Antibiotic Suppositories

Motohiro, T; Aramaki, M; Oda, Keiko; Kawakami, Akira; Tanaka, Kōichi; Koga, T; Shimada, Yasushi; Tomita, S; Sakata, Y; Fujimoto, T; Nishiyama, Tohru; Kuda, N; Ishimoto, K; Tominaga, Kaoru; Yamashita, Fumio

doi:10.1111/j.1442-200x.1986.tb00758.x

Cited by 5 publications

(10 citation statements)

References 2 publications

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“…Suppositories of ceftizoxime formulated with C 10 (3-5%, 15-25mg) had a Tmax of 30 min and the Cmax was 10-12µg/ml, although the extent of enhancement was not examined because all of the formulations contained C 10 [216]. Ceftizoxime suppositories containing C 10 (3%, 15mg) were also assessed in pediatric patients, where the Tmax was also 30 min and the Cmax was 8.9µg/ml [216].…”

Section: [23] Preclinical Safety Data For C 10mentioning

confidence: 99%

“…Ceftizoxime suppositories containing C 10 (3%, 15mg) were also assessed in pediatric patients, where the Tmax was also 30 min and the Cmax was 8.9µg/ml [216]. Rectal antibiotic suppositories containing both ampicillin, Witepsol H5 and C 10 (2% w/w) or ceftizoxime with 3% w/w C 10 were licensed in pediatric patients in Japan in the mid-1980s (Kyoto Pharma Industries and Sumitomo Pharma Co, Japan).…”

Section: [23] Preclinical Safety Data For C 10mentioning

confidence: 99%

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Safety and efficacy of sodium caprate in promoting oral drug absorption: from in vitro to the clinic

Maher

Leonard²,

Jacobsen

et al. 2009

Advanced Drug Delivery Reviews

201

176

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A major challenge in oral drug delivery is the development of novel dosage forms to promote absorption of poorly permeable Class III drugs across the intestinal epithelium.To date, no absorption promoter has been approved in a formulation specifically designed for oral delivery of Class III molecules. Promoters that are designated safe for human consumption have been licensed for use in a recently approved buccal insulin spray delivery system and also for many years as part of an ampicillin rectal suppository.Unlike buccal and rectal delivery, oral formulations containing absorption promoters have the additional technical hurdle whereby the promoter and payload must be coreleased in high concentrations at the small intestinal epithelium in order to generate significant but rapidly reversible increases in permeability. The most advanced promoter in the clinic is the medium chain fatty acid (MCFA), sodium caprate (C 10 ) , a compound already approved as a direct food additive. We discuss how it has evolved to a matrix tablet format suitable for administration to humans under the headings of mechanism of action at the cellular and tissue level and in vitro and in vivo efficacy and safety studies.In specific clinical examples, we review how C 10 -based formulations are being tested for oral delivery of bisphosphonates using Gastro Intestinal Permeation Enhancement Technology, GIPET® (Merrion Pharmaceuticals, Ireland) and in a related solid dose format for anti-sense oligonucleotides (ISIS Pharmaceuticals, USA).Keywords: Oral drug delivery, Sodium caprate (C 10 ), absorption promoter, drug delivery platforms, clinical trials, oral formulation, drug delivery systems.3 TJs form a barrier to the uncontrolled absorption of noxious luminal antigens (gate function), and maintain epithelial polarity (fence function) [8,9]. In general, the TJ consists of a restrictive pathway (shunt) with a sharp molecular size cut off, and a second unrestrictive pathway (small pore) that permits paracellular permeation of molecules of radii <4.0 Å [10,11]. Depending on the intestinal region, TJ pore sizes range from 6-22Å, sufficient to permit mannitol (6.7 Å) and EDTA (10.8 Å) to permeate to an extent, whereas the passage of inulin (30-40 Å) and fluorescent-dextran 4kDa (FD-4, 26 Å) is essentially impeded [12][13][14][15][16].A number of approaches have been used to promote oral delivery of Class III drugs ( Alternatively, the use of nanoparticles comprising biocompatible polymers (e.g. chitosan,polylactide-co-glycolide, starch and glucans) can protect cargoes from GI proteases, increase GI retention and promote absorption across gut associated lymphoid tissue (GALT) and to a lesser extent, enterocytes [45][46][47]. Most data on nanoparticle absorption from rodent models suggest that M cells in the follicle-associated epithelium of Peyer's patches (PP) are the favored site of uptake for particles of diameter 500nm-1000nm [45].Given the paucity of M cells in the GI tract of adults, the relevance of PP uptake remains controversial ...

