Ephedrine solubility

All stated pK values in this book are for data in dilute aqueous solutions unless otherwise stated, although the dielectric constants, ionic strengths of the solutions and the method of measurement, e.g. potentiometric, spectrophotometric etc, are not given. Estimated values are also for dilute aqueous solutions whether or not the material is soluble enough in water. Generally the more dilute the solution the closer is the pK to the real thermodynamic value. The pK in mixed aqueous solvents can vary considerably with the relative concentrations and with the nature of the solvents. For example the pK values for V-benzylpenicillin are 2.76 and 4.84 in H2O and H20/EtOH (20 80) respectively the pK values for (-)-ephedrine are 9.58 and 8.84 in H2O and H20/Me0CH2CH20H (20 80) respectively and for cyclopentylamine the pK values are 10.65 and 4.05 in H2O and H20/EtOH (50 50) respectively. pK values in acetic acid or aqueous acetic acid are generally lower than in H2O. 

For the assay of ephedrine in the total alkaloids a colorimetric method based on the biuret reaction was used by Feng and Read and is described in detail by Feng. Krishna and Chose separated ephedrine and iji-ephedrine by treating the dry mixed hydrochlorides with dry chloroform in which the ephedrine salt is virtually insoluble and the -ephedrine salt soluble. ... 

Ephedrine, CjqHjsON, crystallises from ether in rhombs, m.p. 118-9°, [a]n"° + 51 2° (EtOH), and, unlike ephedrine, is sparingly soluble in water. The hydrochloride, B. HCl, crystallises in colourless, slender needles, m.p. 181-2°, + 62-05° (HjO), and, unlike the ephedrine salt,... 

Co-administration of ofloxacin and chitosan in eyedrops increased the bioavailabUity of the antibiotic [290]. Trimethyl chitosan was more effective because of its solubility (plain chitosan precipitates at the pH of the tear fluid). On the other hand, N-carboxymethyl chitosan did not enhance the corneal permeability nevertheless it mediated zero-order ofloxacin absorption, leading to a time-constant effective antibiotic concentration [291]. Also W,0-carboxymethyl chitosan is suitable as an excipient in ophthalmic formulations to improve the retention and the bioavailability of drugs such as pilocarpine, timolol maleate, neomycin sulfate, and ephedrine. Most of the drugs are sensitive to pH, and the composition should have an acidic pH, to enhance stability of the drug. The delivery should be made through an anion exchange resin that adjusts the pH at around 7 [292]. Chitosan solutions do not lend themselves to thermal sterilization. A chitosan suspension, however. 

The use of dissociable diastereomers for enantiomer resolution may be illustrated by the case where racemic mandelic acid is resolved using en-antiomerically pure a-methylbenzylamine. The n and p salts of a-methylbenzyl-amine mandelate have aqueous solubilities of 49.1 and 180 g/L, respectively, at 25°C [153], A more recent example, which focuses on the crystallographic origin of the solubility differences, is provided by the resolution of ( )-mandelic acid with (-)-ephedrine in water or methanol solution [154], In general, the relative solubilities of the n and p salt pairs are strongly influenced by the choice of solvent medium and temperature, which provide considerable flexiblity in optimizing the crystallization conditions and the efficiency of resolution. This process may be facilitated by the development of a full solubility phase diagram. 

Ephedrine is very soluble in water, so using cold water (almost freezing) we will remove the ephedrine (remember that 4 ml dissolves 1 g of ephedrine so use a very small excess of water). 

Adrenomimetic drugs with no substitutions on their benzene ring (e.g., amphetamine and ephedrine) are generally quite lipid soluble, readily cross the blood-brain barrier, and can cause central nervous system (CNS) stimulation. 

To improve supercritical C02 solubilities of target alkaloidal salts, an appropriate modifier to raise the polarity of C02 had to be used. As previously mentioned, the most common modifier used in SFE is methanol because of its high solvation parameters, which can greatly increase the resultant polarity of C02. Water has been chosen as another modifier because some alkaloidal salts are freely soluble in water as well as methanol. Moreover, the addition of water into C02 has been reported to improve the extraction yield of some alkaloids [29]. Methanol or water as a modifier was added into the extractor at the concentration levels of 1, 5 and 10% (v/v), respectively. The effect of methanol and water on the solubilities of hyoscyamine (1) and scopolamine (2) is shown in Figure 5. Analogous information on ephedrine derivatives such as methylephedrine (3), norephedrine (4), ephedrine (5), and pseudopehedrine is illustrated in Figure 6. 

Figure 6. Effect of methanol (A) and water (B) as a modifier on the solubilities of the hydrochloride salts of ephedrine derivatives in CO, at 80 C and 34.0 MPa. ME = methylephedrine (3) NE = norephedrine (4) E = ephedrine (5) PE = pseudoephedrine (6) [41]. Reproduced with permission from Vieweg Publishing 1999.

For ephedrine derivatives, basified methanol or water showed solubilities greater than for neutral conditions (Figure 10), similar to the results for hyoscyamine (1) and scopolamine (2). 

Ephedrine occurs in white, rosette, or needle crystals, or as an unctuous mass. It is soluble in water, alcohol, chloroform, ether, and in liquid petrolatum, the latter solution being turbid if the ephedrine is not dry. Ephedrine melts between 34 and 40°C, depending upon the amount of water it contains it contains not more than 0.1% of ash its solutions are alkaline to litmus it readily forms salts with acids and it responds to the usual tests for alkaloids. Ephedrine excites the sympathetic nervous system, depressing smooth and cardiac muscle action, and produces effects similar to those of epinephrine. It produces a rather long-lasting rise of blood pressure and mydriasis and diminishes hyperemia. The alkaloid may be used in 0.5 to 2% oil spray. 

Both of these salts are readily soluble in water and in hot alcohol, but not in ether. They have the same pharmacological properties as ephedrine and are used orally in an average dose of 0.25 g. They are also used, in aqueous solution, intramuscularly and intravenously. 

A combination of ( ) -/V- ben zy loxycarbon y I am i no acid (Z-amino acid) and ( )-ephedrine is a good example of one method of affording four diastereomers efficiently if seed crystals of less-soluble salt are obtained in advance (Figure 13). 

The chiral discrimination existing in the diastereomer systems formed by ephedrine and various mandelic acids has been studied in great detail, using a variety of spectroscopic and structural tools. Although significant differences in the solubilities of the n- and p-salts obtained after reaction of ephedrine with mandelic acid were known to exist, both salts were... 

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