Skin Pharmacology and Applied Skin Physiology, 2001
The interactions between piroxicam (Px) and hydroxypropyl-beta-cyclodextrin (HPbetaCD) were thoro... more The interactions between piroxicam (Px) and hydroxypropyl-beta-cyclodextrin (HPbetaCD) were thoroughly investigated both in solution and the solid state. The solubility studies have demonstrated the formation of a Px:HPbetaCD inclusion complex with 1:1 stoichiometry. The addition of propylene glycol to the medium produced less stable complexes, revealing the fact of this co-solvent probably acting as a competing agent. Equimolecular Px:HPbetaCD solid systems were prepared using the co-precipitation method and then fully characterized by X-ray diffractometry, infrared spectra and differential scanning calorimetry. A topical gel formulation containing Px, as inclusion complex with HPbetaCD, was developed in order to study the influence of Px complexation on its release rate and skin percutaneous permeation. The formation of Px:HPbetaCD complexes did not increase either Px release from the vehicle or its skin permeation. However, Px complexation with HPbetaCD allowed the incorporation of a higher quantity of Px into the gel, which resulted in a considerable increase in the Px released and permeated. Skin pretreatment with different HPbetaCD solutions, followed by the application of control gel, showed no enhancing capacity. The amount of Px retained in the skin, after pretreatment experiments, was found to be very similar to that obtained without skin pretreatment and was observed to be related to flux values through the skin.
European Journal of Pharmaceutics and Biopharmaceutics, 2001
The in¯uence of oleic acid (OA) on the in vitro percutaneous absorption of tenoxicam (TEN) and it... more The in¯uence of oleic acid (OA) on the in vitro percutaneous absorption of tenoxicam (TEN) and its combined effect with propylene glycol (PG) was studied using Franz-type diffusion cells. Furthermore, at de®ned concentrations of OA, complexes of the drug with cyclodextrins (MbCD and gCD) were added because their combined use may be an interesting approach to raise TEN¯ux. In addition, the amount of TEN retained in the skin after topical administration of several formulations was determined.
The in vitro release of piroxicam from carbomer gels and its penetration through isopropyl myrist... more The in vitro release of piroxicam from carbomer gels and its penetration through isopropyl myristate impregnated membranes and abdominal rat skin were investigated. Attempts were made to relate the differences in the release rate with physicochemical properties of the drug and the vehicle. The results showed that piroxicam is released from the topical gel formulations and diffuses through skin. It is suggested that although piroxicam flux across abdominal rat skin was lower than through isopropyl myristate membranes, this kind of membranes can be used in preliminary screening among the different piroxicam formulations.
European Journal of Pharmaceutics and Biopharmaceutics, 2000
The enhancing effect of several fatty acids from different subclasses: saturated (lauric acid), m... more The enhancing effect of several fatty acids from different subclasses: saturated (lauric acid), mono-unsaturated (oleic acid) and polyunsaturated (linoleic and linolenic acids) in the percutaneous absorption of piroxicam was investigated. These fatty acids were applied on the skin membrane in three different ways: included in the vehicle, as a pretreatment or both. An increase in piroxicam¯ux value was found for lauric and oleic acids in the following order: skin pretreatment with 5% fatty acids followed by application of gels containing 5% fatty acids . skin pretreatment with 5% fatty acids followed application of control gel . gel containing 5% fatty acids without skin pretreatment. For linoleic and linolenic acids, the piroxicam¯ux in the two pretreatment experiments was almost the same, although higher than when fatty acids were included in the formulation. Skin pretreatment with 5% linolenic acid in propylene glycol followed by application of control gel or a gel containing 5% linolenic acid, showed the highest enhancing capacity. After skin pretreatment with fatty acids, the lag time values decreased nearly three times compared to those obtained when the same fatty acids were included in the formulation. The amount of piroxicam retained in the skin after pretreatment with fatty acids was found to be very similar for all fatty acids and 3-fold higher than in the experiments without skin pretreatment. q
Journal of Pharmaceutical and Biomedical Analysis, 2001
A direct, very sensitive, simple and rapid high-performance liquid chromatographic (HPLC) method ... more A direct, very sensitive, simple and rapid high-performance liquid chromatographic (HPLC) method for the determination of piroxicam, with tenoxicam as internal standard, has been developed and validated. Samples were chromatographed on a 5 mm Scharlau C 18 column. The mobile phase was a mixture of acetonitrile-acetic acid 4% (pH 2.8) (45:55, v/v). Detection was at 354 nm and the run time was 7 min. The limit of detection was 0.025 mg/ml. The detector response was found to be linear in the concentration range 0.05-9 mg/ml. This HPLC assay has been applied to measure the 'in vitro' percutaneous permeation of piroxicam through abdominal hairless rat skin, using Franz-type diffusion cells, in order to obtain the concentration-time profiles of piroxicam.
