The drug tretinoin is often prescribed to treat acne. Due to its structure, however, the substance is susceptible to oxidation and not entirely without snags in the recipe. And occupational safety measures must also be considered during processing. Tretinoin is used to treat keratinization disorders in the skin. It is, therefore, often used to treat various forms of acne but also to treat hyperkeratosis and light-induced skin aging. The active ingredient accumulates in the stratum corneum and causes a thinning and loosening of the stratum corneum.
A blockage of the sebaceous glands is prevented in this way, and the sebum can drain better again. The additional anti-inflammatory and immunomodulating effect of tretinoin can also heal an existing infection of the blocked sebaceous glands. In acne, there is usually a clear improvement in the appearance of the skin after six weeks of treatment, and the duration of therapy is usually between 8 and 10 weeks. The concentration of tretinoin in dermal preparations is usually between 0.025 and 0.1%. The upper guideline concentration is 0.1%.
Properties And Stability
From a chemical point of view, tretinoin is the oxidized form of vitamin A, which is why the drug is also referred to as vitamin A acid. It can be obtained as a yellow or slightly orange crystalline or microfine powder. Tretinoin is practically insoluble in water and lipophilic compounds and is predominantly suspended in most dramatic bases.
Due to its unsaturated structural formula, tretinoin is one of the formulations of raw materials susceptible to oxidation. To improve stability, the substance is stored in a refrigerator at 2 to 8 °C after first opening and can be used for up to two years. For processing, it should be taken out of the refrigerator about 30 minutes beforehand. To protect against light and oxygen, tretinoin-containing formulations are best filled in light-tight packaging such as aluminum tubes or amber glass bottles.
The formulated pH range of the substance is at pH values ≥ 3, with the optimum stability at pH 5. In water-based preparations, the addition of an antioxidant is always necessary. Butylated hydroxytoluene (BHT) is usually used in a concentration of 0.04%. The antioxidant is processed most simply in the form of trituration. For this purpose, a 2% butylated hydroxytoluene paraffin concentrate can be obtained from the pharmacy by NRF regulation p.35. we are getting produced.
Danger From Teratogenic Effects
Since tretinoin is a retinoid with a teratogenic effect, extensive occupational safety measures are required when processing the substance. Wearing a respirator mask, protective rubber gloves and safety goggles are mandatory, and pregnant women are not allowed to prepare any formulations with tretinoin. Direct handling of the formulation substance should be avoided, and a semi-solid formulation concentrate or an alcoholic stock solution should be used instead. Using such concentrates also offers some advantages for galenic reasons: For example, direct weighing of the substance at low concentrations is often problematic due to insufficient accuracy.
A lipophilic concentrate is well suited for processing with various dermatic bases. Is monogrammed. White Vaseline, where the active ingredient is suspended, serves as the basis. To prepare the trituration, the microfine powdered active ingredient is rubbed with the butylated hydroxytoluene paraffin concentrate and then stirred with about one-fifth of the Vaseline without heat. Then the rest of the lipophilic base can be added.
Immediately after completion, the concentrate is filled into an aluminum tube and used to produce recipes for one year. The lipophilic tretinoin formulation concentrates 2% and can be used to make pastes, ointments, and creams and is also suitable for processing with certain hydrophilic bases such as DAC base cream.
Solutions And Gels
For preparing solutions and alcoholic hydrogels, a crystalline formulation substance or an alcoholic stock solution of 3.33 g/L can be used. In contrast to the lipophilic concentrate, this tretinoin solution can be purchased ready-made and, in addition to ethanol, contains ethyl methyl ketone as a solvent and, in addition, butylated hydroxytoluene to protect against oxidative decomposition.
However, ethanolic solutions can also be prepared by weighing the formulation substance. First, the antioxidant butylhydroxytoluene is dissolved in large parts of the 96% ethanol in a beaker. Tretinoin is dispersed in the remaining ethanol in another beaker wrapped in aluminum foil to protect it from light. After adding the butylated hydroxytoluene solution, the drug can be dissolved with a small supply of heat, and the propylene glycol can be added.
Combinations With Other Active Substances
In non-standard regulations, joint processing of tretinoin with other active substances cannot be recommended. Although a combination of the medicinal substance with erythromycin is therapeutically beneficial, it is problematic Galenically because of the different pH values that can be prescribed.