Sodium salts of drugs

Rubin JT. Solubilities and solid state properties of the sodium salts of drugs. J Pharm Sci 1989 78 485-489. 

Further substitution of benzoic acid leads to a drug with antiemetic activity. Alkylation of the sodium salt of p-hydroxy-benzaldehyde (8) with 2-dimethylaminoethyl chloride affords the so-called basic ether (9). Reductive amination of the aldehyde in the presence of ammonia gives diamine, 10. Acylation of that product with 3,4,5-trimethoxybenzoyl chloride affords trimetho-benzamide (11). ... 

In this study, potential oscillation was measured in the presence of lOOmM sodium salts of barbital, allobarbital, phenobarbital, and amobarbital in phase wl [19]. Their chemical structures are shown in Fig. 15. Amplitude and the oscillatory and induction periods were noted to depend on the particular hypnotic used. Amplitude decreased in the order, barbital > allobarbital > phenobarbital > amobarbital. The oscillatory period increased in the order, barbital < allobarbital < phenobarbital < amobarbital. Induction period increased in the order, barbital < allobarbital < phenobarbital < amobarbital. These parameters changed depending on drug concentration. Hypnotics at less than 5 mM had virtually no effect on the oscillation mode. 

The drug discovery route to rizatriptan (1) began with the preparation of 1-(4 -nitrobenzyl)-l,2,4-triazole 5 using 4-nitrobenzyl bromide (4) and 1,2,4-triazole. (Scheme 4.1). Benzylation of the sodium salt of 1,2,4-triazole prepared with NaH was not regioselective and afforded a 1.5 1 mixture of l-(4 -nitrobenzyl)-1,2,4-triazole (5) and its regioisomer, 4-(4 -nitrobenzyl)-l,2,4-triazole. The desired isomer 5 was isolated in 52% yield after silica gel chromatography. Hydrogenation... 

The UV spectrum of valproic acid (0.1% solution) in methanol is shown in Fig. 3, was recorded using a Shimadzu UV Visible Spectrophotometer 160 PC. The acid form of the drug has one maximum at 212 nm. In contrast, the sodium salt of the compound has no UV maximum between 800 and 205 nm, this in agreement with previous results reported by Chang [5]. 

Extending the aforementioned methodology from imidazole to adenine, the Tsuji-Trost reaction between the sodium salt of adenine and allylic acetate 66 gave 67 as a 82 18 mixture of cis trans isomers. Carbocyclic nucleoside 67 was advantageous over normal nucleosides as a drug candidate because it was not susceptible to degradation in vivo by nucleosidases and phosphorylases [52],... 

Morphine Sulfate Morphine sulfate precipitates in alkaline media and drugs that are incompatible with it, including aminophylline, sodium salts of barbiturates, and phenytoin. Precipitate was found after 2 horns when morphine sulfate was formulated with acyclovir sodium.70 Incompatibilities also are reported with chlorpromazine hydrochloride injections containing chlorocresol. Admixture of morphine sulfate (1 mg/mL), doxorubicin in doxorubicin hydrochloride... 

Analytical Procedure Microscopic Examination Place a small amount of a crushed tablet or capsule contents on a slide, mix with a drop of water, and cover carefully with a cover-slip avoiding trapped air bubbles. Observe under low-power magnification. Effervescence will be obvious. If crystalline material is visible, note if it is water-soluble. Check the pH of the solution. An alkaline reaction may indicate the presence of a sodium salt of an acidic drug. Introduce a small drop of silver nitrate solution along one edge of the cover-slip a visible precipitate indicates the possible presence of a hydrochloride salt of a basic drug. 

Furosemide injection may be administered by slow IV injection or by intermittent or continuous IV infusion at a rate not exceeding 4 mL/min. Therefore, the question arises whether photoprotection of the drug reservoir is necessary during parenteral administration. Furosemide injection contains the sodium salt of furosemide formed in situ by the addition of sodium hydroxide during the manufacturing process. The injection solution has a pH of 8 to 9.3. In use, it can be mixed with weakly alkaline and neutral infusion solutions (e.g., 0.9% sodium chloride or Ringer s solution) or with some weakly acidic solutions having a low buffer capacity (e.g., dextrose 5% in water). 

However, factors such as the solubility product (Ksp) of the salt, common-ion effects, and hygroscopi-city may disfavor the salts of first choice using the above criterion, e.g., hydrochloride or sodium salts. The formation of hydrochloride salts does not always enhance solubility above that of the free base. The lower solubility of a hydrochloride salt in dilute HCl, relative to that of the free base, is attributed to the common ion effect of the chloride ion on the solubility product equilibrium of the salts. The common-ion effect suppresses the solubility product equilibrium. This is particularly relevant to the HCl salts of drugs administered orally, resulting in contact with... 

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