What Drugs Can Be Absorbed Through the Skin?

Understanding Skin Drug Absorption

To understand the process of drug absorption through the skin, it's important to explore the skin's barrier function and the various factors that can affect permeation.

Skin Barrier Function

The skin's barrier function is primarily achieved by the stratum corneum (SC), a unique biomembrane that is morphologically and compositionally distinct. The lipids present in the extracellular matrix of the SC provide the sole pathway for diffusion and form a continuous phase from the skin's surface to the base of the SC.

The stratum corneum acts as a protective barrier, preventing the entry of foreign substances into the body while also minimizing water loss. This outermost layer of the skin consists of flattened, keratinized cells called corneocytes, which are surrounded by a lipid-rich matrix. The tight packing of these corneocytes and the composition of the lipid matrix contribute to the skin's impermeability.

Factors Affecting Permeation

Several factors influence the process of drug permeation through the skin. Understanding these factors is crucial for optimizing transdermal drug delivery.

• Physicochemical Characteristics: The physicochemical properties of the drug play a significant role in its ability to permeate the skin. Factors such as molecular weight, lipophilicity, melting point, and solubility in the carrier system can impact drug absorption. For effective permeation, the daily dose of the drug should ideally be less than or equal to 20 mg per day, the molecular weight should be less than 500 Da, the log P-value (oil/water partition coefficient) should be between 1-3, and the melting point should be less than 200°C [1].
• Permeation Enhancers: Certain substances known as skin permeation enhancers can facilitate drug absorption through the skin. These enhancers can alter the lipid structure of the stratum corneum, enhancing drug permeation. However, the selection and use of permeation enhancers must be carefully evaluated to ensure safety and efficacy.
• Temperature: Temperature can significantly influence the rate of drug permeation through the skin. Higher temperatures can fluidize the intercorneocyte lipid tails, increasing the permeability of the skin. Additionally, temperature can affect dermal clearance, impacting drug absorption.
• Other Factors: Various other factors can affect skin permeability, including hydration levels, lipophilicity of the drug, presence of enzymes in the skin, cutaneous microvasculature, and pH of the carrier system. These factors can influence the rate and extent of drug absorption through the skin [2].

Understanding the skin's barrier function and the factors affecting drug permeation is essential for the development of effective transdermal drug delivery systems. Researchers and scientists continue to explore new strategies and technologies to enhance the efficiency and safety of drug absorption through the skin.

Drugs Absorbed Through the Skin

When it comes to drug administration, the skin serves as a potential route of absorption for certain medications. This method, known as transdermal drug delivery, offers several advantages such as convenience, controlled release, and avoidance of first-pass metabolism. Let's explore the drugs that can be absorbed through the skin and how their physicochemical properties influence this process.

List of Absorbable Drugs

Several drugs have been found to be absorbable through the skin. These include:

Drug

• ‍‍Corticosteroids
• Nicotine
• Scopolamine
• Nitroglycerin
• Estradiol

(NCBI Bookshelf)

It's important to note that this list is not exhaustive, and there may be other drugs that can be absorbed through the skin. The absorption of these drugs depends on various factors, including their physicochemical properties.

Physicochemical Properties Influence

The physicochemical properties of drugs play a significant role in their ability to penetrate the skin barrier. Studies have shown that these properties influence the stripping effect on the stratum corneum (SC) of the skin. Water-soluble drugs tend to be more affected by tape stripping, a method used to disrupt the water barrier function of the skin, compared to lipophilic drugs.

Additional factors that can influence the absorption of drugs through the skin include:

• Freezing: Freezing the skin does not appear to modify water absorption but increases the penetration of compounds through the skin.
• Heating: Consistently heating the skin increases the percutaneous absorption of drugs.
• Removal of SC lipids: Removing the lipids present in the stratum corneum may enhance the percutaneous absorption of drugs. Delipidization with chloroform-methanol has been shown to increase the permeability of hydrophilic compounds, but not lipophilic compounds [3].

Understanding the physicochemical properties of drugs and how they interact with the skin barrier is crucial in designing effective transdermal drug delivery systems. This knowledge helps researchers and pharmaceutical companies develop formulations that optimize drug absorption through the skin while ensuring safety and efficacy.

