Pampas

Butane. Butane LPO has been a significant source for the commercial production of acetic acid and acetic anhydride for many years. At various times, plants have operated in the former USSR, Germany, Holland, the United States, and Canada. Only the Hoechst-Celanese Chemical Group, Inc. plants in Pampa, Texas, and Edmonton, Alberta, Canada, continue to operate. The Pampa plant, with a reported aimual production of 250,000 t/yr, represents about 15% of the 1994 installed U.S. capacity (212). Methanol carbonylation is now the dominant process for acetic acid production, but butane LPO in estabhshed plants remains competitive. 

November 14, 1987, three people were killed when two explosions and a tire caused extensive damage to the Hoechst Celanese acetic acid and acetic anhydride plant located near Pampa, ( X. Also on the Pampa site was a specialty resins plant operated by Interez, a unit ol RTZ ( orp. vhieh was interrupted because it depends on power supplied from the main Hoechsi Celanese I pc rati on. 

A plant team working with the Pampa fire department brought the fire under control. The Chemical Manufacturers Association s Community Awareness Emergency Response Program (CARE), developed after the Bhopal disaster was credited with effectiveness of their efforts in putting out the fire. 

The experimental Pjpp data have been used to build predictive models. However, since PAMPA is already a model, an in silica model based on this is a model of a model. The predictability for in vivo permeability or absorption of such in silica PAMPA model can be queshoned (see Eq. 11), since it is two steps from reality ... 

Avdeef, A., Tsinman, O. PAM PA -a drug absorption in vitro model 13. Chemical selectivity due to membrane hydrogen bonding in comho comparisons of HDM-, DOPC-, and DS-PAMPA models. Eur. J. Pharm. Set. 2006, 28, 43-50. 

PAMPA parallel artificial membrane permeation assay... 

The evaluation of the apparent ionization constants (i) can indicate in partition experiments the extent to which a charged form of the drug partitions into the octanol or liposome bilayer domains, (ii) can indicate in solubility measurements, the presence of aggregates in saturated solutions and whether the aggregates are ionized or neutral and the extent to which salts of dmgs form, and (iii) can indicate in permeability measurements, whether the aqueous boundary layer adjacent to the membrane barrier, Umits the transport of drugs across artificial phospholipid membranes [parallel artificial membrane permeation assay (PAMPA)] or across monolayers of cultured cells [Caco-2, Madin-Darby canine kidney (MDCK), etc.]. 

Fig. 3.4 Permeability profiles for (a) warfarin (acid), (b) propranolol (base) and (c) morphine (ampholyte) based on a BBB PAMPA model (plON) composed of animal brain extract of lipids. The data (unpublished) were analyzed with the pCEL-X program (plON), with the refined parameters indicated in the three frames. In all three cases, there was evidence for the permeation of charged...

In PAMPA, the effective permeability coefficient, Pe, is related to the membrane and ABL permeability coefficients, P and Pabl. respectively, as... 

In the BBB-PAMPA lipid formulation illustrated in Fig. 3.4, the diff values, defined as the difference log Pq-log Pi, range from 2.9 (morphine) to 4.2 (warfarin), somewhat similar to the values observed in the octanol-water system. However, it is premature to propose a pdiffi-A approximation, given the limited amount of data reported. With other lipid formulations, larger differences are usually observed. In Double-Sink PAM PA, and especially in hexadecane-PAMPA, transport of ionized drugs has not been reported [84]. 

Avdeef A. HT solubility and permeability MAD-PAMPA analysis. In Pharmacokinetic Profiling in Drug Research, Testa, B., Kramer, S. D., Wunderli-Allenspach, H., Eolkers, G. 

PAMPA is typically used to make a prediction of the passive, transcellular absorption of a compound. Compounds which may be absorbed by a paracellular mechanism or may be substrates for active transport (uptake or efflux) are usually better assessed in a cell based system. A combination of assays can be applied to gain a greater understanding of the permeability and transport properties of a compound. 

Figure 8 shows PAMPA data for a subset of compounds from the two series in Fig. 7. The potential concern about low permeability for Series D is confirmed between the MDCK and PAMPA data. Series C, with the exception of one compound, also demonstrates good correlation between MDCK and PAMPA permeability the compound with low PAMPA permeability should be further analyzed for relevant structure-permeability information.

Fig. 8 PAMPA flux vs clogD. Filled squares and open triangles represent the same chemical series as in Fig. 7 (series C and D, respectively)...

BBB PAMPA Blood brain barrier parallel artificial membrane permeability assay... 

During the characterization process, hits are typically tested for kinetic solubility and permeability in a model of passive diffusion such as PAMPA [22]. As new compounds are synthesized, additional parameters also need to be considered, such as pZa, chemical and plasma stability, and protein binding. Calculated properties such as MW, clogP, and PSA should also be tracked. 

In addition to the data generated from plasma samples in a standard PK study, for targets that are contained within the brain, it is also important to determine brain levels of compound, so that brain/plasma ratios can be determined. Again, these data should be correlated with in vitro assays and calculated properties such as BBB PAMPA [39]... 

The coverage of permeability in this book is more comprehensive than that of solubility, lipophilicity, and ionization. This decision was made because permeability is not as thoroughly treated in the pharmaceutical literature as the other topics, and also because much emphasis is placed on the PAMPA in this book, which is indeed a very new technique [547] in need of elaboration. 

PARALLEL ARTIFICIAL-MEMBRANE PERMEABILITY ASSAY (PAMPA)... 

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