Solid complexes of tenoxicam (TEN) with cyclodextrins (CDs), in a 1:1 molar ratio, were obtained ... more Solid complexes of tenoxicam (TEN) with cyclodextrins (CDs), in a 1:1 molar ratio, were obtained by the coprecipitation method and characterized by x-ray diffractometry, infrared spectroscopy, and differential scanning calorimetry. The binding capacity of the CDs with TEN was also demonstrated in aqueous solution and in water-propylene glycol mixtures. The purpose of this study was to determine the effect of CDs on the in vitro percutaneous penetration of TEN from carbopol gels, taking into account the role of the CD cavity size and the nature of the substituents. The effect of pretreatment was studied too. In vitro permeation experiments were carried out on Franz diffusion cells using cellulose nitrate membranes and abdominal rat skin. In these results, the release rates of the drug scarcely decreased when the CDs were added, probably because of a lower concentration of the free drug and an increased gel viscosity. However, it was also found that CDs, particularly gamma-CD and M-beta-CD, can improve slightly TEN absorption through the skin. Pretreatment studies with CDs, however, provided no effects on TEN permeation, but lag time was markedly reduced, suggesting a faster partitioning of TEN into the skin. Therefore, the use of pretreatment with CDs would be interesting when a quick action of the drug is desired.
The influence of propylene glycol (PG) on the in vitro penetration of diclofenac sodium (DFS) thr... more The influence of propylene glycol (PG) on the in vitro penetration of diclofenac sodium (DFS) through a synthetic membrane and abdominal rat skin from carbopol gels was investigated using Franz-type diffusion cells. The combined effect of isopropyl myristate (IPM) and PG was ...
Journal of Chromatography B-analytical Technologies in The Biomedical and Life Sciences, 2003
CAT ((+)-(13aS)-deoxytylophorinine) is a novel anticancer drug belonging to phenanthroindolizidin... more CAT ((+)-(13aS)-deoxytylophorinine) is a novel anticancer drug belonging to phenanthroindolizidine alkaloids. A sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of CAT and its pharmacologically active 3-O-desmethyl metabolite (S-4) was developed and validated in rat plasma using rotundine as the internal standard (IS). CAT, S-4 and IS were extracted by acetonitrile protein precipitation and separated on an Eclipse XDB-C18 column (1.8μm, 4.6mm×50mm) with acetonitrile-water (27:73, v/v) mobile phase containing 0.1% formic acid at a 0.4mL/min flow rate. Positive ion electrospray ionization in multiple reaction monitoring mode was employed to measure CAT, S-4 and IS by monitoring the transitions m/z 364.2→70.1 for CAT, 350.1→70.1 for S-4 and 356.2→192.2 for IS. Good linear correlation (r(2)>0.991) was achieved for CAT and S-4 over the range of 0.214-128.16 and 0.044-11.00ng/mL, respectively. The lower limit of quantification was 0.214ng/mL for CAT and 0.044ng/mL for S-4, using 50μL rat plasma samples. The intra- and inter-day precisions were not exceed 15% and the accuracy ranged between 94.80% and 108.22%. The average extraction recoveries of both analytes were greater than 94.62%. The method was successfully applied to the pharmacokinetic study of CAT and S-4 in rats after oral administration.
