Resveratrol, a constituent of red wine, has long been suspected to have cardioprotective effects. Interest in this compound has been renewed in recent years, first from its identification as a chemopreventive agent for skin cancer, and subsequently from reports that it activates sirtuin deacetylases and extends the lifespans of lower organisms. Despite scepticism concerning its bioavailability, a growing body of in vivo evidence indicates that resveratrol has protective effects in rodent models of stress and disease. Here, we provide a comprehensive and critical review of the in vivo data on resveratrol, and consider its potential as a therapeutic for humans.

Therapeutic potential of resveratrol: the in vivo evidence.

to be done in this area. Face recognition is a problem that scarcely clamoured for attention before the computer age but, having surfaced, has involved a wide range of techniques and has attracted the attention of some fine minds (David Mumford was a Fields Medallist in 1974). This singular application of mathematical modelling to a messy applied problem of obvious utility and importance but with no unique solution is a pretty one to share with students: perhaps, returning to the source of our opening quotation, we may invert Duncan's earlier observation, 'There is an art to find the mind's construction in the face!'.

Linear and nonlinear waves, by G. B. Whitham. Pp.636. £50. 1999. ISBN 0 471 35942 4 (Wiley).

Cyclooxygenase (COX), first purified in 1976 and cloned in 1988, is the key enzyme in the synthesis of prostaglandins (PGs) from arachidonic acid. In 1991, several laboratories identified a product from a second gene with COX activity and called it COX-2. However, COX-2 was inducible, and the inducing stimuli included pro-inflammatory cytokines and growth factors, implying a role for COX-2 in both inflammation and control of cell growth. The two isoforms of COX are almost identical in structure but have important differences in substrate and inhibitor selectivity and in their intracellular locations. Protective PGs, which preserve the integrity of the stomach lining and maintain normal renal function in a compromised kidney, are synthesized by COX-1. In addition to the induction of COX-2 in inflammatory lesions, it is present constitutively in the brain and spinal cord, where it may be involved in nerve transmission, particularly that for pain and fever. PGs made by COX-2 are also important in ovulation and in the birth process. The discovery of COX-2 has made possible the design of drugs that reduce inflammation without removing the protective PGs in the stomach and kidney made by COX-1. These highly selective COX-2 inhibitors may not only be anti-inflammatory but may also be active in colon cancer and Alzheimer’s disease.

Cyclooxygenases 1 and 2

Improving drug solubility for oral delivery using solid dispersions.

Contributors to Volume 19Contents of Other VolumesBlow-Fill-Seal Aseptic ProcessingDeborah J. JonesCompounding, ContemporaryLoyd V. Allen, Jr.Drug Delivery-Oral Colon SpecificVincent H. L. Lee and Suman K. MukherjeeThe European Agency for the Evaluation of Medicinal Product (EMEA)David JacobsHarmonization-CompendiaLee. T. Grady and Jerome A. HalperinInhalation, Dry PowderLynn Van Campen and Geraldine VenthoyeLiquid Crystals in Drug DeliveryChristel C. Mueller-GoymannMedication Errors: A New Challenge for the Pharmaceutical IndustryDiane R. CousinsMucoadhesive Hydrogels in Drug DeliveryHans E. Junginger, Maya Thanou, and J. Coos VerhoefPeptides and Proteins: Buccal AbsorptionHemant H. Alur, and Thomas P. Johnston, and Ashim K. MitraPharmaceutical Quality Assurance Microbiology LaboratoriesAnthony M. CundellProcess Chemistry in the Pharmaceutical IndustryKumar G. Gadamasetti and Ambarish K. SinghRadiolabeling of Pharmaceutical Aerosols and Gamma Scintigraphic Imaging for Lung DepositionHak-Kim ChanSuper Disintegrants: Characterization and FunctionLarry L. Augsburger, Albert W. Brzeczko, Umang Shah, and Huijeong A. HahmIndex to Volume 20

Encyclopedia of Pharmaceutical Technology

Suppression of Intestinal Polyposis in ApcΔ716 Knockout Mice by Inhibition of Cyclooxygenase 2 (COX-2)

https://onlinelibrary.wiley.com/doi/pdf/10.1021/js9601896

Characteristics and Significance of the Amorphous State in Pharmaceutical Systems

