A Comparative Study of the Transdermal Penetration of a Series of Nonsteroidal Antiinflammatory Drugs

Cordero, José Antonio; Alarcon, L.; Escribano, Elvira; Obach, R.; Domènech, Josep Mestres i

doi:10.1021/js950346l

Cited by 168 publications

(94 citation statements)

References 21 publications

(15 reference statements)

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“…The solubility curves of PX (form I) in methanol and ethanol were determined, with values determined for the latter found to be consistent with previous literature reports of PX solubility 19,20 . The curves are similar in shape, with PX less soluble in ethanol throughout the temperature range ( Figure 12).…”

Section: Solubility Of Multi-component Molecular Crystals Of Pxsupporting

confidence: 86%

Intermolecular hydrogen transfer and solubility tuning in multi-component molecular crystals of the API piroxicam

et al. 2014

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Please cite only the published version using the reference above.See http://opus.bath.ac.uk/ for usage policies.Please scroll down to view the document. CrystEngComm RSCPublishing ARTICLEThis journal is © The Royal Society of Chemistry 2013 J. Name., 2013, 00, 1-3 | 1 A series of twelve multi-component molecular crystals of the active pharmaceutical ingredient (API) piroxicam (PX) have been synthesised and their structures analysed with respect to their supramolecular motifs and degree of intermolecular hydrogen transfer observed on formation of the various complexes. The multi-component crystals of PX formed with a series of basic N-heterocycles are contrasted with those formed with strong haloanilic acids, with PX found to adopt different ionisation states. The effect of the formation of these multi-component molecular crystals on the physical property of solubility, often crucial in API formulation, has been investigated and these solubility determinations are compared with those of the parent PX material. Enhanced solubility is evident in some of the multi-component crystals formed. IntroductionMulti-component crystallisation -also referred to as cocrystallisation -is the method of bringing together two or more different molecules into the same crystal lattice to form a molecular complex or salt 1 . Molecular complexes from cocrystallisation experiments are seen as an increasingly useful tool in the preparation of solid forms of active pharmaceutical ingredients (APIs), with molecular complexes of pharmaceuticals not only having the potential to be patented as new materials 2 , but also for improving the physicochemical properties of an API without compromising the structural integrity 3 . Piroxicam (PX) is a non-steroidal anti-inflammatory drug (NSAID) that has been extensively studied in the solid state [4][5][6][7][8][9][10][11] . Presented here are further investigations of multicomponent molecular crystals of this important API, with particular regard to the crystal engineering potential and the potential modification of relevant physical properties of the multi-component crystals formed, with respect to those of the parent material. In terms of the crystal engineering aspects, the aim is to identify robust synthons which may be utilised for future design of molecular complexes of piroxicam, while the particular physical property under investigation here is that of solubility, relevant to a wide range of APIs in seeking to develop their optimized formulation in manufacturing and processing of pharmaceutical products. In the solid state, piroxicam has previously been shown to exist in two ionisation states when not in its neutral form. While pure piroxicam exists in the non-ionised form in the solid state, it has been shown that in polar solvents, such as acetonitrile which is commonly used in crystallisation experiments with piroxicam, the zwitterionic form is present in large quantities 12,13 . The formation of the zwitterion, through intramolecular hydrogen-transfer, has been observed in solvates and ...

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Section: Solubility Of Multi-component Molecular Crystals Of Pxsupporting

confidence: 86%

Intermolecular hydrogen transfer and solubility tuning in multi-component molecular crystals of the API piroxicam

et al. 2014

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“…Six replicates were used for the concentrations of n-octanol-distilled water solutions for partition coefficient calculations. 20 The same experiment was repeated using soybean oil as an organic phase. 19 …”

Section: Determination Of Drug Solubilitymentioning

confidence: 99%

Transdermal delivery of diclofenac sodium through rat skin from various formulations

Özgüney¹,

Karasulu²,

Kantarcı

et al. 2006

AAPS PharmSciTech

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The aim of this study was to evaluate and compare the in vitro and in vivo transdermal potential of w/o microemulsion (M) and gel (G) bases for diclofenac sodium (DS). The effect of dimethyl sulfoxide (DMSO) as a penetration enhancer was also examined when it was added to the M formulation. To study the in vitro potential of these formulations, permeation studies were performed with Franz diffusion cells using excised dorsal rat skin. To investigate their in vivo performance, a carrageenan-induced rat paw edema model was used. The commercial formulation of DS (C) was used as a reference formulation. The results of the in vitro permeation studies and the paw edema tests were analyzed by repeated-measures analysis of variance. The in vitro permeation studies found that M was superior to G and C and that adding DMSO to M increased the permeation rate. The permeability coefficients (Kp) of DS from M and M+DMSO were higher (Kp = 4.9 × 10 −3 ± 3.6 × 10 −4 cm/h and 5.3 × 10 −3 ± 1.2 × 10 −3 cm/h, respectively) than the Kp of DS from C (Kp = 2.7 × 10 −3 ± 7.3 × 10 −4 cm/h) and G (Kp = 4.5 × 10 −3 ± 4.5 × 10 −5 cm/h). In the paw edema test, M showed the best permeation and effectiveness, and M+DMSO had nearly the same effect as M. The in vitro and in vivo studies showed that M could be a new, alternative dosage form for effective therapy.

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“…Idson (1975) demonstrated that the epidermic barrier was the limiting factor for the percutaneous absorption and that once the drug passed through the stratum corneum of the epidermis, its absorption was guaranteed. Currently, the study of percutaneous absorption has been a priority in the pharmaceutical research as it presentes an alternative route for drug administration, overcoming some of the disadvantages of oral administration, such as the hepatic first-pass effect, or other adverse effects (Cordeiro et al, 1997;Finnin and Morgan, 1999;Idson, 1975;Kitagawa et al, 1998).…”

Section: History and Prospectsmentioning

confidence: 99%

Percutaneous absorption enhancers: mechanisms and potential

Rodrigues

Zanluchi²,

Grebogi

2007

Braz. arch. biol. technol.

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Transdermal applications of drugs present many advantages in terms of absorption, however this is not easily obtained through the transdermal route. The principle barrier is the stratum corneum and one of the strategies that have been found to promote cutaneous drug penetration is through the use of absorption enhancers. Many substances have been identified as absorption enhancers. Although the list of substances that promote absorption is growing, in most cases, there is a direct correlation between the effects of absorption enhancers and their skintoxicity. The use of these substances depends therefore on studies which focus on local and systemic toxicity, as well as action mechanisms.

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A Comparative Study of the Transdermal Penetration of a Series of Nonsteroidal Antiinflammatory Drugs

Cited by 168 publications

References 21 publications

Intermolecular hydrogen transfer and solubility tuning in multi-component molecular crystals of the API piroxicam

Intermolecular hydrogen transfer and solubility tuning in multi-component molecular crystals of the API piroxicam

Transdermal delivery of diclofenac sodium through rat skin from various formulations

Percutaneous absorption enhancers: mechanisms and potential

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