In vitro diffusion cell design and validation. I. A stability-indicating high-performance liquid chromatographic assay for betamethasone 17-valerate in purified isopropyl myristate receptor phase
- Smith, Eric W, Haigh, John M
- Authors: Smith, Eric W , Haigh, John M
- Date: 1989
- Language: English
- Type: text , Article
- Identifier: vital:6431 , http://hdl.handle.net/10962/d1006595
- Description: Introduction: The development of a reliable in vitro permeation system necessitates the use of a precise and accurate method of quantifying the amount of permeant partitioning from the membrane into the cell receptor phase. Aqueous donor and receptor chamber fluids have been used in the majority of reported investigations, which makes quantitative permeant analysis relatively facile. Alternatively, radiolabelled diffusants have been used and flux rates monitored by scintillation counting, obviating the need for chromatographic separation of the receptor-phase components. However, this technique is not applicable when nonlabelled compounds or commercial dosage forms are to be evaluated by a cell system. Furthermore, several studies indicate that aqueous receptor phases may not present an optimal partitioning environment for certain lipophilic permeants (1-4), thereby impairing accurate flux monitoring due to limited diffusant solubility. Several attempts have therefore been made to improve the partitioning environment within these systems, by the addition of surfactants for example (4). A lipophilic receptor environment appears beneficial for corticosteroid partitioning, and thus, the use of isopropyl myristate has been investigated because of its bipolar properties that tend to mimic the biochemical composition of the skin (5,6). Betamethasone 17-valerate and its 21-valerate degradation product are highly soluble in isopropyl myristate and this nonaqueous solvent will not augment C-17-to-C-21 ester degradation reactions.
- Full Text:
- Date Issued: 1989
- Authors: Smith, Eric W , Haigh, John M
- Date: 1989
- Language: English
- Type: text , Article
- Identifier: vital:6431 , http://hdl.handle.net/10962/d1006595
- Description: Introduction: The development of a reliable in vitro permeation system necessitates the use of a precise and accurate method of quantifying the amount of permeant partitioning from the membrane into the cell receptor phase. Aqueous donor and receptor chamber fluids have been used in the majority of reported investigations, which makes quantitative permeant analysis relatively facile. Alternatively, radiolabelled diffusants have been used and flux rates monitored by scintillation counting, obviating the need for chromatographic separation of the receptor-phase components. However, this technique is not applicable when nonlabelled compounds or commercial dosage forms are to be evaluated by a cell system. Furthermore, several studies indicate that aqueous receptor phases may not present an optimal partitioning environment for certain lipophilic permeants (1-4), thereby impairing accurate flux monitoring due to limited diffusant solubility. Several attempts have therefore been made to improve the partitioning environment within these systems, by the addition of surfactants for example (4). A lipophilic receptor environment appears beneficial for corticosteroid partitioning, and thus, the use of isopropyl myristate has been investigated because of its bipolar properties that tend to mimic the biochemical composition of the skin (5,6). Betamethasone 17-valerate and its 21-valerate degradation product are highly soluble in isopropyl myristate and this nonaqueous solvent will not augment C-17-to-C-21 ester degradation reactions.
- Full Text:
- Date Issued: 1989
In vitro systems for the assessment of drug release from topical formulations and trans-membrane permeation
- Smith, Eric W, Haigh, John M
- Authors: Smith, Eric W , Haigh, John M
- Date: 1989
- Language: English
- Type: Book chapter
- Identifier: vital:6441 , http://hdl.handle.net/10962/d1006628
- Description: Numerous experimental methods have been developed to investigate drug release from vehicles and the percutaneous absorption of topically applied chemicals. The objective of this research is often to find correlation between laboratory results and the transdermal absorption experienced by living subjects so that in vivo experimentation may be curtailed. In many instances, the diverse experimental techniques tend to obscure absorption-controlling factors and complicate inter study comparisons, rather than clarify the complex transdermal absorption process. Moreover, lack of agreement between results may occasionally be ascribed to shortcomings in the in vitro methodology employed. The benefits of using an in vitro cell system for the preliminary testing of drug permeation in the laboratory are obvious. The environmental and diffusion variables may be controlled in an attempt to elucidate specific factors affecting the kinetic processes and drug bioavailability. Investigations are complex because of the multiple, interrelated events underlying the processes of drug partitioning from the applied vehicle and diffusion through the portals of the stratum corneum to the myriad of metabolic, binding, and clearance activities in the lower epidermal and dermal strata.
- Full Text:
- Date Issued: 1989
- Authors: Smith, Eric W , Haigh, John M
- Date: 1989
- Language: English
- Type: Book chapter
- Identifier: vital:6441 , http://hdl.handle.net/10962/d1006628
- Description: Numerous experimental methods have been developed to investigate drug release from vehicles and the percutaneous absorption of topically applied chemicals. The objective of this research is often to find correlation between laboratory results and the transdermal absorption experienced by living subjects so that in vivo experimentation may be curtailed. In many instances, the diverse experimental techniques tend to obscure absorption-controlling factors and complicate inter study comparisons, rather than clarify the complex transdermal absorption process. Moreover, lack of agreement between results may occasionally be ascribed to shortcomings in the in vitro methodology employed. The benefits of using an in vitro cell system for the preliminary testing of drug permeation in the laboratory are obvious. The environmental and diffusion variables may be controlled in an attempt to elucidate specific factors affecting the kinetic processes and drug bioavailability. Investigations are complex because of the multiple, interrelated events underlying the processes of drug partitioning from the applied vehicle and diffusion through the portals of the stratum corneum to the myriad of metabolic, binding, and clearance activities in the lower epidermal and dermal strata.
- Full Text:
- Date Issued: 1989
The human skin-blanching assay as an indicator of topical corticosteroid bioavailability and potency: an update
- Smith, Eric W, Meyer, Eric, Haigh, John M, Maibach, Harold I
- Authors: Smith, Eric W , Meyer, Eric , Haigh, John M , Maibach, Harold I
- Date: 1989
- Language: English
- Type: Book chapter
- Identifier: vital:6440 , http://hdl.handle.net/10962/d1006627 , ISBN 0824780361
- Description: The human skin-blanching (or vasoconstrictor) assay has evolved from initial observations that corticosteroids induce a pallor or whitening of the skin to which they are applied. McKenzie and Stoughton (1962) are generally recognized as having developed the first scientific bioassay for comparing corticosteroid potency. The extensive use of this bioassay to compare drug release from topical delivery systems has demonstrated numerous instances in which the topical bioavailability may vary greatly, dependent on the character of the delivery vehicle. It has become evident that simply incorporating an intrinsically potent drug into a formulation does not necessarily produce a clinically efficacious product.
- Full Text:
- Date Issued: 1989
- Authors: Smith, Eric W , Meyer, Eric , Haigh, John M , Maibach, Harold I
- Date: 1989
- Language: English
- Type: Book chapter
- Identifier: vital:6440 , http://hdl.handle.net/10962/d1006627 , ISBN 0824780361
- Description: The human skin-blanching (or vasoconstrictor) assay has evolved from initial observations that corticosteroids induce a pallor or whitening of the skin to which they are applied. McKenzie and Stoughton (1962) are generally recognized as having developed the first scientific bioassay for comparing corticosteroid potency. The extensive use of this bioassay to compare drug release from topical delivery systems has demonstrated numerous instances in which the topical bioavailability may vary greatly, dependent on the character of the delivery vehicle. It has become evident that simply incorporating an intrinsically potent drug into a formulation does not necessarily produce a clinically efficacious product.
- Full Text:
- Date Issued: 1989
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