Improvement of Dissolution and Bioavailability for Mebendazole, an Agent for Human Echinococcosis, by Preparing Solid Dispersion with Polyethylene Glycol.

Chiba, Yukihiro; Kohri, Naonori; Iseki, Ken; Miyazaki, Katsumi

doi:10.1248/cpb.39.2158

Cited by 40 publications

(15 citation statements)

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“…The dissolution rate of poorly water soluble drugs often becomes a rate-limiting step in their absorption from the gastrointestinal tract (6,7). Various solubilization methods have been used to increase the drug solubility and dissolution properties, including the use of surfactants, water-soluble carriers, polymeric conjugates, and solid dispersions (8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Bioavailability of Itraconazole in Rats and Rabbits After Administration of Tablets Containing Solid Dispersion Particles

Yoo¹,

Lee

Kang³

et al. 2000

Drug Development and Industrial Pharmacy

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A tablet dosage form containing solid dispersions of itraconazole (Asd tablets) was prepared by using the spray-drying and wet granulation methods. The dissolution rate of itraconazole from Asd tablets was fast, with more than 90% released within 10 min, compared to less than 20% for a marketed product, Sporanox capsules. The oral absorption of itraconazole from Asd tablets was determined in rats and rabbits and was compared with that for Sporanox capsules. In the rat, there was no difference between the Asd tablets and Sporanox capsules in the mean area under the curve (AUC) (3089.5 +/- 4332.8 ng.hr/ml and 3653.9 +/- 2348.9 ng.hr/ml, respectively) and Cmax (295.0 +/- 344.5 and 390.5 +/- 169.4 ng/ml, respectively). Also, in the rabbit, no difference was found between the two products in the mean AUC (AUMC; 19357.9 +/- 5117.5 ng.hr/ml and 23382.2 +/- 6236.5 ng.hr/ml, respectively) and Cmax (766.4 +/- 276.5 and 1127.5 +/- 577.9 ng/ml, respectively). Despite the rapid in vitro release characteristics of itraconazole from the Asd tablets, the in vivo absorption of itraconazole was comparable to that of Sporanox capsules, with no difference in Tmax in both animal species. Serum levels of the major active metabolite hydroxyitraconazole were also measured. Itraconazole was rapidly converted to hydroxyitraconazole in both rats and rabbits, but there were species-specific differences in their pharmacokinetics. It is concluded that, in addition to drug solubility and dissolution characteristics, other formulation factors such as the physical state of the drug and the granulation process, may also need to be considered in the prediction of the in vivo absorption of itraconazole based on in vitro data.

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Section: Introductionmentioning

confidence: 99%

Bioavailability of Itraconazole in Rats and Rabbits After Administration of Tablets Containing Solid Dispersion Particles

Yoo¹,

Lee

Kang³

et al. 2000

Drug Development and Industrial Pharmacy

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“…19,25,26) The dissolution rate of poorly water-soluble drugs often becomes a rate-limiting step in their absorption from the GI tract. 27,28) Various solubilization methods have been used to increase the drug solubility and dissolution properties, including the use of surfactants, water-soluble carriers, polymeric conjugates, particle size reduction, suitable polymorph, anhydrous or organic solvate forms and solid dispersions. [29][30][31][32][33] However, hydrophobic drugs can be dissolved in SEDDS allowing them to be encapsulated as unit dosage form for peroral administration.…”

