Characterisation of a novel conjugate of ibuprofen with 3-hydroxybutyric acid oligomers

Stasiak, Pawel; Ehrhardt, Carsten; Juzwa, Maria; Sznitowska, Małgorzata

doi:10.1211/jpp.61.08.0017

Cited by 3 publications

(8 citation statements)

References 13 publications

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“…570 Da) containing approximately 2.5% ( w / w ) of non-conjugated IB was provided by the Centre of Polymer and Carbon Materials (Zabrze, Poland). Synthesis and analytical methods confirming purity, structure and molecular weight of the conjugate have been described elsewhere (9,10). …”

Section: Methodsmentioning

confidence: 99%

“…An oily solution of non-conjugated IB (5% w / w ) in Miglyol 812 was prepared as control and also sterilised by filtration as described above. No adverse effects of the thermal sterilisation on the emulsion stability were observed (9). Parameters investigated were pH, droplet size and ibuprofen–OHB concentration.…”

Section: Methodsmentioning

confidence: 99%

“…Parameters investigated were pH, droplet size and ibuprofen–OHB concentration. All formulations were prepared at most 5 days prior to the start of the in vivo experiments, however stability of the formulations at 5 ± 2°C was investigated within 90 days after preparation (9). …”

Section: Methodsmentioning

confidence: 99%

“…Conjugates of carboxylic acid group-bearing non-steroidal anti-inflammatory drugs (NSAIDs) with OHB have recently been developed and characterised at the Centre of Polymer and Carbon Materials of Polish Academy of Sciences. It was reported that these conjugates are biocompatible and show high stability in aqueous solutions of pH 6.0–8.0 (7–9). Ibuprofen–OHB (Fig.…”

mentioning

confidence: 99%

“…It also marked resistance against hydrolytic enzymes ( e.g. , pancreatin) (9), however, no data on the conjugate's pharmacokinetics following parenteral administration has been available.

Fig.…”

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confidence: 99%

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In Vivo Assessment of Parenteral Formulations of Oligo(3-Hydroxybutyric Acid) Conjugates with the Model Compound Ibuprofen

et al. 2010

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Polymer-drug conjugates have gained significant attention as pro-drugs releasing an active substance as a result of enzymatic hydrolysis in physiological environment. In this study, a conjugate of 3-hydroxybutyric acid oligomers with a carboxylic acid group-bearing model drug (ibuprofen) was evaluated in vivo as a potential pro-drug for parenteral administration. Two different formulations, an oily solution and an o/w emulsion were prepared and administered intramuscularly (IM) to rabbits in a dose corresponding to 40 mg of ibuprofen/kilogramme. The concentration of ibuprofen in blood plasma was analysed by HPLC, following solid–phase extraction and using indometacin as internal standard (detection limit, 0.05 μg/ml). No significant differences in the pharmacokinetic parameters (Cmax, Tmax, AUC) were observed between the two tested formulations of the 3-hydroxybutyric acid conjugate. In comparison to the non-conjugated drug in oily solution, the relative bioavailability of ibuprofen conjugates from oily solution, and o/w emulsion was reduced to 17% and 10%, respectively. The 3-hydroxybutyric acid formulations released the active substance over a significantly extended period of time with ibuprofen still being detectable 24 h post-injection, whereas the free compound was almost completely eliminated as early as 6 h after administration. The conjugates remained in a muscle tissue for a prolonged time and can hence be considered as sustained release systems for carboxylic acid derivatives.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

“…It also marked resistance against hydrolytic enzymes ( e.g. , pancreatin) (9), however, no data on the conjugate's pharmacokinetics following parenteral administration has been available.

Fig.…”

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confidence: 99%

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In Vivo Assessment of Parenteral Formulations of Oligo(3-Hydroxybutyric Acid) Conjugates with the Model Compound Ibuprofen

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Polyethylene Prodrugs Using Precisely Placed Pharmaceutical Agents

Leonard

Turek

Sloan

et al. 2010

Macro Chemistry & Physics

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Polyethylene‐based polymeric prodrugs have been prepared by acyclic diene metathesis (ADMET) polymerization; this condensation type, step growth polymerization, affords controlled polymer architectures via exact methylene run lengths between drug branches. Polyethylene was synthesized with the nonsteroidal anti‐inflammatory drug (NSAID) branches ibuprofen and naproxen attached at every 21st backbone carbon through a hydrolysable ester linkage. These ester linkages can have their reactivity tuned by using a variety of spacers that link the drug to the polymer backbone. Two types of spacers, tetraethylene glycol (TEG, hydrophilic) and decanediol (hydrophobic), were incorporated between the drugs and the polymer backbone to observe the effect of spacer properties on the rate of drug release. The rate of hydrolysis and subsequent release of drug was monitored as a direct effect of the spacer and type of reactive linker. With the primary structure of the polymers perfectly known, making such subtle changes to these structures has a dramatic influence on their physical properties. The polymers discussed herein are characterized with NMR, IR, TGA, and DSC. The rate at which these materials hydrolyze and release their pharmaceutical species via enzymatic or chemical hydrolysis was monitored by UV‐vis. Tailoring the type of spacer and hydrolysable linker to a particular drug offers a new class of polyethylene with controllable features that can be used in the application of a new drug delivery material.magnified image

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A perspective review on role of novel NSAID prodrugs in the management of acute inflammation

Peesa

Yalavarthi

Rasheed³

et al. 2016

Journal of Acute Disease

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Characterisation of a novel conjugate of ibuprofen with 3-hydroxybutyric acid oligomers

Abstract: This conjugate is not well suited for oral administration but might be considered a candidate for development of prodrug preparations for parenteral or topical sustained release.

Cited by 3 publications

References 13 publications

In Vivo Assessment of Parenteral Formulations of Oligo(3-Hydroxybutyric Acid) Conjugates with the Model Compound Ibuprofen

In Vivo Assessment of Parenteral Formulations of Oligo(3-Hydroxybutyric Acid) Conjugates with the Model Compound Ibuprofen

Polyethylene Prodrugs Using Precisely Placed Pharmaceutical Agents

A perspective review on role of novel NSAID prodrugs in the management of acute inflammation

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