Decomposition and Stabilization of the Tablet Excipient Calcium Hydrogenphosphate Dihydrate

Calcium hydrogenphosphate dihydrate is a commonly used filler in solid dosage forms. In the literature it is noticed that drug decomposition reactions can be accelerated by the decomposition of CaHPO₄.2H₂O. The present study has been performed to evaluate various types of this commercially available excipient and to elucidate the impact of selected factors on stability.

The influence of both temperature (40, 50 and 60°C) and environmental humidity (26, 34 and 46 % rel. humidity) on the dehydration of calcium hydrogenphosphate dihydrate was studied for a period of two to three months. Five batches of CaHPO₄.2H₂O were used with different contents of magnesium hydrogenphosphate and sodium pyrophosphate, which are often added to stabilize CaHPO₄.2H₂O in preparations like aqueous dentifrices. Disks of CaHPO₄.2H₂O have been prepared in such a way, that the structure of the disks allowed discrimination between the batches in dehydration kinetics. A relatively low velocity of dehydration was found for the batches containing high levels of sodium pyrophosphate. The effect of environmental humidity on the dehydration velocity appeared not to be straightforward: only at 60 °C an acceleration of the dehydration rate was found for all batches due to the increase of relative humidity. The residues after dehydration were analysed by Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFT), Thermogravimetric Analysis and Differential Scanning Calorimetry.

The results demonstrate that, independent of the storage condition and the type of calcium hydrogenphosphate dihydrate used, the main decomposition product is anhydrous calcium hydrogenphosphate. This contrasts with interpretations in the literature, which include the formation of decomposition products like hydroxyapatite and phosphoric acid.

Although no experiments were performed in the presence of drugs, a hypothesis is proposed on the basis of this study for the mechanism of possible drug decomposition in the presence of calcium hydrogenphosphate dihydrate. The mechanism can be simplified to dissolution of drug in accumulated free water due to dehydration within the drug/excipient system with, possibly, interactions between the drug and calcium hydrogenphosphate dihydrate. Obviously, time, temperature and amount of accumulated free water are important factors in determining the amount of drug decomposed. Accumulation of free water in granulates and tablets containing calcium hydrogenphosphate dihydrate should therefore be avoided or at least limited. This will have implications for e.g. the selection of the quality of calcium hydrogenphosphate dihydrate to be used and for the manufacturing practice of solid dosage forms containing this filler excipient.     

Purification and characterization of the agglutinins from the sponge Axinella polypoides and a study of their combining sites

The hemagglutinins from the sponge Axinella polypoides were isolated by affinity chromatography using Sepharose 4B as an absorbent and eluting with DGal. Further separation on DEAE-cellulose and preparative disc electrophoresis on polyacrylamide and agarose gave three fractions. The physicochemical properties and binding specificities of the two main agglutinins were studied. Homogeneity was tested by polyacrylamide electrophoresis and immunoelectrophoresis and by sedimentation analysis. In isoelectric focusing, agglutinin I (mol wt 21 000) showed two bands at pH 3.8 and 3.9. Agglutinin II (mol wt 15 000) showed one band at pH 3.9. Both agglutinins have a carbohydrate content of about 0.5%, are immunochemically unrelated, and differ in amino acid composition. Both precipitate A1, A2, B, Lea, and precursor I blood group substances but to different extents. Inhibition experiments revealed that both agglutinins are inhibited best by terminal nonreducing DGal glycosidically linked beta 1 leads to 6 or by p-nitrophenyl-betaDGal. DGal and DFuc are equally active but about 20 and 12 times less active with agglutinin I and agglutinin II, respectively. DGalNAc and LFuc were inactive even at much higher concentrations. Both agglutinins have similar specificities and react with the immunodominant determinants of blood group B and Lea but not with A and H substances; in A and H substances, reactivity is with side chains in which beta-linked DGal is unsubstituted at the nonreducing terminus. The Axinella polypoides lectins are compared with galactose-specific lectins of different origin and with the aggregation factor system is sponges.     

Many-particle interaction problems computed by special purpose processors,with emphasis on the Ising model

The first part of the article describes the power of special purpose computing registers in solving many-particle interaction problems. Dedicated logic and analog circuits are used in combination with general purpose digital computers to implement specific algorithms in hardware. A significant increase in computational speed can thus be obtained. An example is the fast generation of random numbers for Monte Carlo experiments. Hybrid external processors are able to deliver up to 10⁷ truly random numbers per second. The prospects for these hybrid techniques in computational physics are discussed.Modern semi-automatic design techniques with the availability of medium scale integrated components allow a competitive design time for the hardware construction compared to the conventional software implementation.In the second part of the article results are described for a 100 x 100 Ising model, calculated with the algorithm of Yang. Also a model of the growth of crystals in a saturated solution is numerically evaluated by a hardware implementation of a special algorithm.