Objective: The objective of this investigation is to develop mathematical equation to understand ... more Objective: The objective of this investigation is to develop mathematical equation to understand the impact of variables and establish statistical control over transdermal iontophoretic delivery of tacrine hydrochloride. In addition, possibility of using conductivity measurements as a tool of predicting ionic mobility of the participating ions for the application of iontophoretic delivery was explored. Methods: Central composite design was applied to study effect of independent variables like current strength, buffer molarity, and drug concentration on iontophoretic tacrine permeation flux. Molar conductivity was determined to evaluate electro-migration of tacrine ions with application of Kohlrausch’s law. Results: The developed mathematic equation not only reveals drug concentration as the most significant variable regulating tacrine permeation, followed by current strength and buffer molarity, but also is capable to optimize tacrine permeation with respective combination of independent variables to achieve desired therapeutic plasma concentration of tacrine in treatment of Alzheimer’s disease. Moreover, relative higher mobility of sodium and chloride ions was observed as compared to estimated tacrine ion mobility. Conclusions: This investigation utilizes the design of experiment approach and extends the primary understanding of imapct of electronic and formulation variables on the tacrine permeation for the formulation development of iontophoretic tacrine delivery.
In the recent decade, skin delivery (topical and transdermal) has gained an unprecedented popular... more In the recent decade, skin delivery (topical and transdermal) has gained an unprecedented popularity, especially due to increased incidences of chronic skin diseases, demand for targeted and patient compliant delivery, and interest in life cycle management strategies among pharmaceutical companies. Literature review of recent publications indicates that among various skin delivery systems, lipid-based delivery systems (vesicular carriers and lipid particulate systems) have been the most successful. Vesicular carriers consist of liposomes, ultradeformable liposomes, and ethosomes, while lipid particulate systems consist of lipospheres, solid lipid nanoparticles, and nanostructured lipid carriers. These systems can increase the skin drug transport by improving drug solubilization in the formulation, drug partitioning into the skin, and fluidizing skin lipids. Considering that lipid-based delivery systems are regarded as safe and efficient, they are proving to be an attractive delivery strategy for the pharmaceutical as well as cosmeceutical drug substances. However, development of these delivery systems requires comprehensive understanding of physicochemical characteristics of drug and delivery carriers, formulation and process variables, mechanism of skin delivery, recent technological advancements, specific limitations, and regulatory considerations. Therefore, this review article encompasses recent research advances addressing the aforementioned issues.
Objective: The objective of this investigation is to develop mathematical equation to understand ... more Objective: The objective of this investigation is to develop mathematical equation to understand the impact of variables and establish statistical control over transdermal iontophoretic delivery of tacrine hydrochloride. In addition, possibility of using conductivity measurements as a tool of predicting ionic mobility of the participating ions for the application of iontophoretic delivery was explored. Method: Central composite design was applied to study effect of independent variables like current strength, buffer molarity, and drug concentration on iontophoretic tacrine permeation flux. Molar conductivity was determined to evaluate electro migration of tacrine ions with application of Kohlrausch’s law. Results: The developed mathematic equation not only reveals drug concentration as the most significant variable regulating tacrine permeation, followed by current strength and buffer molarity, but also is capable to optimize tacrine permeation with respective combination of independent variables to achieve desired therapeutic plasma concentration of tacrine in treatment of Alzheimer’s disease. Moreover, relative higher mobility of sodium and chloride ions was observed as compared to estimated tacrine ion mobility. Conclusion: This investigation utilizes the design of exprement approach and extends the primary understanding of imapct of electronic and formulation variables on the tacrine permeation for the formulation development of iontophoretic tacrine delivery.
Objective: To select a suitable ethosome-loaded Carbopol hydrogel formulation, specifically tailo... more Objective: To select a suitable ethosome-loaded Carbopol hydrogel formulation, specifically tailored for transdermal application that exhibits (i) plastic flow with yield stress of approximately 50-80 Pa at low polymer concentration, (ii) relatively frequency independent elastic (G’) and viscous (G”) properties, and (iii) thermal stability. Method: Carbopol (C71, C934, C941, C971 or C974) hydrogels were prepared by dispersing Carbopol in distilled water followed neutralization by sodium hydroxide. The effects of Carbopol grade, Carbopol concentration, ethosome addition and temperature on flow (yield stress and viscosity) and viscoelastic (G’ and G”) properties of Carbopol hydrogel were evaluated. Based on the aforementioned rheological properties evaluated, suitable ethosome-loaded Carbopol hydrogel was selected. In-vitro permeation studies of diclofenac using rat skin were further conducted on ethosome-loaded Carbopol hydrogel along with diclofenac-loaded ethosomal formulation as control. Results: Based on preliminary screening, C934, C971 and C974 grades were selected and further evaluated for flow and viscoelastic properties. It was observed that ethosome-loaded C974 hydrogel at concentration of 0.50% and 0.75% w/w, respectively, demonstrated acceptable plastic flow with distinct yield stress and a frequency independent G’ and G”. Furthermore, the flow and viscoelastic properties were maintained at the 4°C, 25°C and 32°C. The results from in-vitro skin permeation studies indicate that ethosome-loaded C974 hydrogel at 0.5% w/w polymer concentration exhibited similar skin permeation as that of ethosomal formulation. Conclusion: The results indicate that suitable rheological properties of C974 could facilitate in achieving desired skin permeation of diclofenac while acting as an efficient carrier system for ethosomal vesicles.
