Color in pharmaceuticals

RB Patel, MR Patel, AA Patel, AK Shah, AG Patel. Separation and determination of food colors in pharmaceutical preparations by column chromatography. Analyst 111 577-578, 1986. 

Recent discussions within the EU have indicated that the colorant list from 94/36/EC will be rationalized into a new pharmaceutical color directive in the future so that the colorant lists will be aligned. It is now considered acceptable to use these colors in new drug applications even though the formal directives have not yet been finalized. However, each country may have some specific regulations for the use of these colorants in pharmaceuticals that must also be considered. Some non-member European countries, such as some Scandinavian countries, severely restrict the use of synthetic colors and in some cases oppose their use entirely. 

Synonyms Thioindigoid pink R Classification Thioindigoid color Uses Colorant in pharmaceutical orals Regulatory FDA approved for orals Manuf./Distrib. Costec http //www.costec.com-, TKB Trading http //www.wholesalecolors.com-, Warner-Jenkinson http //www.warner-jenkinson.com D C Red No. 31... 

Wintergreen Oil. Water distillation of the leaves of Gaultheriaprocumbens L. yields an oil which consists of essentially one chemical constituent, methyl saUcylate. Because of this, the oil has been almost totally replaced by the synthetic chemical. Natural oil of wintergreen [68917-75-9] is a pale yellow to pinkish colored mobile Hquid of intensely sweet-aromatic odor and flavor. The oil or its synthetic replacement find extensive use in pharmaceutical preparations, candy, toothpaste, industrial products, and in rootbeer flavor. In perfumery, it is used in fougnre or forest-type fragrances. 

Ammonium acetate has limited commercial uses. It serves as an analytical reagent, and in the production of foam mbber and vinyl plastics it is also used as a diaphoretic and diuretic in pharmaceutical appHcations. The salt has some importance as a mordant in textile dyeing. In a hot dye bath, gradual volatilization of ammonia from the ammonium acetate causes the dye solution to become progressively more acidic. This increase in acidity enhances the color and permanence of the dyeing process. 

Mineral fillers are used for light-colored compounds. Talc has a small particle size and is a semireinforcing filler. It reduces air permeabihty and has htde effect on cure systems. Calcined clay is used for halobutyl stoppers in pharmaceutical appHcations. Nonreinforcing fillers, such as calcium carbonate and titanium dioxide, have large particle sizes and are added to reduce cost and viscosity. Hydrated siUcas give dry, stiff compounds, and their acidity reduces cure rate hence, their content should be minimized. 

The phycobiliproteins are accessory photosynthetic pigments aggregated in cells as phycobilisomes that are attached to the thylakoid membrane of the chloroplast. The red phycobiliproteins (phycoerythrin) and the blue phycobiliprotein (phycocy-anin) are soluble in water and can serve as natural colorants in foods, cosmetics, and pharmaceuticals. Chemically, the phycobiliproteins are built from chro-mophores — bilins — that are open-chain tetrapyrroles covalently linked via thio-ether bonds to an apoprotein. ... 

Massaccesi reported the development of a two-phase titration method for the analysis of miconazole and other imidazole derivatives in pure form and in pharmaceutical formulation [14], To the sample (10 mg) are added 10 mL of water, 10 mL of 1 M-sulfuric acid, 25 mL of dichloromethane and 1 mL of 0.05% indophenol blue (C.I. No. 49700) in dichloromethane solution and the solution is titrated with 10 mM sodium dodecyl sulfate until the color of the organic phase changes from blue to pale yellow. Results obtained for the drug in pure form, tablets, suppositories, cream and lotion agreed with the expected values and the coefficient of variation (n = 6) were 0.3-0.35%. Imidazole and the other constituents of the pharmaceutical preparations did not interfere. 

Niclosamide and other some antiamebic and anthelmintic drugs were determined spectrophotometrically in pharmaceuticals based on the formation of colored species with p-N,N-d i met hyI phenyicncdiaminc 2HCI and chloramines-T [48]. The method was simple, sensitive, and reproducible within 1%. 

For identification of oxytetracycline in pharmaceutical preparations, USP 28 [1] describes Method II under identification of tetracycline <193> (see Table 1), BP 2003 [4] describes a TLC and color test. 

Fernandez-Gonzales et al. [16] described a method for determination of OTC in medicated premixes and feeds by second-derivative synchronous spectrofluorome-try. The assay based on the reaction of oxytetracycline with divalent metal ion (Ca2+) at pH 6-10 to form a yellow complex that can be analyzed by synchronous spectrofluorometry (AX = 115 nm). Rao et al. [17] described a spectrophotometric method for the determination of OTC in pharmaceutical formulations based on the color reaction with uranium, which was detected at 413 nm. 