By exploring the drugs that can be absorbed through the skin and understanding how their physicochemical properties influence absorption, we gain valuable insights into the potential of transdermal drug delivery as a route of administration. This knowledge contributes to advancements in drug delivery systems and provides alternative options for patients seeking effective and convenient treatment options.

Enhancing Drug Absorption

When it comes to drug delivery through the skin, various methods and technologies have been developed to enhance the absorption of drugs. In this section, we will explore three approaches: skin permeation enhancers, energy-driven methods, and the use of nanocarriers in drug delivery.

Skin Permeation Enhancers

Skin permeation enhancers are chemical substances that have been utilized to improve the penetration of drugs through the skin. These substances work by disrupting the lipid bilayer of the stratum corneum, the outermost layer of the skin, and enhancing drug permeation. Some examples of skin permeation enhancers include dimethyl sulphoxide (DMSO), azone, fatty acids, alcohols, surfactants, urea, and terpenes.

By altering the structure and properties of the stratum corneum, these enhancers facilitate the passage of drugs into the underlying layers of the skin. However, it is important to note that the use of skin permeation enhancers should be carefully evaluated to ensure safety and minimize potential side effects.

Energy-Driven Methods

Energy-driven methods utilize external sources of energy to enhance drug delivery through the skin. These methods include iontophoresis, sonophoresis, and electroporation.

• Iontophoresis involves the application of a low level of electrical current to drive charged drug molecules through the skin.
• Sonophoresis utilizes ultrasound waves to temporarily disrupt the stratum corneum, enhancing drug penetration.
• Electroporation involves the application of high-voltage pulses to create temporary pores in the skin, allowing for increased drug absorption.

These energy-driven methods have been employed to enhance transdermal absorption of various drugs, providing alternatives to traditional drug delivery routes.

Nanocarriers in Drug Delivery

Nanocarriers, such as solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), liposomes, niosomes, nanocrystals, and natural lipids-based nanoparticles, have shown great potential in transdermal drug delivery. These nanocarriers offer several benefits including controlled release, enhanced bioavailability, improved diffusion, and deposition in tissues.

By encapsulating drugs within these nanocarriers, it is possible to protect the drugs from degradation, improve their stability, and achieve controlled release profiles. These nanocarriers have been utilized for delivering various therapeutic agents for skin hydration, anti-inflammatory effects, and treatment of diseases like cancer and skin inflammatory conditions [5].

The use of nanocarriers in drug delivery provides opportunities for targeted and efficient delivery of drugs through the skin, allowing for improved therapeutic outcomes.

Enhancing drug absorption through the skin using skin permeation enhancers, energy-driven methods, and nanocarriers represents a promising area of research and development. These approaches offer the potential to enhance drug delivery efficiency, improve patient compliance, and provide new therapeutic options for a variety of conditions.

Transdermal Patch Delivery

Transdermal patch delivery is a method of drug administration that offers several advantages over conventional routes. This section explores the benefits, effective drug delivery examples, as well as the challenges and limitations associated with transdermal patch delivery.

Advantages Over Conventional Routes

Transdermal patch delivery provides unique advantages compared to other routes of drug administration. Some of the key benefits include:

• Continuous drug delivery: Transdermal patches are designed to deliver a continuous and controlled dose of medication over an extended period of time. This steady release ensures consistent drug levels in the bloodstream, resulting in more stable therapeutic effects.
• Bypassing the digestive system: Unlike oral medications that need to pass through the digestive system, transdermal patches allow drugs to be absorbed directly through the skin and into the bloodstream. This bypassing of the digestive system can be beneficial for drugs that are susceptible to degradation or have poor oral bioavailability.
• Avoiding first-pass metabolism: When drugs are taken orally, they often undergo first-pass metabolism in the liver, where a portion of the drug is metabolized before reaching systemic circulation. Transdermal patch delivery bypasses this first-pass metabolism, allowing a higher proportion of the drug to reach the target site.