The objective of this study was to fabricate and understand ethosomal formulations of diclofenac ... more The objective of this study was to fabricate and understand ethosomal formulations of diclofenac (DF) for enhanced anti-inflammatory activity using quality by design approach. DF-loaded ethosomal formulations were prepared using 4 Â 5 full-factorial design with phosphatidylcholine:cholesterol (PC:CH) ratios ranging between 50:50 and 90:10, and ethanol concentration ranging between 0% and 30% as formulation variables. These formulations were characterized in terms of physicochemical properties and skin permeation kinetics. The interaction of formulation variables had a significant effect on both physicochemical properties and permeation kinetics. The results of multivariate regression analysis illustrated that vesicle size and elasticity of ethosomes were the dominating physicochemical properties affecting skin permeation, and could be suitably controlled by manipulation of formulation variables to optimize the formulation and enhance the skin permeation of DF-loaded ethosomes. The optimized formulation had ethanol concentration of 22.9% and PC:CH ratio of 88.4:11.6, with vesicle size of 144 ± 5 nm, zeta potential of À23.0 ± 3.76 mV, elasticity of 2.48 ± 0.75 and entrapment efficiency of 71 ± 4%. Permeation flux for the optimized formulation was 12.9 ± 1.0 mg/h cm 2 , which was significantly higher than the drug-loaded conventional liposome, ethanolic or aqueous solution. The in vivo study indicated that optimized ethosomal hydrogel exhibited enhanced anti-inflammatory activity compared with liposomal and plain drug hydrogel formulations.
Freshly excised rat skin and side-by-side permeation cells were used to study the effect of
elect... more Freshly excised rat skin and side-by-side permeation cells were used to study the effect of electronic and formulation variables on transdermal iontophoretic delivery of tacrine. Current strength at 0.1–0.3mA was observed to be the driving force resulting in tacrine permation flux of 30.3–366.6mg/cm 2 /h. Depot formation of tacrine and altered skin permeability resulted in post iontophoretic flux even after termination of applied current. Increase in the duration of current application did not show significant difference in tacrine permeation flux upto 6h. Tacrine permeation was directly proportional to tacrine concentration upto 10mg/ml but further increase in concentration (upto 20mg/ml) exhibited permeation flux plateau. Buffer molarity had an inverse relationship on permeation flux and the presence of co-ions in formulation exhibited reduced permeation flux. Permeation flux decreased when pH of formulation was successively increased from 7.0 to 10.0 suggesting electromigration of tacrine. Alternate buffer systems including HEPES and Tris showed improved tacrine permeation due to their larger ion size compared to phosphate buffer ions. The results of this study show that transdermal tacrine permeation can be controlled by electronic and formulation variables which would be useful for the development of transdermal iontophoretic delivery of tacrine for the treatment of Alzehimer’s disease.
