Development and validation of a cholate binding capacity method for DMP 504, a bile acid sequestrant.

DMP 504, a highly cross-linked insoluble polymer, is a bile acid sequestrant developed by the DuPont Pharmaceuticals Company for serum cholesterol reduction. Since DMP 504 is insoluble, it was necessary to develop unique specific analytical methods to measure and control the quality of different lots of the drug. Since the mechanism of action of DMP 504 is believed to be by sequestration of bile acids, the in-vitro binding capacity of the polymer for cholic acid was chosen as a surrogate of in-vivo performance and used to assess potency of the compound. In this method, individual aliquots of DMP 504 at three different levels were incubated with a cholate solution of known concentration. The residual cholate solution was filtered and analyzed by a reversed-phase HPLC method using refractive index detection. When the bound cholate was plotted versus the mass of DMP 504, the resulting curve was linear. The slope of this curve is the cholate binding capacity of DMP 504. This method has been shown to be precise and robust. Precision of the method was shown to have an RSD of 2.0% with injection precision of 0.4% and stability of cholate solutions up to 73 h. It is also a unique binding capacity method due to its multi-point determination, and it has been shown to be a suitable quality control method for ensuring lot-to-lot consistency of drug substance.

Effect of inline filtration on ViaSpan cold-storage solution.

The effect of filtration on the particulate load in ViaSpan cold-storage solution was studied. Commercially available inline blood transfusion filters (SQ40S, Pall Biomedical) were inserted into the delivery-set port of polyvinyl chloride bags of ViaSpan (DuPont Merck Pharmaceutical). Particles in samples collected in particle-free vials before and after filtration were counted by a light-obscuration technique. The compatibility of key ViaSpan ingredients and of three commonly used additives (penicillin G potassium, dexamethasone sodium phosphate, and human insulin) with the inline filter was also investigated. Filtration removed 56% of particles 5-10 microm in diameter, 71% of particles of > 10-25 microm, and > 99% of particles measuring > 25 microm. Flow rates with the filters were more than adequate for clinical use. Concentrations of constituent hydroxyethyl starch, glutathione, adenosine, allopurinol, raffinose pentahydrate, and lactobionic acid were not significantly affected by filtration, nor were the concentrations of any of the drug additives. Inline filtration of ViaSpan effectively reduced fatty acid salt particulates in the solution and had no deleterious effect on flow rate, ingredient concentrations, or concentrations of commonly added drugs.

Placement of adult retardates from state institutions in community care facilities.

Results of a study evaluating the success of transfers of adult retardates from state institutions to public and private nursing homes indicate that most of the retardates adjusted well to the change, responded to program activities available in the nursing homes and nearby communities, and were visited more often by friends and relatives. Operators of the nursing homes, their staffs, the retardates, their families, and the other residents and their families accepted the placement program. By supporting social functioning at a lesser level of intervention than state institutions, nursing homes allow for greater exercise of even limited independence.