Enhancement of Bioavailability of Griseofulvin by Its Complexation with β-Cyclodextrin

Dhanaraju, Magharla Dasaratha; Kumaran, K. Senthil; Baskaran, T.; Moorthy, M. Sree Rama

doi:10.3109/03639049809085663

Cited by 67 publications

(19 citation statements)

References 5 publications

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“…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

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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) ...

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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

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“…In the pharmaceutical field this phenomenon has been extensively applied to enhance the solubility, dissolution rate and bioavailability of slightly soluble drugs in gas-trointestinal fluids (Vila-Jato et al, 1988;Soliman et al, 1997;Ventura et al, 1997;Dhanaraju et al, 1998;O 8 zdemir and Ordu, 1998;Mura et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Oral bioavailability and hypoglycaemic activity of tolbutamide/cyclodextrin inclusion complexes

Veiga

Fernandes

Teixeira

2000

International Journal of Pharmaceutics

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The purpose of the present study was to evaluate the enhancement of tolbutamide (TBM) oral bioavailability and hypoglycaemic activity through complexation with b-cyclodextrin (b-CD) and hydroxypropyl-b-cyclodextrin (HP-b-CD). TBM and its freeze-dried inclusion complexes were administered to rabbits (New zealand breed; n =6), in a dose of 20 mg/kg. TMB plasma levels were measured by HPLC and glucose levels were analysed according to Trinder (Trinder, P., 1969. Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann. Clin. Biochem. 6, 24-28). The pure drug attained a maximum of plasma concentration (C max ) of 18.5893.27 mg/ml at 8.5 h (T max ), whereas with inclusion complexes, C max increased about two times and appeared at ca. 4 h. AUC 0-24 of complexes was about 1.6 times as much as that of the pure drug. Thus, the extent of oral absorption of TBM from inclusion complexes was significantly greater and faster when compared with drug alone. In addition, without cyclodextrins the maximum hypoglycaemic effect (CVG max ) of TBM (34.1%) was observed at 5.6 h (Tg max ). CVG max of TBM/b-CD and TBM/HP-b-CD inclusion complexes were 34.1% (at 6.5 h) and 37.7% (at 5.1 h), respectively. AAC 0-24 of inclusion complexes was 1.4 times larger than that of pure drug. Hence, the oral administration of complexed TBM not only improved the drug absorption, but also the TBM hypoglycaemic activity.

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“…[13]. Previous studies showed an increase in drug dissolution by complexation with cyclodextrin corresponded with increase oral bioavailability of griseofulvin and spironolactone; but not of naproxen and tolbutamide [14] [15] [16] [17]. In one another study it was reported that release of diclofenac sodium from matrix was inhibited by polymer chitosan via formation of ionic complex between diclofenac sodium and cationic polymer [18].…”

Section: Introductionmentioning

confidence: 99%

Incompatibility of Paracetamol with Pediatric Suspensions Containing Amoxicillin, Azithromycin and Cefuroxime Axetil

Maswadeh¹

2017

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The main objective of this work was to use the Differential Scanning Calorimetry (DSC) and FTIR spectroscopy to study the possible drug-drug or drug-excipient (s) interaction in case of concomitant oral administration of paracetamol with the most common used antibiotics for children. Amoxicillin, azithromycin, cefuroxime axetil and their commercially available suspensions, Amoxil ® , Azithromax ® and Zinnat ® were used. DSC curves for paracetamol, pure antibiotics, commercially available antibiotics and all binary mixtures used in this study showed drug-drug or drug-excipient (s) physical interaction and indicated a possible chemical interaction. To confirm chemical drug-drug or drug-excipient (s) interaction additional ATR-IR spectra for all samples used in this study were obtained. Results obtained from ATR-IR spectra showed drug-excipient (s) interaction in Zinnat ® , Azithromax ® and binary mixture Azithromax ® -paracetamol, while chemical drug-drug interaction was not observed. From this study it can be concluded that the concomitant oral administration of paracetamol with commercially available antibiotics used in this study is not recommended and duration of two hours between the oral administrations of these drugs is strongly recommended to avoid drug-drug or drug-excipient (s) interaction.

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Enhancement of Bioavailability of Griseofulvin by Its Complexation with β-Cyclodextrin

Cited by 67 publications

References 5 publications

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

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

Oral bioavailability and hypoglycaemic activity of tolbutamide/cyclodextrin inclusion complexes

Incompatibility of Paracetamol with Pediatric Suspensions Containing Amoxicillin, Azithromycin and Cefuroxime Axetil

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