Evaluation of diclofenac prodrugs for enhancing transdermal delivery

Lobo, Shabbir; Li, Henan; Farhan, Nashid; Yan, Guang

doi:10.3109/03639045.2013.767828

Cited by 23 publications

(15 citation statements)

References 19 publications

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“…The obtained NMR spectra for DS, Cipro and complexes are shown in Figure 2. Generally, the spectra accorded well with those previously reported [12,13]. Thus, aromatic protons number 1, 2 and 3 in Cipro resonated at 8.7, 7.9 and 7.6, respectively, while protons in DS appeared at 7.50 ppm (protons 1 + 3, d), 7.13 (protons 5 + 7, t), 7.03 (proton 2, t), 6.82 (proton 6, t), and 6.25 (proton 4, d).…”

Section: Nmr Spectrasupporting

confidence: 92%

Studies on the interaction between ciprofloxacin hydrochloride and diclofenac sodium

El-Sabawi¹,

Abu-Dahab²,

Bakri³

et al. 2019

Trop. J. Pharm Res

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Purpose: To study the interaction between ciprofloxacin hydrochloride (Cipro) and diclofenac sodium (DS) in the presence and absence of metal ions. Methods: Complexes were prepared in the aqueous phase at different molar ratios (r) of Cipro:DS (ranged from 0.2-2.0). The complexes were characterized by Fourier transform-infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and high pressure liquid chromatography (HPLC). Their properties, i.e., solubility, dissolution and partition coefficient (log P), were studied along with their permeability across Caco-2 cells. Furthermore, the antimicrobial activity of Cipro and its complexes was determined using standard broth dilution method and expressed as minimum inhibitory concentration (MIC). Results: Cipro formed an ion pair with DS. The product was confirmed to be a combination of the two drugs, DS and Cipro, but in a ratio that is dependent on the added amounts of each component (r = 1:1 or 1:2). The 1:1 product was more lipophilic than the individual components leading to a lower aqueous solubility and a higher octanol/water partition coefficient log P (6.7 vs. 0.77). The presence of DS within the dissolution medium appeared to modify the dissolution of Cipro depending on the concentration. Moreover, ternary complexes involving Cipro, DS and metal ions (iron and/or calcium) exhibited improved antimicrobial effect (MIC, 0.016 µg/ml compared to 0.258 µg/ml for Cipro). Caco-2 cell permeation data indicate that the presence of DS significantly improved the apparent permeability coefficient (Papp) of Cipro (20.6 × 10-6 cm/s) which was three times higher than that of free Cipro (p < 0.05). DS also appeared to counteract the well-known negative effect of metal ions on the bioavailability of Cipro. Conclusion: There is a clinically relevant interaction between DS and Cipro at the absorption level as a result of ion pair formation, which might even counteract the negative effect of metals on the absorption of Cipro. These findings should aid the design of new Cipro ion pairs that provide higher bioavailability than free Cipro.

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Section: Nmr Spectrasupporting

confidence: 92%

Studies on the interaction between ciprofloxacin hydrochloride and diclofenac sodium

El-Sabawi¹,

Abu-Dahab²,

Bakri³

et al. 2019

Trop. J. Pharm Res

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“…Methanol, ethylene glycol, glycerol and 1,3-propylene glycol esters were synthesized and the In vitro fluxes across human epidermal membrane determined using saturated aqueous solutions (vehicle, PBS pH 7.4). The glycerol ester prodrug 27 was the best permeant of all with a flux of 5.54 ± 0.78 nmol/cm 2 /h, which was almost 2-fold higher that of diclofenac itself (2.57 ± 0.29 nmol/cm 2 /h) [70]. Diclofenac displayed higher permeation flux across hairless rat skin than its prodrugs from hydroxy-functionalized polyacrylate patches.…”

Section: The Impact Of Prodrug Strategy On the Percutaneous Absorpmentioning

confidence: 99%

Prodrug Strategies for Enhancing the Percutaneous Absorption of Drugs

N’Da

2014

Molecules

121

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Abstract:The transdermal application of drugs has attracted increasing interest over the last decade or so, due to the advantages it offers, compared to other delivery methods. The development of an efficient means of transdermal delivery can increase drug concentrations, while reducing their systemic distribution, thereby avoiding certain limitations of oral administration. The efficient barrier function of the skin, however, limits the use of most drugs as transdermal agents. This limitation has led to the development of various strategies to enhance drug-skin permeation, including the use of penetration enhancers. This method unfortunately has certain proven disadvantages, such as the increased absorption of unwanted components, besides the drug, which may induce skin damage and irritancy. The prodrug approach to increase the skin's permeability to drugs represents a very promising alternative to penetration enhancers. The concept involves the chemical modification of a drug into a bioreversible entity that changes both its pharmaceutical and pharmacokinetic characteristics to enhance its delivery through the skin. In this review; we report on the in vitro attempts and successes over the last decade by using the prodrug strategy for the percutaneous delivery of pharmacological molecules.

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“…At the same time, it is a potent and selective inhibitor of cycloxygenase-2 enzyme (14,15). Combining these ideal features of 6-MNA with the successful approach of converting the parent drugs into ester prodrugs for topical delivery, and keeping in view some recent work in the field, we planned to synthesize and evaluate a series of novel substituted piperazinylalkyl esters as prodrugs of 6-MNA for potential percutaneous drug delivery (11,(16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

Potential of Piperazinylalkylester Prodrugs of 6-Methoxy-2-Naphthylacetic Acid (6-MNA) for Percutaneous Drug Delivery

et al. 2014

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Abstract. Piperazinylalkyl ester prodrugs (4a-5d) of 6-methoxy-2-naphthylacetic acid (6-MNA) (1) were synthesized and evaluated in vitro for the purpose of percutaneous drug delivery. These ionizable prodrugs exhibited varying aqueous solubilities and lipophilicities depending on the pH of the medium. The prodrugs (4a-5c) showed higher aqueous solubility and similar lipophilicity at pH 5.0 and lower aqueous solubility and higher lipophilicity at pH 7.4 in comparison to 6-MNA. The chemical and enzymatic hydrolyses of the prodrugs was investigated in aqueous buffer solutions (pH 5.0 and 7.4) and in 80% human serum (pH 7.4) at 37°C. The prodrugs showed moderate chemical stability (t 1/2 =6-60 h) but got readily hydrolyzed enzymatically to 6-MNA with half-life ranging from 10-60 min. In the in vitro permeation study using rat skin, the flux of 6-MNA and the prodrugs was determined in aqueous buffers of pH 5.0 and 7.4. The prodrug (5b) showed 7.9-and 11.2-fold enhancement in skin permeation compared to 6-MNA (1) at pH 5.0 and 7.4, respectively. It was concluded that the parent NSAIDs having favorable pharmacokinetic and pharmacodynamic properties coupled with increased skin permeability of their prodrugs could give better options for the treatment of rheumatic diseases.

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Evaluation of diclofenac prodrugs for enhancing transdermal delivery

Cited by 23 publications

References 19 publications

Studies on the interaction between ciprofloxacin hydrochloride and diclofenac sodium

Studies on the interaction between ciprofloxacin hydrochloride and diclofenac sodium

Prodrug Strategies for Enhancing the Percutaneous Absorption of Drugs

Potential of Piperazinylalkylester Prodrugs of 6-Methoxy-2-Naphthylacetic Acid (6-MNA) for Percutaneous Drug Delivery

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