Improvements in the Pharmaceutical Properties of Drugs

Naproxen, a nonsteroidal anti-inflammatory drug, is practically insoluble in water. F or pharmaceutical application, improvement in the dissolution properties has been expected. Dissolution properties of naproxen in the JP first fluid (pH 1.2) were studied according to the JP paddle method (Fig. 8) [18]. A mixture with CPG 120 showed a dissolution curve similar to that of intact naproxen erystals. It is noteworthy that the dissolution of naproxen was significantly improved in the heated sample with CPG 120, especially in the initial stage of dissolution. In... 

However, its low solubility and chemical instability in water have limited the dosage form design and presented a substantial challenge to pharmaceutical scientists (3). Cyclodextrins (CyDs) have been successfully applied to improve the pharmaceutical properties of various drugs (4,5,6). In our preliminary study, it was found that HCFU forms solid complexes with a-, 3 and yCyDs. Thus, the present study dealt with the inclusion complexation of HCFU with three CyDs in an attempt to obtain improved solubility, dissolution rate, chemical stability, and bioavailability of HCFU. 

Piroxicam is a nonsteroidal anti-inflammatory drug used in the treatment of rheumatoid arthritis and osteoarthritis [97]. The solubility of piroxicam is low, with the maximum concentration reached after more than 2 h from the oral administration. The piroxicam forms three known polymorphs and a hydrate. In all these forms piroxicam is present as a neutral, nonionized, species (Scheme 13.15, left) [98]. As the cocrystallization with suitable pharmaceutical coformers is a standard method for improving the physicochemical properties of drugs, piroxicam has naturally been selected as a target for such studies [99,100]. It was shown that some cocrystalline forms with carboxylic acids were yellow and that the piroxicam in these compounds was present as a zwitterion, similarly as in previously reported hydrate or inclusion compound with beta-cyclodextrin [101]. 

A recent trend in the pharmaceutical industry has been to harness the intrinsic tissue-protective properties of NO for improving the gastric tolerance of nonsteroidal antiinflammatory drugs (NS AIDs). This trend has led to the synthesis of hybrid, chimeric molecules containing an NSAID or aspirin moiety and a NO-donor functionality [153, 154]. One such hybrid is a NO-releasing derivative of aspirin, NCX-4016. In a doubleblind, randomized, placebo-controlled gastrointestinal safety assessment in healthy subjects, NCX-4016 (400 or 800 mg twice daily for 7 days) acted like aspirin as an inhibitor of arachidonic acid-induced platelet aggregation in vitro [155]. Whether... 

The new structure of pharmaceutical research has not led to increased productivity or decreased costs, at least in terms of the number of new products introduced (Comanor, Chapter 3), although it may have influenced the therapeutic properties of the new drugs. The new structure for discovery and development of new pharmaceutical products has not improved efficiency if one measures R D output by the number of new molecular entities. However, prescription drugs are potentially important inputs in the production of good health (Sloan and Hsieh, Chapter 1 Cremeiux et al.. Chapter 12 Hsieh et al.. Chapter 13). Thus, the efficiency of pharmaceutical research is more appropriately evaluated in terms of its contribution to improvements... 

Cyclodextrins (CDs) have a wide range of application in the pharmaceutical field due to their unique structure, which allows them to include hydrophobic molecules in their apolar cavity and to mask the physicochemical properties of the included molecule. This results in the enhancement of drug bioavailability by improving aqueous solubility and the physical and chemical stability of the drug, masking undesired side effects such as irritation, taste, or odor, and overcoming compatibility problems or interactions between drugs and excipients. 

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