Pamoate salt

Taste improvement is quite an important aspect of drug modification, especially in pediatric medicine. The extremely bitter taste of some antibiotics, such as clindamycin (3.36) or chloramphenicol (3.37), can be masked successfully by preparing esters or pamoate salts of these drugs, which are very insoluble and therefore have no taste. 

Pyrantel exliibits absorption, distribution, biotransformation, and elimination profiles similar to those of morantel. Pyrantel tartrate is well absorbed with peak plasma levels occurring 2-3 h after dosing. In ruminants, urinary excretion accounts for about 25% of the administered dose, while much of the remainder passes unchanged in feces. However, the pamoate salt is very poorly absorbed, most of the dose being excreted in feces. 

Asterisks designate chiral centers. Available as insoluble pamoate salt for long-acting IM use. 

Pyrantel is a broad-spectrum anthelmintic directed against pinworm, roundworm, and hookworm infections. Pyrantel is given as the pamoate salt and has the following structure ... 

For sodium or potassium salts of weak acids, the pH of the solution in a diffusion layer is greater than the pH of the diffusion layer for the corresponding weak acid. On the other hand, the pH of the solution in the diffusion layer for hydrochloride salts of weak bases is always smaller than the diffusion layer of the corresponding free base. Therefore, effective solubility and dissolution rate of soluble salts on drug absorption are available in the literature. The potassium salt of penicillin V yields a higher peak plasma concentration of antibiotic than the corresponding free acid (42). Sodium salts of barbiturates are reported by Anderson (43) to provide a rapid onset of sedation. Some salts have a lower solubility and dissolution rate than their parent compounds. Examples include aluminum salts of weak acids and pamoate salts of weak bases. In these particular examples, insoluble films of either weak acids or pamoic acid appear to form in the dissolving solids and further retard the dissolution rate. 

Imipramine is a 10,11 -dihydrodibenzazepine tertiary amine TCA (Fig. 21.15) that is marketed as hydrochloride and pamoate salts, both of which are administered orally. Although the hydrochloride salt may be administered in divided daily doses, imipramine s long duration of action suggests that the entire oral daily dose may be administered at one time. On the other hand, imipramine pamoate usually is administered as a single daily oral dose. Imipramine preferentially inhibits 5-HT reuptake over NE however, the formation of its N-desmethyl metabolite removes whatever 5-HT activity imipramine had, with the net result of enhanced noradrenergic activity from inhibition of NE reuptake at the presynaptic neuronal membrane. Imipramine shares the pharmacological and adverse-effect profile of the other tertiary TCAs. 

The first drug designed as a repository antimalarial was the pamoate salt of the active metabolite of proguanil, l-(4-chlorophenyl)-4,6-diamino-l,2-dihydro-2,2-dimethyl-j-triazine pamoate (cycloguanil pamoate or embonate, Camolar, CI-501, 37), single intramuscular doses of which protected mice for weeks against blood-induced infections with P. berghei [174] and monkeys... 

The pamoate salt (Cl U03-A) of tris ( -aminophenyl)carbonium (XXl) was effective in the treatment of japonicum dien given orally in a maxi mum dosage of 35- 0 mg/kg/day for as many as 52 days spread over a total treatment period of 203 days.This is in accord with previous findings95 The effects of tris (p-aminophenyl)carbonium salts (TAC) on mannoni are as follows 1) a reduction of glycogen in the cuticular tubercviles of males, 2) morphologic and functional alterations on the female reproductive system that lead to abnormal egg production and 3) inhibition of acetylcholinesterase activity in the nervous system of the worm. ... 

The treatment of psychoses with enantiomers of 3- 2-[4-(6-fluoro-l,2-benzisoxazol-3-yl)-l-piperidinyl]ethyl -2-methyl-4-oxo-6,7,8,9-tetrahydro-4/f-pyrido[l,2-n]pyrimidine-9-sulfonic acid and 12 was patented (99MIP6, 99MIP7). Pamoate acid salt of 11 was prepared and patented (94MIP7). 

The tartrate salt is recrystallized by dissolving in hot methanol, filtering, adding hot ethanol to the filtrate and cooling. The product is collected and air-dried. MP 148°-150°C. A second crop is obtained from the filtrate for a total yield of 59%. The tartrate is then metathe-sized with pamoic acid (Merck Index 6867) to give pyrantel pamoate as the product. 

Various carboxylic acid salts have also been reported. Gallardo35 produced the maleate salt of neomycin which, it was claimed, improved the aqueous stability of the antibiotic. A practically tasteless compound, the citrate salt,has been described by Szyszka3 . Neomycin mandelate has been claimed to be particularly useful in the treatment of urogenital infections3 while the di-hydroxy-dinaphthylmethane-dicarboxylate4(3 and the pamoate salts43,67,68 have a low intestinal absorption and are thus effective treatments for intestinal infections. 

Hydroxyzine pamoate is designated chemically as l-(p-chlorobenzhydryl)4-[2-(2-hydroxyethoxy) ethyl] diethyl-enediamine salt of l.l -methylene bis (2 hydroxyl-naphthalene carboxylic acid). Hydroxyzine pamoate 25 mg/5... 

MIP6, 99MIP7). Pamoate acid salt of 11 was prepared and patented (94MIP7). 

Three pyrantel salts (pamoate, embonate and tartrate) are indicated for use in the horse. The pyrimidines are selective agonists at synaptic and extrasynaptic nicotinic acetylcholine receptors on nematode muscle cells, which produce spastic paralysis of the parasites. 

Only pyrantel salts have label claim for good efficacy (> 90%) for the removal of tapeworm infections. Use pyrantel pamoate 13.2 mg/kg p.o. (USA), or pyrantel embonate 38 mg/kg p.o. (Europe), or praziquantel 1 mg/kg p.o. 

Insoluble salts Pamoate (embonate), polystyrene sulphonate (resinate)... 

Many drug substances are used in the form of a salt. The identification of these materials may also include a test for the specific counterion used. Common counterions used in pharmaceuticals are sodium, chloride, and pamoate ions as illustrated later in Figure 5. 

Because poly (ortho esters) are stable in base and because naltrexone is a base with a pKa of 8.13 which produces a saturated aqueous solution having a pH of about 10, it can not be used as such and a neutral or slightly acidic salt must be used. Therefore, the salt naltrexone pamoate was used. Use of pamoates to decrease water solubility of various drugs has been described. 

Metformin pamoate [as emboate] 2376 Methanearsonic acid, disodium salt 1499... 

Formulating a suspension from the slightly soluble salt or less soluble component (see Sect. 18.1). Examples are taking ferrous fumarate instead of ferrous sulfate, taking amitriptyline pamoate [40] instead of its HCl salt, which is also applicable to other phenothiazines. Of course bioavailability has to be assessed anew. 

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