Thermosensitive and mucoadhesive in situ gel based on poloxamer as new carrier for rectal administration of nimesulide

Yuan, Yuan; Cui, Ying; Zhang, Li; Zhu, Huiping; Guo, Yi Sha; Zhong, Bo; Hu, Xia; Zhang, Ling; Wang, Xiao Hui; Chen, Li

doi:10.1016/j.ijpharm.2012.03.054

Cited by 116 publications

(64 citation statements)

References 34 publications

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“…16,17 Nevertheless, both rectal formulations exhibited a high absolute bioavailability of more than 28%, which could be attributed to a combination of various factors including excellent appreciable gel strength, high mucoadhesive force, and nanosized spherical particles that would facilitate the internalization. 13,14 This bioavailability is nearly 10-fold higher than that of the orally administered DCT, as we reported previously. 29 In the same study, we reported a 17% increase in bioavailability of the drug by DCT-loaded self-nanoemulsifying drug delivery systems (oral), which was the highest reported value until this point in time.…”

supporting

confidence: 70%

“…[1][2][3] However, critical drawbacks, including low aqueous solubility (5 µg/mL, highly lipophilic nature) and poor oral bioavailability (~5%, high first pass metabolism and p-glycoprotein efflux transporter/Rectal administration of the drug in a suitable dosage form remains a viable alternative to oral and intravenous (IV) administration in order to effectively counter the drawbacks and increase the therapeutic profile of DCT. 12,13 We recently reported enhanced bioavailability and anti-tumor potential of DCT by incorporation of thermosensitive and bioadhesive nanomicelles. Owing to appreciable bioadhesive interaction with rectal mucosa, the liquid suppository substantially increased the therapeutic concentration of the drug in the blood circulation and remarkable tumor regression was observed with no overt signs of drug or carrier related toxicity.…”

Section: Introductionmentioning

confidence: 99%

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The influence of bile salt on the chemotherapeutic response of docetaxel-loaded thermosensitive nanomicelles

Kim¹,

Ramasamy²,

Choi³

et al. 2014

IJN

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The primary aim of this work was to investigate the potential of bile salt, sodium taurocholate (NaTC), in improving the bioavailability and anti-tumor efficacy of docetaxel (DCT) upon rectal administration. Poloxamer-based nanomicelles with thermosensitive and mucoadhesive properties were prepared using the cold method. The optimized nanomicellar formulation was evaluated in terms of physicochemical and viscoelastic parameters. Nanomicelles containing bile salt maintained sufficient gelation strength (234×10 2 mPa·s) and mucoadhesive force (17.3×10 2 dyne/cm 2 ) to be retained in the upper part of the rectum. They significantly enhanced the DCT internalization across the rectal mucosa and showed a high plasma level during the first 4 hours of the study period, compared to nanomicelles with no bile salt. As a result, a slightly higher rectal bioavailability of ~33% was observed in nanomicelles containing bile salt, compared to ~28% from the latter system. The higher pharmacokinetic parameters for rectally administered DCT/P407/P188/Tween 80/NaTC (0.25%/11%/15%/10%/0.1% by weight, respectively) resulted in significant anti-tumor efficacy. However, the tumor regression rate for the NaTC group was not statistically different from that for nanomicelles without NaTC. Therefore, overall results suggest that thermosensitive nanomicelles could be a potential dosage form for improvement of the bioavailability and chemotherapeutic profile of DCT.

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supporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

The influence of bile salt on the chemotherapeutic response of docetaxel-loaded thermosensitive nanomicelles

Kim¹,

Ramasamy²,

Choi³

et al. 2014

IJN

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“…This drug presents a very low aqueous solubility (0.01 mg/mL), an octanol-water partition coefficient (logP) of 2.60 and low bioavailability, therefore, it has been classified as Class II drug according to Biopharmaceutics Classification System (BCS) (6,7). Poor bioavailability of this drug may leads to local toxicity at the site of aggregation and hinders reaching desired therapeutic effects (7).…”

Section: Figurementioning

confidence: 99%

“…Poor bioavailability of this drug may leads to local toxicity at the site of aggregation and hinders reaching desired therapeutic effects (7). Taking into consideration the physicochemical properties and poor bioavailability of nimesulide, it can be a good candidate for transdermal drug delivery as an alternative to oral route of its delivery.…”

Section: Figurementioning

confidence: 99%

Applying response surface methodology to optimize nimesulide permeation from topical formulation

Shahzad¹,

Afreen²,

Shah³

et al. 2012

Pharmaceutical Development and Technology

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Nimesulide is a non-steroidal anti-inflammatory drug that acts through selective inhibition of COX-2 enzyme. Poor bioavailability of this drug may leads to local toxicity at the site of aggregation and hinders reaching desired therapeutic effects. This study aimed at formulating and optimizing topically applied lotions of nimesulide using an experimental design approach, namely response surface methodology. The formulated lotions were evaluated for pH, viscosity, spreadability, homogeneity and in vitro permeation studies through rabbit skin using Franz diffusion cells. Data were fitted to linear, quadratic and cubic models and best fit model was selected to investigate the influence of permeation enhancers, namely propylene glycol and polyethylene glycol on percutaneous absorption of nimesulide from lotion formulations. The best fit quadratic model explained that the enhancer combination at equal levels significantly increased the flux and permeability coefficient. The model was validated by comparing the permeation profile of optimized formulations' predicted and experimental response values, thus, endorsing the prognostic ability of response surface methodology.

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“…The advantages of dialysis over other methods are in the ease of sampling and replacement of receptor media due to the physical separation of the formulation (by semipermeable dialysis membrane) from the receptor media. However, it is important to emphasize that non-critical interpretation of the obtained results can lead to flawed conclusions about the kinetics of drug release from the colloidal carriers [40,41] and other formulation types [42][43][44][45][46]. The presence of the drug in the receptor medium is the result of drug release from the carrier to the continuous phase in the donor compartment and diffusion of the drug through the membrane from the donor to the receptor compartment.…”

Section: Membrane Diffusion Methodsmentioning

confidence: 99%

In vitro dissolution/release methods for mucosal delivery systems

et al. 2017

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Thermosensitive and mucoadhesive in situ gel based on poloxamer as new carrier for rectal administration of nimesulide

Cited by 116 publications

References 34 publications

The influence of bile salt on the chemotherapeutic response of docetaxel-loaded thermosensitive nanomicelles

The influence of bile salt on the chemotherapeutic response of docetaxel-loaded thermosensitive nanomicelles

Applying response surface methodology to optimize nimesulide permeation from topical formulation

In vitro dissolution/release methods for mucosal delivery systems

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