Development of nanocrystal formulation of meloxicam with improved dissolution and pharmacokinetic behaviors

Ochi, Mitsukazu; Kawachi, Takaki; Toita, Eri; Hashimoto, Issei; Yuminoki, Kayo; Onoue, Satomi; Hashimoto, Naofumi

doi:10.1016/j.ijpharm.2014.08.022

Cited by 56 publications

(28 citation statements)

References 29 publications

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“…Numerous techniques are now available that can enhance solubility of such compounds [3,4]. These include changing their physicochemical properties such as increasing the exposed surface area by reducing the particle size or using a form that possesses a less ordered crystal structure [5,6]. The solubility of amorphous form of drug was typically 2-4 times higher than that of the crystalline form [7].…”

Section: Introductionmentioning

confidence: 99%

Impact of pore characteristics of silica materials on loading capacity and release behavior of ibuprofen

Numpilai

Muenmee

Witoon

2016

Materials Science and Engineering: C

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Section: Introductionmentioning

confidence: 99%

Impact of pore characteristics of silica materials on loading capacity and release behavior of ibuprofen

Numpilai

Muenmee

Witoon

2016

Materials Science and Engineering: C

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“…In order to reach high bioavailability in vivo , the supersaturated state should be able to be maintained and precipitation hindered or delayed. Certain polymers, like PVP [ 76 , 77 ], methacrylate co-polymers [ 78 ], HPMC [ 79 ], and hydroxypropyl methylcellulose acetate succinate (HPMC-AS) [ 79 ] are known to maintain, at least partly, the supersaturation level. However, if the precipitation enhancer is forming micelles, sometimes the affinity of the drug can be higher to the micelles instead of permeation, which decreases the drug adsorption in vivo [ 80 ].…”

Section: Effect Of Stabilizers On Cell Layers and Drug Transportmentioning

confidence: 99%

“…However, if the precipitation enhancer is forming micelles, sometimes the affinity of the drug can be higher to the micelles instead of permeation, which decreases the drug adsorption in vivo [ 80 ]. Ochi et al formulated meloxicam nanocrystals with polymers helping to maintain the supersaturation as stabilizers [ 77 ]. The most efficient polymeric stabilizer was PVP; nanocrystalline meloxicam with PVP as a stabilizer reached an in vitro supersaturation number of 13.74, as compared to bulk meloxicam.…”

Section: Effect Of Stabilizers On Cell Layers and Drug Transportmentioning

confidence: 99%

Stabilizing Agents for Drug Nanocrystals: Effect on Bioavailability

2016

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Drug nanocrystals are a versatile option for drug delivery purposes, and while the number of poorly soluble drug materials is all the time increasing, more research in this area is performed. Drug nanocrystals have a simple structure—a solid drug core is surrounded by a layer of stabilizing agent. However, despite the considerably simple structure, the selection of an appropriate stabilizer for a certain drug can be challenging. Mostly, the stabilizer selection is based purely on the requirement of physical stability, e.g., maintaining the nanosized particle size as long as possible after the formation of drug nanocrystals. However, it is also worth taking into account that stabilizer can affect the bioavailability in the final formulation via interactions with cells and cell layers. In addition, formation of nanocrystals is only one process step, and for the final formulation, more excipients are often added to the composition. The role of the stabilizers in the final formulation can be more than only stabilizing the nanocrystal particle size. A good example is the stabilizer’s role as cryoprotectant during freeze drying. In this review, the stabilizing effect, role of stabilizers in final nanocrystalline formulations, challenges in reaching in vitro–in vivo correlation with nanocrystalline products, and stabilizers’ effect on higher bioavailability are discussed.

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“…A novel nanocrystal colloidal dispersion formulation of meloxicam (N1539; Recro Pharma, Inc., Malvern, PA, USA) has recently been developed for bolus intravenous (IV) administration, providing faster onset of analgesia than can be achieved with oral administration. 19 In a randomized, double-blind, placebo-controlled study in females who underwent abdominal hysterectomy, the IV nanocrystal formulation of meloxicam was effective in relieving moderate-to-severe postoperative pain. 20 All single doses of meloxicam IV evaluated (5 mg to 60 mg) resulted in significantly lower pain intensity (PI) scores and better global pain-control scores than placebo; doses >5 mg also achieved significantly better pain-relief scores than morphine (10 mg to 15 mg), and the use of rescue medication was lower in all meloxicam IV dose groups than in the morphine and placebo groups.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the safety and efficacy of an intravenous nanocrystal formulation of meloxicam in the management of moderate-to-severe pain after bunionectomy

Gottlieb¹,

Tunick²,

Mack³

et al. 2018

JPR

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ObjectiveThis randomized, double-blind, placebo-controlled study evaluated the safety and efficacy of an intravenous (IV) nanocrystal formulation of meloxicam in subjects with moderate-to-severe pain following a standardized unilateral bunionectomy.MethodsFifty-nine subjects aged 18–72 years were randomized to receive doses of either 30 mg (n=20) or 60 mg (n=20) meloxicam IV or placebo (n=19), administered once daily as bolus IV injections over 15–30 seconds (two or three doses). Safety, the primary objective, was assessed by physical examination, clinical laboratory tests, and the incidence of adverse events (AEs). Efficacy was evaluated by examining summed pain intensity differences over the first 48 hours (SPID48) using analysis of covariance models. Use of opioid rescue analgesic agents was evaluated.ResultsGenerally, AEs were mild-to-moderate in intensity, and their incidence was similar across the three treatment groups. No serious AEs were reported; there were no withdrawals due to AEs, including injection-related AEs. The estimated effect size for SPID48 versus placebo was 1.15 and 1.01 for meloxicam IV doses 30 mg and 60 mg, respectively (P≤0.01). Both doses produced significantly greater pain reductions versus placebo (P≤0.05) at all evaluated times/ intervals during the 48-hour period. The proportions of subjects with ≥30% and ≥50% overall reduction in pain from baseline after 6 and 24 hours were significantly higher with meloxicam IV 30 mg doses versus placebo, but not with meloxicam IV 60 mg doses. The time to first use of rescue medication was significantly longer versus placebo with meloxicam IV 60 mg (P<0.05), but not with meloxicam IV 30 mg doses.ConclusionMeloxicam IV was generally safe and well tolerated in subjects with moderate-to-severe post-bunionectomy pain. Once-daily administration of meloxicam IV 30 mg and 60 mg exhibited rapid onset of analgesia (as early as 15 minutes) with maintenance of analgesic effect for two consecutive 24-hour periods.

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Development of nanocrystal formulation of meloxicam with improved dissolution and pharmacokinetic behaviors

Cited by 56 publications

References 29 publications

Impact of pore characteristics of silica materials on loading capacity and release behavior of ibuprofen

Impact of pore characteristics of silica materials on loading capacity and release behavior of ibuprofen

Stabilizing Agents for Drug Nanocrystals: Effect on Bioavailability

Evaluation of the safety and efficacy of an intravenous nanocrystal formulation of meloxicam in the management of moderate-to-severe pain after bunionectomy

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