][98][99][100][101] 2) CyDs prevent the degradation or disposition of chemically unstable drugs in gastrointestinal tracts as well as during storage, [102][103][104][105][106][107][108][109][110][111] 3) CyDs perturb the membrane fluidity to lower the barrier function, which consequently enhances the absorption of drugs including peptide and protein drugs through the nasal and rectal mucosa, [112][113][114][115][116][117][118][119][120][121] 4) competitive inclusion complexation with third components (bile acid, cholesterol, lipids, etc.) to release the included drug, [122][123][124][1...…”