Abstract
Objective: To select a suitable ethosome-loaded Carbopol hydrogel
formulation, specific... more Abstract Objective: To select a suitable ethosome-loaded Carbopol hydrogel formulation, specifically tailored for transdermal application that exhibits (i) plastic flow with yield stress of approximately 50-80 Pa at low polymer concentration, (ii) relatively frequency independent elastic (G’) and viscous (G”) properties, and (iii) thermal stability. Method: Carbopol (C71, C934, C941, C971 or C974) hydrogels were prepared by dispersing Carbopol in distilled water followed neutralization by sodium hydroxide. The effects of Carbopol grade, Carbopol concentration, ethosome addition and temperature on flow (yield stress and viscosity) and viscoelastic (G’ and G”) properties of Carbopol hydrogel were evaluated. Based on the aforementioned rheological properties evaluated, suitable ethosome-loaded Carbopol hydrogel was selected. In-vitro permeation studies of diclofenac using rat skin were further conducted on ethosome-loaded Carbopol hydrogel along with diclofenac-loaded ethosomal formulation as control. Results: Based on preliminary screening, C934, C971 and C974 grades were selected and further evaluated for flow and viscoelastic properties. It was observed that ethosome-loaded C974 hydrogel at concentration of 0.50% and 0.75% w/w, respectively, demonstrated acceptable plastic flow with distinct yield stress and a frequency independent G’ and G”. Furthermore, the flow and viscoelastic properties were maintained at the 4°C, 25°C and 32°C. The results from in-vitro skin permeation studies indicate that ethosome-loaded C974 hydrogel at 0.5% w/w polymer concentration exhibited similar skin permeation as that of ethosomal formulation. Conclusion: The results indicate that suitable rheological properties of C974 could facilitate in achieving desired skin permeation of diclofenac while acting as an efficient carrier system for ethosomal vesicles
The objective of this study was to fabricate and understand ethosomal formulations of diclofenac ... more The objective of this study was to fabricate and understand ethosomal formulations of diclofenac (DF) for enhanced anti-inflammatory activity using quality by design approach. DF-loaded ethosomal formulations were prepared using 4 Â 5 full-factorial design with phosphatidylcholine:cholesterol (PC:CH) ratios ranging between 50:50 and 90:10, and ethanol concentration ranging between 0% and 30% as formulation variables. These formulations were characterized in terms of physicochemical properties and skin permeation kinetics. The interaction of formulation variables had a significant effect on both physicochemical properties and permeation kinetics. The results of multivariate regression analysis illustrated that vesicle size and elasticity of ethosomes were the dominating physicochemical properties affecting skin permeation, and could be suitably controlled by manipulation of formulation variables to optimize the formulation and enhance the skin permeation of DF-loaded ethosomes. The optimized formulation had ethanol concentration of 22.9% and PC:CH ratio of 88.4:11.6, with vesicle size of 144 ± 5 nm, zeta potential of À23.0 ± 3.76 mV, elasticity of 2.48 ± 0.75 and entrapment efficiency of 71 ± 4%. Permeation flux for the optimized formulation was 12.9 ± 1.0 mg/h cm 2 , which was significantly higher than the drug-loaded conventional liposome, ethanolic or aqueous solution. The in vivo study indicated that optimized ethosomal hydrogel exhibited enhanced anti-inflammatory activity compared with liposomal and plain drug hydrogel formulations.
Identification of lead compounds with higher molecular weight and lower aqueous solubility
has be... more Identification of lead compounds with higher molecular weight and lower aqueous solubility has become increasingly prevalent with the advent of high throughput screening. Poor aqueous solubility of these lipophilic compounds can drastically affect the dissolution rate and subsequently the drug absorbed in the systemic circulation, imposing a significant burden of time and money during drug development process. Various pre-formulation and formulation strategies have been applied in the past that can improve the aqueous solubility of lipophilic compounds by manipulating either the crystal lattice properties or the activity coefficient of a solute in solution or both, if possible. However, despite various strategies available in the armor of formulation scientist, solubility issue still remains an overriding problem in the drug development process. It is perhaps due to the insufficient conceptual understanding of solubility and dissolution phenomenon that hinders the judgment in selecting suitable strategy for improving aqueous solubility and/or dissolution rate. This article, therefore, focuses on (i) revisiting the theoretical and mathematical concepts associated with solubility and dissolution, (ii) their application in making rationale decision for selecting suitable pre-formulation and formulation strategies and (iii) the relevant research performed in this field in past decade.
Objective: The objective of this investigation is to develop mathematical equation to understand ... more Objective: The objective of this investigation is to develop mathematical equation to understand the impact of variables and establish statistical control over transdermal iontophoretic delivery of tacrine hydrochloride. In addition, possibility of using conductivity measurements as a tool of predicting ionic mobility of the participating ions for the application of iontophoretic delivery was explored. Methods: Central composite design was applied to study effect of independent variables like current strength, buffer molarity, and drug concentration on iontophoretic tacrine permeation flux. Molar conductivity was determined to evaluate electro-migration of tacrine ions with application of Kohlrausch’s law. Results: The developed mathematic equation not only reveals drug concentration as the most significant variable regulating tacrine permeation, followed by current strength and buffer molarity, but also is capable to optimize tacrine permeation with respective combination of independent variables to achieve desired therapeutic plasma concentration of tacrine in treatment of Alzheimer’s disease. Moreover, relative higher mobility of sodium and chloride ions was observed as compared to estimated tacrine ion mobility. Conclusions: This investigation utilizes the design of experiment approach and extends the primary understanding of imapct of electronic and formulation variables on the tacrine permeation for the formulation development of iontophoretic tacrine delivery.