European Journal of Pharmaceutics and Biopharmaceutics, 2003
Acyclovir is one of the most effective and selective agents against viruses of the herpes group. ... more Acyclovir is one of the most effective and selective agents against viruses of the herpes group. In order to increase its antiviral activity, acyclovir loaded microparticles, prepared by an O/W solvent evaporation method were developed. Their antiviral activity against herpes simplex virus type 1 (HSV-1) and toxicity were evaluated on Vero cells and then compared with those presented by a drug solution. The 50% inhibitory concentration (IC 50 ) values for acyclovir loaded microspheres determined by plaque reduction assays at 48 and 96 h, were found to be 1.06^0.01 mM and 0.15^0.03 mM, respectively, while the equivalent values obtained for an acyclovir solution were 1.28^0.04 mM at 48 h and 0.27^0.02 mM at 96 h. These results indicate that acyclovir shows a higher antiviral activity, against herpes simplex virus type 1, when this drug was loaded in microparticles rather than as a drug solution, especially after 96 h of incubation. The toxicity of these microparticles was determined by the MTT test at 48 and 96 h. At 48 h only a small toxicity was found (cell viability ranged from 72 to 82%, with the higher concentration tested) and it could not be attributed to the microparticles, since the acyclovir control solution showed similar toxicity values. However, after 96 h a higher toxicity was observed with acyclovir microparticles as well as with the unloaded ones (cell viability located between 60 and 70%). In summary, acyclovir-loaded microparticles have shown to be promising carriers for the effective delivery of acyclovir in the treatment of HSV-1 infections in cells so they can have a potential use in vivo. q
The goal of this work was to increase the amount of acyclovir (ACV) in the basal epidermis, site ... more The goal of this work was to increase the amount of acyclovir (ACV) in the basal epidermis, site of Herpes virus simplex infections, using microparticles as carriers.
A direct, simple and rapid high-performance liquid chromatographic method has been developed for ... more A direct, simple and rapid high-performance liquid chromatographic method has been developed for the determination of ketoprofen with ibuprofen as internal standard. Samples were chromatographed on a 5 mm Kromasil 100 C column. The 18 mobile phase was a mixture of acetonitrile-0.01 M KH PO adjusted to pH 1.5 with orthophosphoric acid 85% (60:40, 2 4 v / v). Detection was at 260 nm and the run time was 10 min. The detector response was found to be linear in the concentration range 0.02 to 40 mg / ml. This HPLC assay has been applied to measure the ''in vitro'' percutaneous penetration of ketoprofen through rat skin.
European Journal of Drug Metabolism and Pharmacokinetics, 1998
Nonionic surfactants, which are a safe class of enhancers, may offer means of enhancing drug perm... more Nonionic surfactants, which are a safe class of enhancers, may offer means of enhancing drug permeation through the skin. In order to determine this effect, the influence of four nonionic surfactants on the percutaneous absorption of diclofenac sodium from carbopol gels containing 40% propylene glycol was investigated. In vitro diffusion experiments were carried out using excised full-thickness abdominal rat skin as well as cellulose nitrate membranes. The data of this study clearly revealed that Tween 80 decreased diclofenac penetration rate. This was due to a decrease in thermodynamic activity as a result of micellar complexation. In contrast, the more hydrophobic sorbitans enhanced diclofenac skin penetration, probably due to changes in the barrier properties of the skin and in the vehicle-stratum corneum partition coefficient. The most enhancing effect was induced by Span 20, a surfactant with a C12 saturated hydrophobic group. However, diffusional lag times for all the tested surfactants were longer than for the control gel.
Skin Pharmacology and Applied Skin Physiology, 2001
The interactions between piroxicam (Px) and hydroxypropyl-beta-cyclodextrin (HPbetaCD) were thoro... more The interactions between piroxicam (Px) and hydroxypropyl-beta-cyclodextrin (HPbetaCD) were thoroughly investigated both in solution and the solid state. The solubility studies have demonstrated the formation of a Px:HPbetaCD inclusion complex with 1:1 stoichiometry. The addition of propylene glycol to the medium produced less stable complexes, revealing the fact of this co-solvent probably acting as a competing agent. Equimolecular Px:HPbetaCD solid systems were prepared using the co-precipitation method and then fully characterized by X-ray diffractometry, infrared spectra and differential scanning calorimetry. A topical gel formulation containing Px, as inclusion complex with HPbetaCD, was developed in order to study the influence of Px complexation on its release rate and skin percutaneous permeation. The formation of Px:HPbetaCD complexes did not increase either Px release from the vehicle or its skin permeation. However, Px complexation with HPbetaCD allowed the incorporation of a higher quantity of Px into the gel, which resulted in a considerable increase in the Px released and permeated. Skin pretreatment with different HPbetaCD solutions, followed by the application of control gel, showed no enhancing capacity. The amount of Px retained in the skin, after pretreatment experiments, was found to be very similar to that obtained without skin pretreatment and was observed to be related to flux values through the skin.
