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The chemical, microbiological and visual stability of frozen solutions of cefamandole nafate was studied. Solutions of cefamandole nafate were prepared by diluting 1 g of drug with 3 ml of Water for Injection, USP, or 0.9% Sodium Chloride Injection, USP, or 5% Dextrose Injection, USP (i.m. dilutions); or with 50 or 100 ml of the latter two diluents (i.v. dilutions). Stability of samples stored in glass and polyvinyl chloride plastic containers for up to 52 weeks at -10 and -20 C was measured by microbiologic, polarographic, iodometric, nephelometric and chromatographic assay and pH was measured. In mice, LD50 tests were performed using the i.m. dilutions. I.M. dilutions of cefamandole nafate were stable for 52 weeks when stored at -20 C; at -10 C, however, some samples did not freeze completely and were turbid when thawed. I.V. dilutions were stable for 26 weeks when stored at -20 C. I.V. dilutions with D5W stored at -10 C developed a transient haze. A gradual decrease in pH, which was a function of storage time, was noted for the frozen solutions. Six months of freezing did not alter the LD50 in mice. Solutions of cefamandole nafate are stable for at least 26 weeks when stored at -20 C in glass or PVC containers.

The components of quality control in the pharmaceutical industry are discussed as they apply to hospital pharmacy admixture services. The pharmaceutical industry complies with the FDA's Current Good Manufacturing Practices, which require manufacturers to have written procedures for ensuring sterility and nonpyrogenicity of injectable products. Because FDA specifies only what outcome measures must be assessed (rather than specific means of assessment), pharmaceutical companies have developed a multiplicity of quality-control systems. However, each system consists of a master formula (quantitative listing of all ingredients), master manufacturing instructions (the recipe for each product), master packaging instructions, and batch records. Documents used by quality control personnel include the specifications (identification, tests, and limits for products), test methods, and sampling procedures. Hospitals should have similar quality-control programs. These programs should systematically prevent or identify and correct deficiencies, measure overall quality, and provide information for managers. Hospital pharmacists whose departments do not have comprehensive programs should consult colleagues who have developed such procedures. Techniques used in industry should be applied when possible. To protect the integrity of manufacturers' drug products during compounding in hospitals, every hospital admixture service must have its own quality-control system.

A Ferranti-Shirley cone and plate viscometer was utilized to characterize the spreading properties of white petrolatum U.S.P., white ointment U.S.P., and anhydrous lanolin U.S.P. Data were obtained for structural breakdown during repetitive cycling and for structural breakdown at constant shear. The problem of slippage at the revolving cone/sample interface is discussed. An attempt is made to relate rheological differences and molecular structure.

Rheograms were obtained with a Ferranti-Shirley cone and plate viscometer at 20, 2 5, 30, and 35° for 13 pharmaceutical semisolids. As the temperature was raised, all the products studied showed a decrease in viscosity, thixotropy, and yield value. For many of the semisolids there appears to be a straight line relationship between thixotropic area and temperature. For ointments whose base is predominatety white ointment, the viscosity is reduced by a factor of 0.5 for every 5° rise in temperature. At 35° many of the products studied showed similar values for thixotropy and viscosity.

A study has been made on the effect of emulsification temperature and cooling rate on certain physical properties of a beeswax-mineral oil emulsion. The emulsion, which was prepared at five temperatures and cooled at three rates, was evaluated for plastic viscosity, thixotropy, yield value, water separation rate, and initial average particle size. It was shown that both the emulsification temperature and cooling rate significantly altered these properties.

The stability of frozen solutions of cefazolin sodium was investigated in nine commonly used diluents at concentrations of 1 g with 2.5 ml, 500 mg with 100 ml and 10 g with 45 ml in both glass and polyvinylchloride plastic containers. The diluents were: Water for Injection USP; 0.9% Sodium Chloride Injection USP; 5% Dextrose Injection USP (D5W); D5W with 0.02% sodium bicarbonate; D5W in Lactated Ringer's Injection USP; Lactated Ringer's Injection USP; Ionosol B in D5W; Normasol M in D5W; and Plasmalyte in D5W. Frozen cefazolin sodium solutions, containing Water for Injection USP, 5% Dextrose Inection USP or 0.9% Sodium Chloride Injection USP as the diluents, retained more than 90% of labeled potency for up to 26 weeks when frozen within one hour after reconstitution and held at -10 C or -20 C. Frozen cefazolin sodium solutions, made with other diluents, were stable for up to four weeks when frozen within one hour after reconstitution and held at -10 C.

A physicochemical approach to the preparation of drug-containing matrix systems is described in which a soluble anionic drug may be entrapped on a molecular scale in coagulated (gelled) polymer emulsion systems. The resultant dried product (or drug-xerogel system) was designed to provide controlled, prolonged release. The phenomenon of gelation of the polymer emulsions by the addition of a divalent cation (Mg+2) was utilized for the entrapment of various drug materials. A solid, highly reproducible entrapment compound of sodium phenobarbital, magnesium sulfate, and a styrene-acrylic copolymer latex was prepared and subjected to in vitro and in vivo prolonged-release studies. The physical factors influencing both entrapment and drug release were investigated. A significantly increased duration of therapeutic effectiveness was established by the in vivo results. Rats, fed dry polymer powder in their diet, exhibited no toxic effects in a 27-day study. The validity and reproducibility of the entrapment procedure were demonstrated.