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Dear Colleagues, this week we will examine together a preparation used in the treatment of various warts (verruca) seen on the extremities, prescribed by dermatology specialists in Spain, containing the active substance 5-fluorouracil, which is used in the topical treatment of superficial pre-malignant and malignant skin lesions. We should recall that warts are well-circumscribed, contagious epithelial tumors with a flesh-colored, often round and raised shape, and a dry, rough surface, resulting from the proliferation of epidermal cells on the skin surface due to the human papillomavirus. At least 60 different types of human papillomaviruses are causative agents of warts.Formula
Rp.
5-Fluorouracil 5%
Para-aminobenzoic acid 5%
Triamcinolone acetonide 1%
Hydrophilic ointment qs 20 g
Ingredients in the formula:
5-Fluorouracil – Fluorouracil – Fluorouracilum – WR-69596; Fluorouracil is a white or practically white, practically odorless crystalline powder. It is sparingly soluble in water; slightly soluble in alcohol; practically insoluble in chloroform, benzene, and ether. The pH of its 1% solution is around 4.5-5.0. The pH of its injectable solution ranges between 8.6-9.4 according to USP and 8.5-9.1 according to BP.
Fluorouracil (5-FU) is a cell cycle-specific antineoplastic agent derived from fluorinated pyrimidine that acts as an antimetabolite. Although fluorouracil is generally administered intravenously, it is also applied topically in cases of malignant keratosis of the skin. Fluorouracil was approved by the FDA in 1962. In October 2000, the FDA approved a new cream formulation of 5-FU prepared in a microsponge drug delivery system. This new topical delivery system allows for once-daily application by providing sustained release of fluorouracil. It is included in topical formulations at a concentration of 1-5%.
It is used in cases of keratoses including senile, actinic, and arsenical forms, keratoacanthoma, Bowen’s disease, and superficial basal cell carcinoma. In pre-malignant conditions, the cream should be applied in a thin layer to the affected area once or twice daily; an occlusive dressing is not necessary. The cream does not harm healthy skin. Treatment should be continued until a marked inflammatory response is achieved in the applied area and, preferably in pre-malignant conditions, some erosions are observed. Severe discomfort can be soothed using a topical steroid cream. The normal duration of application in the initial treatment course is three to four weeks, but this period may be extended. Its use is contraindicated during pregnancy and in breastfeeding mothers. Hands should be washed thoroughly after application. In addition, care should be taken to avoid contact with mucous membranes and eyes when applying the cream. It is applied 2-3 times a day. The average treatment duration is 6 weeks. When deemed appropriate, treatment may be continued for approximately 1 more week. It should be applied only onto the wart and must not come into contact with the surrounding healthy skin. For very small warts, application can be performed with the aid of a toothpick. The area to be treated is 25 cm2must not exceed (25 cm2= an area of 5 cm x 5 cm). It must not be used in infants. There are no data regarding the efficacy and safety of its use in children. It must not be used in dihydropyrimidine dehydrogenase enzyme deficiency. The dihydropyrimidine dehydrogenase (DPD) enzyme plays an important role in the breakdown of 5-fluorouracil. Accumulation of 5-fluorouracil may occur as a result of deficiency, inhibition, or decreased activity of this enzyme. For external use only.
In formulations containing salicylic acid, if areas with a thin epidermis are being treated, the frequency of cream application should be reduced and treatment monitoring should be conducted more closely. Otherwise, unwanted scarring may develop due to the potent keratolytic effect of salicylic acid in the formula. Contact with fabrics and acrylic materials should be avoided, as it may cause permanent staining. If contact with healthy skin occurs, it should be wiped off with a tissue and the affected area washed if necessary.Side effects:Very common: Erythema, inflammation, burning sensation, irritation, pain, pruritus,
Common: Bleeding, erosion, crust formation,
Uncommon: Dermatitis, edema, ulceration.
In addition; due to its softening effect on the stratum corneum, discoloration in the form of whitening around the wart, skin flaking, and, depending on the Salicylic acid it contains, contact allergic reactions and irritation symptoms such as dermatitis may occur in some patients. Such contact allergic reactions may present with pruritus, erythema, and the formation of small vesicles that may also appear outside the application area. 5-Fluorouracil is a cytostatic agent with an antimetabolite effect. Due to its structural similarity to the Thymine (5-methyluracil) molecule found in nucleic acids, it prevents the formation and utilization of thymine. Thus, it inhibits both DNA and RNA synthesis.
Thanks to its keratolytic effect, Salicylic acid loosens corneocytes, facilitating the penetration that is especially difficult in warts, thereby increasing the penetration of 5-Fluorouracil into the wart tissue. In addition, dimethyl sulfoxide, which is present as an excipient in the formulation, increases the solubility of 5-Fluorouracil. 5-Fluorouracil is absorbed through the skin after topical application. Studies conducted in humans demonstrate that the absorption of the 5-Fluorouracil molecule after application to the skin is below 0.1%..jpg)
Sample formulas:
Rp.
