Freeze drying, penicillin

The pH of the mixture was adjusted to 7.5 by adding a saturated sodium bicarbonate solution. After being washed twice with diethyl ether, the reaction solution was acidified to pH 2 with dilute hydrochloric acid and extracted with ether. The ether solution containing the free penicillin was washed twice with water and then extracted with 50 ml of N potassium bicarbonate solution. After freeze drying of the obtained neutral solution, the potassium salt of o-azidobenzylpenicillin was obtained as a slightly colored powder (11.2 grams, 54% yield) with a purity of 55% as determined by the hydroxylamine method (the potassium salt of penicillin G being used as a standard). 

The salt was prepared by dissolving the free acid form of the penicillin in the equivalent amount of aqueous sodium bicarbonate and freeze drying the resulting solution. The hydrated salt so obtained was shown by alkalimetric assay to be 94% pure and to contain 6% water. 

In the first example, procaine penicillin, an aqueous vehicle containing the soluble components (such as lecithin, sodium citrate, povidone, and polyoxyethylene sorbitan monooleate) is filtered through a 0.22 pm membrane filter, heat sterilized, and transferred into a presterilized mixing-filling tank. The sterile antibiotic powder, which has previously been produced by freeze-drying, sterile crystallization, or spray-drying, is aseptically added to the sterile solution while mixing. After all tests have been completed on the bulk formulation, it is aseptically filled. 

The freeze drying of antibiotics and blood serum have largely represented the beginning of industrial lyophilization. Neumann [3.34] wrote in 1952 The (freeze drying) temperature for the older, not well purified Penicillin preparations had to be kept surprisingly low. It could not exceed -25 °C or -40 °C and later on Today Peniciilin is manufactured as crystals without the need of freeze drying . 

Industrial freeze-drying began with the production of preserved blood plasma and penicillin, as shown by E. W. Flosdorf in his book Freeze-drying in 1949. 

Natural penicillin is fragile and breaks down in the presence of impurities and enzymes, having a half-life of just 2.5 h even when cooled to 0 °C. The method of choice for stabilizing penicillin for storage and shipment turned out to be the freeze-drying method. Penicillin is frozen in trays at —30 °C it is then placed in a chamber at a pressure of 0.1-0.6 Torr to sublimate the ice crystals into water vapor and removed. 

Penicillins have several properties that are characteristic of /i-lactam antibiotics. They are obtained in relatively pure form as off-white, tan, or yellow freeze-dried or spray-dried solids that are usually amorphous. Alternatively they are sometimes obtained as crystalline solids, often as hydrates. Penicillins do not usually have sharp melting points, but decompose upon heating to elevated temperatures. Most natural members have a free carboxyl group and commercial preparations are generally either supplied as salts, most frequently as sodium salts, or in zwitterionic form as hydrates, e.g.. amoxicillin trihydrate. The acid strength of the carboxyl group in aqueous solution varies from pAT = 2.73 for oxacillin to p= 3.06 for carbenicillin. 

Mathews and his coworkers 8 described an unusual behavior for samples of freeze-dried potassium benzylpenicillin and potassium phenoxymethyl penicillin. These samples absorbed moisture from the air up to a maximum content of 7-14 per cent. Then the samples suddenly contracted in volume and began to lose weight until they had returned to their original weight. 

Penicillin proved a difficult compound to isolate and purify. Although Fleming recognized the antibiotic qualities of penicillin and its remarkable non-toxic nature to man, he disregarded it as a useful drug since it appeared too unstable. He could isolate it in solution, but whenever he tried to remove the solvent, the drug was destroyed. Now that we know the structure of penicillin (Chapter 9), its instability under the purification procedures of the day is understandable and it was not until the development of a new procedure called freeze-drying that a successful isolation of penicillin was achieved. 

Freeze, vacuum, batch (conduction) drying temperature serum, -9 to -12 °C plasma, -20 to -25 °C penicillin -28 to -32 °C size vacuum pump to remove the water vapor avoid air leaks pressure 10 to 200 Pa or 1/4 to 1/2 the vapor pressure at the temperature 7-8 h drying cycle 2800 kj/kg water sublimated. Continuous ... 

---