Release study procedure

As in any study involving human research volunteers, an Institutional Review Board (IRB) must approve the study protocol and consent from. When the IRB office has released the stamped consent form to the investigator, participants can he enrolled in the study. The consent form consists of a description of study procedures, any risks that are involved, monetary compensation if any, and investigators contact information should participants have questions or concerns. When a participant understands all aspects of the study and potential risks, the investigator and participant sign the consent form a copy is given to the participant. 

In vitro drug release studies have been employed as a quality control procedure in pharmaceutical production, in product development, etc. Sensitive and reproducible release data derived from physicochemically and hydrodynamically defined conditions are necessary however, no standard in vitro method has yet been developed. Different workers have used apparatus of varying designs and under varying conditions, depending on the shape and application of the dosage form developed. 

For the drug release profile of homopolymer of DOX, pH 7.4 as well as acidic conditions was decided as the normal pH of blood for sustaining human life is about 7.4, while the endosomes and lysosomes of cells have a more acidic environment [11c]. Therefore, drug release study of homopolymer was carried out in pH 7.4 in phosphate buffer solution and pH 5.5 and 6 in acetate buffer solutions, respectively. A 1 mg of homopolymer was dissolved in 1 ml of distilled water (partially soluble) and loaded in dialysis tube (3,500 Dalton cut-off) and dialyzed against 70 ml of a buffer solution whose pH was maintained at 5.5. An aliquot of the sample was removed and its absorbance at 480 nm was measured as an indication of the release of doxorubicin. Fluorescence also recorded by exciting the solution at 510 nm. Emissions from the free DOX released from homopolymer were observed at 560 nm and 590 nm. The sample was then added back to the solution to maintain the volume of the solution. This procedure was repeated for every 1 h and results were observed for 48 h. It was observed that after 24 h, there was no significance increase in the intensity of fluorescence and UV intensity. The similar procedure was repeated to monitor the drug release at pH 6.0 as well as pH 7.4 and the results are shown in (Fig. 18). The DOX release from homopolymer at pH 7.4 was very minimal. 

Initiating events, in this study, initiate plant scram or setback. Other initiators, such as refueling discharge accidents, do not necessarily cause a reactor shutdown but may lead t< minor fuel damage and radioactive releases. The list of initiators for nuclear power plants has litf ance for HFBR because of size and design differences. A list of HFBR-specific initiators was developed from " st prepared with the HFBR staff, the FSAR, the plant design manual, the procedures manual, techn specifications, monthly operating reports, and the HFIR PRA (Johnson, 1988). 

The human factors audit was part of a hazard analysis which was used to recommend the degree of automation required in blowdown situations. The results of the human factors audit were mainly in terms of major errors which could affect blowdown success likelihood, and causal factors such as procedures, training, control room design, team communications, and aspects of hardware equipment. The major emphasis of the study was on improving the human interaction with the blowdown system, whether manual or automatic. Two specific platform scenarios were investigated. One was a significant gas release in the molecular sieve module (MSM) on a relatively new platform, and the other a release in the separator module (SM) on an older generation platform. 

Extensive studies have been reported with cisplatin in the field of chemoembolization (59,98). Microspheres prepared by a solvent evaporation procedure were characterized in vitro and critical processing parameters in regard to drug release kinetics were identified. 

Until the recent development of appropriate HPLC techniques capable of detecting pmol amounts (see Flentge et al. 1997) ACh could only be measured chemically by relatively lengthy and expensive procedures (e.g. gas chromotography), which were not always very sensitive, or by bioassays. Although the latter, using muscle preparations that responded to ACh, such as the dorsal muscle of the leech, the rectus abdominus of the frog or certain clam hearts, were reasonably sensitive they were tiresome and not easily mastered. Thus studies on the release and turnover of ACh have not been as easy as for the monoamines. 

As 1,2,5-thiadiazole analogues, potent HlV-1 reverse transcriptase inhibitors, some simple 1,2,5-oxadiazoles, compounds 4-6 (Fig. 9), have been synthesized using the traditional Wieland procedure as key for the heterocycle formation [121]. Such as thiadiazole parent compounds, derivative with chlorine atoms on the phenyl ring, i.e., 5, showed the best anti-viral activity. Selectivity index (ratio of cytotoxic concentration to effective concentration) ranked in the order of 5 > 6 > 4. The activity of Fz derivative 6 proved the N-oxide lack of relevance in the studied bioactivity. These products have been claimed in an invention patent [122]. On the other hand, compound 7 (Fig. 9) was evaluated for its nitric oxide (NO)-releasing property (see below) as modulator of the catalytic activity of HlV-1 reverse transcriptase. It was found that NO inhibited dose-dependently the enzyme activity, which is hkely due to oxidation of Cys residues [123]. 

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