European Journal of Pharmaceutics and Biopharmaceutics, 2001
The in¯uence of oleic acid (OA) on the in vitro percutaneous absorption of tenoxicam (TEN) and it... more The in¯uence of oleic acid (OA) on the in vitro percutaneous absorption of tenoxicam (TEN) and its combined effect with propylene glycol (PG) was studied using Franz-type diffusion cells. Furthermore, at de®ned concentrations of OA, complexes of the drug with cyclodextrins (MbCD and gCD) were added because their combined use may be an interesting approach to raise TEN¯ux. In addition, the amount of TEN retained in the skin after topical administration of several formulations was determined.
The in vitro release of piroxicam from carbomer gels and its penetration through isopropyl myrist... more The in vitro release of piroxicam from carbomer gels and its penetration through isopropyl myristate impregnated membranes and abdominal rat skin were investigated. Attempts were made to relate the differences in the release rate with physicochemical properties of the drug and the vehicle. The results showed that piroxicam is released from the topical gel formulations and diffuses through skin. It is suggested that although piroxicam flux across abdominal rat skin was lower than through isopropyl myristate membranes, this kind of membranes can be used in preliminary screening among the different piroxicam formulations.
European Journal of Pharmaceutics and Biopharmaceutics, 2000
The enhancing effect of several fatty acids from different subclasses: saturated (lauric acid), m... more The enhancing effect of several fatty acids from different subclasses: saturated (lauric acid), mono-unsaturated (oleic acid) and polyunsaturated (linoleic and linolenic acids) in the percutaneous absorption of piroxicam was investigated. These fatty acids were applied on the skin membrane in three different ways: included in the vehicle, as a pretreatment or both. An increase in piroxicam¯ux value was found for lauric and oleic acids in the following order: skin pretreatment with 5% fatty acids followed by application of gels containing 5% fatty acids . skin pretreatment with 5% fatty acids followed application of control gel . gel containing 5% fatty acids without skin pretreatment. For linoleic and linolenic acids, the piroxicam¯ux in the two pretreatment experiments was almost the same, although higher than when fatty acids were included in the formulation. Skin pretreatment with 5% linolenic acid in propylene glycol followed by application of control gel or a gel containing 5% linolenic acid, showed the highest enhancing capacity. After skin pretreatment with fatty acids, the lag time values decreased nearly three times compared to those obtained when the same fatty acids were included in the formulation. The amount of piroxicam retained in the skin after pretreatment with fatty acids was found to be very similar for all fatty acids and 3-fold higher than in the experiments without skin pretreatment. q
Journal of Pharmaceutical and Biomedical Analysis, 2001
A direct, very sensitive, simple and rapid high-performance liquid chromatographic (HPLC) method ... more A direct, very sensitive, simple and rapid high-performance liquid chromatographic (HPLC) method for the determination of piroxicam, with tenoxicam as internal standard, has been developed and validated. Samples were chromatographed on a 5 mm Scharlau C 18 column. The mobile phase was a mixture of acetonitrile-acetic acid 4% (pH 2.8) (45:55, v/v). Detection was at 354 nm and the run time was 7 min. The limit of detection was 0.025 mg/ml. The detector response was found to be linear in the concentration range 0.05-9 mg/ml. This HPLC assay has been applied to measure the 'in vitro' percutaneous permeation of piroxicam through abdominal hairless rat skin, using Franz-type diffusion cells, in order to obtain the concentration-time profiles of piroxicam.
