Crystalline Formulation

Paper partition chromatographic methods have been widely applied to the analysis of tetracyclines (128, 129). Pharmaceutical aqueous suspensions for oral use are acidified with HC1 and diluted with methanol. Crystalline formulations are dissolved only in methanol. A paper chromatographic method for TC determination in pharmaceutical preparations is based on the complexation of the antibiotic with a mixture of urea and disodium edetate on paper at pH 7.4. Urea helped in the separation of degradation products and led to the formation of well defined spots (130). Samples from fermentations must be acidified with oxalic acid to liberate TC from the mycelium. TC in filtrates may be precipitated in saturated solution of sodium tetraphenyl borate, precipitate dissolved in ethyl or butyl acetate and applied for paper chromatography. Various solvent systems and hRp values for paper chromatography are given in Table 4. 

NIR Water content, crystallinity, formulation structure Can be used during in-process control. Interpretation difficult... 

Incorporation of CysA in both liquid crystalline formulations enhanced the in vitro penetration of the peptide in the skin, probably due to the action of monoolein (in combination with oleic acid in the case of hexagonal phase) as a penetration enhancer [60]. Several differences between the two liquid crystalline phases were detected (Fig. 12.16). The cubic phase increased the penetration of CysA in the SC and [E -b D], but did not influence the percutaneous delivery of the peptide compared with the control formulation. The hexagonal phase increased the penetration of CysA in the [E -b D] as well as its percutaneous delivery. No enhancement of the peptide concentration in the SC was observed when the hexagonal phase was used, since the increased penetration of CysA was into deeper skin layers and through the skin. Whereas the cubic phase formulation favored retention of CysA in the skin in vitro, the hexagonal phase favored its penetration into deeper skin layers and its percutaneous delivery. 

In a relative bioavailability study comparing MBP formulations of Drug E against crystalline form (unstable crystalline form 1), the MBP formulations exhibited much higher exposures after a single dose of MBP compared to crystalline formulation, as seen in Fig. 12.19 (Shah et al. 2013). The relative bioavailability of the MBP formulations was four to fivefold higher than the crystalline formulation (capsule formulation). Furthermore, unlike the crystalline capsule formulation that reached a plateau at 600 mg dose, the exposure for MBP was dose-linear from up to 1200 mg. 

The dihydrochloride is a white crystalline powder, m.p. about 225 C (decomp.). Used as an antiseptic and skin sterilizing agent, and as a bacteriostat in some pharmaceutical formulations. 

When mixed with Lewis acids, dinitrogen pentoxide yields crystalline white solids, which were identified as the corresponding nitronium salts by their infra-red spectra. The reaction with boron trifluoride can be formulated in the following way... 

Gyclodextrins. As indicated previously, the native cyclodextrins, which are thermally stable, have been used extensively in Hquid chromatographic chiral separations, but their utihty in gc appHcations was hampered because their highly crystallinity and insolubiUty in most organic solvents made them difficult to formulate into a gc stationary phase. However, some functionali2ed cyclodextrins form viscous oils suitable for gc stationary-phase coatings and have been used either neat or diluted in a polysiloxane polymer as chiral stationary phases for gc (119). Some of the derivati2ed cyclodextrins which have been adapted to gc phases are 3-0-acetyl-2,6-di-0-pentyl, 3-0-butyryl-2,6-di-0-pentyl,... 

Mercuric Nitrate. Mercuric nitrate [10045-94-0] Hg(N02)2, is a colorless dehquescent crystalline compound prepared by the exothermic dissolution of mercury in hot, concentrated nitric acid. The reaction is complete when a cloud of mercurous chloride is not formed when the solution is treated with sodium chloride solution. The product crystallizes upon cooling. Mercuric nitrate is used in organic synthesis as the starting material and for the formulation of a great many other mercuric products. 