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Section: [23] Preclinical Safety Data For C 10mentioning

confidence: 99%

Section: [23] Preclinical Safety Data For C 10mentioning

confidence: 99%

Safety and efficacy of sodium caprate in promoting oral drug absorption: from in vitro to the clinic

Maher

Leonard²,

Jacobsen

et al. 2009

Advanced Drug Delivery Reviews

201

176

View full text Add to dashboard Cite

show abstract

“…but the practical use of them has been very limited 12,13) because of the potential local toxicity to gastrointestinal mucosa. 2,4) In order to develop the safe formulation that can improve the absorption of drugs categorized into BCS Class IV such as rebamipide, [14][15][16][17][18][19][20] we have compared the suppository that contains sodium laurate (C12) as an absorption enhancer and taurine (Tau) as a cytoprotective adjuvant with the commercial suppository that contains sodium caprate (C10) as an absorption enhancer.…”

mentioning

confidence: 99%

“…As a technique of the improvement of solubility, micronization, amorphousization and the addition of surfactant such as Tween 80 and Captisol ® are well known. As for the improvement of permeability, the use of absorption enhancers is well known, [1][2][3][4][5][6][7][8][9][10][11] but the practical use of them has been very limited 12,13) because of the potential local toxicity to gastrointestinal mucosa. 2,4) In order to develop the safe formulation that can improve the absorption of drugs categorized into BCS Class IV such as rebamipide, [14][15][16][17][18][19][20] we have compared the suppository that contains sodium laurate (C12) as an absorption enhancer and taurine (Tau) as a cytoprotective adjuvant with the commercial suppository that contains sodium caprate (C10) as an absorption enhancer.…”

mentioning

confidence: 99%

Optimization of Suppository Preparation Containing Sodium Laurate and Taurine That Can Safely Improve Rectal Absorption of Rebamipide

Miyake

Minami

Oka

et al. 2006

Biological & Pharmaceutical Bulletin

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Drug absorption from gastrointestinal tract is mainly influenced by solubility and permeability. As a technique of the improvement of solubility, micronization, amorphousization and the addition of surfactant such as Tween 80 and Captisol ® are well known. As for the improvement of permeability, the use of absorption enhancers is well known, [1][2][3][4][5][6][7][8][9][10][11] but the practical use of them has been very limited 12,13) because of the potential local toxicity to gastrointestinal mucosa. 2,4) In order to develop the safe formulation that can improve the absorption of drugs categorized into BCS Class IV such as rebamipide, [14][15][16][17][18][19][20] we have compared the suppository that contains sodium laurate (C12) as an absorption enhancer and taurine (Tau) as a cytoprotective adjuvant with the commercial suppository that contains sodium caprate (C10) as an absorption enhancer. [21][22][23] We have found that C12, a mediumchain fatty acid salt, is a promising absorption enhancer and better than C10 in terms of the absorption improving ability, 24) and that Tau has the most effective cytoprotective activity among amino acids examined. 25) Cytoprotective action by Tau has been evidenced by both biochemical [25][26][27] and histopathological 25) approaches and it has been partially related with the suppression of intracellular Ca 2ϩ level elevated by C12 and the inhibition of histamine release induced by C12. L-Glutamine (L-Gln) also has the cytoprotective action, which is partially attributed to the induction of heat-shock protein 70 (HSP70), 27) a factor protecting cells from injuries caused by several kinds of stresses. 28,29) Furthermore, basic studies for suppository were performed in rats by administering the fatty or water-soluble base preparation containing rebamipide, C12 and Tau or L-Gln into rats. The combinatorial use of them, especially for the fatty base (FB) suppository, has been evidenced to be promising in terms of both improvement of bioavailability and safety to rat rectal mucosa.30) However, the success in the scaling-up study must be necessary for developing the formulation available for human use.In the present study, we have, therefore, performed the scaling-up study of animal and formulation size using FB suppositories of rebamipide and have compared our new preparations with the commercial suppository containing C10 (15 or 25 mg) in terms of the drug dissolution, absorption improvement and safety to the rectal mucosa of rabbits. MATERIALS AND METHODSMaterials C12, C10 and Tau were purchased from Tokyo Chemical Industry Co. (Tokyo, Japan). Hydroxypropyl methylcellulose (HPMC) TC-5E (HPMC 2910) was purchased from Shin-etsu Kagaku Co. (Tokyo). Witepsol ® H-15 was obtained from Mitsuba Boueki Co. Ltd. (Tokyo). Rebamipide and OPC-12853, an internal standard, were obtained from Otsuka Pharmaceutical Co. Ltd. (Tokushima, Japan). All other reagents were analytical grade commercial products.Animals Male Japan-White rabbits (Kitayama Labes, Ina, Japan), maintained at 23°C and 60% hum...

