Tretinoin formulations

Tretinoin formulations available today include the traditional topical tretinoin cream (0.025%, 0.05%, 0.1%), gel (0.025%, 0.01%) or liquid (0.025%) developed for acne therapy (Retin-A ),... 

Use of topical retinoids (tretinoin, tazaro-tene, retinol formulations) for 2-6 weeks prior... 

Use of topical retinoids (tretinoin, tazaro-tene, retinol formulations) for 2 to 6 weeks prior to peeling thins the stratum cornemn, reduces the content of epidermal melanin, and expedites epidermal healing. Retinoids also enhance the penetration of the peeling agent. They should be discontinued several days prior to the peeling procedure. Retinoids can be resumed post-operatively after all evidence of... 

A new combination formulation containing hydroquinone 4%, tretinoin. 05% and fluocino-lone. 01% was approved in the United States for treatment of melasma. This combination has been approved for use in South America, Singapore, Korea, and Mexico. The formulation was based on the KligmanAVillis formula [44]. In addition, other new hydroquinone formulations contain 4% hydroquinone plus retinol in concentrations of 0.15 or 0.3%. These formulations also improve the dyschromia of photoaging. 

Retinoids, which are highly effective in the treatment of acne, stimulate epithelial cell turnover and aid in unclogging blocked pores. Retinoids also exhibit anti-inflammatory properties through the inhibition of neutrophil and monocyte chemotaxis.8 Because of these comedolytic and antiinflammatory effects, topical retinoids are recommended as first-line treatment for mild to moderate comedonal and inflammatory acne.3 While success is seen with monotherapy, using a retinoid in combination with benzoyl peroxide or topical antibacterials is also an appropriate and effective therapeutic treatment option.3 Tretinoin, adapalene, and tazarotene are topical retinoids available for use in the treatment of acne. Table 62-2 describes the strengths and formulations of these agents. 

Comparative studies on the bioavailability of three different tretinoin gel formulations showed that the dimensions of the sampling area may play a critical role in determining the extent of dermal drug uptake [33, 34], If, by lateral spreading, a substance is distributed over an area sufficiently larger than the sampling area, significant proportions of compound will not be recovered and hence permeability will be underestimated. 

Pharmacokinetics The transdermal absorption of tretinoin from various topical formulations ranged from 1 % to 31 % of applied dose, depending on whether it was applied to healthy skin or dermatitic skin. 

Topical retinoic acid is applied initially in a concentration sufficient to induce slight erythema with mild peeling. The concentration or frequency of application may be decreased if too much irritation occurs. Topical retinoic acid should be applied to dry skin only, and care should be taken to avoid contact with the corners of the nose, eyes, mouth, and mucous membranes. During the first 4-6 weeks of therapy, comedones not previously evident may appear and give the impression that the acne has been aggravated by the retinoic acid. However, with continued therapy, the lesions will clear, and in 8-12 weeks optimal clinical improvement should occur. A timed-release formulation of tretinoin containing microspheres (Retin-A Micro) delivers the medication over time and may be less irritating for sensitive patients. 

The effects of tretinoin on keratinization and desquamation offer benefits for patients with photo damaged skin. Prolonged use of tretinoin promotes dermal collagen synthesis, new blood vessel formation, and thickening of the epidermis, which helps diminish fine lines and wrinkles. A specially formulated moisturizing 0.05% cream (Renova) is marketed for this purpose. 

It is very important to protect this formulation from light to avoid the isomerization and degradation of tretinoin. 

Side effects associated with use of topical tretinoin ointment include transient hyperemia, irritation, or burning. Ocular pharmacokinetic studies in rabbits show low levels of drug in the aqueous humor after topical application of [ H]-tretinoin, with major tissue uptake in the surface epithelium and the iris. Because retinoic acid has poor stability in the presence of light and oxygen and is insoluble in water, its formulations and clinical use are limited. Although it is capable of reversing squamous metaplasia and keratinization, these ocular surface changes are seen only in severe, not mild to moderate, cases of dry eye. 

A novel intravenous liposomal formulation of tretinoin (Atragen , Aronex Pharmaceuticals Inc, The Woodlands, TX), which provides a reliable dose for... 

If this dose is well tolerated, it is possible to go immediately or gradually to a concentration of 0.05%. This concentration is common in proprietary medicines, but if prescription medicines are preferred, it is possible to prescribe 0.05% tretinoin in the following formulation ... 

Formulations in alcohol gels dry out the skin, increase the penetration of the tretinoin and make the treatment more uncomfortable. Gels should only be used on thick and oily skins. 

Some commercial creams have interesting formulations with AHAs (to enhance penetration of the other active products), tretinoin precursors, lactic acid, extracts of Morus Alba and kojic acid, combined with Transcutol , an adjuvant that concentrates the active products near the basal layer and the melanocytes. 

By altering the formulations given above 7.5 mg tretinoin in 60 g of cream. 

Two reformulations of tretinoin include a porous bead (0.01% gel) (microspheres) and liquid polymer (0.025% cream and 0.025% gel). These are less irritating than standard vehicles for tretinoin. In the topical gel formulation containing polyolprepolymer-2, tretinoin penetration was signiflcantly reduced while epidermal deposition was enhanced, compared with a commercially available gel preparation at the same concentration. Polyolprepolymer-2 promotes retention of drug molecules on the skin surface and in the upper layers of the skin. ... 

Adapalene, a derivative of naphthoic acid, is a synthetic retinoid-like compound that is available in solution, cream, and gel formulations for topical use. In addition to displaying typical retinoid effects, it also has antiinflammatory properties. Adapalene has similar efficacy to tretinoin, but unlike tretinoin, it is stable in sunlight and tends to be less irritating in nature. 

A 0.5% emollient cream formulation of tretinoin (Renova) is one formulation approved for treatment of photoaged skin. Nightly application produces maximum response within 1 year, and application one to three times weekly is said to maintain improvement. Treatment must be combined with a rigorous program of photoprotection, including sunscreens, sun avoidance, and photoprotective clothing. 

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