Amorphous spironolactone-hydroxypropylated cyclodextrin complexes with superior dissolution and oral bioavailability

Soliman, Osama A.; Kimura, Kenta; Hirayama, Fumitoshi; Uekama, Kaneto; El-Sabbagh, H. M.; El-Gawad, A. Abd; Hashim, Fahima

doi:10.1016/s0378-5173(96)04862-4

Cited by 46 publications

(20 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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...…”

Section: Enhancement Of Drug Absorption By Hydrophilic Cydsmentioning

confidence: 99%

See 1 more Smart Citation

Design and Evaluation of Cyclodextrin-Based Drug Formulation

2004

Self Cite

View full text Add to dashboard Cite

Section: Enhancement Of Drug Absorption By Hydrophilic Cydsmentioning

confidence: 99%

“…Combinations of CyDs with pharmaceutical excipients [139][140][141] or with different kind of CyDs 142,143) were successfully applied to obtain a prolonged release of water-soluble drugs. The gel forming property of HP-b-CyD is useful to design the prolonged release of metoprorol.…”

Section: )mentioning

confidence: 99%

Design and Evaluation of Cyclodextrin-Based Drug Formulation

2004

Self Cite

View full text Add to dashboard Cite

“…3,4) In the pharmaceutical field this complexation phenomenon has been extensively applied to enhance the solubility, dissolution rate, and bioavailability of sparingly soluble drugs in gastrointestinal fluids. [5][6][7][8][9][10] Because of the increasing interest in CDs and their inherent usefulness, several studies have been conducted to clarify the mechanism of complexation.…”

mentioning

confidence: 99%

Molecular Modelling and 1H-NMR: Ultimate Tools for the Investigation of Tolbutamide: .BETA.-Cyclodextrin and Tolbutamide: Hydroxypropyl-.BETA.-Cyclodextrin Complexes.

et al. 2001

View full text Add to dashboard Cite

Cyclodextrins (CDs) are cyclic oligosaccharides composed of ␣-1,4-linked D-glucopyranose units. The most common of these ring-shaped molecules are the a-, b-, and g-CDs formed by six, seven, and eight glucose units, respectively. 1)CDs are toroidal molecules with a truncated cone structure where the secondary hydroxyl groups are located on the wider side of the ring, while the primary hydroxyl groups are positioned on the opposite, narrower side of the torus. The -CH groups carrying the H-1, H-2, and H-4 protons are located on the exterior of the molecule and the hydroxyl groups are oriented to the cone exterior, which makes the external faces of CDs decidedly hydrophilic. The interior of the torus, which offers an environment of much lower polarity than that present in water, is lined by two rings of -CH groups (H-3 and H-5) and by a ring of glycosidic "ether oxygens" (O-4), with H-6 located near the cavity.2) A great variety of "guest" molecules of suitable size and shape may be entirely or partially included in this hydrophobic cavity, resulting in a stable association without formation of covalent bonds. The complexation driving forces have been attributed to hydrophobic interactions, van der Waals-London dispersion forces, and hydrogen bonds. 3,4) In the pharmaceutical field this complexation phenomenon has been extensively applied to enhance the solubility, dissolution rate, and bioavailability of sparingly soluble drugs in gastrointestinal fluids.5-10) Because of the increasing interest in CDs and their inherent usefulness, several studies have been conducted to clarify the mechanism of complexation.In previous studies, the ability of b-CD and hydroxypropyl-b-cyclodextrin (HP-b-CD) to form inclusion complexes with tolbutamide (TBM), in order to increase its solubility, dissolution rate, 11) and oral bioavailability 12) was evaluated. Important information on the solid-phase structure of these complexes may be obtained via X-ray analysis when a suitable crystal of the product is available. However, X-ray diffractograms of the lyophilized TBM:CD complexes previously reported 11) have demonstrated the complete amorphousness of the product obtained, making it impossible to gain more detailed information from them. Although solubility studies indicated the existence of complexation between TBM and b-CD or HP-b-CD in solution, 11) the exact mechanism of complexation could not be deduced.The use of computer-aided molecular modelling and 1 H-NMR studies has proved to hold promise for such purposes, especially for systems or molecules of biological interest which "act" in aqueous medium. These techniques have been used as important tools for investigating the conformation of the most favored complexes and to obtain a better knowledge of the geometry of the system and the topology of the interactions between guest and CDs. [13][14][15][16][17] Therefore in the present study we coupled these techniques, which allowed us to compare and to integrate the theoretical findings obtained in a vacuum (molecular modelling) ...

show abstract

“…However, highest solubility was observed in water because of its salt form physical state. Solubilisation of poorly soluble drugs complexed with cyclodextrin, because of a rise in dissolution kinetics, is often mentioned as the reason for improved drug bioavailability when complexed with cyclodextrins and used for dosing [20]. Because pH varies throughout the gastrointestinal tract, pH-dependent solubility studies would benefit us greatly in assessing the oral bioavailability of NM β-CD complexes.…”

Section: Discussionmentioning

confidence: 99%