Physicochemical and Structural Properties of Non‐Steroidal Anti‐inflammatory Oxicams

Abstract

Using the five therapeutic oxicams 1-5, we showed that isosteric replacements result in remarkable changes in the physicochemical and structural properties of congeners. Thus, the acidity of the phenolic OH group is relatively higher in the oxicams containing a pyridinyl moiety, i.e. in piroxicam (l), tenoxicam (2), and lornoxicam (3), due to their zwitterionic nature. This consequently influences their lipophilicity profile at different ionization states. Furthermore, partitioning behaviour in octan-1 -ol/H,O and heptane/H,O systems suggests an internal H-bond between the enolic OH and the amide C=O group. The anionic oxicams readily partition into the octanol phase at pH 7.4 and not at all into the heptane phase. Only the partition coefficients of oxicams measured in the heptane/H20 system, but not in the octanol/H20 system, correlate with their transfer across the blood-brain barrier. This implies that only the neutral form of oxicams crosses the blood-brain barrier.

Determination of pKa values of nonsteroidal antiinflammatory drug‐oxicams by RP–HPLC and their analysis in pharmaceutical dosage forms

“…2. The correlation between the experimental capacity factors of the compounds studied over the whole experimental pH range was good, as shown in In this study, the pK a values of the enolic OH group of the oxicams and carboxylic group of naproxen were determined by using LC methodology [38]. The simultaneous determination of pK a values together with the k HA and k A from k/pH data was carried out by using the software NLREG 4.0 [39].…”

Synthesis of water-soluble bioconjugate piroxicam—arabinogalactan sulfate

“…It is known that pir oxicam can exist in the zwitterionic form in aqueous solutions 41,45,48 or at acidic pH values as a result of the protonation of the pyridine fragment of the molecule. 44,47,49 Earlier, the transforma tion of piroxicam  form to its  form 21 and the zwitteri on 21,23 was also observed during the preparation of mech anocomposites of piroxicam with biopolymers (chitosan and cellulose).…”

Carbon ceramic electrode incorporated with zeolite ZSM-5 for determination of Piroxicam

“…Several studies related with the acid-base behavior of Piroxicam have been reported in the literature [32][33][34][35][36][37]. Being a diprotic amphoteric drug with pKa values differing by less than 4 units, the deprotonation-protonation of one group affects the other depending on the pH values of the media.…”