In the recent decade, skin delivery (topical and transdermal) has gained an unprecedented popular... more In the recent decade, skin delivery (topical and transdermal) has gained an unprecedented popularity, especially due to increased incidences of chronic skin diseases, demand for targeted and patient compliant delivery, and interest in life cycle management strategies among pharmaceutical companies. Literature review of recent publications indicates that among various skin delivery systems, lipid-based delivery systems (vesicular carriers and lipid particulate systems) have been the most successful. Vesicular carriers consist of liposomes, ultradeformable liposomes, and ethosomes, while lipid particulate systems consist of lipospheres, solid lipid nanoparticles, and nanostructured lipid carriers. These systems can increase the skin drug transport by improving drug solubilization in the formulation, drug partitioning into the skin, and fluidizing skin lipids. Considering that lipid-based delivery systems are regarded as safe and efficient, they are proving to be an attractive delivery strategy for the pharmaceutical as well as cosmeceutical drug substances. However, development of these delivery systems requires comprehensive understanding of physicochemical characteristics of drug and delivery carriers, formulation and process variables, mechanism of skin delivery, recent technological advancements, specific limitations, and regulatory considerations. Therefore, this review article encompasses recent research advances addressing the aforementioned issues.
Objective: The objective of this investigation is to develop mathematical equation to understand ... more Objective: The objective of this investigation is to develop mathematical equation to understand the impact of variables and establish statistical control over transdermal iontophoretic delivery of tacrine hydrochloride. In addition, possibility of using conductivity measurements as a tool of predicting ionic mobility of the participating ions for the application of iontophoretic delivery was explored. Method: Central composite design was applied to study effect of independent variables like current strength, buffer molarity, and drug concentration on iontophoretic tacrine permeation flux. Molar conductivity was determined to evaluate electro migration of tacrine ions with application of Kohlrausch’s law. Results: The developed mathematic equation not only reveals drug concentration as the most significant variable regulating tacrine permeation, followed by current strength and buffer molarity, but also is capable to optimize tacrine permeation with respective combination of independent variables to achieve desired therapeutic plasma concentration of tacrine in treatment of Alzheimer’s disease. Moreover, relative higher mobility of sodium and chloride ions was observed as compared to estimated tacrine ion mobility. Conclusion: This investigation utilizes the design of exprement approach and extends the primary understanding of imapct of electronic and formulation variables on the tacrine permeation for the formulation development of iontophoretic tacrine delivery.
Objective: To select a suitable ethosome-loaded Carbopol hydrogel formulation, specifically tailo... more Objective: To select a suitable ethosome-loaded Carbopol hydrogel formulation, specifically tailored for transdermal application that exhibits (i) plastic flow with yield stress of approximately 50-80 Pa at low polymer concentration, (ii) relatively frequency independent elastic (G’) and viscous (G”) properties, and (iii) thermal stability. Method: Carbopol (C71, C934, C941, C971 or C974) hydrogels were prepared by dispersing Carbopol in distilled water followed neutralization by sodium hydroxide. The effects of Carbopol grade, Carbopol concentration, ethosome addition and temperature on flow (yield stress and viscosity) and viscoelastic (G’ and G”) properties of Carbopol hydrogel were evaluated. Based on the aforementioned rheological properties evaluated, suitable ethosome-loaded Carbopol hydrogel was selected. In-vitro permeation studies of diclofenac using rat skin were further conducted on ethosome-loaded Carbopol hydrogel along with diclofenac-loaded ethosomal formulation as control. Results: Based on preliminary screening, C934, C971 and C974 grades were selected and further evaluated for flow and viscoelastic properties. It was observed that ethosome-loaded C974 hydrogel at concentration of 0.50% and 0.75% w/w, respectively, demonstrated acceptable plastic flow with distinct yield stress and a frequency independent G’ and G”. Furthermore, the flow and viscoelastic properties were maintained at the 4°C, 25°C and 32°C. The results from in-vitro skin permeation studies indicate that ethosome-loaded C974 hydrogel at 0.5% w/w polymer concentration exhibited similar skin permeation as that of ethosomal formulation. Conclusion: The results indicate that suitable rheological properties of C974 could facilitate in achieving desired skin permeation of diclofenac while acting as an efficient carrier system for ethosomal vesicles.
The objective of this study was to fabricate and understand ethosomal formulations of diclofenac ... more The objective of this study was to fabricate and understand ethosomal formulations of diclofenac (DF) for enhanced anti-inflammatory activity using quality by design approach. DF-loaded ethosomal formulations were prepared using 4 Â 5 full-factorial design with phosphatidylcholine:cholesterol (PC:CH) ratios ranging between 50:50 and 90:10, and ethanol concentration ranging between 0% and 30% as formulation variables. These formulations were characterized in terms of physicochemical properties and skin permeation kinetics. The interaction of formulation variables had a significant effect on both physicochemical properties and permeation kinetics. The results of multivariate regression analysis illustrated that vesicle size and elasticity of ethosomes were the dominating physicochemical properties affecting skin permeation, and could be suitably controlled by manipulation of formulation variables to optimize the formulation and enhance the skin permeation of DF-loaded ethosomes. The optimized formulation had ethanol concentration of 22.9% and PC:CH ratio of 88.4:11.6, with vesicle size of 144 ± 5 nm, zeta potential of À23.0 ± 3.76 mV, elasticity of 2.48 ± 0.75 and entrapment efficiency of 71 ± 4%. Permeation flux for the optimized formulation was 12.9 ± 1.0 mg/h cm 2 , which was significantly higher than the drug-loaded conventional liposome, ethanolic or aqueous solution. The in vivo study indicated that optimized ethosomal hydrogel exhibited enhanced anti-inflammatory activity compared with liposomal and plain drug hydrogel formulations.
