Gaining strategic advantages through partnerships with public health departments.

Public health officials have advocated in public health and public policy journals for collaboration with private sector health care organizations for nearly a decade. There has been little written in the management literature on this topic, however. There are several important areas in which public health departments have expertise that could be valuable to private sector health care organizations, including health maintenance organizations (HMOs). These include the delivery of services in some geographic areas and to some special populations, provision of preventive and health promotion services to HMO members, performance of epidemiology services, assistance in accreditation, and repair of the damaged image of HMOs. HMOs and local health departments in many parts of the country are already entering into contracts for these purposes. Such partnerships between HMOs and local health departments can improve the health of the members of HMO plans and contribute to improving the health of the community.

Stability of reserpine injections and tablets submitted by U.S. hospitals.

The stability of reserpine injections and tablets that had been stored in hospital pharmacies across the United States was studied. Through a voluntary FDA drug stability program, all hospital pharmacies in the United States were asked to complete a response card indicating information about the reserpine injections and tablets they had in stock. Based on the responses, FDA selected 93 samples of reserpine injections and 51 samples of reserpine tablets. The samples of injections were subjected to tests for identification, pH, presence of other alkaloids, presence of 3,4-dehydroreserpine, and strength. All samples of reserpine injections met USP requirements. Two samples of reserpine tablets representing one lot each from two manufacturers failed to meet USP requirements for content uniformity. Reserpine injections and tablets appear to be stable under actual marketplace conditions.

Stability of pilocarpine hydrochloride and pilocarpine nitrate ophthalmic solutions submitted by U.S. hospitals.

The stability of pilocarpine hydrochloride and pilocarpine nitrate ophthalmic solutions stored in hospital pharmacies across the United States was studied. Through a voluntary drug stability program, FDA selected 252 samples (representing 11 manufacturers) from pharmacies representing an adequate cross section of the country. The samples were analyzed for strength, identification, pH, and isopilocarpine and pilocarpic acid impurities. All samples of pilocarpine nitrate met USP requirements. Eight samples of pilocarpine hydrochloride had tablets that exceeded the USP upper limit for strength. All of these samples were in 1- and 2-mL bottles. The amount of isopilocarpine found ranged from 1 to 6.4%, and the amount of pilocarpic acid from 1.5 to 10.1%. Although pilocarpine salts in ophthalmic solution decompose into isopilocarpine and pilocarpic acid under various conditions of storage, an amount of pilocarpine is maintained that is within the compendial limits. However, there is a problem of evaporation from some of the 1- and 2-mL containers in which this product is supplied.

Stability of nitroglycerin tablets submitted by U.S. hospitals.

The stability of nitroglycerin tablets that had been stored in hospitals across the United States was studied. Through a voluntary FDA drug stability program, all hospital pharmacies in the United States were asked in October 1981 to complete a response card indicating information about nitroglycerin tablets they had in stock. Based on the responses, FDA selected 167 samples (representing three manufacturers and all available tablet strengths) from pharmacies that represented an adequate cross section of the country. The samples were analyzed for content uniformity, strength, identification, and disintegration; samples that left a residue on the screen of the tablet disintegration basket were tested for dissolution by three methods and compared with samples that did not leave a residue. All samples met USP requirements for content uniformity, strength, and disintegration. Six samples that showed unusual disintegration characteristics dissolved slowly by one or more methods; however, other samples also showed slow dissolution. Nitroglycerin tablets appear to be stable when stored under actual marketplace conditions. The USP disintegration test will not distinguish between rapidly and slowly dissolving tablets.

Stability of sterile dexamethasone acetate suspensions and dexamethasone sodium phosphate injections submitted by U.S. hospitals.

The stability of sterile dexamethasone acetate suspensions and dexamethasone sodium phosphate injections that had been stored in hospital pharmacies across the United States was studied. Through a voluntary FDA drug stability program, all hospital pharmacies in the United States were asked in October 1981 to complete a response card indicating information about the sterile dexamethasone acetate suspensions and dexamethasone sodium phosphate injections they had in stock. Based on the responses, FDA selected 21 samples of sterile dexamethasone acetate suspensions (representing two manufacturers) and 114 samples of dexamethasone sodium phosphate injection (representing 11 manufacturers). These samples were analyzed for identification, pH, and strength. All samples of sterile dexamethasone acetate suspension met USP requirements. Eleven samples of dexamethasone sodium phosphate injection representing 10 lots from three manufacturers failed USP assay requirements for strength. All samples that failed to meet strength requirements showed evidence of degradation by oxidation. Sterile dexamethasone acetate suspensions appear to be stable when stored under actual marketplace conditions, but there is a problem with the shelf-life stability of dexamethasone sodium phosphate injections made by some manufacturers.

Stability of digitoxin tablets submitted by U.S. hospitals.

