Steroid triamcinolone acetonide

In Figure 3, the active steroid (triamcinolone acetonide) and preservative (benzyl alcohol) are determined from a steroid cream. The higher molecular weight components of the cream base are well separated from the analytes. The ability to elute all the components of a cream or ointment in a SMGPC analysis gives an important sample preparation advantage over competing separation techniques. 

Another example of an inhalation study is the investigation of pulmonary distribution of the anti-inflammatory steroid triamcinolone acetonide. Drug deposition following inhalation of [ C]triamcinolone using the Azmacort inhaler was investigated with PET (Berridge et al. 2000). 

Figure 3. Determination of triamcinolone acetonide and benzyl alcohol from a steroid cream.

Examples of group I, i.e. weak or low efficacy topical steroids, are hydrocortisone acetate in various concentrations, methylprednisolone 1.0% and prednisolone 0.5%. Group II, the moderately potent steroids, includes alclometasone dipropionate 0.05%, hydrocortisone butyrate 0.1%, triamcinolone acetonide 0.025% and fluocinolone ace-tonide 0.01%. Group III, the potent steroids, contains among others betamethasone valerate 0.1%, betamethasone dipropionate 0.05%, budesonide 0.025%, desoximetasone 0.05%, fluticasone propionate 0.05%, amcinonide 0.1%, fluocinonide 0.05% and mometasone furoate 0.1%. Group IV comprises the very potent agents such as clobetasol propionate 0.05% and halobetasol propionate 0.05%. 

Topical preparations usually contain relatively insoluble steroids, such as clobetasol propionate, triamcinolone acetonide, or triamcinolone diacetate. Side effects of this mode of drug application are usually milder and more transient than those seen after systemically administered steroids. However, potent topical corticosteroids, such as clobetasol propionate (Temovate), can suppress adrenal function when used in large amounts for a long time, especially when the skin surface is denuded or when occlusive dressings are employed. Since the high potency topical preparations carry a higher risk of local side effects, their use should be held in reserve. 

Research teams at Glaxo then undertook the synthesis of derivatives of betamethasone that might afford superior local anti-inflammatory and anti-allergic effectiveness. Using McKenzie and Stoughton s [21] new human-based pharmacologic test that could identify with ease the relative topical potency of steroid inflammatory compounds, a series of 17-esters of betamethasone prepared by Elks [22] was evaluated. This resulted in compounds with new standards of topical potency such as triamcinolone acetonide and fluocinolone acetonide. It was then discovered, that potency peaked with betamethasone-17-valerate and betamethasone-17,21-dipropionate, which were between four- and ten-fold more potent than the standard. 

FIGURE 5-41. Determination of triamcinolone acetonide (peak A) and benzyl alcohol (peak B) from a steroid cream. Column 500 A Ultrastyragel 7.8 mm ID x 30 cm. Mobile phase THF. Flow rate 1 mL/min. Detection UV, 254 nm, 0.2 AUFS. (Reprinted from reference 13 with permission.)... 

Intralesional injection of steroid can lead to adrenal suppression. Infents and small children are especially susceptible, because a given amoimt of steroid is distributed in a smaller volume of fluid and tissue compartments. Infents injected with mixtiu es of triamcinolone acetonide and betamethasone or dexamethasone fiar periocular hemangiomas exhibited depressed serum cortisol and adrenocorticotropic hormone levels. The adrenal suppression can last up to 5 months and can result in weight loss and growth retardation. It is not known whether other corticosteroid preparations would produce similar effects or which other fectors might influence these results. In general, topical and periocular use of steroids produces minimal systemic effects. Withdrawal of topical or periocular steroids does not generally cause adrenal crisis. 

The therapeutic effectiveness of topically applied corticosteroids is attributed primarily to their antiinflammatory activity. The relative efficacy of topical corticosteroids appears to be in the following order hydrocortisone, prednisolone, betamethasone < hydrocortisone valerate or butyrate, betamethasone valerate, triamcinolone acetonide, flucinolone acetonide < betamethasone dipropionate, fluocino-nide. In addition to the nature of the corticosteroid, its solubility, and, to a lesser extent, the concentration used, clinical efficacy is influenced by the formulation of the preparation. Glucocorticoids appear to have greater efficacy when formulated in ointment bases than in cream or lotion vehicles. This could be attributed to the occlusive effect provided by ointments. The application of an occlusive dressing further enhances penetration and persistence of the steroid (reservoir effect) in the stratum corneum. " ... 

The penetration rates of four steroids through intact abdominal autopsy skin were, in the order of their physiological activity, betamethasone 17-valerate (I) > desonide > triamcinolone acetonide (II) > hydrocortisone (III). Triamcinolone itself is five times more active systemically than hydrocortisone, but has only one-tenth of its topical activity. The acetonide of triamcinolone has a topical activity 1000 times that of the parent steroid... 

R. J. Mesley in a discussion of "The infrared spectra of steroids in the solid state" assigns the following bands (cm-1) to triamcinolone acetonide ... 

For identification and differentiation from other steroids in formulations triamcinolone acetonide can be reacted with phenol and hydroquinone in a phosphoric sulfuric acid mixture producing a pink color2... 

Paper chromatographic Rf values of triamcinolone acetonide and related steroids in... 

