Synthesis, characterization and pharmacological evaluation of amide prodrugs of Flurbiprofen

Mishra, Abha; Veerasamy, Ravichandran; Jain, Prateek; Dixit, Vinod Kumar; Agrawal, Ram Kishore

doi:10.1590/s0103-50532008000100014

Cited by 24 publications

(16 citation statements)

References 9 publications

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“…Many gastrointestinal side effects caused due to the presence of free carboxylic acid group (Figure 1), are produced by its oral administration, such as dyspepsia, cramping, gastric bleeding and peptic ulcer, causing non-compliance among patients, which ultimately results in treatment failure (Mishra et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Physicochemical, in vitro and in vivo evaluation of flurbiprofen microemulsion

Naeem

Rahman

Tavares

et al. 2015

An. Acad. Bras. Ciênc.

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Flurbiprofen, a potent nonsteroidal anti-inflammatory drug, is widely used for relief of pain in patients suffering from rheumatic diseases, migraine, sore throat and primary dysmenorrheal. However, this drug has many gastrointestinal side effects produced by its oral administration, such as gastric bleeding and peptic ulcer. These effects were responsible for non-compliance among patients, which ultimately results in treatment failure. The physicochemical properties of flurbiprofen, make it a suitable candidate for transdermal drug delivery, which can overcome the drawbacks of oral administration. In this sense, microemulsions have been proved to increase the cutaneous absorption of lipophilic drugs when compared to conventional drug delivery systems. The purpose of this study was to formulate and characterize gel based microemulsions, for topical delivery of flurbiprofen. Different gel bases, containing microemulsion and hydro-alcoholic solution of flurbiprofen, were developed and compared. In vitro study showed that gels containing microemulsion had a higher permeation rate than those containing hydro-alcoholic solutions. Additionally, formulation of Carbopol-I (microemulsion) showed higher percent of inhibition of inflammation than others bases. Further, skin irritation study demonstrated that Carbopol-I was none irritating. Flurbiprofen microemulsion incorporated on Carbopol-I showed physicochemical, in vitro and in vivo characteristics suitable for the development of alternative transdermal delivery formulation.

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Section: Introductionmentioning

confidence: 99%

Physicochemical, in vitro and in vivo evaluation of flurbiprofen microemulsion

Naeem

Rahman

Tavares

et al. 2015

An. Acad. Bras. Ciênc.

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“…The reaction mixture was stirred mechanically for 30 min at room temperature and then in an ice bath. Sulindac acid chloride (1.78 g, 0.005 mol/L) was added in small portions and stirred continuously for 6-7 h. The solid that separated out was filtered off, and the crude conjugate was re-crystallized from methanol (iii) (Scheme 1, Table 1) [6,7].…”

Section: Synthesis Of Amino Acid Conjugates Of Sulindacmentioning

confidence: 99%

“…The meltingpoints of the synthesized conjugates were determined in open capillary tubes in a melting-point apparatus and are reported uncorrected. Infrared, nuclear magnetic resonance and mass spectra of the conjugates were obtained [7]. …”

Section: Partition Coefficientmentioning

confidence: 99%

Amino acid esters as prodrugs of an arylalkanoic acid COX inhibitor: Synthesis and biopharmaceutical and pharmacological evaluation

Nirmal

Rajput

Sarkar

et al. 2015

Journal of Taibah University for Science

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Sulindac is an analgesic and anti-inflammatory agent. It has the general side-effects of non-steroidal anti-inflammatory drugs, owing to presence of a free carboxylic acid group. The aim of the study was to retard the adverse gastrointestinal effects of the drug. Various conjugates of sulindac were synthesized by amidation with methyl esters of 10 amino acids. The synthesized conjugates were characterized by melting-point, thin-layer chromatography and Fourier transform infrared, nuclear magnetic resonance and mass spectroscopy. The synthesized conjugates were evaluated pharmacologically for analgesic, anti-inflammatory and ulcerogenic activity. Amide conjugation had a synergistic potentiating effect, with less disruption of mucosal surfaces. This conjugate approach can therefore be used successfully to minimize gastrointestinal toxicity with no loss of the desired anti-inflammatory and analgesic activities of the drug. Methyl 2-(2-((7Z)-1-(4-(methylsulfinyl)benzlidene)-5-fluoro-2-methyl-1H-inden-3-yl)acetamido)-3-phenylpropanoate and methyl 2-(2((6Z)-1-(4-(methylsulfinyl)benzlidene)-5-fluoro-2-methyl-1H-inden-3-yl)acetamido)-3-methylbutanoate showed excellent pharmacological responses and encouraging hydrolysis rates in simulated gastric fluid, simulated intestinal fluid and 80% human plasma. Conjugates with longer aliphatic side chains or aromatic substituents had higher partition coefficients but lower dissolution and hydrolysis rates. These conjugates could be considered for sustained release preparations.

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“…[23][24] Paracetamol (acetaminophen) esters of some acidic NSAIDs. 25 Naproxen propyphenazone mutual prodrugs.…”

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confidence: 99%

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2011

IJPSR

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Mutual prodrug is a form of prodrug in which two pharmacologically active agents are attached to each other in such a way that each drug acts as a promoiety/carrier for each other and vice versa. The association may be "synergistic" if the carrier shows the same biological action as that of parent drug or may provide "additional" benefit if it shows new pharmacological action which is lacking in parent drug. The mutual prodrug concept has shown its marked therapeutic gain in case of well-accepted and useful drugs with minor undesirable properties and in those active compounds that suffer from severe limitations, like lack of site specificity, poor bioavailability or lack of particular activity. Now a days Anticancer, cardiovascular, antiviral, antipsychotic and anti-inflammatory drugs are best utilizing the concept of mutual prodrug designing for their better effect. In this paper, we have reviewed mechanism of activation, contribution of mutual prodrug approach in different therapeutic areas and the development in this field during the last few decades including a list of patents. This review not only describes various design approaches, methods of synthesis, pharmacological evaluations for mutual prodrugs, but has also highlighted the emerging fields of docking studies and their relevance to the pharmacokinetics of mutual prodrugs.

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Synthesis, characterization and pharmacological evaluation of amide prodrugs of Flurbiprofen

Cited by 24 publications

References 9 publications

Physicochemical, in vitro and in vivo evaluation of flurbiprofen microemulsion

Physicochemical, in vitro and in vivo evaluation of flurbiprofen microemulsion

Amino acid esters as prodrugs of an arylalkanoic acid COX inhibitor: Synthesis and biopharmaceutical and pharmacological evaluation

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