Skin Pharmacology and Applied Skin Physiology, 2001
The interactions between piroxicam (Px) and hydroxypropyl-beta-cyclodextrin (HPbetaCD) were thoro... more The interactions between piroxicam (Px) and hydroxypropyl-beta-cyclodextrin (HPbetaCD) were thoroughly investigated both in solution and the solid state. The solubility studies have demonstrated the formation of a Px:HPbetaCD inclusion complex with 1:1 stoichiometry. The addition of propylene glycol to the medium produced less stable complexes, revealing the fact of this co-solvent probably acting as a competing agent. Equimolecular Px:HPbetaCD solid systems were prepared using the co-precipitation method and then fully characterized by X-ray diffractometry, infrared spectra and differential scanning calorimetry. A topical gel formulation containing Px, as inclusion complex with HPbetaCD, was developed in order to study the influence of Px complexation on its release rate and skin percutaneous permeation. The formation of Px:HPbetaCD complexes did not increase either Px release from the vehicle or its skin permeation. However, Px complexation with HPbetaCD allowed the incorporation of a higher quantity of Px into the gel, which resulted in a considerable increase in the Px released and permeated. Skin pretreatment with different HPbetaCD solutions, followed by the application of control gel, showed no enhancing capacity. The amount of Px retained in the skin, after pretreatment experiments, was found to be very similar to that obtained without skin pretreatment and was observed to be related to flux values through the skin.
European Journal of Pharmaceutics and Biopharmaceutics, 2001
The in¯uence of oleic acid (OA) on the in vitro percutaneous absorption of tenoxicam (TEN) and it... more The in¯uence of oleic acid (OA) on the in vitro percutaneous absorption of tenoxicam (TEN) and its combined effect with propylene glycol (PG) was studied using Franz-type diffusion cells. Furthermore, at de®ned concentrations of OA, complexes of the drug with cyclodextrins (MbCD and gCD) were added because their combined use may be an interesting approach to raise TEN¯ux. In addition, the amount of TEN retained in the skin after topical administration of several formulations was determined.
The in vitro release of piroxicam from carbomer gels and its penetration through isopropyl myrist... more The in vitro release of piroxicam from carbomer gels and its penetration through isopropyl myristate impregnated membranes and abdominal rat skin were investigated. Attempts were made to relate the differences in the release rate with physicochemical properties of the drug and the vehicle. The results showed that piroxicam is released from the topical gel formulations and diffuses through skin. It is suggested that although piroxicam flux across abdominal rat skin was lower than through isopropyl myristate membranes, this kind of membranes can be used in preliminary screening among the different piroxicam formulations.
European Journal of Pharmaceutics and Biopharmaceutics, 2000
The enhancing effect of several fatty acids from different subclasses: saturated (lauric acid), m... more The enhancing effect of several fatty acids from different subclasses: saturated (lauric acid), mono-unsaturated (oleic acid) and polyunsaturated (linoleic and linolenic acids) in the percutaneous absorption of piroxicam was investigated. These fatty acids were applied on the skin membrane in three different ways: included in the vehicle, as a pretreatment or both. An increase in piroxicam¯ux value was found for lauric and oleic acids in the following order: skin pretreatment with 5% fatty acids followed by application of gels containing 5% fatty acids . skin pretreatment with 5% fatty acids followed application of control gel . gel containing 5% fatty acids without skin pretreatment. For linoleic and linolenic acids, the piroxicam¯ux in the two pretreatment experiments was almost the same, although higher than when fatty acids were included in the formulation. Skin pretreatment with 5% linolenic acid in propylene glycol followed by application of control gel or a gel containing 5% linolenic acid, showed the highest enhancing capacity. After skin pretreatment with fatty acids, the lag time values decreased nearly three times compared to those obtained when the same fatty acids were included in the formulation. The amount of piroxicam retained in the skin after pretreatment with fatty acids was found to be very similar for all fatty acids and 3-fold higher than in the experiments without skin pretreatment. q
Journal of Pharmaceutical and Biomedical Analysis, 2001
A direct, very sensitive, simple and rapid high-performance liquid chromatographic (HPLC) method ... more A direct, very sensitive, simple and rapid high-performance liquid chromatographic (HPLC) method for the determination of piroxicam, with tenoxicam as internal standard, has been developed and validated. Samples were chromatographed on a 5 mm Scharlau C 18 column. The mobile phase was a mixture of acetonitrile-acetic acid 4% (pH 2.8) (45:55, v/v). Detection was at 354 nm and the run time was 7 min. The limit of detection was 0.025 mg/ml. The detector response was found to be linear in the concentration range 0.05-9 mg/ml. This HPLC assay has been applied to measure the 'in vitro' percutaneous permeation of piroxicam through abdominal hairless rat skin, using Franz-type diffusion cells, in order to obtain the concentration-time profiles of piroxicam.
