中 . EN
Copyright © Indetek Laboratory
苏ICP备2023008818号

Dermatological diseases and transdermal drug delivery systems

01.

The structure and function of human skin

The skin is the largest organ of the human body, and the total area of adult skin is about 1.5 m2. The thickness of human skin varies greatly by individual, age and location, generally from 0.5 to 4 mm, with the skin of the eyelids being thinnest and the skin of the soles of the feet being thickest. The function of the skin is very important to the health of human body. Skin protects the human body from harmful factors in the surrounding environment, senses/react to external stimulation, generates stress responses, prevents loss of water, electrolytes and other substances in the body, excretes metabolites through sebum and sweat glands, and maintains the stability of the body's internal environment and the dynamic balance of the skin by periodically renewing the epidermis. At the same time, certain abnormal physiological conditions can also be observed through the skin reactions. Human skin is composedof the epidermis, the dermis and the subcutaneous tissues. The epidermis is connected to the dermis by a band of basement membrane. In addition to various skin appendages (such as hair follicles, sebaceous glands, sweat glands and nails), the skin also contains abundant blood vessels, lymphatic vessels, as well as nerves and muscles.
02.

Market of dermatology

Skin diseases are common diseases with high incidence, and some skin diseases are not curable and prone to relapse. Common skin diseases include:
  • infectious skin diseases

    (bacteria, fungi, viruses, etc.)

  • pigmentary disorders

    (melasma, vitiligo, etc.)

  • sebaceous sweat gland skin diseases

    (acne, rosacea, etc.)

  • allergic skin diseases

    (contact dermatitis, atopic dermatitis & eczema,, urticaria, etc.)

  • erythematous papulosquamous skin diseases

    (psoriasis, pityriasis, etc.)

  • Hair disorders

    (androgenetic alopecia, baldness, etc.)

Typical treatments include epidermal anesthesia, localized fat accumulation, skin and hair care, etc.

It is estimated that the global skin disease medicine market size will reach to $100 billion in the next five years. The domestic market of skin disease medicine has exceeded RMB 50 billion, with a CAGR >10%. The domestic market for dermal treatment and care has reached a size of RMB 500 billion.

There are still many unmet medical needs in the dermatology area in China, among which, "limited treatment options", "poor efficacy " and "poor compliance " are the leading ones.

  • Many skin diseases have limited treatment options. For certain indications, there isno effective treatment.

  • For certain compound, efficacy of topical products can be restricted by itsthe poor transdermal efficiency, while oral and injectableproducts pose additional risk of systemic exposure.

  • Few topical dosage forms are available for clinical use. Typical topical dosage forms are in either ointment orcream form, which are sticky and difficult to apply; quite often the color of the ointment/cream is not visually preferred and therefore has negative impact on patient compliance.

  • Topical product applied on skincan be easily removed by sweat, moisture and other physical means, which adversely affects the efficacy of the product.

03.

Transdermal drug deliver system

Transdermal drug delivery system refers to the dosage form that delivers active ingredient through skin absorption to the site of action for disease treatment or prevention. In general, transdermal drug delivery system includes dermal drug delivery system, which acts on the skin or subcutaneous tissue, and transdermal drug delivery system, which is absorbed through the skin into the circulatory system to achieve systemic therapeutic effects. The transdermal drug delivery system can avoid the first-pass effect of the liver, the destruction of drugs in the gastrointestinal tract and the irritation of drugs to the gastrointestinal tract caused by oral administration, as well as the trauma and stinging caused by injections, and improve the patient compliance; at the same time, it provides a new way of drug delivery for drugs which are not suitable to be taken orally or injected. In the TA of skin disease, topical transdermal forms account for 93% of clinical use.

Drug transdermal absorption capability is determined by multiple factors, such as drug diffusion in the stratum corneum, drug distribution between the stratum corneum and the active epidermis, drug diffusion between the active epidermis and the dermis, and drug absorption through skin capillaries or capillary lymphatic vessels. The influencing factors include:

  • Skin factors. Such as age and gender, race and anatomical site, pathological factors
  • Drug factors. The ideal transdermal drug should have the following physicochemical or pharmacological characteristics:
    (1) molecular weight <500 Da;
    (2) melting point <200°C;
    (3) moderate lipophilicity and hydrophilicity, with a logarithmic oil-water partition coefficient of 1~3;
    (4) low skin irritation;
    (5) strong pharmacological activity.
  • Formulation factors. The composition of the drug formulation affects the release rate of the drug, the faster the drug release, the more favorable the transdermal absorption; the composition of the matrix in the formulation has an effect on the degree of hydration of the stratum corneum, the mixing of the drug with skin lipids and skin permeability; in addition, the matrix affects the dissolution state of the drug, the drug is completely dissolved in the matrix than the undissolved solid particles are released more quickly and better absorbed.