Section: -6)mentioning

confidence: 99%

Improving the High Variable Bioavailability of Griseofulvin by SEDDS

2007

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Self-emulsifying drug delivery systems (SEDDS) are mixtures of oils and surfactants, ideally isotropic, and sometimes containing cosolvents, which emulsify spontaneously to produce fine oil-in-water emulsions when introduced into aqueous phase under gentle agitation.1) Recently, SEDDS have been formulated using medium chain triglyceride oils and nonionic surfactants, the latter being less toxic. Upon peroral administration, these systems form fine emulsions (or microemulsions) in gastro-intestinal tract (GIT) with mild agitation provided by gastric mobility.2,3) Potential advantages of these systems include enhanced oral bioavailability enabling reduction in dose, more consistent temporal profiles of drug absorption, selective targeting of drug(s) toward specific absorption window in GIT, and protection of drug(s) from the hostile environment in gut. [4][5][6] The process of self-emulsification proceeds through formation of liquid crystals (LC) and gel phases, the properties of which significantly affect the formation of droplets and interface available for partitioning of drug.5-9) Many workers claim various rational applications of SEDDS for delivering and targeting lipophilic drugs (e.g., WIN 54954, 1) N-4472, 10) idebenone, 11) coenzyme Q10, 12) vitamin E, 13) halofantrine, 14) and cyclosporin A. 15) However, very few reports are available of SEDDS of water insoluble or poorly soluble hydrophobic compounds. Therefore the concept of using griseofulvin in SEDDS was considered for the present study, where the drug is present in solution form.Griseofulvin is an antifungal agent first isolated from a Penicillium spp. in 1939. It is effective after oral ingestion and reaches the skin and hair. It is deposited primarily in keratin precursor cells. Ingestion with a heavy meal and reduction in particle size enhances the absorption of griseofulvin.16) Griseofulvin systematic (IUPAC) name is (2S,6ЈR)-7-chloro-2Ј,4,6-trimethoxy-6Ј-methyl-3H,4ЈH-spiro[1-benzofuran-2,1Ј-cyclohex[2]ene]-3,4Ј-dione (Fig. 1), and its formula is C 17 H 17 ClO 6 with molecular weight 352.766 g/mol. The compound is insoluble in water (8.64 mg/l). It has a logP/hydrophobicity 2.15 (partition system octanol/water), and its pK a /isoelectric point is not available.17) Griseofulvin inhibits fungal mitosis by disrupting the mitotic spindle through interaction with polymerized microtubules. 18)Griseofulvin is administered orally. Its microcrystalline and ultramicrocrystalline forms are available as tablets. The microcrystalline form also comes in a pediatric suspension form. The typical dose of microcrystalline form is 500-1000 mg/d. Ultramicrocrystalline form is administered at doses of 330-990 mg/d. 19) Since the bioavailability of poorly water-soluble drugs can be influenced by interactions with food or by the physicochemical conditions in the gastrointestinal (GI) tract, 20) oral preparation of griseofulvin is commonly prescribed to be administered according to a fixed dosing schedule. The oral bioavailability of griseofulvin is highly varia...

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“…Mebendazole (MBZ) is the only drug of choice in treatment of alveolar echinococcosis, which requires continuous treatment for at least 2 years and patient monitoring for 10 years (Garg 2014). However, it is not successful because of its poor solubility and bioavailability , and recurrence in certain cases of alveolar echinococcosis cause death of the patient (Chiba et al 1991). Th erefore, it is necessary to increase the drug ' s GI absorption (Garg et al 2 S. Chaudhary et al safety (Singh et al 2014a).…”

Section: Introductionmentioning

confidence: 99%

Enhancing the bioavailability of mebendazole by integrating the principles solid dispersion and nanocrystal techniques, for safe and effective management of human echinococcosis

Chaudhary

Garg

Rath

et al. 2015

Artificial Cells, Nanomedicine, and Biotechnology

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The method based on integrating the principles of solid dispersion and nanocrystal techniques was developed to prepare polymer crystals (PCs) of mebendazole (MBZ) and polyethylene glycol (PEG). Powder X-Ray diffraction (PXRD) of the PC crystals shows the required integrated crystalline and amorphous regions. The in vitro solubility studies showed a 32-fold increase in the solubility of the drug. Tests of dissolution of the PCs showed that the crystals have an enhanced dissolution rate in comparison to those in the MF. The results of the pharmacokinetic study showed a 2.12-fold increase in the bioavailability of the drug. Thus, the present study has proved the potential in enhancing solubility, dissolution, and bioavailability of the drug.

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Improvement of Dissolution and Bioavailability for Mebendazole, an Agent for Human Echinococcosis, by Preparing Solid Dispersion with Polyethylene Glycol.

Cited by 40 publications

References 0 publications

Bioavailability of Itraconazole in Rats and Rabbits After Administration of Tablets Containing Solid Dispersion Particles

Bioavailability of Itraconazole in Rats and Rabbits After Administration of Tablets Containing Solid Dispersion Particles

Improving the High Variable Bioavailability of Griseofulvin by SEDDS

Enhancing the bioavailability of mebendazole by integrating the principles solid dispersion and nanocrystal techniques, for safe and effective management of human echinococcosis

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