What is the clinical evidence for using Dimethyl Sulfoxide (DMSO) as a penetration enhancer?

Clinical Evidence for DMSO as a Penetration Enhancer

DMSO is an effective penetration enhancer for topical drug delivery with established clinical evidence, though its use should be limited to concentrations below 10% to minimize adverse reactions while maintaining efficacy. 1

Mechanism and Efficacy

DMSO functions as a pharmaceutical penetration enhancer through several mechanisms:

• Facilitates transdermal delivery of both hydrophilic and lipophilic medications 1
• Enables localized drug delivery by enhancing skin permeation 1
• Has demonstrated a 4-fold increase in estradiol skin permeation compared to controls in transdermal patch formulations 2
• Serves as an effective vehicle for topical administration of NSAIDs 1

Clinical Applications

DMSO has established clinical uses as a penetration enhancer:

• Used in FDA-approved diclofenac sodium topical solution for osteoarthritis 1
• Approved in Europe for idoxuridine topical solution for herpes zoster treatment 1, 3
• Enhances photodynamic therapy efficacy in dermatological applications, with DMSO + EDTA increasing clinical clearance rates from 67% to 90% for nodular basal cell carcinomas < 2mm thick 4
• Can be combined with 23% ALA gel and red light PDT for treating sarcoidosis 4

Dosing and Administration Guidelines

The concentration and volume of DMSO are critical factors affecting both efficacy and safety:

• The organic solvent portion (DMSO) in formulations should not exceed 10% for any route of administration 5
• Starting with lower concentrations (around 50%) is recommended to minimize skin irritation 4
• For transdermal patches, DMSO concentrations should be carefully controlled during manufacturing (drying at 35-40°C) to retain effective amounts while removing other solvents 2

Safety Profile and Adverse Reactions

DMSO has a well-documented safety profile with mostly transient adverse effects:

• Most common adverse reactions are gastrointestinal and skin-related 6
• Adverse reactions are dose-dependent, with higher concentrations causing more side effects 6
• Local reactions include erythema, skin rash, and pruritus, especially at higher concentrations 4
• DMSO appears safe when used in small doses 6
• Can cause a characteristic garlic-like odor on breath and skin after application

Clinical Considerations and Precautions

Important considerations when using DMSO include:

• Safety of DMSO in combination with other drugs is not fully established, with reported neurotoxic interactions with sulindac 4, 3
• Local erythema may affect correct evaluation of tissue damage 4
• DMSO is not readily acceptable for clinical use in some formulations due to potential irritation 5
• Avoid application to open wounds or broken skin 4
• Use with caution in patients with known hypersensitivity or severe cardiovascular disease 4

Comparative Efficacy

When comparing DMSO to other penetration enhancers:

• Oleic acid has shown similar clearing effects to DMSO in experimental studies 7
• Oleic acid may be considered as an alternative enhancer with potentially fewer safety concerns 7
• DMSO has the additional benefit of inhibiting drug recrystallization in transdermal formulations, improving product stability 2

DMSO's long history in pharmaceutics has generated robust safety and efficacy data over the past three decades, supporting its clinical use as a penetration enhancer when properly formulated and administered 1.