Journal of parenteral science and technology : a publication of the Parenteral Drug Association最新文献

To minimize ocular discomfort while maintaining efficacy, a delivery system for a topical cardioselective beta-adrenoceptor antagonist, betaxolol was developed. Betaxolol was formulated at 0.25% concentration in a cationic exchange resin, as a suspension. A polyacrylic acid polymer was added to increase viscosity and to increase residence time in the cul-de-sac. No significant settling was observed throughout a four-week observation period. Thus, resuspension of the formulation by frequent shaking was not required for uniformity. In rabbits, the ocular bioavailability of 0.25% betaxolol suspension was equivalent to that of 0.5% betaxolol solution.

Filter manufacturers characterize a given filter type by a single acceptable maximum diffusive air flow level. A too high value is prudently rejected as signalling the possible presence of flaws. Values lower than the stipulated maximum are accepted. However, the presence of single pores, whatever their sizes, is not being revealed. Only their influence within the total porosity is measured by the diffusive air flow. Single point diffusive air flow integrity testing may invite misleading conclusions because it offers possibilities for lower air flows to mask the presence of flaws or of outsized pores. This is particularly so where initial (prefiltration) and final integrity are being compared. The filtrative accretion of retained material, viable or not, must inevitably come to block or diminish the size of the pores. This results in decreased total porosity, directly expressed in lower diffusive air flow values. Sufficient drop in such final air flow values may mask the presence of a flaw developed in the filter subsequent to its initial testing. For this reason a filter's entire air flow permeation curve, particularly including its bubble point, must be characterized. It is this measurement, and this measurement alone, that is capable of unambiguously revealing the existence of insufficiently retentive pores. The inquiry into such presence is the very purpose of filter integrity testing.

The objective of the present work is to provide additional experimental evidence which can help to differentiate between a direct solubilization mechanism versus an intracellular calcium mechanism of organic cosolvent-induced creatine kinase release from isolated rat skeletal muscles. An increase in cytosolic free calcium levels following exposure to propylene glycol was evaluated indirectly through the measurement of skeletal muscle glycogen levels. Skeletal muscle glycogen levels decreased significantly in propylene glycol-treated muscles compared to normal saline-treated controls; providing further evidence for the possible role of increased cytosolic calcium in organic cosolvent-induced muscle damage. The possible involvement of prostaglandins and leukotrienes which disrupt membrane integrity leading to propylene glycol-induced creatine kinase release was investigated via the use of cyclo-oxygenase and lipoxygenase inhibitors. Organic cosolvent-induced creatine kinase release was not significantly reduced when the muscles were incubated in the presence of cyclo-oxygenase inhibitors, lipoxygenase inhibitors, or a combination of a cyclo-oxygenase and lipoxygenase inhibitor. These findings suggest that in this experimental system prostaglandins and leukotrienes do not seem to be involved in organic cosolvent-induced alterations in sarcolemma integrity leading to the release of creatine kinase.

An IV injection formulation of sodium dichloroacetate (DCA) was prepared without heat sterilization, and examined for stability. DCA is heat labile in aqueous solutions. Its decomposition involves dehalogenation and production of hydrogen ions. Decomposition occurs relatively rapidly at relatively low pH values, and is promoted by heating. Injection solutions should be prepared aseptically and sterilized by filtration. Solutions prepared aseptically and sterilized by filtration are stable stored at 4 degrees C for at least four yrs.

The intent of this note is to describe in more detail the calibration process for these sensors with particular emphasis on the method of obtaining the best calibration curve from the raw data. A new method of assessing the accuracy of the calibration curve is also described.

Validation of tangential flow filtration is required to ensure the process delivers a product of consistent quality, safety, and efficacy. A thorough and sound validation program not only satisfies regulatory requirements, but also provides a valuable source of information which facilitates development of future processes, training of production personnel, and trouble shooting for the validated process. Validation of TFF shares many common elements with validation of other traditional operations and equipment. Existing personnel and procedures should be readily adapted to execute the TFF validation protocols. IQ's and OQ's will most likely follow familiar formats. In performance qualification, key areas needing attention include: assessment of compatibles, testing of parameters affecting membrane retention and selectivity, cleaning, sanitization, and membrane lifetime. Finally, the hallmark of a sound validation program is the quality of its scientific approach and its congruence with the definition of validation contained in the 1987 guidelines (6).