Steroids formulations

Topical corticosteroids are of no use for urticarial conditions and are contraindicated in infection, e.g. fungal, herpes, impetigo, scabies, because the infection will exacerbate and spread. Where appropriate, an adrenal steroid formulation may include an antimicrobial, e.g. miconazole, fusidic acid, in infected eczema. 

Many publications dealing with TLC-HPTLC steroid analysis have appeared every year. The publications can be summarized into categories as follows analytical control of steroid formulations (drug preparations), determination of steroids in biological media and natural resources, and analytical control of the production of steroids (including raw material, syntheses, and biotransformation). A cumulative database of thousands of TLC methods (including steroids) is provided in compact-disk (CD) format by Camag [6]. 

HOBr. The A -steroid formulated was treated with NBA in aqueous acetone the A"< "-steroid was suspended in dioxane and 0.46 A perchloric acid and treated with solid NBA. In each case the adduct is truns-diaxiai. 

RD Schoenwald, JJ Bollralik. A bioavailabihty comparison in rabbits of two steroids formulated as, high viscosity gels and reference aqueous preparations. Invest Ophthalmol Vis Sci 18 61-66, 1979... 

Little further was substantiated about cholic acid (or about bile acids generally) for nearly five decades. The name, cholic acid, had become well established, but trivial names based partly on imperfect characterization were common, so that consideration of nomenclature was a part of Wieland s first report on the bile acids in 1912 (56). A review of the evidence then available included that cholic acid was a trihydroxy, monocarboxylic acid and that two of the alcohols were secondary. The final presentation of the structure of cholic acid awaited the correct steroid formulation in 1932 (113, 114). By that time the structural relationship between the sterols and bile acids was well established. The preparation of cholanic acid from cholic acid had been reported in the paper by Wieland and Weil in 1912 (56). The preparation of cholanic acid from cholesterol (through coprostane) was reported in 1919 by Windaus and Neukirchen (55). 

A fully automated electrically controlled extraction apparatus has been developed by Amin (12). This apparatus can be used for the extraction of steroid formulations including ointments, tablets, and oily injections. This method using various extraction solvents is capable of extracting nanogram amounts of steroids from pharmaceutical preparations and allows for the removal of coextracted fats and oils. 

The field of steroid analysis includes identification of steroids in biological samples, analysis of pharmaceutical formulations, and elucidation of steroid stmctures. Many different analytical methods, such as ultraviolet (uv) spectroscopy, infrared (ir) spectroscopy, nuclear magnetic resonance (nmr) spectroscopy, x-ray crystallography, and mass spectroscopy, are used for steroid analysis. The constant development of these analytical techniques has stimulated the advancement of steroid analysis. 

Squalene is also an intermediate in the synthesis of cholesterol. StmcturaHy, chemically, and biogeneticaHy, many of the triterpenes have much in common with steroids (203). It has been verified experimentally that squalene is the precursor in the biosynthesis of all triterpenes through a series of cyclization and rearrangement reactions (203,204). Squalene is not used much in cosmetics and perfumery formulations because of its light, heat, and oxidative instabiUty however, its hydrogenated derivative, squalane, has a wide use as a fixative, a skin lubricant, and a carrier of Hpid-soluble dmgs. 

Jojoba. Jojoba oil [61789-91-1] is obtained from the seeds of the jojoba plant grown in semiarid regions of Costa Rica, Israel, Mexico, and the United States. The oil is made up of ca 80 wt % of esters of eicos-ll-enoic and docos-13-enoic acids, and eicos-ll- -l-ol, and docos-13- -l-ol, ca 17 wt % of other hquid esters, with the balance being free alcohols, free acids, and steroids. Jojoba oil is used primarily in the formulation of cosmetics. Hydrogenated jojoba oil is a wax used in candles and other low volume specialty apphcations. 

In Older to improve the poor oral absorption of carbenicillin [4697-36-3] a bpophilic rndanyl ester has been formulated, Geocillin [33331-88-3] (5). Prednisolone [30-24-8] a steroid, is derivatized to its C-21 hemisuccinate sodium salt (6) to make it extremely water-soluble (108). 