A column partition chromatographic procedure for triamcinolone acetonide and related steroids has been worked out by Poet31, following essentially the procedure described by Smith et. al.13 The samp] e (40 mg) is fractionated on Celite (25 g) using a dioxane cyclohexane 2-methoxyethanol water 40 80 10 8 solvent system, followed by a methanol strip. The ultraviolet absorption of the eluate is monitored, and individual fractions are quantitated with isonicotinic acid hydrazide. The order of elution is 1,2-dihydrotriamcinolone acetonide, triamcinolone acetonide and finally triamcinolone (in the methanol strip). 

Corticosteroids also may be delivered by injection. The intramuscular route is preferable in patients with compliance problems, since a depot effect is achieved. Depot forms of corticosteroids include triamcinolone acetonide, triamcinolone hexacetonide, and methylprednisolone acetate. This provides the patient with 2 to 8 weeks of symptomatic control. The depot effect provides a physiologic taper, avoiding withdrawal reaction associated with hypothalamic-pituitary axis suppression. It should be noted that the onset of effect via this route may be delayed by several days. Intravenous corticosteroids may be used to provide the patient with large amounts of drug during a steroid burst to control severe symptoms. Intra-articular injections of depot forms of corticosteroids can be useful in treating synovitis and pain when a small number of joints are affected. The onset and duration of symptomatic relief are similar to those of intramuscular injection. The intra-articular route often is preferred because it is associated with the fewest number of systemic adverse effects. If efficacious, intra-articular injections may be repeated every 3 months. No one joint should be injected more than two to three times per year because of the risk of accelerated joint destruction and atrophy of tendons. Soft tissues such as tendons and bursae also may be injected. This may help control the pain and inflammation associated... 

The APC did not have a good linear relation with LD50. Dexamethasone valerate, betamethasone valerate, dexamethasone acetate and triamcinolone acetonide were approximately 1-fold more toxic and difluoro-substituted steroids were approximately 1-fold less toxic than that estimated from the partial charge. Specifically, steroids with a fluorine at the 6th position were less toxic. The correlation coefficient between LD50 and Aatomic partial charge was calculated... 

Periocular injections, subconjunctival, subtenons, and retrobulbar injection of drugs have been frequently investigated as a means to increase ocular availability. Subtenon injections of steroids, such as triamcinolone acetonide, are frequently used to control inflammatory conditions of the posterior segment such as cystoid macular edema, although this delivery route carries a risk of inadvertent intraocular injection (45). 

Efficacy. Corticosteroids have an inhibitory effect on the growth of fibroblasts (47,48). Triamcinolone acetonide inhibits experimental intraocular proliferation in rabbits (36). Intravitreal injection of 1 mg of triamcinolone significantly reduced both retinal neovascularization and retinal detachment in an experimentally induced rabbit model (36). A 4-mg intravitreal triamcinolone injection inhibited preretinal and optic nerve head neovascularization in a pig model of iatrogenic branch vein occlusion all untreated eyes developed neovascularization by six weeks (49). Intravitreal triamcinolone is also a potent inhibitor of laser-induced CNV in a rat model however, this animal model may not be ideal since laser-induced CNV may be caused by a traumatic repair process or inflammatory response and may be more susceptible to steroids than neovascularization in human disease states (50). In addition, the intravitreal triamcinolone acetonide was administered at the time of laser treatment thus, the treatment may only inhibit new vessel formation and not existing neovascularization. 

Recently, macular edema associated with uveitis (29), diabetic retinopathy (30), and central retinal vein occlusion (31,32) has been treated with intravitreal injection of triamcinolone acetonide. Macular edema decreased after treatment but recurred three to six months after injection. A sustained-release steroid delivery system may be more attractive than a simple injection of triamcinolone as it could reduce or eliminate the need for multiple intravitreal injections. 

In contrast 4 mg of triamcinolone acetonide, a minimally water-soluble steroid, injected intravitreally has a mean elimination half-life of 18 days in nonvitrectomized... 

Dexamethasone alcohol and triamcinolone acetonide have been studied in PVR animal models (30-33). These agents are particularly suited for local delivery as they are both relatively lipophilic, and therefore, may be administered as a suspension. The crystalline drug then acts as a depot, providing relatively long-term intraocular levels of steroid that can be given at high doses without apparent retinal toxicity (33). While direct delivery of corticosteroids has been demonstrated to be both safe and effective in the treatment of PVR, few studies have been performed in humans (31,32). 

Currently, there are three main pharmacologic approaches to the treatment of DME in practice or under study steroids (the intravitreal injection of triamcinolone acetonide, fluocinolone acetonide sustained drug delivery implant, dexamethasone biodegradable implant), PKC inhibitors, and VEGF inhibitors. 

As discussed previously, corticosteroids downregulate VEGF production in experimental models and possibly reduce breakdown of the blood retinal barrier (15,16). Similarly, corticosteroids have antiangiogenic properties possibly due to attenuation of the effects of VEGF (20,21). These properties of steroids are commonly used. Clinically, triamcinolone acetonide is used locally as a periocular injection to treat cystoid macular edema secondary to uveitis or as a result of intraocular surgery (22,23). In animal studies, intravitreal triamcinolone acetonide has been used to prevent proliferative vitreoretinopathy and retinal neovascularization (24—27). Intravitreal triamcinolone acetonide has been used clinically to treat proliferative vitreoretinopathy and choroidal neovascularization (28-31). 

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