![]() 0.5 g of this PG extract, normal PG, lanolin, and petrolatum were dispersed in 10 ml nitric acid and 2 ml of hydrogen peroxide in a Teflon tube in a MDS 2000 lab microwave (CEM Corporation, Matthews, NC, USA). The PG phase was separated from the lanolin-petrolatum phase by using a syringe. At 60☌, the ointment is phase separated in a PG and a lanolin-petrolatum phase. This mixture was stored at 60☌ for 1 month. PG was mixed with lanolin and petrolatum in a ratio of 1:1:8 (i.e., the ratio of the ointment formulation). The Metal Content in the Excipients of the Ointment End point (solubility) was defined as the amount of TCA where solid dispersed particles were still observed after intensive stirring for 10 min.Īdditionally, TCA ointment sample was analyzed for microscopic structure using a light microscope (Euromex ME-2880 microscope, Euromex, Arnhem, the Netherlands) with a magnification of × 40. One hundred grams of lanolin or petrolatum was added to stainless steel mortars that were heated to 60☌ on a water bath (Ika Werke HB4 Basic, Strufen, Germany). One hundred grams of PG was added to an Erlenmeyer flask and heated to 60☌ on a magnetic stirrer hot plate (IKA C-MAG HS4, Staufen, Germany). The Solubility of TCA in the Ointment Components and Microscopical Structure of TCA Ointment Distilled, deionized water was prepared by an Elga Centra R 60/120 system (Woodridge, IL, USA). 2016)): TCA (Newchem, Milan, Italy), PG (Brenntag, Dordrecht, the Netherlands), lanolin (Stella Lanolines, Mouscron, Belgium), petrolatum (Sonneborn, Amsterdam, the Netherlands), copper(II) acetate (Cu(Ac) 2) (Alfa Aesar, Haverhill, MA, USA), tert-butyl peroxybenzoate (TBPB), sodium metabisulfite and 1,10-phenanthroline (Sigma-Aldrich, St Louis, MO, USA), hexane and acetonitrile (Avantor Performance Materials, Center Valley, PA, USA), and phosphoric and acetic acid (Boom, Meppel, the Netherlands). The following chemicals and reagents were used (all materials complied with the quality requirements of the European Pharmacopoeia (Ph. The mechanism by which these are formed remains unclear however. For a water-free environment such as the TCA ointment, it was shown that the 21-aldehyde and 17-carboxylic acid are the main degradation products ( 10). Other degradation products concern degradation of the A ring ( 6, 7, 8) or hydrolysis of the acetonide moiety ( 9). ![]() Second, for hydrocortisone and flurandrenolide the formation of a 17-carboxylic acid in alkaline environment was demonstrated by using O 2 and OH − as reagents ( 2, 3). This 21-aldehyde is formed by a reaction between TCA and molecular oxygen (O 2) that is catalyzed by metal salts ( 4). 1) first, a 21-aldehyde degradation product which formation is described in aqueous and alcoholic solutions (Fig. Amongst other degradation products, two are the most often mentioned for corticosteroids with the same 17-side chain as TCA (Fig. This particular degradation predominantly occurs at the 17-side chain of the corticosteroid molecules ( 2, 3, 4, 5). TCA and molecularly similar corticosteroids are prone to oxidative degradation. Various similar products are used worldwide. The ointment consists of 0.1% TCA, 10% propylene glycol (PG), 10% lanolin, and 79.9% petrolatum. In the Netherlands, TCA ointment 0.1% FNA (Formulary of Dutch Pharmacists) was available until it was withdrawn from the market after license holders reported poor chemical stability ( 1). A selection of these products is for dermal application, such as ointments. Based on the mechanism of degradation, the ointment can be stabilized by the addition of sodium metabisulfite which was shown to reside also in the PG phase within the ointment.Ĭorticosteroids are widely used in a broad range of products. The 21-aldehyde was confirmed to be a primary degradation product, while the 17-carboxylic acid was identified as a secondary degradation product. In accordance with these findings, TCA degrades faster in PG that is present in the ointment formulation than in regular PG. It was shown that trace metals are extracted from lanolin and petrolatum by PG, increasing the concentration in PG. Logically, the content of trace metals has a profound effect on the degradation rate. The 21-aldehyde is formed after TCA is oxidized by O 2, a reaction that is catalyzed by trace metals. Two predominant degradation products were identified: a 21-aldehyde and a 17-carboxylic acid. TCA appeared to be concentrated in propylene glycol (PG) which in turn is dispersed in a lanolin-petrolatum mixture. Degradation of triamcinolone acetonide (TCA) in an ointment was investigated.
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