Solid complexes of tenoxicam (TEN) with cyclodextrins (CDs), in a 1:1 molar ratio, were obtained ... more Solid complexes of tenoxicam (TEN) with cyclodextrins (CDs), in a 1:1 molar ratio, were obtained by the coprecipitation method and characterized by x-ray diffractometry, infrared spectroscopy, and differential scanning calorimetry. The binding capacity of the CDs with TEN was also demonstrated in aqueous solution and in water-propylene glycol mixtures. The purpose of this study was to determine the effect of CDs on the in vitro percutaneous penetration of TEN from carbopol gels, taking into account the role of the CD cavity size and the nature of the substituents. The effect of pretreatment was studied too. In vitro permeation experiments were carried out on Franz diffusion cells using cellulose nitrate membranes and abdominal rat skin. In these results, the release rates of the drug scarcely decreased when the CDs were added, probably because of a lower concentration of the free drug and an increased gel viscosity. However, it was also found that CDs, particularly gamma-CD and M-beta-CD, can improve slightly TEN absorption through the skin. Pretreatment studies with CDs, however, provided no effects on TEN permeation, but lag time was markedly reduced, suggesting a faster partitioning of TEN into the skin. Therefore, the use of pretreatment with CDs would be interesting when a quick action of the drug is desired.
The influence of propylene glycol (PG) on the in vitro penetration of diclofenac sodium (DFS) thr... more The influence of propylene glycol (PG) on the in vitro penetration of diclofenac sodium (DFS) through a synthetic membrane and abdominal rat skin from carbopol gels was investigated using Franz-type diffusion cells. The combined effect of isopropyl myristate (IPM) and PG was ...
Journal of Chromatography B-analytical Technologies in The Biomedical and Life Sciences, 2003
CAT ((+)-(13aS)-deoxytylophorinine) is a novel anticancer drug belonging to phenanthroindolizidin... more CAT ((+)-(13aS)-deoxytylophorinine) is a novel anticancer drug belonging to phenanthroindolizidine alkaloids. A sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of CAT and its pharmacologically active 3-O-desmethyl metabolite (S-4) was developed and validated in rat plasma using rotundine as the internal standard (IS). CAT, S-4 and IS were extracted by acetonitrile protein precipitation and separated on an Eclipse XDB-C18 column (1.8μm, 4.6mm×50mm) with acetonitrile-water (27:73, v/v) mobile phase containing 0.1% formic acid at a 0.4mL/min flow rate. Positive ion electrospray ionization in multiple reaction monitoring mode was employed to measure CAT, S-4 and IS by monitoring the transitions m/z 364.2→70.1 for CAT, 350.1→70.1 for S-4 and 356.2→192.2 for IS. Good linear correlation (r(2)>0.991) was achieved for CAT and S-4 over the range of 0.214-128.16 and 0.044-11.00ng/mL, respectively. The lower limit of quantification was 0.214ng/mL for CAT and 0.044ng/mL for S-4, using 50μL rat plasma samples. The intra- and inter-day precisions were not exceed 15% and the accuracy ranged between 94.80% and 108.22%. The average extraction recoveries of both analytes were greater than 94.62%. The method was successfully applied to the pharmacokinetic study of CAT and S-4 in rats after oral administration.