Abou-Ouf et al. [16] described a spectrophotometric method for the determination of primaquine phosphate in pharmaceutical preparation. Two color reactions for the analysis of primaquine phosphate dosage form, which are based on 2,6-dichlor-oquinone chlorimide and l,2-naphthoquinone-4-sulfonate, were described. The reactions depend on the presence of active centers in the primaquine molecule. These are the hydrogen atoms at position 5 of the quinoline nucleus and the primary amino group of the side chain. The method was applied to tablets of primaquine phosphate and a combination of primaquine phosphate and amodiaquine hydrochloride. 

Hassan et al. [39] used a sensitive color reaction method for the determination of primaquine in pharmaceutical preparation. Primaquine was treated with diazo-p-nitroaniline in acidic medium to give an orange-yellow product with an absorbance maximum at 478 nm. When the medium was made alkaline, bathochromic, and hypochromic shifts occurred the new maximum was located at 525 nm. The mean percentage recoveries for authentic samples amounted to 100 and 100.21 by the acid and alkaline procedures, respectively (P = 0.05). Both reactions could be used to determine primaquine salts in pharmaceutical preparations. The results obtained were in good agreement with those of the official methods. Recoveries were quantitative by both methods. 

Part—I has three chapters that exclusively deal with General Aspects of pharmaceutical analysis. Chapter 1 focuses on the pharmaceutical chemicals and their respective purity and management. Critical information with regard to description of the finished product, sampling procedures, bioavailability, identification tests, physical constants and miscellaneous characteristics, such as ash values, loss on drying, clarity and color of solution, specific tests, limit tests of metallic and non-metallic impurities, limits of moisture content, volatile and non-volatile matter and lastly residue on ignition have also been dealt with. Each section provides adequate procedural details supported by ample typical examples from the Official Compendia. Chapter 2 embraces the theory and technique of quantitative analysis with specific emphasis on volumetric analysis, volumetric apparatus, their specifications, standardization and utility. It also includes biomedical analytical chemistry, colorimetric assays, theory and assay of biochemicals, such as urea, bilirubin, cholesterol and enzymatic assays, such as alkaline phosphatase, lactate dehydrogenase, salient features of radioimmunoassay and automated methods of chemical analysis. Chapter 3 provides special emphasis on errors in pharmaceutical analysis and their statistical validation. The first aspect is related to errors in pharmaceutical analysis and embodies classification of errors, accuracy, precision and makes... 

A solution containing an amino acid is passed through a polymeric bed containing Cu(II) ions, forming a complex which is further reacted with zincon (149) and the blue color measured at 600 nm in a FTA system. This was applied for fast determination of amino acids in pharmaceutical formulations344. 

There is some psychologic basis to drug therapy, and the odor, taste, and color of a pharmaceutical preparation can play a part. An appropriate drug will have its most beneficial effect when it is accepted and taken properly by the patient. The proper combination of flavor, fragrance, and color in a pharmaceutical product contributes to its acceptance. 

Coloring agents are used in pharmaceutical preparations for purposes of esthetics. A distinction should be made between agents that have inherent color and those that are employed as colorants. Certain agents such as sulfur (yellow), riboflavin (yellow), cupric sulfate (blue), ferrous sulfate (bluish green), and cyanocobalamin (red), have inherent color and are not thought of as pharmaceutical colorants in the usual sense of the term. 

Although most pharmaceutical colorants in use today are of synthetic origin, a few are obtained from natural mineral and plant sources. For example, red ferric oxide is mixed in small proportions with zinc oxide powder to prepare calamine, giving the latter its characteristic pink color, which is intended to match the skin tone upon application. 

Soda niter or sodium nitrate (NaNO ) is the most abundant of the nitrate minerals. It is used for fertilizer, explosives, and preservatives. The natural deposits are located in northern Chile, which was the original source for many years. More recently, nitrogen fixation, which extracts nitrogen from air, has been used for producing sodium nitrate. This synthetic process has greatly increased the availability of this useful sodium salt by ehminating the need for the natural source. It is used to preserve and cure meats and is used in photography, in pharmaceuticals, and as a color fixative in fabrics. 

Reactions based on the presence of the 21-hydroxy-20-keto functionality (ketol group) are much more specifie for corticosteroids, and these methods have been used for the determination of corticosteroids in pharmaceutical formulations or in biological fluids [72]. For instance, only 21-unesterified corticosteroids react with sodium molybdate in acetic acid medium [81]. The blue color obtained by reducing the ketol group allows the determination of 40-200 pg of these steroids. 

Salama and Omar have described a rapid, specific, and convenient colorimetric method for the determination of procaine hydrochloride in pharmaceutical preparations [40]. The method is based on an intensity measurement of the orange-red color developed when the drug is allowed to react with l,2-naphthoquinone-4-sulfonic acid (sodium salt) in an aqueous solution. The method is suited for routine analysis of official preparations of procaine. 

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