Nortriptyline hydrochloride skin absorption: development of a transdermal patch
Ana Melero1, T M Garrigues, P Almudever
1Department of Pharmacy and Pharmaceutical Technology, Universitat de València, Valencia, Spain.
Summary
Propylene glycol, ethanol, and oleic acid influence nortriptyline hydrochloride skin penetration, with pH 5.5 significantly reducing permeation compared to pH 7.4. Polysorbate 80 and ethanol/PG/OA combinations showed maximum enhancement for transdermal delivery systems.
Area of Science:
- Pharmaceutical Sciences
- Dermal Drug Delivery
- Physical Chemistry
Background:
- Nortriptyline hydrochloride (NTH) is an antidepressant.
- Optimizing transdermal drug delivery requires understanding penetration enhancers and formulation pH.
- Human epidermis presents a significant barrier to topical and transdermal drug absorption.
Purpose of the Study:
- To investigate the influence of propylene glycol (PG), ethanol, and oleic acid (OA) on NTH penetration through human epidermis.
- To evaluate the effect of pH (5.5 and 7.4) on NTH permeation and the efficacy of penetration enhancers.
- To identify optimal vehicles for developing a NTH transdermal delivery system (NTH-TDS).
Main Methods:
- In vitro permeation studies using Heat Separated Epidermis.
- Assessment of NTH penetration enhancement by PG, ethanol, OA, lactic acid, and polysorbate 80 at pH 5.5 and 7.4.
- Formulation and evaluation of NTH-TDS using hydroxypropyl methylcellulose with selected enhancers.
Main Results:
- NTH permeation was significantly lower at pH 5.5 (Kp = 0.011±0.004 x 10⁻⁶ cm/s) compared to pH 7.4 (Kp = 0.36±0.04 x 10⁻⁶ cm/s).
- At pH 5.5, enhancers increased NTH permeation in the order: polysorbate 80 > ethanol/PG/OA > PG > ethanol > ethanol/lactic acid > lactic acid.
- Polysorbate 80 and ethanol/PG/OA exhibited maximum enhancement ratios of 10.72 and 3.90, respectively.
- NTH-TDS formulations demonstrated enhanced permeation, with the ethanol/PG/OA system showing an enhancement ratio of 2.09, and the addition of polysorbate 80 increasing it to 5.82.
Conclusions:
- The pH of the donor solution significantly impacts NTH permeation through human epidermis, with lower pH reducing penetration.
- Certain vehicles, particularly polysorbate 80 and the ethanol/PG/OA combination, act as effective penetration enhancers for NTH at acidic pH.
- These enhancers are suitable for developing NTH transdermal delivery systems, with polysorbate 80 offering the highest enhancement potential.
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