Freshly excised rat skin and side-by-side permeation cells were used to study the effect of
elect... more Freshly excised rat skin and side-by-side permeation cells were used to study the effect of electronic and formulation variables on transdermal iontophoretic delivery of tacrine. Current strength at 0.1–0.3mA was observed to be the driving force resulting in tacrine permation flux of 30.3–366.6mg/cm 2 /h. Depot formation of tacrine and altered skin permeability resulted in post iontophoretic flux even after termination of applied current. Increase in the duration of current application did not show significant difference in tacrine permeation flux upto 6h. Tacrine permeation was directly proportional to tacrine concentration upto 10mg/ml but further increase in concentration (upto 20mg/ml) exhibited permeation flux plateau. Buffer molarity had an inverse relationship on permeation flux and the presence of co-ions in formulation exhibited reduced permeation flux. Permeation flux decreased when pH of formulation was successively increased from 7.0 to 10.0 suggesting electromigration of tacrine. Alternate buffer systems including HEPES and Tris showed improved tacrine permeation due to their larger ion size compared to phosphate buffer ions. The results of this study show that transdermal tacrine permeation can be controlled by electronic and formulation variables which would be useful for the development of transdermal iontophoretic delivery of tacrine for the treatment of Alzehimer’s disease.
Abstract
Objective: To select a suitable ethosome-loaded Carbopol hydrogel
formulation, specific... more Abstract Objective: To select a suitable ethosome-loaded Carbopol hydrogel formulation, specifically tailored for transdermal application that exhibits (i) plastic flow with yield stress of approximately 50-80 Pa at low polymer concentration, (ii) relatively frequency independent elastic (G’) and viscous (G”) properties, and (iii) thermal stability. Method: Carbopol (C71, C934, C941, C971 or C974) hydrogels were prepared by dispersing Carbopol in distilled water followed neutralization by sodium hydroxide. The effects of Carbopol grade, Carbopol concentration, ethosome addition and temperature on flow (yield stress and viscosity) and viscoelastic (G’ and G”) properties of Carbopol hydrogel were evaluated. Based on the aforementioned rheological properties evaluated, suitable ethosome-loaded Carbopol hydrogel was selected. In-vitro permeation studies of diclofenac using rat skin were further conducted on ethosome-loaded Carbopol hydrogel along with diclofenac-loaded ethosomal formulation as control. Results: Based on preliminary screening, C934, C971 and C974 grades were selected and further evaluated for flow and viscoelastic properties. It was observed that ethosome-loaded C974 hydrogel at concentration of 0.50% and 0.75% w/w, respectively, demonstrated acceptable plastic flow with distinct yield stress and a frequency independent G’ and G”. Furthermore, the flow and viscoelastic properties were maintained at the 4°C, 25°C and 32°C. The results from in-vitro skin permeation studies indicate that ethosome-loaded C974 hydrogel at 0.5% w/w polymer concentration exhibited similar skin permeation as that of ethosomal formulation. Conclusion: The results indicate that suitable rheological properties of C974 could facilitate in achieving desired skin permeation of diclofenac while acting as an efficient carrier system for ethosomal vesicles
The objective of this study was to fabricate and understand ethosomal formulations of diclofenac ... more The objective of this study was to fabricate and understand ethosomal formulations of diclofenac (DF) for enhanced anti-inflammatory activity using quality by design approach. DF-loaded ethosomal formulations were prepared using 4 Â 5 full-factorial design with phosphatidylcholine:cholesterol (PC:CH) ratios ranging between 50:50 and 90:10, and ethanol concentration ranging between 0% and 30% as formulation variables. These formulations were characterized in terms of physicochemical properties and skin permeation kinetics. The interaction of formulation variables had a significant effect on both physicochemical properties and permeation kinetics. The results of multivariate regression analysis illustrated that vesicle size and elasticity of ethosomes were the dominating physicochemical properties affecting skin permeation, and could be suitably controlled by manipulation of formulation variables to optimize the formulation and enhance the skin permeation of DF-loaded ethosomes. The optimized formulation had ethanol concentration of 22.9% and PC:CH ratio of 88.4:11.6, with vesicle size of 144 ± 5 nm, zeta potential of À23.0 ± 3.76 mV, elasticity of 2.48 ± 0.75 and entrapment efficiency of 71 ± 4%. Permeation flux for the optimized formulation was 12.9 ± 1.0 mg/h cm 2 , which was significantly higher than the drug-loaded conventional liposome, ethanolic or aqueous solution. The in vivo study indicated that optimized ethosomal hydrogel exhibited enhanced anti-inflammatory activity compared with liposomal and plain drug hydrogel formulations.
