Benzathine salt

The activity of penicillin G was originally defined in units. Crystalline sodium penicillin G contains approximately 1600 units per mg (1 unit = 0.6 meg 1 million units of penicillin = 0.6 g). Semisynthetic penicillins are prescribed by weight rather than units. The minimum inhibitory concentration (MIC) of any penicillin (or other antimicrobial) is usually given in mcg/mL. Most penicillins are dispensed as the sodium or potassium salt of the free acid. Potassium penicillin G contains about 1.7 mEq of K+ per million units of penicillin (2.8 mEq/g). Nafcillin contains Na +, 2.8 mEq/g. Procaine salts and benzathine salts of penicillin G provide repository forms for intramuscular injection. In dry crystalline form, penicillin salts are stable for years at 4°C. Solutions lose their activity rapidly (eg, 24 hours at 20°C) and must be prepared fresh for administration. 

Cephapirin, a first-generation cephalosporin, is used in form of benzathine or sodium salts for intramammary treatment of mastitis in dry and lactating cows. In the United States, the benzathine intramammary formulations are sold for use by dairy farmers without a prescription. The benzathine salts are further used for intrauterine treatment of endometritis, whereas the sodium salts for parenteral... 

Procaine salts and benzathine salts of penicillin G provide repository forms for intramuscular injection. In dry crystalline form, penicillin salts are stable for long periods (eg, for years at 4 °C). Solutions lose their activity rapidly (eg, 24 hours at 20 °C) and must be prepared fresh for administration. 

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. 

In another study by Cotton et al. (1994), a salt selection procedure was carried out because the free acid of L-649,923, an orally active leukotriene D4 antagonist, was inherently unstable because it rapidly hydrolyzed to a less active form of the compound. Therefore, to ensure that this did not occur, the compound had to be isolated as a salt. The physical and chemical properties of the sodium, calcium, ethylene diamine and benzathine salts were evaluated, and the calcium salt was selected as the most pharmaceutically acceptable form of the compound. 

Saesmaa and Halmekoski (1987) have reviewed the slightly water-soluble salts of the (3-lactam antibiotics, and their paper consists of much information on the early literature of these compounds. As examples, they describe the use of the benzathine salts of penicillin G and V for depot injections. The benzathine salt of penicillin V has also been used to mask the... 

It is worth adding a note of caution with regard to salt formation. In a series of benzathine and emboate salts of the (3 -lactam antibiotics—ampicillin, amoxicillin, cephalexin and talampicillin—studied by XRPD (Saesmaa et al. 1990), the results showed that the emboate salts of ampicillin, amoxicillin and cephalexin were nearly identical in structure to that of the stoichiometric physical mixture of the two starting materials. Furthermore, the XRPD of benzathine amoxicillin and amoxicillin trihydrate were identical. In contrast, the benzathine salts of ampicillin and cephalexin were formed, illustrating that formation of the salt should always be confimed by solid-state characterization tehniques. 

Benzathine salt. CHHMCl3Ns0ltSj. Boviclox, Dry-Clox, Noroclox DC, Optictox. Orbenln Dry Cow, Triclox. 

Benzathine salts have particularly low aqueous solubility and, when injected intramuscularly, form a depot from which dissolution occurs slowly. Indeed, all benzathine benzylpenicillin salts have been banned from use in the food-producing animals in the EU, because of persistence at and erratic rate of depletion from injection sites and a consequent perceived hazard to human health. Procaine salts, on the other hand, are somewhat more water-soluble and remain in widespread use, formulated as aqueous or oily suspensions. These formulations provide flip-flop pharmacokinetics with terminal half-lives in the range of 8.9-17.0 h after intramuscular or subcutaneous dosing to calves and adult cattle. In some studies, absorption... 

In contrast to the sodium or potassium salt of benzyl penicillin, which is very water soluble and has a short duration of action, the procaine and benzathine salts (or more accurately, the ion-pair complexes) shown in Figure 8.27 are only sparingly soluble in water and very lipophilic. They are dissolved in an oily vehicle, such as ethyl oleate or sesame oil, and administered by intramuscular injection to create a depot from which the penicillin anion is slowly released into the bloodstream, achieving a sustained-release profile. An added advantage of these depot penicillins is their superior stability compared to benzylpenicillin. 

Benzylpenicillin is rapidly absoibed and rapidly excreted However, certain sparingly soluble salts of benzylpenicillin (benzathine, benethamine and procaine) slowly release penicillin into the circulation over a period of time, thus giving a continuous high concentration in the blood. Simultaneous administration of benzylpenicillin (see Fortified Proeaine Penieillin, BP) may be given initially. 

Intramuscular administration in depot form. In its anionic form (-COO ) penicillin G forms poorly water-soluble salts with substances containing a positively charged amino group (procaine, p. 208 clemizole, an antihistamine benzathine, dicationic). Depending on the substance, release of penicillin from the depot occurs over a variable interval. 

The rates of absorption, clearance, and elimination of penicillin G are influenced by its formulation. Penicillin G is available in a number of different salts either with inorganic ions including sodium, potassium, or calcium or with organic cations including procaine and benzathine. These salts have differing solubilities and hence differing durations of action. 

The beta-lactam antibiotics are commonly used because of their safety, efficacy, relatively low cost and the variety of dosage forms available. Both penicillins and cephalosporins have a four-membered beta-lactam ring that is responsible for the instability of these compounds. The penicillins are also relatively insoluble they are prepared as various salts by the substitution of the hydroxyl group or the hydrogen of the carboxyl group with sodium, potassium, benzathine or procaine. 

Benzathine benzylpenicillin is a very insoluble salt. It is administered i.m. in "long-acting" formulations that contain one-half procaine benzylpenicillin (procaine penicillin) and one-half benzathine benzylpenicillin. Any clinical effect is from the procaine benzylpenicillin (procaine penicillin) portion of these formulations since the benzathine penicillin provides persistent but sub-therapeutic plasma concentrations. 

Saesmaa T, Makela T, Tannienen VP. Physical studies on the benzathine and emanate salts of some /3-lactam antibiotics. Part 1. X-ray powder diffractometric study. Acta Pharm Perm 1990 99 157-162. 

Answer B. Indications for the use of penicillin G are currently limited for a number of reasons. The drug has a narrow spectrum, is susceptible to beta-lactamases, and may cause hypersensitivity, and alternative antibiotics are available. However, penicillin G remains the drug of choice in syphilis, usually given IM as benzathine penicillin G, but as the Na or K salt IV in neurosyphilis. What would you do for patients who are highly allergic to penicillins (Consider tetracyclines, or possibly desensitization.)... 

Penicillin G benzathine suspension is the aqueous suspension of the salt obtained by the combination of 1 mol of an ammonium base and 2 mol of penicillin G to yield A/,A -dibenzylethylenediamine dipenicilhn G. The salt itself is 0.02% soluble in water. The long persistence of penicillin in the blood after a suitable IM dose reduces cost, the need for repeated injections, and local trauma. The local anesthetic effect of penicillin G benzathine is comparable with that of penicillin G procaine. 

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