β‐Cyclodextrin Derivatives, SBE4‐β‐CD and HP–β‐CD, Increase the Oral Bioavailability of Cinnarizine in Beagle Dogs

Järvinen, Tomi; Järvinen, Kristiina; Schwarting, Nancy; Stella, Valentino J.

doi:10.1002/jps.2600840306

Cited by 90 publications

(32 citation statements)

References 22 publications

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“…A number of chemically modified CDs have been prepared to improve the inclusion capacity and the physicochemical properties as compared to the natural CDs. The CD derivatives, 2-hydroxypropyl-b-CD (2OHpbCD) and sulfobutyl ether b-CD, have been widely investigated within the pharmaceutical literature on account of their fast dissolution rate, high solubility in water and low toxicity [7][8][9]. Other orally acceptable modified b-CDs, e.g., 2-O-methyl-b-CD (mbCD), and derivatives of both a-and g-CDs also exist, however, these are investigated to a much lesser degree in the literature.…”

Section: Introductionmentioning

confidence: 99%

Complexation of tauro‐ and glyco‐conjugated bile salts with three neutral β‐CDs studied by ACE

et al. 2007

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Complexation of the bile salts (BS) taurocholate, tauro-beta-muricholate, taurodeoxycholate, taurochenodeoxycholate, glycocholate, glycodeoxycholate, and glycochenodeoxycholate common in rat, dog, and man with natural beta-CD and the chemically modified beta-CDs 2-hydroxypropyl-beta-CD and 2-O-methyl-beta-CD was studied using mobility shift ACE. The CDs were selected due to their frequent use in preformulation and drug formulation as oral excipients for the solubilization of drug substances with low aqueous solubility. ACE was demonstrated to be a feasible and efficient technique for investigation of the interactions between BS and beta-CDs. All the investigated BS possessed affinity for the three CDs with stability constants ranging from 2x10(3) to 4x10(5) M(-) (1). The requirements and assumptions related to the use of ACE for estimating high affinity stability constants were discussed. The extent and pattern of hydroxylation significantly influenced the affinity of the glyco- and tauro-conjugated BS toward the beta-CDs (chenodeoxycholates >> deoxycholates > cholates) whereas the nature of the beta-CD derivatization and BS conjugation played a minor role only. The results indicate that displacement of drug substances from beta-CD inclusion complexes is likely to occur in the small intestine where BS are present potentially influencing drug bioavailability.

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Section: Introductionmentioning

confidence: 99%

Complexation of tauro‐ and glyco‐conjugated bile salts with three neutral β‐CDs studied by ACE

et al. 2007

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“…The complexation can be used, for example, to increase aqueous solubility, dissolution rate, and bioavailability, and to decrease local irritation and increase the stability of drugs [Loftsson and Brewster, 1996;Rajewski and Stella, 1996;Irie and Uekama, 1997]. In oral formulations, the primary use of CDs is to increase drug bioavailability through the increased rate and extent of drug solubility and dissolution [Järvinen et al, 1995;Panini et al, 1995;Soliman et al, 1997;Savolainen et al, 1998].…”

Section: Introductionmentioning

confidence: 99%

Effects of aqueous solubility and dissolution characteristics on oral bioavailability of entacapone

et al. 2000

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“…These results could be explained by the fact that the substitution of the hydrophilic edges of the b-CD molecule by hydroxypropyl or sulfobutyl groups led to an extension of the length channel of the b-CD cavity, resulting possibly in an additional masking of the lipophilic regions of the (þ)-UA molecule. Interestingly, from a practical point of view, these two chemically substituted CDs were shown to be excellent solubilizers for many drugs (Loftsson and Sigurô ardó ttir, 1994;Järvinen et al, 1995;Rajewski and Stella, 1996;Irie and Uekama, 1997;Stella and Rajewski, 1997;Stella and He, 2008). Not surprisingly, these hydrophilic CD derivates were much more effective than natural CDs for increasing the apparent solubility, because of the formation of highly water soluble complexes with (þ)-UA.…”

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confidence: 96%

Elucidation of the complexation mechanism between (+)‐usnic acid and cyclodextrins studied by isothermal titration calorimetry and phase‐solubility diagram experiments

Segura‐Sánchez¹,

Bouchemal²,

Lebas³

et al. 2009

J of Molecular Recognition

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In the present work the complexation mechanism between (+)-usnic acid (UA) and cyclodextrins (CDs) has been investigated by isothermal titration calorimetry (ITC) and phase-solubility diagrams using pH as a tool for modifying the molecule ionization. ITC experiments have been employed to evaluate the stoichiometry of interaction (N), affinity constants (K), and thermodynamic parameter variation associated with complexation between (+)-UA and alpha-, beta-, HP-beta-, SBE-beta-, and gamma-CD. It was shown that (+)-UA did not interact with alpha-CD and tended to interact more favorably with gamma-CD (K = 1030 M(-1), DeltaG = -17.18 kJ x mol(-1)) than beta-CD (K = 153 M(-1), DeltaG = -12.46 kJ x mol(-1)) forming 1:1 complexes. It was also demonstrated using ITC and solubilization experiments that chemical modifications of the parent beta-CD resulted in stronger and more spontaneous interactions (K = 281 M(-1), DeltaG = -13.97 kJ x mol(-1) for SBE-beta-CD and K = 405 M(-1), DeltaG = -14.87 kJ x mol(-1) for HP-beta-CD). Analysis of the thermodynamic data suggested that van der Waals forces and hydrogen bonds were responsible for the formation of complexes with a predominance of van der Waals forces. Finally, pH induced modifications of (+)-UA ionization provided important informations relative to the topology of the interaction between (+)-UA molecule and the gamma-CD cavity, which were confirmed by molecular modeling.

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β‐Cyclodextrin Derivatives, SBE4‐β‐CD and HP–β‐CD, Increase the Oral Bioavailability of Cinnarizine in Beagle Dogs

Cited by 90 publications

References 22 publications

Complexation of tauro‐ and glyco‐conjugated bile salts with three neutral β‐CDs studied by ACE

Complexation of tauro‐ and glyco‐conjugated bile salts with three neutral β‐CDs studied by ACE

Effects of aqueous solubility and dissolution characteristics on oral bioavailability of entacapone

Elucidation of the complexation mechanism between (+)‐usnic acid and cyclodextrins studied by isothermal titration calorimetry and phase‐solubility diagram experiments

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