Naltrexone is a drug widely known for its ability to block opioid receptors in the brain, making it an important tool in the treatment of opioid addiction and alcoholism. Traditionally, naltrexone has been administered as oral tablets or intramuscular injections. In recent years, transdermal administration of naltrexone has emerged as a promising alternative with several advantages over classical dosage forms. Given the high incidence of patient admissions to emergency centers caused by alcohol and opioid poisoning, Naltrexone patches represent a possible measure to address these serious problems.

Mechanism of action and traditional pharmaceutical forms

Naltrexone was initially used to treat opioid addiction, including heroin treatment. Recovering addicts taking naltrexone no longer experienced the pleasurable sensations associated with opioid use and were therefore less motivated to continue drug abuse. The same was found to be true for alcoholics. Naltrexone (and its active metabolite 6-beta-naltrexone) is pharmacologically effective against alcohol and opioid abuse by blocking the mu opioid receptor. Naltrexone is also a weaker antagonist of the kappa and delta opioid receptors. Endogenous opioids participate in the modulation of alcohol and opioids, reinforcing their effects.

Naltrexone must be administered under a doctor’s prescription and is most effective when taken along with other forms of treatment, including other medications, therapy, counseling, and specialized programs.

Currently, naltrexone is available in 50 mg oral tablets (), with the usual dose for the treatment of alcohol being 50 to 100 mg. There are also intramuscular injections of naltrexone (380 mg/vial) for prolonged release or “depot” for monthly application.

Benefits of the transdermal administration route compared to traditional pharmaceutical forms

• Better Treatment Compliance: Transdermal administration eliminates the need to remember to take a daily dose, which can significantly improve treatment compliance. For patients with substance use disorders, where treatment adherence can be a challenge, this delivery modality is especially beneficial.
• Stability of Blood Levels: Transdermal administration allows for continuous, controlled release of medication through the skin, which may maintain more stable blood levels compared to the fluctuations seen with oral or intramuscular administration. This can help reduce withdrawal symptoms and prevent relapses.
• Reduction of Gastrointestinal Side Effects: Naltrexone tablets may cause gastrointestinal side effects, such as nausea and stomach upset, especially during the first weeks of treatment. Transdermal administration bypasses the gastrointestinal tract, reducing the incidence and severity of these side effects.
• Reduced Administrative Burden: The need for frequent visits to healthcare facilities for intramuscular injections can represent a significant administrative burden for patients and public healthcare services. Transdermal administration may reduce this burden by requiring fewer visits and avoiding invasive procedures.
• Potential Greater Efficacy: By maintaining stable plasma levels and avoiding first-pass metabolism in the liver, transdermal administration can potentially improve the therapeutic efficacy of naltrexone in the treatment of addiction and other conditions.
• Lower incidence of adverse effects at the local level. Numerous cases of local adverse reactions to intramuscular injections have been reported, such as pain at the application site, cellulitis, abscess and necrosis, which may lead to discontinuation of treatment. Transdermal patches, being a non-invasive treatment, represent an improvement in this aspect.

The skin as a new route of administration of naltrexone

Although the physicochemical properties of naltrexone are not favorable for the drug to cross the skin barrier, progress has been made in the administration of naltrexone in patients whose skin was previously treated with microneedles and then, by applying a patch of naltrexone, blood levels of the drug reached the therapeutic range. Volunteers reported that the microneedling treatment was painless and was generally well tolerated. Transdermal administration without prior microneedle treatment produced levels of naltrexone not detected for that formulation. However, it is known that drug release can be improved through the correct selection of pressure-sensitive adhesives and permeation enhancers, with a design space for transdermal patches without the need for prior use of microneedles. The challenge posed consists of the development of drug in adhesive type patches where naltrexone remains dissolved in the matrix, with a low risk of crystallization, achieving an acceptable release of the drug.

Conclusions

In summary, transdermal administration of naltrexone presents several significant advantages over conventional forms of administration, including improved treatment compliance, stability of blood levels, reduction of gastrointestinal and intramuscular application site side effects, and reduced demand for naltrexone. hospital care. While more research is still needed, this route of administration has the potential to improve the treatment of opioid addictions and alcoholism. Given the positive impact that addiction treatment using transdermal naltrexone patches could have, it is important to continue pharmaceutical development and additional clinical studies to fully ensure the safety and effectiveness of this dosage form.

References:

• Transdermal drug delivery Mark R Prausnitz & Robert Langer Nature Biotechnologyvolume 26, pages1261–1268 (2008) Transdermal drug delivery | Nature Biotechnology
• Transdermal delivery of naltrexol and skin permeability lifetime after microneedle treatment in hairless guinea pigs. Stan L. Banks,a Raghotham R. Pinninti,a Harvinder S. Gill,b Kalpana S. Paudel,a Peter A. Crooks,a Nicole K. Brogden,a Mark R. Prausnitz,b,c and Audra L. Stinchcomb J Pharm Sci. 2010 Jul; 99(7): 3072–3080.
• Naltrexone Prodrugs for Transdermal Delivery
  Stinchcomb, Audra L.University of Kentucky, Lexington, KY, United States
• SAMHSA, Center for Behavioral Health Statistics and Quality. 2022 National Survey on Drug Use and Health. Table 2.25A—Alcohol use in lifetime: among people aged 12 or older; by age group and demographic characteristics, numbers in thousands, 2021 and 2022. Section 2 PE Tables – Results from the 2022 National Survey on Drug Use and Health: Detailed Tables, SAMHSA, CBHSQ