Response Surface Methodology for Optimization of Ultrasound-Assisted Transdermal Delivery and Skin Retention of Asenapine Maleate

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Abstract

Purpose: Asenapine maleate (ASP) is an antipsychotic agent used in the treatment of schizophrenia and bipolar disorder. It has extremely low oral bioavailability of < 2%, necessitating the utilization of alternate route of administration. The objective of this work is to study and optimize the sonophoretic transdermal delivery and skin retention of ASP statistically, in Sprague-Dawley rat skin, using response surface methodology in Design of Experiments (DoE). Method: I-optimal design was employed, using the ultrasound (US) parameters viz., duration of US application, amplitude of US, and mode of US application (simultaneous application or pretreatment) as the input variables. Steady-state flux (J ss ) of ASP and amount of drug retained in skin after 24 h was taken as the output responses. Results: The model and dependent variables were found to be significant and representative of the data and response surface. While passive diffusion yielded J ss of 2.575 μg/cm 2 /h, the same values with US application ranged from 8.18 to 127.68 μg/cm 2 /h. Passive diffusion of drug showed 46.22 ± 5.2 μg/cm 2 of ASP retained in 24 h, while US application resulted in 99.07 to 1495.6 μg/cm 2 of drug retained in skin in 24 h. Based on the findings from optimization studies, 30 min of US application, with amplitude of 27–28, and simultaneous application mode was found to achieve the optimal transdermal drug flux, with slightly lower retention values in skin. Conclusion: The study found that the sonophoretic transdermal permeation and retention of ASP in vitro could be optimized using response surface methodology.

Original languageEnglish
JournalJournal of Pharmaceutical Innovation
DOIs
Publication statusAccepted/In press - 01-01-2019

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Skin
Pharmaceutical Preparations
Bipolar Disorder
Antipsychotic Agents
Biological Availability
Sprague Dawley Rats
Schizophrenia
Asenapine

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science
  • Drug Discovery

Cite this

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title = "Response Surface Methodology for Optimization of Ultrasound-Assisted Transdermal Delivery and Skin Retention of Asenapine Maleate",
abstract = "Purpose: Asenapine maleate (ASP) is an antipsychotic agent used in the treatment of schizophrenia and bipolar disorder. It has extremely low oral bioavailability of < 2{\%}, necessitating the utilization of alternate route of administration. The objective of this work is to study and optimize the sonophoretic transdermal delivery and skin retention of ASP statistically, in Sprague-Dawley rat skin, using response surface methodology in Design of Experiments (DoE). Method: I-optimal design was employed, using the ultrasound (US) parameters viz., duration of US application, amplitude of US, and mode of US application (simultaneous application or pretreatment) as the input variables. Steady-state flux (J ss ) of ASP and amount of drug retained in skin after 24 h was taken as the output responses. Results: The model and dependent variables were found to be significant and representative of the data and response surface. While passive diffusion yielded J ss of 2.575 μg/cm 2 /h, the same values with US application ranged from 8.18 to 127.68 μg/cm 2 /h. Passive diffusion of drug showed 46.22 ± 5.2 μg/cm 2 of ASP retained in 24 h, while US application resulted in 99.07 to 1495.6 μg/cm 2 of drug retained in skin in 24 h. Based on the findings from optimization studies, 30 min of US application, with amplitude of 27–28, and simultaneous application mode was found to achieve the optimal transdermal drug flux, with slightly lower retention values in skin. Conclusion: The study found that the sonophoretic transdermal permeation and retention of ASP in vitro could be optimized using response surface methodology.",
author = "Jyothsna Manikkath and Shenoy, {Gautham G.} and Sureshwar Pandey and Srinivas Mutalik",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s12247-019-09386-4",
language = "English",
journal = "Journal of Pharmaceutical Innovation",
issn = "1872-5120",
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T1 - Response Surface Methodology for Optimization of Ultrasound-Assisted Transdermal Delivery and Skin Retention of Asenapine Maleate

AU - Manikkath, Jyothsna

AU - Shenoy, Gautham G.

AU - Pandey, Sureshwar

AU - Mutalik, Srinivas

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Purpose: Asenapine maleate (ASP) is an antipsychotic agent used in the treatment of schizophrenia and bipolar disorder. It has extremely low oral bioavailability of < 2%, necessitating the utilization of alternate route of administration. The objective of this work is to study and optimize the sonophoretic transdermal delivery and skin retention of ASP statistically, in Sprague-Dawley rat skin, using response surface methodology in Design of Experiments (DoE). Method: I-optimal design was employed, using the ultrasound (US) parameters viz., duration of US application, amplitude of US, and mode of US application (simultaneous application or pretreatment) as the input variables. Steady-state flux (J ss ) of ASP and amount of drug retained in skin after 24 h was taken as the output responses. Results: The model and dependent variables were found to be significant and representative of the data and response surface. While passive diffusion yielded J ss of 2.575 μg/cm 2 /h, the same values with US application ranged from 8.18 to 127.68 μg/cm 2 /h. Passive diffusion of drug showed 46.22 ± 5.2 μg/cm 2 of ASP retained in 24 h, while US application resulted in 99.07 to 1495.6 μg/cm 2 of drug retained in skin in 24 h. Based on the findings from optimization studies, 30 min of US application, with amplitude of 27–28, and simultaneous application mode was found to achieve the optimal transdermal drug flux, with slightly lower retention values in skin. Conclusion: The study found that the sonophoretic transdermal permeation and retention of ASP in vitro could be optimized using response surface methodology.

AB - Purpose: Asenapine maleate (ASP) is an antipsychotic agent used in the treatment of schizophrenia and bipolar disorder. It has extremely low oral bioavailability of < 2%, necessitating the utilization of alternate route of administration. The objective of this work is to study and optimize the sonophoretic transdermal delivery and skin retention of ASP statistically, in Sprague-Dawley rat skin, using response surface methodology in Design of Experiments (DoE). Method: I-optimal design was employed, using the ultrasound (US) parameters viz., duration of US application, amplitude of US, and mode of US application (simultaneous application or pretreatment) as the input variables. Steady-state flux (J ss ) of ASP and amount of drug retained in skin after 24 h was taken as the output responses. Results: The model and dependent variables were found to be significant and representative of the data and response surface. While passive diffusion yielded J ss of 2.575 μg/cm 2 /h, the same values with US application ranged from 8.18 to 127.68 μg/cm 2 /h. Passive diffusion of drug showed 46.22 ± 5.2 μg/cm 2 of ASP retained in 24 h, while US application resulted in 99.07 to 1495.6 μg/cm 2 of drug retained in skin in 24 h. Based on the findings from optimization studies, 30 min of US application, with amplitude of 27–28, and simultaneous application mode was found to achieve the optimal transdermal drug flux, with slightly lower retention values in skin. Conclusion: The study found that the sonophoretic transdermal permeation and retention of ASP in vitro could be optimized using response surface methodology.

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