409067-32-9Relevant academic research and scientific papers
MANUFACTURING PROCESS FOR NO-DONATING COMPOUNDS SUCH AS NO-DONATING DICLOFENAC
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Page 41; 42, (2008/06/13)
The present invention relates to a new process for the preparation of NO-donating compounds using a sulfonated intermediate. The invention relates to new intermediates prepared therein suitable for large scale manufacturing of NO-donating compounds. The i
In vitro and in vivo evaluation of polyoxyethylene esters as dermal prodrugs of ketoprofen, naproxen and diclofenac
Bonina, Francesco Paolo,Puglia, Carmelo,Barbuzzi, Tony,de Caprariis, Paolo,Palagiano, Francesco,Rimoli, Maria Grazia,Saija, Antonella
, p. 123 - 134 (2007/10/03)
Novel polyoxyethylene esters of ketoprofen (1a-e), naproxen (2a-e) and diclofenac (3a-e) were synthesized and evaluated as potential dermal prodrugs of naproxen, ketoprofen and diclofenac. These esters were obtained by coupling these drugs with polyoxyethylene glycols by a succinic acid spacer. The aqueous solubilities, lipophilicities and hydrolysis rates of esters 1a-e, 2a-e and 3a-e were determined in a buffered solution and in porcine esterase. The permeation of these prodrugs through excised human skin was studied in vitro. Furthermore we investigated the in vivo topical anti-inflammatory activity of esters 1d, 2e and 3e, which showed the best in vitro profile, evaluating the ability of these compounds to inhibit methyl nicotinate (MN)-induced skin erythema on healthy human volunteers. Esters 1a-e, 2a-e and 3a-e showed good water stability and rapid enzymatic cleavage and their hydrolysis rates, both chemical and enzymatic, were not significantly affected by the length of the polyoxyethylenic chain used as promoiety. Concerning in vitro percutaneous absorption studies, only esters 1d-e, 2d-e and 3c-e showed an increased flux through stratum corneum and epidermis membranes compared to their respective parent drugs. In vivo results showed an interesting delayed and sustained activity of esters 1d and 3e compared to the parent drugs. In conclusion polyoxyethylene glycols could prove to be suitable promoieties for ketoprofen, naproxen and diclofenac design since esters 1d-e, 2d-e and 3c-e showed some requirements (chemical stability, enzymatic lability and an increased skin permeation) needed to obtain successful dermal prodrugs. Furthermore, was observed an appreciable and sustained in vivo topical anti-inflammatory activity of esters 1d and 3e, compared to the parent drugs, using MN-induced erythema in human volunteers as inflammation model. Copyright