The stability of digitoxin tablets that had been stored in hospital pharmacies across the United States was studied. Through a voluntary FDA drug stability program, all hospital pharmacies in the United States were asked in October 1981 to complete a response card indicating information about the digitoxin products they had in stock. Based on the responses, FDA selected 25 samples (representing seven manufacturers) from pharmacies that represented an adequate cross section of the country. These samples were analyzed for content uniformity, strength, dissolution, identification, and other digitoxosides. Of the 25 samples, 19 lots were represented, including 11, 6, 1, and 1 lots of 0.1-mg, 0.2-mg, 0.15-mg and 0.05-mg tablets, respectively. Samples from two lots failed to meet USP requirements for strength, content uniformity, and dissolution; samples from four lots failed to meet the requirements for dissolution only. All six defective lots did not show an expiration date, indicating that they were manufactured before 1975. Digitoxin tablet products still within the expiration date showed no evidence of degradation after storage under actual marketplace conditions.

Systematic error associated with apparatus 2 of the USP dissolution test IV: effect of air dissolved in the dissolution medium.

Acceptable concentrations of gases in a medium are not well defined in USP dissolution tests. A sample of 10-mg prednisone tablets, known to be sensitive to dissolved gases, was tested with batches of purified water that contained different concentrations of air. The data suggest that the results from Apparatus 2 can be influenced by the concentration of air in the dissolution medium unless the medium remains unsaturated with air for the duration of the test. The repeatability of means of six results was markedly improved when the air concentration in the medium was accurately controlled at the beginning of the test.

Effect on dissolution of tablet storage in counting machines.

The effects of storage in an automatic counting and dispensing machine on dissolution rates on five drug products with known or suspected bioequivalence problems were studied. Amitriptyline hydrochloride, digoxin, prednisone, hydrochlorothiazide, and tolbutamide tablets exposed and unexposed to automatic counting machines were collected from 10 pharmacies located in various parts of the country. A 60-tablet unexposed sample was taken from a previously unopened container and placed in a tight, light-resistant container. Another 60-tablet sample of the same brand and lot number was collected 30 days after the initial filling of the counting machine or when it had to be refilled, whichever came first. Each sample was tested for dissolution rate and content uniformity. Twenty-seven paired samples representing 23 lots from 10 manufacturers were collected. There were no substantial differences in dissolution rate or content uniformity between the exposed and unexposed samples. Average temperatures in the pharmacies during the three-month sampling period ranged from 72 to 79 degrees F. Storage times of the drug product samples in the automatic counting machines varied from 9 to 46 days. The environmental conditions to which these tablets were exposed had no noticeable effect on the dissolution of these formulations.

Stability of digoxin tablets collected from U.S. hospitals.

The stability of digoxin tablets that had been stored in hospitals across the United States was studied. All hospital pharmacies in the U.S. were contacted in February 1980 to inform them about the program, the reimbursement procedures, the sampling requirement, and the process by which laboratory results would be distributed. A response card was included for those who wanted to participate. Ninety-two samples, representing three manufacturers and an adequate cross-section of the country, as well as typical dosage forms and packaging variations, were selected for laboratory analyses of content uniformity, strength, dissolution, identification, and related fluorescing substances. Eighty-five samples met the current compendial standards and seven samples failed the dissolution specifications. All seven were manufactured before July 1975 when the UPS dissolution requirements were changed. The digoxin products studied were not adversely affected by the variable stresses of the marketplace.

Decomposition of aminophylline in suppository formulations.

An aminophylline suppository product, when stored at room temperature, was found to be deficient in ethylenediamine content by the USP XIX assay and by a specific method for primary amines. The product also had a melting point that was considerably higher than body temperature. An accelerated decomposition experiment, conducted on normal suppositories of identical original composition, yielded a product refractory at steam bath temperatures and containing no ethylenediamine measurable by the USP assay. The suppositories from both the original sample and the decomposition experiment contained considerable amounts of a white material, which melted at similar to or approximately 150 degrees and which consisted of the diamide products formed by the reaction of ethylenediamine and the fatty acids present in coconut and palm kernel oils. The results, which confirmed the work of Cieszynski, showed that the ethylenediamine constituent of aminophylline can react with suppository base materials to produce insoluble amide decomposition products.

Stability study of nitroglycerin sublingual tablets.

Nitroglycerin sublingual tablets were studied over a 1-year period to determine tablet stability in terms of loss of strength, uniformity of tablets, and degradation of the drug itself. Tablets from six different firms were analyzed by a semiautomated procedure. The samples included two molded tablets and four compressed tablets, ranging in age at the time of initial assay from 40 days to over 1 year. The results indicated that there is a loss of strength of nitroglycerin tablets and that refrigeration slows down this loss. The study also indicated that these tablets were stable during the year of testing in terms of tablet uniformity and degradation of nitroglycerin.