Identification of lead compounds with higher molecular weight and lower aqueous solubility
has be... more Identification of lead compounds with higher molecular weight and lower aqueous solubility has become increasingly prevalent with the advent of high throughput screening. Poor aqueous solubility of these lipophilic compounds can drastically affect the dissolution rate and subsequently the drug absorbed in the systemic circulation, imposing a significant burden of time and money during drug development process. Various pre-formulation and formulation strategies have been applied in the past that can improve the aqueous solubility of lipophilic compounds by manipulating either the crystal lattice properties or the activity coefficient of a solute in solution or both, if possible. However, despite various strategies available in the armor of formulation scientist, solubility issue still remains an overriding problem in the drug development process. It is perhaps due to the insufficient conceptual understanding of solubility and dissolution phenomenon that hinders the judgment in selecting suitable strategy for improving aqueous solubility and/or dissolution rate. This article, therefore, focuses on (i) revisiting the theoretical and mathematical concepts associated with solubility and dissolution, (ii) their application in making rationale decision for selecting suitable pre-formulation and formulation strategies and (iii) the relevant research performed in this field in past decade.
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impact of variables and establish statistical control over transdermal iontophoretic delivery of tacrine hydrochloride.
In addition, possibility of using conductivity measurements as a tool of predicting ionic mobility of
the participating ions for the application of iontophoretic delivery was explored.
Methods: Central composite design was applied to study effect of independent variables like current
strength, buffer molarity, and drug concentration on iontophoretic tacrine permeation flux. Molar conductivity
was determined to evaluate electro-migration of tacrine ions with application of Kohlrausch’s law.
Results: The developed mathematic equation not only reveals drug concentration as the most significant
variable regulating tacrine permeation, followed by current strength and buffer molarity, but also is capable
to optimize tacrine permeation with respective combination of independent variables to achieve desired
therapeutic plasma concentration of tacrine in treatment of Alzheimer’s disease. Moreover, relative higher
mobility of sodium and chloride ions was observed as compared to estimated tacrine ion mobility.
Conclusions: This investigation utilizes the design of experiment approach and extends the primary understanding
of imapct of electronic and formulation variables on the tacrine permeation for the formulation
development of iontophoretic tacrine delivery.
can increase the skin drug transport by improving drug solubilization in the formulation, drug partitioning into the skin, and fluidizing skin lipids. Considering that lipid-based delivery systems are regarded as safe and efficient, they are proving to be an attractive delivery strategy for the pharmaceutical as well as cosmeceutical drug substances. However, development of these delivery systems requires comprehensive understanding of physicochemical characteristics of drug and delivery carriers, formulation and process variables, mechanism of skin delivery, recent technological advancements, specific limitations, and regulatory considerations. Therefore, this review article encompasses recent
research advances addressing the aforementioned issues.
Method: Central composite design was applied to study effect of independent variables like current strength, buffer molarity, and drug concentration on iontophoretic tacrine permeation flux. Molar conductivity was determined to evaluate electro migration of tacrine ions with application of Kohlrausch’s law.
Results: The developed mathematic equation not only reveals drug concentration as the most significant variable regulating tacrine permeation, followed by current strength and buffer molarity, but also is capable to optimize tacrine permeation with respective combination of independent variables to achieve desired therapeutic plasma concentration of tacrine in treatment of Alzheimer’s disease. Moreover, relative higher mobility of sodium and chloride ions was observed as compared to estimated tacrine ion mobility.
Conclusion: This investigation utilizes the design of exprement approach and extends the primary understanding of imapct of electronic and formulation variables on the tacrine permeation for the formulation development of iontophoretic tacrine delivery.
electronic and formulation variables on transdermal iontophoretic delivery of tacrine. Current
strength at 0.1–0.3mA was observed to be the driving force resulting in tacrine permation flux
of 30.3–366.6mg/cm
2
/h. Depot formation of tacrine and altered skin permeability resulted in
post iontophoretic flux even after termination of applied current. Increase in the duration of
current application did not show significant difference in tacrine permeation flux upto 6h.
Tacrine permeation was directly proportional to tacrine concentration upto 10mg/ml but
further increase in concentration (upto 20mg/ml) exhibited permeation flux plateau. Buffer
molarity had an inverse relationship on permeation flux and the presence of co-ions in
formulation exhibited reduced permeation flux. Permeation flux decreased when pH of
formulation was successively increased from 7.0 to 10.0 suggesting electromigration of tacrine.