An ingenious approach to the synthesis of steroids incorporating a tropone A ring has been developed by Birch and co-workers. Addition of dibromocarbene to 3-methoxyestra-2,5(10)-dien-17-one 17-ethylene ketal (42) gives a monodibromocarbene adduct formulated as (43) accompanied by a minor amount of a bisadduct. This confirms earlier observations that electrophilic halocarbenes add mainly to 2,3- or 2,5-dihydroanisoles at the double bond bearing the methoxyl group. 

The earlier work of Miller (35), Outright (37), and Brady (5) on nonmedicated implants provided an excellent basis for further studies on specific controlled release formulations such as the determination of the biodegradation rates of lactide/glycolide drug-loaded microspheres (38). Those studies were done with l c-iabeled polymers produced from DL-lactic acid and glycolide. The final formulations tested in rats were microspheres loaded with H-labeled steroid and polymer as the matrix. The microspheres were administered intramuscularly and animals were serially sacrificed over a period of about a year. 

The steroid-loaded formulations are prepared by a patented solvent evaporation process (45,46). Basically, the wall-forming polymer and the steix>id are added to a volatile, water-immiscible solvent. The dispersion or solution is added to an aqueous solution to form an oil-in-water emulsion. The volatile solvent is then removed to afford solid microparticles. The microparticles are usually subd vided with sieves to isolate fractions of the desired diameters. It is i nper-ative that a reliable and reproducible microencapsulation procedure be used to fabricate long-acting formulations. 

The in vitro release profiles of many microsphere formulations including steroids can be determined by an ethanol/water model (74). By adjusting the ethanol/water ratio in the receiving fluid, the rate and duration of release can be optimized to afford a rapid evaluation tool for developmental and quality control purposes. The model is not intended to have one-to-one correlation with in vivo results. 

The rate and duration of steroid release is affected by (1) polymer composition, (2) drug/polymer ratio (3) microsphere size distribution, and (4) microsphere quality (75). The ratio of glycolide to lactide in the copolymer has been found to be more dominant than the polymer molecular weight in the design of controlled release formulations. Microspheres of smaller size provide in vivo drug profiles of higher levels and shorter durations because of greater surface area. 

The steroid microsphere systems are probably the most successful drug delivery formulations thus far ba.sed on lactide/glycolide polymers. Several of these products appear to be on track for human and animal applications in the 1990s. The success of these formulations is due to the known safety of the polymer, the reproducibility of the microencapsulation process, reliability in the treatment procedure, and in vivo drug release performance (80). 

Several antiinflammatory compounds have been formulated in lactide/ glycolide polymers (107-111). Methylprednisolone microspheres based on an 85 15 DL-lactide/glycolide copolymer were developed for intra-articulate administration (111). The microspheres, prepared by a solvent evaporation procedure, are 5—20 jam in diameter and are designed to release low levels of the steroid over a extended period in the joint. Controlled experiments in rabbits with induced arthritis showed that the microspheres afforded an antiinflammatory response for up to 5 months following a single injection. 

Budesonide is a high-potency glucocorticoid used in CD that has low systemic bioavailability when administered orally.23 The formulation releases budesonide in the terminal ileum for treatment of disease involving the ileum or ascending colon. Due to its reduced bioavailability, budesonide may prevent some long-term adverse effects in patients who have steroid-dependent IBD.23,24... 

Suspension. If the drug is not sufficiently soluble, it can be formulated as a suspension. A suspension may also be desired to improve stability, bioavailability, or efficacy. The major topical ophthalmic suspensions are the steroid anti-inflammatory agents prednisolone acetate, dexamethasone, fluorometholone, and rimex-olone. Water-soluble salts of prednisolone phosphate and dexamethasone phosphate are available however, they have a lower steroid potency and are poorly absorbed. 

Surfactants. The use of surfactants is greatly restricted in formulating ophthalmic solutions. The order of surfactant toxicity is anionic > cationic >> nonionic. Several nonionic surfactants are used in relatively low concentrations to aid in dispersing steroids in suspensions and to achieve or to improve solution clarity. Those principally used are the sorbitan ether esters of oleic acid (Polysorbate or Tween 20 and 80), polymers of oxyethylated octyl phenol (Tyloxapol), and polyoxyl 40 stearate. The lowest concentration possible is used to perform the desired function. Their effect on preservative efficacy and their possible binding by macromolecules must be taken into account, as well as their effect on ocular irritation. The use of surfactants as cosolvents for an ophthalmic solution of chloramphenicol has been described [271]. This com-... 

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