Effective Drug Delivery Examples

Transdermal patch delivery has proven to be effective for various medications. Here are some examples:

• Fentanyl and Buprenorphine: These opiates, used for severe pain management and opiate addiction treatment, respectively, can be delivered via transdermal patches. This method of administration provides a slower, steadier dose with fewer side effects, making it harder to misuse compared to other forms of administration.
• Selegiline: Transdermal selegiline patches have shown efficacy as an antidepressant with quicker relief compared to other treatment options. Clinical trials have also demonstrated reduced risk of side effects and suicidal tendencies compared to oral antidepressants.
• Methylphenidate: Transdermal delivery of methylphenidate, used for ADHD treatment in children aged six to 17, offers a lower likelihood of abuse compared to oral stimulants, particularly among teenagers. This makes it a favorable option for managing ADHD symptoms.
• Scopolamine: Used for motion sickness and post-surgery nausea, scopolamine delivered through transdermal patches provides a slower, steady delivery over a span of up to three days. This offers improved effectiveness at a lower dose compared to other forms of administration.

Challenges and Limitations

While transdermal patch delivery has several advantages, it also presents challenges and limitations. Some of these include:

• Limited drug compatibility: Not all drugs can be effectively delivered via transdermal patches. Some drugs may have physicochemical properties that make it difficult for them to permeate through the skin barrier.
• Skin irritation and allergies: Some individuals may experience skin irritation or allergic reactions in response to the adhesive or components of the patch. Proper patch placement and regular rotation of application sites can help mitigate this issue.
• Dosage limitations: Transdermal patches have limitations in terms of the maximum dosage that can be delivered due to the size of the patch and the drug's solubility. Some drugs may require alternative routes of administration for higher doses.
• Slow onset of action: Transdermal patches generally have a slower onset of action compared to other routes of administration. This may not be ideal for drugs that require rapid relief or immediate effects.

Despite these challenges, transdermal patch delivery remains a valuable and effective method for drug administration, offering advantages that make it a preferred option for certain medications. It is important to consult with healthcare professionals to determine the suitability of transdermal patch delivery for specific drugs and individual needs.

Nanocarriers in Transdermal Delivery

In the field of transdermal drug delivery, nanocarriers have emerged as a promising approach to enhance drug absorption through the skin. These nanocarriers, such as nanoparticles, ethosomes, dendrimers, and liposomes, encapsulate drugs and facilitate their delivery across the stratum corneum, the outermost layer of the skin. Nanocarriers offer versatility in delivering both lipophilic and hydrophilic drugs, making them suitable for a wide range of drug delivery applications.

Types of Nanocarriers

Nanocarriers are classified as colloidal structures with a mean diameter of fewer than 500 nanometers. Several types of nanocarriers have been extensively used in transdermal drug delivery. These include:

• Liposomes: Liposomes are lipid-based nanoparticles that consist of phospholipid bilayers. They can encapsulate both hydrophilic and lipophilic drugs, offering a versatile carrier system for drug delivery. Their composition allows for controlled release and increased solubility of drugs, enhancing their absorption through the skin.
• Solid Lipid Nanoparticles (SLNs): SLNs are lipid-based nanocarriers composed of solid lipids. They provide stability to the encapsulated drug and can be designed to release the drug in a controlled manner. SLNs have shown potential in improving drug penetration through the skin and enhancing therapeutic efficacy.
• Niosomes: Niosomes are similar to liposomes, but instead of phospholipids, they consist of nonionic surfactants. Niosomes can entrap both hydrophilic and lipophilic drugs, and their properties can be modified to achieve desired drug release kinetics. They have been investigated as effective carriers for transdermal drug delivery.
• Nanostructured Lipid Carriers (NLCs): NLCs are lipid-based nanoparticles that combine solid lipids and liquid lipids. They offer improved drug loading capacity and controlled drug release compared to other lipid-based carriers. NLCs have shown promise in enhancing skin permeation of drugs.