European Journal of Pharmaceutics and Biopharmaceutics, 2003
Acyclovir is one of the most effective and selective agents against viruses of the herpes group. ... more Acyclovir is one of the most effective and selective agents against viruses of the herpes group. In order to increase its antiviral activity, acyclovir loaded microparticles, prepared by an O/W solvent evaporation method were developed. Their antiviral activity against herpes simplex virus type 1 (HSV-1) and toxicity were evaluated on Vero cells and then compared with those presented by a drug solution. The 50% inhibitory concentration (IC 50 ) values for acyclovir loaded microspheres determined by plaque reduction assays at 48 and 96 h, were found to be 1.06^0.01 mM and 0.15^0.03 mM, respectively, while the equivalent values obtained for an acyclovir solution were 1.28^0.04 mM at 48 h and 0.27^0.02 mM at 96 h. These results indicate that acyclovir shows a higher antiviral activity, against herpes simplex virus type 1, when this drug was loaded in microparticles rather than as a drug solution, especially after 96 h of incubation. The toxicity of these microparticles was determined by the MTT test at 48 and 96 h. At 48 h only a small toxicity was found (cell viability ranged from 72 to 82%, with the higher concentration tested) and it could not be attributed to the microparticles, since the acyclovir control solution showed similar toxicity values. However, after 96 h a higher toxicity was observed with acyclovir microparticles as well as with the unloaded ones (cell viability located between 60 and 70%). In summary, acyclovir-loaded microparticles have shown to be promising carriers for the effective delivery of acyclovir in the treatment of HSV-1 infections in cells so they can have a potential use in vivo. q
The goal of this work was to increase the amount of acyclovir (ACV) in the basal epidermis, site ... more The goal of this work was to increase the amount of acyclovir (ACV) in the basal epidermis, site of Herpes virus simplex infections, using microparticles as carriers.
A direct, simple and rapid high-performance liquid chromatographic method has been developed for ... more A direct, simple and rapid high-performance liquid chromatographic method has been developed for the determination of ketoprofen with ibuprofen as internal standard. Samples were chromatographed on a 5 mm Kromasil 100 C column. The 18 mobile phase was a mixture of acetonitrile-0.01 M KH PO adjusted to pH 1.5 with orthophosphoric acid 85% (60:40, 2 4 v / v). Detection was at 260 nm and the run time was 10 min. The detector response was found to be linear in the concentration range 0.02 to 40 mg / ml. This HPLC assay has been applied to measure the ''in vitro'' percutaneous penetration of ketoprofen through rat skin.
European Journal of Drug Metabolism and Pharmacokinetics, 1998
Nonionic surfactants, which are a safe class of enhancers, may offer means of enhancing drug perm... more Nonionic surfactants, which are a safe class of enhancers, may offer means of enhancing drug permeation through the skin. In order to determine this effect, the influence of four nonionic surfactants on the percutaneous absorption of diclofenac sodium from carbopol gels containing 40% propylene glycol was investigated. In vitro diffusion experiments were carried out using excised full-thickness abdominal rat skin as well as cellulose nitrate membranes. The data of this study clearly revealed that Tween 80 decreased diclofenac penetration rate. This was due to a decrease in thermodynamic activity as a result of micellar complexation. In contrast, the more hydrophobic sorbitans enhanced diclofenac skin penetration, probably due to changes in the barrier properties of the skin and in the vehicle-stratum corneum partition coefficient. The most enhancing effect was induced by Span 20, a surfactant with a C12 saturated hydrophobic group. However, diffusional lag times for all the tested surfactants were longer than for the control gel.
Skin Pharmacology and Applied Skin Physiology, 2001
The interactions between piroxicam (Px) and hydroxypropyl-beta-cyclodextrin (HPbetaCD) were thoro... more The interactions between piroxicam (Px) and hydroxypropyl-beta-cyclodextrin (HPbetaCD) were thoroughly investigated both in solution and the solid state. The solubility studies have demonstrated the formation of a Px:HPbetaCD inclusion complex with 1:1 stoichiometry. The addition of propylene glycol to the medium produced less stable complexes, revealing the fact of this co-solvent probably acting as a competing agent. Equimolecular Px:HPbetaCD solid systems were prepared using the co-precipitation method and then fully characterized by X-ray diffractometry, infrared spectra and differential scanning calorimetry. A topical gel formulation containing Px, as inclusion complex with HPbetaCD, was developed in order to study the influence of Px complexation on its release rate and skin percutaneous permeation. The formation of Px:HPbetaCD complexes did not increase either Px release from the vehicle or its skin permeation. However, Px complexation with HPbetaCD allowed the incorporation of a higher quantity of Px into the gel, which resulted in a considerable increase in the Px released and permeated. Skin pretreatment with different HPbetaCD solutions, followed by the application of control gel, showed no enhancing capacity. The amount of Px retained in the skin, after pretreatment experiments, was found to be very similar to that obtained without skin pretreatment and was observed to be related to flux values through the skin.
