Transdermal therapeutic system (TTS) refers to a controlled-release formulation that achieves local or systemic therapeutic effects through transdermal administration. The prominent advantages of TTS include avoiding the first-pass effect of the liver and degradation of drugs in the gastrointestinal tract, reducing gastrointestinal irritation; maintaining a steady-state blood drug concentration, avoiding the peak and trough phenomenon caused by oral administration, and reducing toxic side effects; providing long-lasting effects, extending the dosing interval, reducing the frequency of administration, and facilitating patient use.

Traditional Chinese medicine gel patches (originally gel or plaster preparations) refer to patches made by mixing traditional Chinese medicine raw materials with suitable hydrophilic matrices and applying them to backing materials. As an important component of TTS, traditional Chinese medicine gel patches not only possess the advantages of TTS but also, compared to traditional black plasters and rubber plasters, have advantages such as good moisturizing properties, good compatibility with the skin, breathability, and the ability to be reapplied, which have increasingly attracted the attention of researchers.

Guided by the theory of traditional Chinese medicine, traditional Chinese medicine gel patches inherit the foundation of traditional Chinese medicine ointments while fully integrating modern gel preparation techniques and quality requirements, providing a new direction for theoretical research in external treatment of traditional Chinese medicine and secondary development of Chinese medicinal resources. This article reviews the current development status, matrix excipients, preparation processes, and quality control of traditional Chinese medicine gel patches.

1 Development Status of Traditional Chinese Medicine Gel Patches

Since their rapid development in the 1980s, traditional Chinese medicine gel patches were first included in the 2000 edition of the Chinese Pharmacopoeia and named as plasters, with corresponding quality specifications. The 2010 edition of the Chinese Pharmacopoeia renamed plasters as gel patches and established relevant regulations for the production and storage conditions of gel patches, as well as specified inspection indicators such as the content of the gel, formability, adhesion, and microbial limits, providing a legal basis for quality control of gel patches. The 2015 edition of the Chinese Pharmacopoeia redefined them as gel patches, categorizing them under the patch category. The former CFDA has announced that there are currently 9 types of traditional Chinese medicine products on the market, including anti-inflammatory and analgesic plasters, wind-damp bone pain plasters, compound purple-bellflower pain relief plasters, bone friend plasters, toad venom analgesic gel patches, toad venom gel patches, joint pain plasters, pain relief plasters, and Shaolin rheumatism and trauma gel patches, which are mainly used externally for soft tissue injuries, rheumatism, arthritis, and other conditions. The number of patent applications and new drug research related to traditional Chinese medicine gel patches is continuously increasing, involving drugs for various systemic diseases such as cardiovascular, skin, respiratory, and circulatory diseases. By reviewing research literature on traditional Chinese medicine gel patches from the past five years in China National Knowledge Infrastructure and summarizing it, some research examples are shown in Table 1. While traditional Chinese medicine gel patches are rapidly developing, there are also many issues: first, the complexity of traditional Chinese medicine components, which are mostly compound-based, leads to a large dosage, and the drug loading capacity of the gel is limited; unreasonable matrix ratios result in unstable product quality, prone to peeling and leaking, and poor adherence to the skin; the quality evaluation system is not perfect, with low technical levels of quality evaluation and a lack of unified and standardized quality standards; production equipment and technology are relatively backward, greatly limiting the industrialization and large-scale development of traditional Chinese medicine gel patches.

2 Composition of the Matrix in Traditional Chinese Medicine Gel Patches

Traditional Chinese medicine gel patches consist of a backing layer, a gel layer, and a protective layer, where the gel layer is the key component, serving as a reservoir for the drug and determining the quality of the gel patch. The matrix of the gel layer can be divided into non-crosslinked and crosslinked matrices, with crosslinked matrices becoming the focus of research. The composition of crosslinked matrices is complex, and the formulation design of the matrix plays a key role in the overall adhesion, flowability, transdermal absorption, and moisturizing properties of the gel.

2.1 Crosslinked Framework

The framework materials in the matrix generate viscosity, allowing the gel to adhere to the skin surface, while also supporting the internal molecules of the gel to form a network structure, providing sufficient cohesion, elasticity, and certain strength. Common hydrophilic gel frameworks include synthetic, semi-synthetic, and natural polymer materials. Synthetic and semi-synthetic polymers include sodium polyacrylate, polyvinylpyrrolidone, polyvinyl alcohol, carbomer, sodium carboxymethyl cellulose, methylcellulose, etc.; common natural polymer materials include gelatin, gum arabic, astragalus gum, white peony gum, alginates, agar, etc.

In the preparation of the matrix, polymers such as sodium polyacrylate, carbomer, and gelatin undergo crosslinking and curing reactions by adding crosslinking agents and crosslinking regulators, where high-valent metal ions chelate with the crosslinked framework, and crosslinking regulators can adjust the reaction time and degree of crosslinking. The linear molecular chains of the polymers bond with each other to form a crosslinked network structure. Common crosslinking agents are mainly high-valent metal ions, with aluminum salts being the most commonly used, including aluminum glycinate, glyceryl aluminum, aluminum chloride, aluminum hydroxide, etc.; common crosslinking regulators include citric acid, tartaric acid, lactic acid, malic acid, and ethylenediaminetetraacetic acid (EDTA).

2.2 Fillers

Fillers play an important role in the shaping of the gel, and they also affect the adhesion and cohesion of the gel, improving the excessive stickiness caused by the swelling of water-soluble polymer materials. Common fillers include kaolin, micro-powdered silica, soapstone, white clay, titanium dioxide, calcium carbonate, zinc oxide, and drug fine powders.

2.3 Moisturizers

Hydrophilic gel-type frameworks have a high water content, and the addition of moisturizers can slow down the dehydration of the matrix, promote skin hydration, and also affect the formability, adhesion, and drug release of the matrix. Common moisturizers include glycerin, propylene glycol, polyethylene glycol, and sorbitol, with a composite system of two moisturizers showing better moisturizing effects.

2.4 Permeation Enhancers

Due to the barrier limiting effect of the skin's stratum corneum, the transdermal rate of most drugs is slow and the amount absorbed is low. By adding an appropriate amount of transdermal absorption enhancers, the skin structure can be reversibly altered, reducing the resistance encountered by the drug as it passes through the skin, allowing the drug to achieve local treatment or systemic absorption.