Benzylpenicillin salts

Benzylpenicillin Salts of benzylpenicillin are hydrolyzed in aqueous solutions, particularly in acids, alkalis, and concentrated solutions. Instability is minimum (about pH 6.8) using titrated buffers can enhance its stability. 

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... 

Determination of various benzylpenicillin salts Phosphate-borate buffer supplemented with SDS 14.4 g/L MEKC [173]... 

Sodium benzylpenicillin see -benzylpenicillin sodium salt on p. 514 in Chapter 6. 

Chemical Nama D-a-(imidazolidin-2-on-1-yl-carbonylamino)benzylpenicillin, sodium salt Common Nama —... 

Monobenzyl phenylmalonate (13.3 g) in dry benzene (100 ml) was refluxed with thionyl chloride (6.45 g) for 90 minutes, then concentrated in vacuo. The residual oil was dissolved In dry acetone (50 ml) and added to a stirred, ice-cooled solution of 6-aminopenlcillanic acid (9.7 g) in N sodium bicarbonate solution (135 ml), water (150 ml), and acetone (300 ml). The mixture was stirred for 30 minutes at 0°C and then for 90 minutes at room temperature, then concentrated under reduced pressure to remove acetone. The aqueous solution was brought to pH 2 with dilute hydrochloric acid and extracted with ether (3 X 100 ml). The ether solution was washed with water and then itself extracted with sufficient N sodium bicarbonate solution to give an aqueous phase of pH 7,5. The aqueous layer was separated and evaporated at low temperature and pressure to leave the Impure sodium salt of a-(benzyloxycarbonyl) benzylpenicillin. 

Oxidation of phenyl hexyl sulphide with sodium metaperiodate gave also only a trace amount of the corresponding sulphoxide72. On the other hand, Hall and coworkers73 prepared benzylpenicillin and phenoxymethyl penicillin sulphoxides from the corresponding benzyl esters by oxidation with sodium metaperiodate in dioxane solution with a phosphate buffer. A general procedure for the synthesis of penicillin sulphoxides was reported later by Essery and coworkers74 which consists in the direct oxidation of penicillins or their salts with sodium metaperiodate in aqueous solution at pH 6.5-7.0. 1-Butadienyl phenyl sulphoxide 4475 and a-phosphoryl sulphoxides 4576 were also prepared by the same procedure. 

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. 

Benzylpenicillin is produced as various salts according to its intended use, whether as an input to semisynthetic /3-lactam antibiotics manufacture or for clinical use in its own right. 

The treatment of the crude penicillin extract varies according to the objective but involves formation of an appropriate salt, probably followed by treatment to remove pyrogens, and by sterilization. This last is usually achieved by filtration but pure metal salts of benzylpenicillin can be safely sterilized by dry heat if desired. 

Theory Benzylpenicillin (sodium or potassium salt) may be assayed gravimetrically by quantitative conversion to the 1-ethylpiperidinium benzylpenicillin derivative. The ultimate precipitation is caused by 1-ethyl piperidine after the respective sodium or potassium salt of benzylpencillin has been duly converted with phosphoric acid to the corresponding penicillanic acid (i.e. parent acid) and the latter finally extracted with amyl alcohol. The reactions may be expressed as follows ... 

Chemical Name D-a-(Imidazolidin-2-on-l-yl-carbonylamino)benzylpenicillin, sodium salt... 

The reaction between 6-aminopenicillanic acid (6.5 g) and 3-o-chlorophenyl-5-methylisoxazole4-carbonyl chloride (7.66 g) gave the sodium salt of 3-o-chlorophenyl-5-methyl-4-isoxazolylpenicillin (9.98 g) as a pale yellow solid. Colorimetric assay with hydroxylamine against a benzylpenicillin standard indicated a purity of 68%. 

Heparin and its salts are incompatible with many drugs including alteplase, amikacin sulfate, amiodarone hydrochloride, ampicillin sodium, aprotinin, benzylpenicillin potassium or sodium, cephalothin sodium, ciprofloxacin lactate, cytarabine, dacarbazine, daunorubicin hydrochloride, diazepam, dobutamine hydrochloride, doxorubicin hydrochloride, droperidol, erythromycin lactobionate, gentamicin sulfate, haloperidol lactate, hyaluronidase, hydrocortisone sodium succinate, kanamycin sulfate, methicillin sodium, netilmicin sulfate, some opioid analgesics, oxytetracycline hydrochloride, some phenothiazines, polymyxin B sulfate, streptomycin sulfate, tetracycline hydrochloride, tobramycin sulfate, vancomycin hydrochloride, vinblastine sulfate, cisatracurium besylate, labetalol hydrochloride, nicardipine hydrochloride, cefmetazole, sodium ions, and fat emulsion.110 112... 

SYNS AMERICAN PENICILLIN BENZYL-PENICILLIN SODIUM CRYSTAPEN MYCOFARM NOVOCILLIN PEN-A-BRASIVE PENICILLIN-G, MONOSODIUM SALT PENICILLIN G, SODIUM PENICILLIN G, SODIUM SALT PENILARYN PENZYLPENICILLIN SODIUM SALT SODIUM BENZYLPENICILLIN SODIUM BENZYLPENICILLIN G SODIUM BENZYLPENICILLINATE SODIUM PENICILLIN SODIUM PENICILLIN G SODIUM PENICILLIN II VETICILLIN... 

The different neutral esters are nearly or wholly ineffective, but in vivo they show activity when administered other than orally to mouse, rat or guinea-pig. In vivo, in man, monkey or dog these esters are not active. In the case of alkyl and aralkyl esters a dosage for complete inhibition against Strept. hemolyticus in mouse is 0.01-0.05 g/mouse (intra-peritoneal) vs. 0.1 g/mouse for the sodium salt of benzylpenicillin [109]. These data can be explained by the fact that the serum of these animals contained an esterase capable of hydrolyzing the esters to the free acid [124-126]. 

Procaine penicillin, given i.m. only, is a stable salt and liberates benzylpenicillin over 12-24 h, according to the dose administered. Usually this is 360 mg 12-24-hourly. There is no general agreement on its place in therapy, and it is no longer available in a number of countries. It is best to use benzylpenicillin in the most severe infections, especially at the outset, as procaine penicillin will not give therapeutic blood concentrations for some hours after injection and peak concentrations are much lower. 

Procaine benzylpenicillin (procaine penicillin) is a poorly soluble salt that is absorbed slowly following i.m. or s.c. injection. It is the most commonly used formulation of penicillin in horses. Injections s.c. cause severe local inflammation and hemorrhage, as well as leaving deposits of... 

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. 

---