European Journal of Pharmaceutics and Biopharmaceutics, 2001
The in¯uence of oleic acid (OA) on the in vitro percutaneous absorption of tenoxicam (TEN) and it... more The in¯uence of oleic acid (OA) on the in vitro percutaneous absorption of tenoxicam (TEN) and its combined effect with propylene glycol (PG) was studied using Franz-type diffusion cells. Furthermore, at de®ned concentrations of OA, complexes of the drug with cyclodextrins (MbCD and gCD) were added because their combined use may be an interesting approach to raise TEN¯ux. In addition, the amount of TEN retained in the skin after topical administration of several formulations was determined.
The in vitro release of piroxicam from carbomer gels and its penetration through isopropyl myrist... more The in vitro release of piroxicam from carbomer gels and its penetration through isopropyl myristate impregnated membranes and abdominal rat skin were investigated. Attempts were made to relate the differences in the release rate with physicochemical properties of the drug and the vehicle. The results showed that piroxicam is released from the topical gel formulations and diffuses through skin. It is suggested that although piroxicam flux across abdominal rat skin was lower than through isopropyl myristate membranes, this kind of membranes can be used in preliminary screening among the different piroxicam formulations.
European Journal of Pharmaceutics and Biopharmaceutics, 2000
The enhancing effect of several fatty acids from different subclasses: saturated (lauric acid), m... more The enhancing effect of several fatty acids from different subclasses: saturated (lauric acid), mono-unsaturated (oleic acid) and polyunsaturated (linoleic and linolenic acids) in the percutaneous absorption of piroxicam was investigated. These fatty acids were applied on the skin membrane in three different ways: included in the vehicle, as a pretreatment or both. An increase in piroxicam¯ux value was found for lauric and oleic acids in the following order: skin pretreatment with 5% fatty acids followed by application of gels containing 5% fatty acids . skin pretreatment with 5% fatty acids followed application of control gel . gel containing 5% fatty acids without skin pretreatment. For linoleic and linolenic acids, the piroxicam¯ux in the two pretreatment experiments was almost the same, although higher than when fatty acids were included in the formulation. Skin pretreatment with 5% linolenic acid in propylene glycol followed by application of control gel or a gel containing 5% linolenic acid, showed the highest enhancing capacity. After skin pretreatment with fatty acids, the lag time values decreased nearly three times compared to those obtained when the same fatty acids were included in the formulation. The amount of piroxicam retained in the skin after pretreatment with fatty acids was found to be very similar for all fatty acids and 3-fold higher than in the experiments without skin pretreatment. q
Journal of Pharmaceutical and Biomedical Analysis, 2001
A direct, very sensitive, simple and rapid high-performance liquid chromatographic (HPLC) method ... more A direct, very sensitive, simple and rapid high-performance liquid chromatographic (HPLC) method for the determination of piroxicam, with tenoxicam as internal standard, has been developed and validated. Samples were chromatographed on a 5 mm Scharlau C 18 column. The mobile phase was a mixture of acetonitrile-acetic acid 4% (pH 2.8) (45:55, v/v). Detection was at 354 nm and the run time was 7 min. The limit of detection was 0.025 mg/ml. The detector response was found to be linear in the concentration range 0.05-9 mg/ml. This HPLC assay has been applied to measure the 'in vitro' percutaneous permeation of piroxicam through abdominal hairless rat skin, using Franz-type diffusion cells, in order to obtain the concentration-time profiles of piroxicam.
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Papers by Susana Santoyo