(C) Means to enhance penetration

Swenson, Eugene S.; Curatolo, William

doi:10.1016/0169-409x(92)90015-i

Cited by 199 publications

(38 citation statements)

References 169 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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.…”

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

View full text Add to dashboard Cite

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...

show abstract

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

View full text Add to dashboard Cite

show abstract

“…One of the proposed mechanisms was based on the changes of the membrane structure and fluidity by the enhancers, resulting in significant permeability changes. 15) This surfactant-induced change in intestinal permeability is correlated with acute epithelial damage, as evidenced by release of cellular components from damaged intestinal epithelium which is attributable to the surfactants. 16,17) On the other hand, the toxicity of Labrasol and Gelucire 44/14 is very low, with Labrasol especially being quite safe because of its LD 50 value of 22 g/kg in rats.…”

Section: Discussionmentioning

confidence: 99%

Studies on the Intestinal Absorption of Low Molecular Weight Heparin Using Saturated Fatty Acids and Their Derivatives as an Absorption Enhancer in Rats

Mori

Matsuura

Prasad

et al. 2004

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

“…The main rate-limiting barrier for drug absorption/diffusion is the single layer of intestinal epithelial cells. High content of surfactants in SMEDDS could enhance the permeability by disturbing the cell membrane (21). The surfactant with the best enhancement ability requires both hydrophilic and lipophilic domains, such as Tween 80.…”

Section: Bioavailabilitymentioning

confidence: 99%

Development of a self-microemulsifying drug delivery system of domperidone: In vitro and in vivo characterization

et al. 2013

View full text Add to dashboard Cite

Domperidone, a dopamine D2 receptor antagonist, is used as a prokinetic and antiemetic agent for the treatment of gastroparesis, nausea and vomiting (1). It is a poor water soluble drug and is rapidly absorbed from the gastrointestinal (GI) tract. Its oral bioavailability was reported in a range of 13-17 % (2). Poor aqueous solubility and extensive first pass metabolism are the reasons for its low oral bioavailability. The approaches used to improve oral bioavailability were: incorporation of the active lipophilic component The main objective of this work was to prepare a self-micro emulsifying drug delivery system (SMEDDS) for enhancement of oral bioavailability of domperidone, a poorly water soluble drug. The solubility of the drug was determined in various vehicles. A pseudo ternary phase diagram was constructed to identify the self-micro emulsification region. The in vitro self-micro emulsification properties and droplet size analysis of SMEDDS were studied following their addition to water under mild agitation. Further, the resultant formulations were investigated for clarity, phase separation, globule size, effect of pH and dilutions (1:100, 1:500, 1:1000) and freeze-thaw stability. The optimized formulation, SMEDDS-B used for in vitro dissolution and bioavailability assessment, contained oil (Labrafac CC, 25 %, m/m), surfactant (Tween 80, 55 %, m/m), and co-surfactant (Transcutol ® , 20 %, m/m). The preliminary oral bioavailability of domperidone from SMEDDS was 1.92-fold higher compared to that of domperidone suspension in rats.The AUC 0-24 and c max values were 3.38 ± 0.81 µg h mL -1 and 0.44 ± 0.03 µg mL -1 for SMEDDS-B formulation in comparison with 1.74 ± 0.18 µg h mL -1 and 0.24 ± 0.02 µg mL -1 for domperidone suspension, suggesting a significant increase (p < 0.05) in oral bioavailability of domperidone from SMEDDSS.

show abstract

(C) Means to enhance penetration

Cited by 199 publications

References 169 publications

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

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

Studies on the Intestinal Absorption of Low Molecular Weight Heparin Using Saturated Fatty Acids and Their Derivatives as an Absorption Enhancer in Rats

Development of a self-microemulsifying drug delivery system of domperidone: In vitro and in vivo characterization

Contact Info

Product

Resources

About