Benefits of Nanoparticle Technology

Nanoparticle technology in transdermal drug delivery offers several advantages. These include:

• Enhanced bioavailability: Nanocarriers can improve drug bioavailability by protecting the drug from degradation and increasing its stability during delivery. They can also enhance drug retention at the site of action, resulting in improved therapeutic outcomes.
• Targeted delivery: Nanocarriers can be designed to target specific tissues or cells, increasing drug specificity and reducing systemic side effects. This targeted delivery approach allows for more efficient drug delivery and better patient compliance.
• Tunable release kinetics: Nanoparticles offer the ability to control the release kinetics of drugs, allowing for sustained release or triggered release at the desired site within the skin. This control over drug release kinetics enhances the therapeutic efficacy of medications.

Success Stories in Medicine

Nanoparticle-based drug delivery has achieved remarkable success in various medical fields. Nanocarriers have been utilized to overcome the challenges associated with low drug bioavailability and to enhance therapeutic outcomes while reducing side effects. Some notable success stories include:

• Treatment of cancers: Nanoparticle-based drug delivery systems have been developed to target and deliver anticancer drugs specifically to tumor cells, reducing systemic toxicity and improving treatment efficacy. These advancements have opened new avenues in cancer treatment.
• Treatment of infectious disorders: Nanoparticles have been used to enhance the delivery of antimicrobial agents, helping to combat infectious disorders that were challenging to treat in the past. The targeted delivery and controlled release of drugs using nanocarriers have significantly improved therapeutic outcomes in infectious disease management.

The use of nanocarriers in transdermal drug delivery holds great promise for enhancing drug absorption through the skin. By leveraging nanoparticle technology, researchers and medical professionals can improve drug bioavailability, achieve targeted delivery, and enhance therapeutic efficacy. Continued advancements in this field are expected to revolutionize drug delivery and improve patient outcomes across various medical conditions.

Factors Influencing Percutaneous Absorption

When it comes to percutaneous (through the skin) drug absorption, several factors come into play. These factors can significantly impact the ability of a drug to penetrate the skin and reach the systemic circulation. Two key factors that influence percutaneous absorption are the characteristics of the drug itself and the ideal properties for transdermal drugs.

Influence of Drug Characteristics

The characteristics of the drug play a crucial role in its percutaneous absorption. Some of the key physicochemical properties that influence drug absorption include:

• Daily Dose: Ideally, the daily dose of the drug should be less than or equal to 20 mg per day. This helps ensure that the drug can be effectively delivered through the skin without exceeding safe limits.
• Molecular Weight: The molecular weight of the drug is also an important consideration. Drugs with a molecular weight less than 500 Daltons (Da) are more likely to penetrate the stratum corneum, the outermost layer of the skin, and reach the underlying tissues. Larger molecules may have difficulty crossing this barrier.
• Lipophilicity: The lipophilicity of a drug refers to its affinity for lipids (fats). Drugs with a log P-value between 1–3 are considered ideal for percutaneous absorption. Lipophilic drugs are more likely to pass through the lipid-rich stratum corneum and enter the bloodstream.
• Melting Point: The melting point of a drug also plays a role in its absorption through the skin. Ideally, the melting point should be less than 200°C to ensure that the drug can be effectively delivered through topical formulations.

Drugs applied through the transdermal delivery route should also be non-irritating and non-immunogenic. These characteristics are important to minimize skin irritation and potential allergic reactions.

Ideal Properties for Transdermal Drugs

For a drug to be suitable for transdermal delivery, it should possess certain ideal properties. These properties contribute to the effectiveness and safety of transdermal drug delivery. Some of the ideal properties for transdermal drugs include:

• Molecular Weight: To ensure efficient percutaneous absorption, the molar mass of the drug should be less than 500 Da. This allows for significant permeation through the skin.
• Daily Dose: The therapeutic dose of the drug should ideally be less than 10 mg per day. This helps prevent excessive drug exposure and potential side effects.
• Non-Irritating and Non-Immunogenic: Transdermal drugs should be formulated in a way that minimizes skin irritation and the potential for immune reactions. This is crucial for patient comfort and safety.

Understanding the influence of drug characteristics and the ideal properties for transdermal drugs is essential for designing effective and safe transdermal drug delivery systems. By considering these factors, researchers and healthcare professionals can develop formulations that optimize drug absorption through the skin while minimizing potential risks.