Studies on the In-vitro Percutaneous Penetration of Indomethacin from Gel Systems in Hairless Mice

Liu, Cheng‐Hsiung; Ho, Hsiu O.; Hsieh, Meng‐Chen; Sokoloski, Theodore D.; Sheu, Ming Thau

doi:10.1111/j.2042-7158.1995.tb05812.x

Cited by 10 publications

(3 citation statements)

References 17 publications

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“…The effect of the presence of propylene glycol in a topical formulation is well known. Percutaneous absorption of a wide variety of chemical substances can be enhanced by inclusion of propylene glycol in the vehicle [15][16][17], It can also be used as a co-solvent to enhance non-immunological im mediate contact reactions [18]. As well as being a solvent, propylene glycol has keratolytic properties [ 19] and may therefore induce changes in the stratum corneum which may in turn lead to enhanced penetration.…”

Section: Resultsmentioning

confidence: 99%

Pharmacokinetics of Topically Applied Metronidazole in Two Different Formulations

Dykes

Hill

Marks³

1997

Skin Pharmacol Physiol

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Topical metronidazole is effective in the treatment of papulo-pustular rosacea, a common inflammatory disease of the face. In this study, a comparison of the bio-availability of two topical formulations (A and B) of 0.75% metronidazole has been made. Twenty-four subjects took part in a double-blind study where each was randomly allocated to four groups corresponding to 0.5, 1, 2 and 4 h of treatment. A single application was made to each forearm and after increasing times of contact, samples of stratum corneum were removed by the skin surface biopsy (SSB) technique. After SBB removal, a full-thickness skin biopsy was taken. The tissues were extracted and analysed by an HPLC method. Both formulations showed rapid percutaneous penetration. Formulation A gave the highest concentrations at the lowest levels of the stratum corneum at 4 h. Thus in SSB5, the mean drug concentrations at 4 h were as follows: A, 6.20 ± 1.16 μg cm^-2; B, 1.93 ± 0.98 μg cm-². A similar difference was observed when the levels in the punch biopsies were determined. At 4 h, the mean drug levels were: A, 6.07 ± 2.17 μgmg^-1; B, 0.95 ± 1.16 μgmg^-1. Formulation A clearly gives a higher rate of percutaneous penetration leading to higher tissue levels of drug. Whether this increase leads to a clinically more effective treatment has yet to be determined.

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Section: Resultsmentioning

confidence: 99%

Pharmacokinetics of Topically Applied Metronidazole in Two Different Formulations

Dykes

Hill

Marks³

1997

Skin Pharmacol Physiol

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“…The magnitude and direction of the effect can be related to the relative solubility parameters of the diffusant, enhancer and skin (15). It has been estimated that the solubility …”

Section: Partition -Solubility Effectsmentioning

confidence: 99%

Recent developments in topical and transdermal delivery

Hadgraft

1996

European Journal of Drug Metabolism and Pharmacokinetics

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Over the past decade there has been considerable interest shown in an understanding of the mechanisms of skin penetration and its enhancement. Sophisticated biophysical techniques have been used to probe, at a molecular level, the ways in which chemical and physical enhancement can be achieved. Two types of chemical penetration enhancers can be identified and their co-administration can result in synergistic effects. Another attractive method for enhancing skin penetration is the use of supersaturation but problems associated with stability must be addressed. Biotech drugs are inherently difficult to administer and recent progress using iontophoresis and sonophoresis has identified that medicines of this type can be delivered percutaneously. It is also possible to use the percutaneous route to monitor plasma levels non-invasively. Coupling non invasive monitoring with controlled delivery allows the possibility of creating transdermal systems which act with bio feedback.

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“…Response surfaces fitted for each method identified a region of optimum, and this region was tested for robustness, using a Doehlert design, with some success. Liu et al [49] studied the influence of co-solvents on the in vitro percutaneous penetration of indomethacin from gel systems using a mixture design.…”

Section: Mixture Designmentioning

confidence: 99%

Multivariate methods in pharmaceutical applications

Gabrielsson

Lindberg

Lundstedt

2002

Journal of Chemometrics

182

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This review covers material published within the field of pharmacy in the last five years. Articles concerning experimental design, optimization and applications of multivariate techniques have been published, from factorial designs to multivariate data analysis, and the combination of the two in multivariate design. The number of publications on this topic testifies to the good results obtained in the studies. Much of the published material highlights the usefulness of experimental design, with many articles dealing with optimization, where much effort is spent on getting useful results. Examples of multivariate data analysis are comparatively few, but these methods are gaining in use. The employment of multivariate techniques in different applications has been reviewed. The examples in this review represent just a few of the possible applications with different aims within pharmaceutical applications. A number of companies are using experimental design as a standard tool in preformulation and in combination with response surface modeling. The properties of e.g. a tablet can be optimized to fulfill a well-specified aim such as a specific release profile, hardness, disintegration time etc. However, none of the companies apply multivariate methods in all steps of the drug development process. As this is still very much a growing field, it is only a question of time before experimental design, optimization and multivariate data analysis are implemented throughout the entire formulation process, from performulation to multivariate process control.

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Studies on the In-vitro Percutaneous Penetration of Indomethacin from Gel Systems in Hairless Mice

Cited by 10 publications

References 17 publications

Pharmacokinetics of Topically Applied Metronidazole in Two Different Formulations

Pharmacokinetics of Topically Applied Metronidazole in Two Different Formulations

Recent developments in topical and transdermal delivery

Multivariate methods in pharmaceutical applications

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