Napsylate salt

Use in moderate pain Weak analgesic most effective when used with NSAIDs, aspirin, or acetaminophen This drug is not recommended in the elderly Will cause carbamazepine levels to increase 100 mg of napsylate salt = 65 mg of HCI salt Third-line agent for moderate-to-severe pain... 

Propoxyphene is an analogue of methadone that is widely used as an analgesic. However, single-dose studies have shown that the analgesic properties of propoxyphene are no better than those of placebo. When propoxyphene is used alone in usual analgesic doses (32 to 65 mg of the hydrochloride salt or 50 to 100 mg of the napsylate salt),... 

Propoxyphene Napsylate, USP. Propoxyphene nap-sylale. (+ )-a-4-dimethylamino-3-melhyl-1.2-diphenyl-2-bulanol propanoate (c.sicr) 2-naphlhylenc.sulfonalc (salt) (Darvon-N). is very slightly soluble in water, but soluble in alcohol, chloroform, and acetone. The napsylate salt of propoxyphene was introduced shortly before the patent on Darvon expired. The insoluble salt form is claimed to be less prone to abu.se because il cannot be readily dissolved for injection and. on oral administration, gives a slower, less pronounced peak bhxxl level. 

As described previously, unpleasant tasting drugs for administration as oral liquids are often presented as suspensions of insoluble salts to improve patient acceptability. An example of this is the bitter tasting analgesic drug, propoxyphene, which is presented as the hydrochloride salt in tablets and as the napsylate salt in oral suspension formulations. 

The choice of salt is often determined by taste consideration, such as the use of benzathine salts of penicillin V low solubility salts have lesser taste, but also dissolve slowly, and are often used for preparing depot preparations, such as benzathine salts of penicillin G and V. Similarly, the napsylate salt provides better organoleptic properties as a result of its low solubility when compared with hydrochloride forms. 

Usually salt formation is carried out to increase the solubility of the base, however, salts with lower solubilities are sometimes prepared to, e.g., mask taste, provide slower dissolution and increase chemical stability. An example of salt formation to decrease dissolution rate is described by Benjamin and Lin (1985), who prepared a range of salts of an experimental antihypertensive as shown in Table 3.10. The solubilities and intrinsic dissolution rates (IDR) of the prepared salts of this compound are also shown in Table 3.10. These in vitro tests showed that there were significant differences in the dissolution rate when the experiments were performed in water and buffer. However, the difference in the IDRs of the salts was similar in 0.1 M HC1. Hence, it was recommended that ebonate, 3-hydroxynaphthoate or napsylate salts should be formulated as enteric-coated dosage forms. This would avoid dissolution in the stomach acid, which could cause local GI irritation, and would still provide release of the compound. 

Taste acceptability is a particular issue with oral liquid dosage forms, lozenges, and chewable tablets. The problem may be overcome by the preparation of poorly soluble salts. Thus the bitterness of erythromycin and of bacitracin may be ameliorated by use of the estolate (lauryl sulfate) and zinc salts, respectively. Propoxaphene may be taste masked by forming the napsylate, the solubility of which may be further reduced and the taste improved by adding a common-ion salt such as sodium or calcium napsylate. 

Gruber, C.M., Jr. Stephens, V.C. Tirrell, P.M. Propoxyphene napsylate chemistry and experimental design. Toxicol. Appl. Pharmacol. 1971, July, 19 (3), 423 26. Campbell, J.A. Slater, J.G. Modification of physical properties of certain antitussive and antihistaminic agents by formation of A-cyclohexylsulfamate salts. J. Pharm. Sci. 1962, Oct, 51, 931-934. 

A salt can also provide improved chemical stability compared to the parent drug substance. An example of this was reported for xilobam, whose structure is shown in Fig. 13 (15). In order to protect xilobam from the effects of high temperature and humidities without decreasing the dissolution rate, three arylsul-fonic acid salts (tosylate, 1-napsylate, and 2-napsylate), as well as the saccharate salt, were prepared. The 1-napsylate was found to be the most chemically stable form at 70°C and 74% RH after 7 days. Dissolution data from compressed tablets... 

In another study, Walkling et al. (1983) found that xilobam, as the free base, was sensitive to high humidity and temperature. In an effort to overcome this problem, the tosylate, 1-napsylate, 2-napsylate and saccarinate salts were prepared and assessed with respect to their... 

Salt Free Base Tosylate Saccharinate 2-Napsylate 1-Napsylate... 

Salts are sometimes chosen with regard to their organoleptic properties and, for Instance dextropropoxyphene napsylate (Fig. 3.18), is sometimes used because it is not as bitter as the hydrochloride. 

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