Retinoids, commercial

Vitamin A constitutes the most significant sector of the commercial retinoid market and is used primarily in the feed area. In the pharmaceutical area, there are several important therapeutic dermatologic agents which stmcturaHy resemble vitamin A and they are depicted in Figure 2 (see Pharmaceuticals). The carotenoids as provitamin A compounds also represent an important commercial class of compounds with P-carotene [7235-40-7] (10) occupying the central role (Fig. 3) (9). 

Retinoids. Table 1 Indications and mode of administration of commercially available retinoids in dermatological therapy... 

A simple and rapid RP-HPLC method was developed for the determination of retinoid in galenicals. Commercial preparations were diluted, filered and used for separation. Measurements were carried out in an ODS column (150 X 4.6 mm i.d. particle size 3 /xm). Solvents A and B were methanol-10 mM ammonium acetate (75 25, v/v) and methanol-THF (84 16, v/v), respectively. The flow rate was 0.8ml/min. Gradient conditions were 0-25 min, 0 per cent B 35 min, 100 per cent B, isocratic for 10 min. Typical chromatograms are shown in Fig. 2.37. The repeatability of peak area ranged between 0.48 -3.2 per cent for UV-DAD and 0.57 - 3.1 per cent for fluorescence detection. The reproducibility varied between 0.26 - 4.6 per cent. It was found that the method is precise, selective, sensitive and linear, therefore, it can be employed for the routine quality control of this class of drags [85],... 

Liposome-encapsulated tretinoin has been tested in hairless mice as well as in man. The animal experiment has demonstrated the favorable uptake of the retinoid, whereas the liposomal lipids appear to be more retained in the homy layer [53], Moreover, with phospholipid-based liposomes belonging to the gel-state type, tretinoin penetration in murine skin appears to be confined to the epidermis [54] and, thus, is close to prednicarbate penetration described above. In patients with acne vulgaris, we could demonstrate a better tolerability of liposomal tretinoin as compared to a commercial gel while efficiency remains the same [55],... 

Fig. 2. Commercially important retinoids retinoic acid [302-79-4] (Tretinoin) (7), 13-Z-retinoic acid [4759-48-2] (Isotretinoin) (8), and etretinate...

Retinoic acid, available as an oral commercial preparation for the treatment of severe cystic acne (Accutane) has been one of the great successes in dermatology. However, it is not without side effects, some of which are severe. Oral retinoids are potent teratogens, and approximately one-fourth of all exposed fetuses develop birth defects. Their teratogenic potential has led to strict guidelines governing their use in women of child-bearing potential. Other side effects, such as elevated liver function tests, elevated serum lipids, and nyctalopia have also limited their use (43). 

Reversed-phase TLC on small commercial C-18 plates (1 x 3 in) is convenient for solvent scouting when one is preparing reversed-phase HPLC conditions for a new retinoid. Mobile phase compositions that give Rf m the range 0.3 to 0.7 on TLC will usually give capacity factors (k ) in the range 1-10 on HPLC. 

Etretinate, a synthetic aromatic retinoid, has been used as an investigational drug in many thousands of patients throughout the world for various dermatologic disorders it is commercially available by prescription in several European countries for treatment of psoriasis and some disorders of keratinization. As with isotretinoin, the side effects manifested during therapy with etretinate are predominantly mucocutaneous. 

Retinoids currently on the market are outlined in Table 1. The goal of this article is to evaluate the processes en loyed for preparation of these confounds, since no review of this work has previously been con iled. The synthetic routes presented, identified by evaluation of publications and patents, are believed to be those performed on commercial scale. A comparison to the routes used pre-clinically is difficult due to the problem in obtaining this information in the... 

The major approach for synthesis of retinoids of the tetraenoic acids involves the Wittig-Homer-Emmons reaction. The photochemical reaction has also proved viable and conditions to perform this reaction on commercial scale have been identified. Identification of receptor selective retinoids expanded the chemistry of file retinoids to aryl (Bexarotene, Adapalene) and heteroaryl (Tazarotene) platforms. These analogs are prepared rapidly and efficiently and this chemistry should facilitate both the SAR and commercial development of more novel and selective members of the retinoid class. 

Tretinoin is the best studied retinoid in the treatment of photoaging. It is used as a component of many commercial products that are advertised as being able to slow skin aging or remove wrinkles... 

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