5-Fluorouracil 5%
D.M.S.O 15 G
Rp.
5-Fluorouracil 5%
Salicylic Acid 10%
Flexible collodion q.s.p. 20 g
PABA- Aminobenzoic Acid- P-Aminobenzoic acid- Para-aminobenzoate- Acidum para-aminobenzoicum;Para-aminobenzoic acid is found as white or light yellow, odorless or very faintly odorous crystals or crystalline powder. Its color gradually darkens under the influence of air and light. It is slightly soluble in water, ether, and chloroform; freely soluble in alcohol; and soluble in solutions of alkali hydroxides and carbonates. It is considered to belong to the B-vitamin group. It is associated with the growth, lactation, and hair pigmentation of mice. Para-aminobenzoic acid (PABA) is a chemical substance that exhibits a protective effect against sun rays (photoprotection). In addition to preventing sunburns, sunscreen agents play an important role in protection against actinic or solar keratoses, skin cancers, premature skin aging, and photosensitivity reactions to ultraviolet (UV) rays. PABA is only used in combination with other sunscreen agents, such as padimate O or oxybenzone. Para-aminobenzoic acid (PABA) is administered orally and topically. When applied topically, its absorption through the skin varies depending on the solvent used in the formulation. Alcoholic solvents allow chemical sunscreen agents to penetrate the epidermis to the maximum and deepest extent. Following its application to the skin, PABA passes into the stratum corneum layer. Reaching peak concentration in this layer takes approximately 2 hours. It does not penetrate into the deeper layers of the skin to a significant degree. It is not systemically absorbed.
When taken orally, PABA is absorbed from the gastrointestinal tract. It is metabolized in the liver and excreted in the urine unchanged and as metabolites. It is used in atopic eczema, vitiligo, and scleroderma. It dissolves in alkaline solutions; therefore, it is recommended to be taken together with oral sodium bicarbonate. It may cause side effects such as nausea, vomiting, rashes, etc. It is highly toxic in high doses. It is recommended not to be used together with sulfonamides. There is antagonism between them. It causes urinary retention.Triamcinolone acetonide- Acétonide de triamcinolone- Triamcinolonum acetonidum;Triamcinolone acetonide is a white or cream-white, practically odorless, crystalline powder. 11 mg of triamcinolone acetonide is approximately equivalent to 10 mg of triamcinolone. It is practically insoluble in water; sparingly soluble in alcohol, chloroform, or methyl alcohol; and very slightly soluble in ether. According to the British Pharmacopoeia (BP) and the United States Pharmacopeia (USP), the pH of the sterile suspension is between 5.0 and 7.5.
Triamcinolone acetonide is a more potent derivative of triamcinolone. Triamcinolone and its derivatives are synthetic glucocorticoids used as anti-inflammatory and immunosuppressive agents. Although the antiallergic mechanism of action of corticosteroids is not fully understood, they are known to be highly effective against allergies. Although triamcinolone itself has been determined to be approximately 2-3 times more potent than prednisone in animal inflammation models, triamcinolone acetonide is 8 times more potent than prednisone. Triamcinolone exhibits very little mineralocorticoid activity and is therefore not used in the treatment of adrenal insufficiency unless administered with a more potent mineralocorticoid. Triamcinolone is available in oral, nasal, parenteral, topical, and aerosol forms. When applied topically, bioavailability depends on the characteristics of the skin tissue in the applied area. Absorption from its topical preparations is higher in damaged, inflamed, occluded areas, or regions where the stratum corneum is thinned, such as the eyelids, genitalia, and face. Absorption into the systemic circulation from topical solutions is low and becomes particularly significant when applied to the oral mucosa.
The topical corticosteroid is included in the formula considering the adverse effects that the sun may cause on the skin and potential irritation.Hydrophilic ointment;Contains no active substance. It is used as a vehicle (carrier) in the preparation of formulations containing active substances.Nipagin 0.025 g
Nipasol 0.015 g
Sodium lauryl sulfate 1 part
Propylene glycol 12 parts
Lanette wax 25 parts
Soft petrolatum 25 parts
Distilled water 37 parts
Preparation of the formulaLanette wax and white petrolatum are stirred with a glass rod in a hot water bath at 75°C. In a glass beaker, sodium lauryl sulfate, nipagin, and nipasol dissolved in water are heated to 75° C with the addition of propylene glycol and mixed into the previously melted fat components. The powdered 5-Fluorouracil is softened with a small amount of glycerin or sorbitol, and with the addition of PABA and triamcinolone acetonide, mixed with hydrophilic ointment until a homogeneous mixture is obtained to finalize the formula.
The preparation is applied to the affected area once or twice a day. Treatment lasts 10–12 days.
Wishing you a good week…Source
La Formulacion Magistral en la Oficina de Farmacia valencia, 1981Exp. Pharm. Ahmet Nezihi Pekcan
Pekcan Pharmacy – Konya
[email protected]
Tel: (332) 3520657http://www.majistralformul.com/
