Pharmacokinetic Properties and Tolerability of Low-dose SoluMatrix Diclofenac

Desjardins, Paul J.; Olugemo, Kemi; Solorio, D.; Young, Clarence L.

doi:10.1016/j.clinthera.2014.10.018

Cited by 19 publications

(12 citation statements)

References 26 publications

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“…Without modification of the starting material, subsequent dissolution of the active ingredient may be variable or slow due to the presence of large or agglomerated particles [ 185 , 186 ]. SoluMatrix ® Fine Particle Technology™ is a proprietary process that produces drug particles that are 200–800 nm in diameter without altering the chemical properties of the active therapeutic ingredient [ 116 ]. The dry milling process increases drug particle surface area relative to mass, resulting in improved dissolution properties compared with diclofenac potassium immediate-release tablets, promoting rapid absorption [ 187 ].…”

Section: Solumatrix Diclofenac Acidmentioning

confidence: 99%

Advances in NSAID Development: Evolution of Diclofenac Products Using Pharmaceutical Technology

Altman¹,

Bosch

Brune

et al. 2015

Drugs

376

193

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Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) of the phenylacetic acid class with anti-inflammatory, analgesic, and antipyretic properties. Contrary to the action of many traditional NSAIDs, diclofenac inhibits cyclooxygenase (COX)-2 enzyme with greater potency than it does COX-1. Similar to other NSAIDs, diclofenac is associated with serious dose-dependent gastrointestinal, cardiovascular, and renal adverse effects. Since its introduction in 1973, a number of different diclofenac-containing drug products have been developed with the goal of improving efficacy, tolerability, and patient convenience. Delayed- and extended-release forms of diclofenac sodium were initially developed with the goal of improving the safety profile of diclofenac and providing convenient, once-daily dosing for the treatment of patients with chronic pain. New drug products consisting of diclofenac potassium salt were associated with faster absorption and rapid onset of pain relief. These include diclofenac potassium immediate-release tablets, diclofenac potassium liquid-filled soft gel capsules, and diclofenac potassium powder for oral solution. The advent of topical formulations of diclofenac enabled local treatment of pain and inflammation while minimizing systemic absorption of diclofenac. SoluMatrix diclofenac, consisting of submicron particles of diclofenac free acid and a proprietary combination of excipients, was developed to provide analgesic efficacy at reduced doses associated with lower systemic absorption. This review illustrates how pharmaceutical technology has been used to modify the pharmacokinetic properties of diclofenac, leading to the creation of novel drug products with improved clinical utility.

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Section: Solumatrix Diclofenac Acidmentioning

confidence: 99%

Advances in NSAID Development: Evolution of Diclofenac Products Using Pharmaceutical Technology

Altman¹,

Bosch

Brune

et al. 2015

Drugs

376

193

View full text Add to dashboard Cite

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“…The manufacturing process, which does not alter the active therapeutic ingredient, was previously shown to promote rapid absorption of new formulations of diclofenac and meloxicam [11, 12]. The present study in healthy subjects indicates that the use of SoluMatrix Fine Particle Technology™ enhances the bioavailability of abiraterone acetate.…”

Section: Discussionmentioning

confidence: 49%

“…Reduced particle size leads to an enhanced surface area, and this in turn leads to an enhanced rate of dissolution and absorption [11, 12]. The absorption of OAA is reported to be nearly saturated at a dose of 1000 mg [7, 8].…”

Section: Discussionmentioning

confidence: 99%

Comparison of a Novel Formulation of Abiraterone Acetate vs. the Originator Formulation in Healthy Male Subjects: Two Randomized, Open-Label, Crossover Studies

Goldwater¹,

Hussaini²,

Bosch³

et al. 2017

Clin Pharmacokinet

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Background and ObjectiveAbiraterone acetate is approved for the treatment of metastatic castration-resistant prostate cancer. The originator abiraterone acetate (OAA) formulation is poorly absorbed and exhibits large pharmacokinetic variability in abiraterone exposure. Abiraterone acetate fine particle (AAFP) is a proprietary formulation (using SoluMatrix Fine Particle Technology™) designed to increase the oral bioavailability of abiraterone acetate. Here, we report on two phase I studies in healthy male subjects aged 18–50 years.MethodsIn Study 101, 20 subjects were randomized in a crossover design to single doses of AAFP 100, 200, or 400 mg or OAA 1000 mg taken orally under fasting conditions. Results suggested that AAFP 500 mg would be bioequivalent to OAA 1000 mg in the fasted state. To confirm the bioequivalence hypothesis and to further expand the AAFP dose range, in Study 102, 36 subjects were randomized in a crossover design to single doses of AAFP 125, 500, or 625 mg or OAA 1000 mg. Both studies included a 7-day washout period between administrations.ResultsDose-dependent increases in the area under the plasma concentration–time curve and maximum plasma concentration with AAFP were observed in both studies. The AAFP 500-mg bioavailability relative to OAA 1000 mg measured by the geometric mean ratio for area under the plasma concentration–time curve from time zero to the time of the last quantifiable concentration was 93.4% (90% confidence interval 85.3–102.4), area under the plasma concentration–time curve from time zero to infinity was 91.0% (90% confidence interval 83.3–99.4), and maximum plasma concentration was 99.8% (90% confidence interval 86.3–115.5). Dose proportionality was seen across all AAFP dose levels (100–625 mg). Abiraterone acetate fine particle was found to be safe and well tolerated in this study.ConclusionAbiraterone acetate fine particle 500 mg was demonstrated to be bioequivalent to OAA 1000 mg in healthy volunteers under fasted conditions.Electronic supplementary materialThe online version of this article (doi:10.1007/s40262-017-0536-2) contains supplementary material, which is available to authorized users.

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“…Some error bars are not visible because they are smaller than the size of the symbols 1000 mg. The application of the proprietary technology used in the manufacture of AAFP provides a smaller drug particle size and is intended to increase dissolution in vivo [15], which may explain the improved bioavailability of AAFP under fasted conditions compared with OAA [13]. The improved bioavailability may be important for highly lipophilic drugs such as AA, which needs to be administered under fasted conditions.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Food on the Absorption of Abiraterone Acetate from a Fine Particle Dosage Form: A Randomized Crossover Trial in Healthy Volunteers

et al. 2017

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Pharmacokinetic Properties and Tolerability of Low-dose SoluMatrix Diclofenac

Cited by 19 publications

References 26 publications

Advances in NSAID Development: Evolution of Diclofenac Products Using Pharmaceutical Technology

Advances in NSAID Development: Evolution of Diclofenac Products Using Pharmaceutical Technology

Comparison of a Novel Formulation of Abiraterone Acetate vs. the Originator Formulation in Healthy Male Subjects: Two Randomized, Open-Label, Crossover Studies

The Effect of Food on the Absorption of Abiraterone Acetate from a Fine Particle Dosage Form: A Randomized Crossover Trial in Healthy Volunteers

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