Alternate buffer systems including HEPES and Tris showed improved tacrine permeation due to
their larger ion size compared to phosphate buffer ions. The results of this study show that
transdermal tacrine permeation can be controlled by electronic and formulation variables
which would be useful for the development of transdermal iontophoretic delivery of tacrine for
the treatment of Alzehimer’s disease.
Objective: To select a suitable ethosome-loaded Carbopol hydrogel
formulation, specifically tailored for transdermal application that exhibits (i)
plastic flow with yield stress of approximately 50-80 Pa at low polymer
concentration, (ii) relatively frequency independent elastic (G’) and viscous
(G”) properties, and (iii) thermal stability.
Method: Carbopol (C71, C934, C941, C971 or C974) hydrogels were
prepared by dispersing Carbopol in distilled water followed neutralization
by sodium hydroxide. The effects of Carbopol grade, Carbopol
concentration, ethosome addition and temperature on flow (yield stress
and viscosity) and viscoelastic (G’ and G”) properties of Carbopol hydrogel
were evaluated. Based on the aforementioned rheological properties
evaluated, suitable ethosome-loaded Carbopol hydrogel was selected. In-vitro permeation studies of diclofenac using rat skin were further conducted on ethosome-loaded Carbopol
hydrogel along with diclofenac-loaded ethosomal formulation as control.
Results: Based on preliminary screening, C934, C971 and C974 grades were selected and further evaluated
for flow and viscoelastic properties. It was observed that ethosome-loaded C974 hydrogel at concentration of
0.50% and 0.75% w/w, respectively, demonstrated acceptable plastic flow with distinct yield stress and a
frequency independent G’ and G”. Furthermore, the flow and viscoelastic properties were maintained at the
4°C, 25°C and 32°C. The results from in-vitro skin permeation studies indicate that ethosome-loaded C974
hydrogel at 0.5% w/w polymer concentration exhibited similar skin permeation as that of ethosomal
formulation.
Conclusion: The results indicate that suitable rheological properties of C974 could facilitate in achieving
desired skin permeation of diclofenac while acting as an efficient carrier system for ethosomal vesicles
has become increasingly prevalent with the advent of high throughput screening. Poor
aqueous solubility of these lipophilic compounds can drastically affect the dissolution rate and
subsequently the drug absorbed in the systemic circulation, imposing a significant burden of
time and money during drug development process. Various pre-formulation and formulation
strategies have been applied in the past that can improve the aqueous solubility of lipophilic
compounds by manipulating either the crystal lattice properties or the activity coefficient of a
solute in solution or both, if possible. However, despite various strategies available in the armor
of formulation scientist, solubility issue still remains an overriding problem in the drug
development process. It is perhaps due to the insufficient conceptual understanding of
solubility and dissolution phenomenon that hinders the judgment in selecting suitable strategy
for improving aqueous solubility and/or dissolution rate. This article, therefore, focuses on
(i) revisiting the theoretical and mathematical concepts associated with solubility and
dissolution, (ii) their application in making rationale decision for selecting suitable pre-formulation and formulation strategies and (iii) the relevant research performed in this field in
past decade.
impact of variables and establish statistical control over transdermal iontophoretic delivery of tacrine hydrochloride.
In addition, possibility of using conductivity measurements as a tool of predicting ionic mobility of
the participating ions for the application of iontophoretic delivery was explored.
Methods: Central composite design was applied to study effect of independent variables like current
strength, buffer molarity, and drug concentration on iontophoretic tacrine permeation flux. Molar conductivity
was determined to evaluate electro-migration of tacrine ions with application of Kohlrausch’s law.
Results: The developed mathematic equation not only reveals drug concentration as the most significant
variable regulating tacrine permeation, followed by current strength and buffer molarity, but also is capable
to optimize tacrine permeation with respective combination of independent variables to achieve desired
therapeutic plasma concentration of tacrine in treatment of Alzheimer’s disease. Moreover, relative higher
mobility of sodium and chloride ions was observed as compared to estimated tacrine ion mobility.
Conclusions: This investigation utilizes the design of experiment approach and extends the primary understanding
of imapct of electronic and formulation variables on the tacrine permeation for the formulation
development of iontophoretic tacrine delivery.
can increase the skin drug transport by improving drug solubilization in the formulation, drug partitioning into the skin, and fluidizing skin lipids. Considering that lipid-based delivery systems are regarded as safe and efficient, they are proving to be an attractive delivery strategy for the pharmaceutical as well as cosmeceutical drug substances. However, development of these delivery systems requires comprehensive understanding of physicochemical characteristics of drug and delivery carriers, formulation and process variables, mechanism of skin delivery, recent technological advancements, specific limitations, and regulatory considerations. Therefore, this review article encompasses recent
research advances addressing the aforementioned issues.