Purpose To evaluate the magnitude of the solubility advantage foramorphous pharmaceutical materials when compared to their crystallinecounterpartsMethods The thermal properties of several drugs in their amorphousand crystalline states were determined using differential scanningcalorimetry From these properties the solubility advantage for theamorphous form was predicted as a function of temperature using a simplethermodynamic analysis These predictions were compared to theresults of experimental measurements of the aqueous solubilities of theamorphous and crystalline forms of the drugs at several temperaturesResults By treating each amorphous drug as either an equilibriumsupercooled liquid or a pseudo-equilibrium glass, the solubilityadvantage compared to the most stable crystalline form was predicted to bebetween 10 and 1600 fold The measured solubility advantage wasusually considerably less than this, and for one compound studied indetail its temperature dependence was also less than predicted It wascalculated that even for partially amorphous materials the apparentsolubility enhancement (theoretical or measured) is likely to influencein-vitro and in-vivo dissolution behaviorConclusions Amorphous pharmaceuticals are markedly more solublethan their crystalline counterparts, however, their experimental solubility advantage is typically less than that predicted from simplethermodynamic considerations This appears to be the result of difficulties indetermining the solubility of amorphous materials under trueequilibrium conditions Simple thermodynamic predictions can provide a useful indication of the theoretical maximum solubility advantage foramorphous pharmaceuticals, which directly reflects the driving forcefor their initial dissolution

/pdf/what-is-the-true-solubility-advantage-for-amorphous-494qziae2i.pdf

What is the true solubility advantage for amorphous pharmaceuticals

Purpose. To measure the molecular mobility of amorphous pharmaceutical solids below their glass transition temperatures (Tg), using indomethacin, poly (vinyl pyrrolidone) (PVP) and sucrose as model compounds. 
Methods. Differential scanning calorimetry (DSC) was used to measure enthalpic relaxation of the amorphous samples after storage at temperatures 16-47 K below Tg for various time periods. The measured enthalpy changes were used to calculate molecular relaxation time parameters. Analogous changes in specimen dimensions were measured for PVP films using thermomechanical analysis. 
Results. For all the model materials it was necessary to cool to at least 50 K below the experimental Tg before the molecular motions detected by DSC could be considered to be negligible over the lifetime of a typical pharmaceutical product. In each case the temperature dependence of the molecular motions below Tg was less than that typically reported above Tg and was rapidly changing. 
Conclusions. In the temperature range studied the model amorphous solids were in a transition zone between regions of very high molecular mobility above Tg and very low molecular mobility much further below Tg. In general glassy pharmaceutical solids should be expected to experience significant molecular mobility at temperatures up to fifty degrees below their glass transition temperature.

Molecular mobility of amorphous pharmaceutical solids below their glass transition temperatures.

The glass transition temperature of an amorphous pharmaceutical solid is a critical physical property which can dramatically influence its chemical stability, physical stability, and viscoelastic properties. Water frequently acts as a potent plasticizer for such materials, and since many amorphous solids spontaneously absorb water from their surroundings the relationship between the glass transition temperature and the water content of these materials is important. For a wide range of amorphous and partially amorphous pharmaceutical solids, it was found that there is a rapid initial reduction in the glass transition temperature from the dry state as water is absorbed, followed by a gradual leveling off of the response at higher water contents. This plasticization effect could generally be described using a simplified form of the Gordon–Taylor/ Kelley–Bueche relationships derived from polymer free volume theory. Most of the systems considered showed a nearly ideal volume additivity and negligible tendency to interact. This is consistent with the hypothesis that such mixtures behave as concentrated polymer solutions and indicates that water acts as a plasticizer in a way similar to that of other small molecules and not through any specific or stoichiometric interaction process(es).

Bruno C. Hancock

Papers

Suppression of Intestinal Polyposis in ApcΔ716 Knockout Mice by Inhibition of Cyclooxygenase 2 (COX-2)

Characteristics and Significance of the Amorphous State in Pharmaceutical Systems

What is the true solubility advantage for amorphous pharmaceuticals

Molecular mobility of amorphous pharmaceutical solids below their glass transition temperatures.

The relationship between the glass transition temperature and the water content of amorphous pharmaceutical solids.