Physical characterization of polyethylene glycols by thermal analytical technique and the effect of humidity and molecular weight.

Polyethylene glycols (PEGs) are well known as excipients in tablet dosage formulations. PEGs are generally known to be inert and have very few interactions with other components in the solid dosage forms. However, the physical nature of PEGs and how they affect the disintegration of tablets is not very well understood for the different molecular weights of PEGs. The knowledge of the effect of molecular weight of PEGs on their physical properties and the effect of humidity on the physical properties of PEGs are important parameters for the choice of a PEG to be acceptable as an excipient in pharmaceutical formulations. This study was done to determine the precision of the DSC physical properties for a wide range of PEGs with varying molecular weights from 194 to 23000 daltons. Nine different molecular weights of PEGs were examined in a DSC controlled Heat-Cool-Heat-Cool-Heat (HCHCH) cycle and the observed reproducible values of melting temperature, heat of fusion, crystallization temperature and the heat of crystallization were compared with values obtained from the literature and the observed percent crystallinity was again cross-checked by X-ray Diffraction (XRD) studies. The comparison values indicated acceptable precision. This study was also done to check the effect of humidity on the DSC physical properties for the entire range of PEGs. The results indicated that humidity probably has a higher effect on the physical properties of the low molecular weight PEGs as compared to the high molecular weight PEGs.

Evaluation of the drug-polymer interaction in calcium alginate beads containing diflunisal.

Calcium alginate gel beads have been developed in recent years as a unique vehicle for oral drug delivery due to their excellent biocompatibility, biodegradability, simple method of preparation, abundant sources, low cost and minimal processing requirements. The objective of this study was to evaluate the drug-polymer interaction in calcium alginate beads containing diflunisal. Diflunisal loaded calcium alginate beads were successfully prepared by ionotropic gelation from solution of sodium alginate and diflunisal into calcium chloride solution. The weight ratio of drug to polymer was selected as 1:1. The calcium alginate beads were characterized by size, Scanning Electron Microscopy (SEM), weight uniformity and drug entrapment efficiency. The existence of a possible interaction between diflunisal and the calcium alginate was investigated by Differential Scanning Calorimetry (DSC), Powder X-Ray Diffraction (PXRD) and Fourier Transform Infra-Red (FTIR) analysis. Drug loaded beads were spherical to oval in shape with low drug entrapment efficiency. The drug was found to be present inside the beads as crystalline to semicrystalline form with no significant physical or chemical interaction between drug and excipients. The results implied that calcium alginate beads can be used as a suitable controlled release carrier for diflunisal.

Crystal forms of tolbutamide from acetonitrile and 1-octanol: effect of solvent, humidity and compression pressure.

The possibility of obtaining tolbutamide polymorphs was investigated using the solvents acetonitrile and 1-octanol. Tolbutamide is an oral hypoglycemic agent that exists in four polymorphic forms. Characterization of the various polymorphs was carried out by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), infrared spectroscopy (FTIR), optical microscopy and dissolution studies. Form A, crystallized from acetonitrile, resembled the form I polymorph, while form O, crystallized from 1-octanol, resembled the form III polymorph. Tablets of both form A and form O were produced at compression pressures of 2500 lbs and 5000 lbs using cornstarch and talc and were exposed to 40%, 75% and 95% RH conditions. DSC and PXRD studies did not show any significant drug-excipient interaction. Moreover, the change in the crystalline state of either form upon exposure to humidity was not evident. Dissolution studies showed a significantly lower drug release rate from form O tablets compressed at 5000 lbs pressure and exposed to 95% RH. Pressure and humidity had no significant effect on the dissolution profiles on the form A tablets. It was concluded that form A was the robust choice for further formulation development.

The effect of human organ preservation and albumin flush solution on in vitro cell metabolic activity.

In liver transplantation, the organ during the recipient's operation is traditionally flushed with 4.5% of human albumin solution to wash away the potassium-rich University of Wisconsin (UW) solution. It has been argued whether albumin could be useful at this stage. We used a new simple non-toxic assay to determine cell viability in vitro. Alamar Blue incorporates a redox indicator which changes colour from blue (oxidised form) to magenta (reduced form) in response to metabolic activity. Cultured human hepatocyte and HUVEC cell lines were exposed for 3, 6, 12 or 24 hours to plain medium, UW solution, human albumin 4.5% solution, UW-containing effluents before and after preservation as well as albumin flushes from different transplantation cases. After addition of Alamar Blue the optical density was measured at 570 nm and the background measured at 600 nm was subtracted. The studies showed a significantly lower metabolic rate of the cells exposed to albumin and albumin-containing flushes at all time periods, even after a short exposure such as 3 hours (p < 0.001). On the other hand, there was no significant difference of growth and metabolic activity rate between cells exposed to UW solution, different UW-containing flushes and medium for up to 12 hours. In conclusion, human albumin is a very poor solution for cell maintenance. In contrast, UW solution has comparable results with the full growth medium for up to 12 hours of exposure.