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“…Although many compounds have been reported to have absorption enhancing ability, medium-chain fatty acids and medium-chain glycerides are thought to be relatively safe because they are used as nutritional dietary supplements. Currently, only sodium caprete (C10) has been used and marketed as an absorption enhancer in ampicillin suppository marketed in Japan, Denmark, and Sweden, and in ceftizoxime suppository in Japan [26,27] . Furthermore, Miyake et al demonstrated that C12 was a more effective and safer adjuvant than C10 at the same concentration.…”

Section: Discussionmentioning

confidence: 99%

Permeabilities of rebamipide via rat intestinal membranes and its colon specific delivery using chitosan capsule as a carrier

Huang¹,

Li²,

Luo³

et al. 2008

WJG

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AIM:To investigate the permeability characteristics of rebamipide across intestinal mucosa, and examine the effects of some absorption enhancers on the permeability across the colonic tissue. Another purpose is to demonstrate the colon-specific delivery of rebamipide with or without absorption enhancers using chitosan capsule as a carrier. METHODS: The permeability of rebamipide was evaluated using an in vitro diffusion chamber system, and the effects of some absorption enhancers on the permeability via colon were further investigated. The release of rebamipide from chitosan or gelatin capsule was studied by Japan Pharmacopoeia rotating basket method. The colonic and plasma concentrations were analyzed by high performance liquid chromatography (HPLC) to evaluate colon-targeting action after oral administration of various dosage forms, and rebamipide with absorption enhancers in chitosan dosage forms. RESULTS: The permeability of rebamipide across the jejunal or ileal membranes was higher than the colonic membranes. Both sodium laurate (C12) and labrasol significantly increased permeability across the colon membranes. On the other hand, the release of rebamipide from chitosan capsule was less than 10% totally within 6 h. The area under concentration-time profile of drug in the colon mucosa using chitosan capsules (AUCLI, 1 6011.2 ng · h/g) was 2.5 times and 4.4 times greater than using gelatin capsules and CMC suspension, respectively. Meanwhile, the area under concentration-time profile of drug in the plasma (AUCPL) was 1016.0 ng · h/mL for chitosan capsule, 1887.9 ng · h/mL for CMC suspension p and 2163.5 ng·h/mL for gelatin capsule. Overall, both AUCLI and AUCPL were increased when C12 was coadministrated, but the increase of AUCLI was much greater; the drug delivery index (DDI) was more than 1 compared with simple chitosan capsule group. CONCLUSION: There was a regional difference in the permeability of Rebamipide across the jejunum, ileum and the colon, and passive diffusion seems to be one of the major transport mechanisms of rebamipide. Absorption enhancers can increase the permeability of rebamipide across the colon tissue significantly. In addition, chitosan capsule may be a useful carrier to deliver rebamipide to the colon specifically and the coadministration of C12 with rebamipide may also be very useful in local treatment.© 2008 The WJG Press. All rights reserved.Key words: Rebamipide; Diffusion chamber; Permeability; Sodium laurate; Chitosan capsule; Colon-specific delivery Peer reviewer: Atsushi Nakajima, Professor, Yokohama City University Hospital, 3-9 Fukuura Kanazawaku, Yokohama 236, Japan Huang BB, Li GF, Luo JH, Duan L, Nobuaki K, Akira Y. Permeabilities of rebamipide via the rat intestinal membranes and its colon specific delivery using chitosan capsule as a carrier.

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Antibiotic Suppositories

Cited by 5 publications

References 2 publications

Safety and efficacy of sodium caprate in promoting oral drug absorption: from in vitro to the clinic

Safety and efficacy of sodium caprate in promoting oral drug absorption: from in vitro to the clinic

Optimization of Suppository Preparation Containing Sodium Laurate and Taurine That Can Safely Improve Rectal Absorption of Rebamipide

Permeabilities of rebamipide via rat intestinal membranes and its colon specific delivery using chitosan capsule as a carrier

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