UVA is the major contributor to the photodegradation of tretinoin and isotretinoin: Implications for development of improved pharmaceutical formulations

Abstract

The chemical stability of tretinoin (RA) and isotretinoin (13RA) in ethanol and dermatological cream preparations exposed to solar simulated light (SSL), UVA, and visible light has been studied. Photostability was monitored by an HPLC method that allowed simultaneous analysis of RA and 13RA, thus allowing photodegradation due to isomerization to other retinoids and photolysis to nonretinoid products to be monitored. Both retinoids undergo both isomerization and photolysis following SSL, UVA and visible light exposure but RA is more sensitive to photodegradation than 13RA. Degradation of both retinoids by photolysis is considerably greater in cream formulations than in ethanol and the photodegradation follows second order kinetics. Rate constants and half-lives for degradation of RA and 13RA in ethanol solution and cream preparations subjected to different light sources are reported. The UVA component of SSL is the major contributor to photodegradation. Since UVA penetrates deeply into skin, our results suggest that photodegradation of RA may contribute to the photosensitivity associated with RA therapy. Our studies suggest that development of improved formulations and the use of effective UVA sunscreens may reduce the side effects of RA therapy.

β-Cyclodextrin Nanosponges as Multifunctional Ingredient in Water-Containing Semisolid Formulations for Skin Delivery

“…In fact, atRA is degraded upon exposure to light‐forming isomers, mainly 13‐cis retinoic acid and 9‐cis retinoic acid . Photodegradation of atRA appears to correlate with specific light conditions and can be influenced by the vehicle technology used to formulate the product . Thus, the stability of atRA in dermatological formulations is critical, prompting to the development of more or less sophisticated strategies to protect the drug from light‐induced degradation …”

“…Formulation (around 13 mg) was exposed to sun light up to 3 h. After collection, the sample was treated with 1 mL ethanol under stirring for 10 min, centrifuged, and analyzed by HPLC as reported in HPLC Analysis of DIC and atRA . Half‐life ( t 1/2 ) of atRA was calculated according to second‐order kinetics of degradation …”

“…21 Photodegradation of atRA appears to correlate with specific light conditions and can be influenced by the vehicle technology used to formulate the product. [22][23][24] Thus, the stability of atRA in dermatological formulations is critical, prompting to the development of more or less sophisticated strategies to protect the drug from lightinduced degradation. [25][26][27][28] From the data reported in Figure 5, it is clear that atRA conversion to 13-cis derivative was very fast in ethanol solution and significantly slowed down in $NS-PYRO-CB gel.…”

Role of topical combination drug containing clindamycin and benzoyl peroxide 279 in the treatment of common acne

“…Also, it exhibits a special affinity for epithelial retinoic acid receptors RAR-γ (tretinoin has identical affinity for RAR-α, RAR-β and RAR-γ) [27]. Adapalene blocks the activity of polynuclear leukocytes (it is a potent inhibitor of the activity of neutrophil lipoxygenase) and immune responses mediated by arachidonic acid (preventing the development of leukotriene-dependent inflammatory mechanisms) [28]. It blocks the migration of leukocytes and the synthesis of prostaglandin E2.…”

Derivative spectrophotometric method for simultaneous determination of clindamycin phosphate and tretinoin in pharmaceutical dosage forms

“…There are some reported articles in the literature for the determination of clindamycin [3-8] or tretinoin [9,10] alone or via the combination of the two drugs [11] by HPLC and gas chromatography in bulk or in pharmaceutical dosage form. HPLC method has been used in the USP35- NF30 for determination of clindamycin phosphate and tretinoin in separate gel dosage form but no simultaneous method is reported [12].…”