The Effect of Nonionic Surfactant Brij 35 on Solubility and Acid–Base Equilibria of Verapamil

Abstract

Protolytic equilibria and solubility of verapamil were investigated in the presence and in the absence of nonionic surfactant Brij 35 at a constant ionic strength (0.1 mol/L NaCl) and temperature 25 °C. In surfactant free media the intrinsic solubility, S 0 = 4.51 × 10 −5 mol/L (only the neutral form is present in the solution) and pHdependent solubility, S (neutral and ionized form in solution) of verapamil were determined. On the basis of the solubility data, the apparent pK a value 9.15 of verapamil was indirectly obtained. In micellar media (10 −3 mol/L Brij 35) the solubility of verapamil free base (S 0,s = 2.76 × 10 −3 mol/L) and the apparent pK a,s = 6.35, were determined. The shift in the protolytic equilibria (ΔpK a = −2.80) and the increased solubility of verapamil free base (approximately 60 times) caused by Brij 35 point out to specific interactions between verapamil and the inner part of Brij 35 micelles. The most significant changes in distribution of verapamil equilibrium forms were observed at biopharmaceutically important pH 7.4 which potentially indicates interactions with biomolecules in blood plasma.

Understanding the Effect of Differently Charged Surfactants on the Protolytic Equilibria of the Drug Naproxen in Micellar Solution

“…In this work, the activity coefficients γ are constant (but are not equal to one) because the ionic strength of the medium is kept constant. Also, the γ values are hardly estimable, especially when the surfactants are present in the system . Accordingly, in the present work, the p K a value is termed the stoichiometric p K a , defined as the negative logarithm of K a c .…”

“…Also, the γ values are hardly estimable, especially when the surfactants are present in the system. 5 Accordingly, in the present work, the pK a value is termed the stoichiometric pK a , defined as the negative logarithm of K a c . It is concluded from Figure 1 that pK a is referred to as the protonation of the carboxyl OH group.…”

“…Moreover, the interactions between drugs and micelle systems within different body compartments can affect the drug distribution. 5 Aqueous micellar media have significant importance for drug delivery purposes because they can enhance permeability across the physiological barriers and reduce toxicity or other side effects as well as undergo a substantial change in drug distribution. 6 Naproxen (C 14 H 14 O 3 , NAP) or 2-(6-methoxynaphthalen-2yl) propanoic acid (Figure 1) belongs to the nonsteroidal class of drugs that is widely used in medicine and veterinary medicine as an analgesic, anti-inflammatory, and antipyretic agent.…”

“…When the concentration of amphiphilic surfactant molecules in the aqueous solution arrives above a certain concentration, they form colloidal particles called micelles. , Micellar media of surfactants can increase the solubility of poorly water-soluble drugs and shift the protonation equilibria of ionizable drugs. Moreover, the interactions between drugs and micelle systems within different body compartments can affect the drug distribution . Aqueous micellar media have significant importance for drug delivery purposes because they can enhance permeability across the physiological barriers and reduce toxicity or other side effects as well as undergo a substantial change in drug distribution …”

Acid–Base Equilibria of Rupatadine Fumarate in Aqueous Media

“…Therefore, interactions observed between the drugs and the micelles can point to a possible drug distribution within the body compartments . Moreover, our previous research − has shown that one cannot generally anticipate whether the acidity of drugs would increase or decrease, not even in the case of the structurally similar compounds belonging to the same pharmacological class. Consequently, it is necessary to experimentally investigate for each individual compound its ionization pattern in a micellar solution.…”