Inclusion metoprolol

The two-component lipid models were also characterized in the absence of sink conditions (Table 7.8). Comparisons between models 7.0 (Table 7.7) and 1.0 (Table 7.5) suggest that negative charge in the absence of sink causes the permeabilities of many of the bases to decrease. Exceptions are quinine, prazosin, primaquine, ranitidine, and especially metoprolol. The inclusion of 0.6% PA causes Pe of metoprolol to increase nearly 10-fold, to a value twice that of propranolol, a more lipophilic molecule than metoprolol (based on the octanol-water scale). Naproxen and ketoprofen become notably more permeable in the two-component system. Surprisingly, the neutral progesterone becomes significantly less permeable in this system. 

For CyD complexes a number of stoichiometric ratios has been observed [2]. The most commonly reported ratios are H G = 1 1 and H G = 2 1. However, other stoichiometries as well as ternary CyD-containing complexes [47] are known. An example of 2 1 stoichiometry is the camphor-a-CyD complex in which the guest molecule is embedded inside a capsule formed by two host molecules [48]. Fenbu-fen (y-oxo-[l,l -biphenyl]-4-butanoic acid) is an interesting example of a compound which shows stoichiometry dependence on the CyD cavity size. It does not form an inclusion complex with a-CyD, but displays H G = 1 1 stoichiometry with f-CyD and H G = 1 2 stoichiometry with y-CyD [49, 50]. Metoprolol is another such compound which forms 1 1 complexes with a-CyD and f-CyD but with y-CyD it forms an H G = 1 2 complex [51]. A similar phenomenon detected using HPLC for a complex with a first-generation dendrimer is presented in Chapter 5 [52]. On the other hand, 1-adamantanecarboxylic acid and f-CyD form a complex with temperature-dependent stoichiometry, H G = 1 1 at 25 °C and H G = 1 2 at 0 °C [28]. For the complexation of dodecyltrimethylammonium bromide with a-CyD two competing associations with stoichiometries of H G = 1 1 and H G = 2 1 have been reported [53]. Use of the method of continuous variations in such situations becomes questionable and information about the complex stoichiometry is revealed directly from the titration measurement described in Section 9.2.3. 

Fig. 14.10. Proposed inclusion modes of metoprolol (Met) with three native CyDs [23] (A) a-CyD complex with the methoxyethyl-benzene moiety of Met inserted from the seconda7 hydroxyl side of a-CyD (B) jS-CyD complex with the methoxyethylbenzene moiety...

S. Siddique, A. Bose, J. Khanam, Modulation of drug (metoprolol succinate) release by inclusion of hydrophobic polymer in hydrophilic matrix. Drug Dev Ind Pharm, 37 (9), 1016-1025, 2011. 

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