Method: Central composite design was applied to study effect of independent variables like current strength, buffer molarity, and drug concentration on iontophoretic tacrine permeation flux. Molar conductivity was determined to evaluate electro migration of tacrine ions with application of Kohlrausch’s law.
Results: The developed mathematic equation not only reveals drug concentration as the most significant variable regulating tacrine permeation, followed by current strength and buffer molarity, but also is capable to optimize tacrine permeation with respective combination of independent variables to achieve desired therapeutic plasma concentration of tacrine in treatment of Alzheimer’s disease. Moreover, relative higher mobility of sodium and chloride ions was observed as compared to estimated tacrine ion mobility.
Conclusion: This investigation utilizes the design of exprement approach and extends the primary understanding of imapct of electronic and formulation variables on the tacrine permeation for the formulation development of iontophoretic tacrine delivery.
electronic and formulation variables on transdermal iontophoretic delivery of tacrine. Current
strength at 0.1–0.3mA was observed to be the driving force resulting in tacrine permation flux
of 30.3–366.6mg/cm
2
/h. Depot formation of tacrine and altered skin permeability resulted in
post iontophoretic flux even after termination of applied current. Increase in the duration of
current application did not show significant difference in tacrine permeation flux upto 6h.
Tacrine permeation was directly proportional to tacrine concentration upto 10mg/ml but
further increase in concentration (upto 20mg/ml) exhibited permeation flux plateau. Buffer
molarity had an inverse relationship on permeation flux and the presence of co-ions in
formulation exhibited reduced permeation flux. Permeation flux decreased when pH of
formulation was successively increased from 7.0 to 10.0 suggesting electromigration of tacrine.
Alternate buffer systems including HEPES and Tris showed improved tacrine permeation due to
their larger ion size compared to phosphate buffer ions. The results of this study show that
transdermal tacrine permeation can be controlled by electronic and formulation variables
which would be useful for the development of transdermal iontophoretic delivery of tacrine for
the treatment of Alzehimer’s disease.
Objective: To select a suitable ethosome-loaded Carbopol hydrogel
formulation, specifically tailored for transdermal application that exhibits (i)
plastic flow with yield stress of approximately 50-80 Pa at low polymer
concentration, (ii) relatively frequency independent elastic (G’) and viscous
(G”) properties, and (iii) thermal stability.
Method: Carbopol (C71, C934, C941, C971 or C974) hydrogels were
prepared by dispersing Carbopol in distilled water followed neutralization
by sodium hydroxide. The effects of Carbopol grade, Carbopol
concentration, ethosome addition and temperature on flow (yield stress
and viscosity) and viscoelastic (G’ and G”) properties of Carbopol hydrogel
were evaluated. Based on the aforementioned rheological properties
evaluated, suitable ethosome-loaded Carbopol hydrogel was selected. In-vitro permeation studies of diclofenac using rat skin were further conducted on ethosome-loaded Carbopol
hydrogel along with diclofenac-loaded ethosomal formulation as control.
Results: Based on preliminary screening, C934, C971 and C974 grades were selected and further evaluated
for flow and viscoelastic properties. It was observed that ethosome-loaded C974 hydrogel at concentration of
0.50% and 0.75% w/w, respectively, demonstrated acceptable plastic flow with distinct yield stress and a
frequency independent G’ and G”. Furthermore, the flow and viscoelastic properties were maintained at the
4°C, 25°C and 32°C. The results from in-vitro skin permeation studies indicate that ethosome-loaded C974
hydrogel at 0.5% w/w polymer concentration exhibited similar skin permeation as that of ethosomal
formulation.
Conclusion: The results indicate that suitable rheological properties of C974 could facilitate in achieving
desired skin permeation of diclofenac while acting as an efficient carrier system for ethosomal vesicles
has become increasingly prevalent with the advent of high throughput screening. Poor
aqueous solubility of these lipophilic compounds can drastically affect the dissolution rate and
subsequently the drug absorbed in the systemic circulation, imposing a significant burden of
time and money during drug development process. Various pre-formulation and formulation
strategies have been applied in the past that can improve the aqueous solubility of lipophilic
compounds by manipulating either the crystal lattice properties or the activity coefficient of a
solute in solution or both, if possible. However, despite various strategies available in the armor
of formulation scientist, solubility issue still remains an overriding problem in the drug
development process. It is perhaps due to the insufficient conceptual understanding of
solubility and dissolution phenomenon that hinders the judgment in selecting suitable strategy
for improving aqueous solubility and/or dissolution rate. This article, therefore, focuses on
(i) revisiting the theoretical and mathematical concepts associated with solubility and
dissolution, (ii) their application in making rationale decision for selecting suitable pre-formulation and formulation strategies and (iii) the relevant research performed in this field in
past decade.