Trisodium phosphate is strongly alkaline many of its appHcations depend on this property. For example, many heavy-duty cleaning compositions contain trisodium phosphate as a primary alkalinity source. The crystalline dodecahydrate itself is marketed as a cleaning compound and paint remover. Traditionally, trisodium phosphate has been used in water softening to remove polyvalent metal ions by precipitation as insoluble phosphates. Because the hypochlorite complex of trisodium phosphate provides solutions that are strongly alkaline and contain active chlorine, it is used in disinfectant cleaners, scouring powders, and automatic dishwashing formulations. 

Several crystalline condensed phosphates may also be formed by the dehydration of monosodium phosphate (MSP). Maddrell s salt exists as Form 11 (high temperature MaddreU, NaPO -ll, insoluble metaphosphate-11) and Form 111 (low temperature MaddreU, NaPO -lll, insoluble metaphosphate-111). Both forms are highly polymerized and difficult (slow) to dissolve in water. Mixtures of the two forms are marketed as a dental abrasive for toothpaste formulations containing soluble fluoride. Maddrell s salt is also used with disodium phosphate as a cheese emulsifying aid. 

In Parenteral and Enteral Nutrition. Amino acid transfusion has been widely used since early times to maintain basic nitrogen metaboHsm when proteinaceous food caimot be eaten. It was very difficult to prepare a pyrogen-free transfusion from protein hydrolysates. Since the advances in L-amino acid production, the crystalline L-amino acids have been used and the problem of pyrogen in transfusion has been solved. The formulation of amino acid transfusion has been extensively investigated, and a solution or mixture in which the ratio between essential and nonessential amino acid is 1 1, has been widespread clinically. Special amino acid mixtures (eg, branched chain amino acids-enriched solution) have been developed for the treatment of several diseases (93). 

Although the main uses for benzoic acid are as a chemical raw material, it also has numerous direct uses. Benzoic acid is used in substantial quantities to improve the properties of various alkyd resin coating formulations, where it tends to improve gloss, adhesion, hardness, and chemical resistance. Benzoic acid terminates chain propagation in alkyd resins (qv) and promotes crystallinity in the final product. 

The name boric acid is usually associated with orthoboric acid, which is the only commercially important form of boric acid and is found ia nature as the mineral sassoflte. Three crystalline modifications of metaboric acid also exist. AH these forms of boric acid can be regarded as hydrates of boric oxide and formulated as B2O3 3H20 for orthoboric acid and B2O3 H20 for metaboric acid. 

In 1943 the reaction of anhydrous RhCl and CO at 80°C under pressure with a haUde acceptor, such as copper, was reported to produce a black crystalline product formulated as Rh4(CO) (42). The correct stmcture of the complex was... 

A water-soluble white crystalline sofld, CS is disseminated as a spray, as a cloud of dust or powder, or as an aerosol generated thermally from pyrotechnic compositions. The formulation designated CSl is CS mixed with an anti-agglomerant when dusted on the ground, it may remain active for as long as five days. CS2 formulated from CSl and a siUcone water repellent, may persist for as long as 45 days (6). 

Syndiotactic Polybutadiene. Syndiotactic polybutadiene is a unique material that combines the properties of plastic and mbber. It melts at high (150—220°C) temperatures, depending on the degree of crystallinity in the sample, and it can be molded into thin films that are flexible and have high elongation. The unique feature of this plastic-like material is that it can be blended with natural mbber. 1,4-Polybutadiene and the resulting blends exhibit a compatible formulation that combines the properties of plastic and mbber. 

Coa.ting S. CR has been used to coat a variety of substrates, from cloth for rainwear to concrete decks for protection against salt water. A sol-type latex is preferred to ensure good adhesion to concrete decks. A crystalline polymer latex is preferred where added durabUity is needed. The compound includes a nonionic surfactant to improve its chemical stabUity. A number of thin coatings are appUed to the surface to allow better coverage and facUitate drying. A similar formulation could be used to coat the interior of tanks, but an accelerator is needed to improve toughness. 

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