Liquid chromatography of short chain carboxylic acids using a glutamic acid surfactant coated C18 stationary phase

Ali, Abd al-karim F.; Danielson, Neil D.

doi:10.1016/j.talanta.2020.120807

Cited by 6 publications

(3 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This high abundance for the interaction between these two moieties has grounded the choice of generically recognized as safe (GRAS) carboxylic acids to cocrystallize with adiphenine. Therefore, citric and oxalic acids were chosen, and salt formation was already expected since their pK a1 at 25 °C (3.13 and 1.23) 24 differs more than 3 units from that of adiphenine (7.7). 25 The crystal structures of adiphenine oxalate and adiphenine citrate were elucidated by the single-crystal X-ray diffraction technique in the centrosymmetric space groups Pbca and P2 1 / c, respectively.…”

Section: Resultsmentioning

confidence: 99%

New Multicomponent Crystal Forms of Adiphenine with Low Hygroscopicity

Ribeiro

Silva

Neto

et al. 2022

Crystal Growth & Design

View full text Add to dashboard Cite

Adiphenine is an acetylcholine receptor inhibitor used as an antispasmodic drug due to its strong smooth muscle relaxant action. Adiphenine hydrochloride is largely marketed in drug associations to treat muscle spasms and relieve pain in colic and cramps. However, it presents serious problems with hygroscopicity and chemical stability under high humidity conditions, which have limited its use as an active pharmaceutical ingredient (API). Here, we have solved the adiphenine solid-state hygroscopicity problem through the preparation of stable, nonhygroscopic multicomponent crystal forms thereof. Two new salts of adiphenine were designed by recognition of intermolecular interaction patterns in the Cambridge Structural Database (CSD) and ΔpK a rules. Two generically recognized as safe (GRAS) coformers, namely, citric acid and oxalic acid, were chosen and formed monobasic salts with adiphenine. Crystal structure elucidation reveals that adiphenine adopts different conformations in our salts, while in the literature, hydrochloride adopts one, which is related to different intermolecular arrays. In the dynamic vapor sorption (DVS) analysis, it was verified that adiphenine citrate and adiphenine oxalate starts to incorporate water slowly from 50 to 70% of relative humidity (RH), increasing up to 3.2 and 2.6% of their initial masses in 90% of RH, respectively. At the end of the desorption cycle (RH = 0%), the samples retained only 0.12 and 0.08% of water relative to their initial masses. On the other hand, adiphenine hydrochloride exhibits a classical high hygroscopicity behavior, which retains water fast from 50% of relative humidity (RH), increasing up to 22% of its initial mass in 90% of RH and a net mass gain of 5% at the end of the desorption cycle (RH = 0%). Notably, both carboxylic acid salts had similar solubility as a function of medium pH, while the hydrochloride one was more soluble than them by factors ranging from 6.7 (relative to citrate in pH 1.2) to 28.2 (relative to oxalate in pH 4.5). Nevertheless, the pharmacokinetic parameters of adiphenine after oral administration of the capsules containing the salt forms did not reflect these solubility differences, since all adiphenine salt forms can be considered highly soluble drugs according to the Biopharmaceutics Classification System (dose/solubility ratio < 250 mL). It was observed that the rats treated with capsules containing adiphenine hydrochloride had an increase in AUC 0−∞ (1537 vs 914 vs 991 min μg mL −1 ) compared with rats treated with adiphenine citrate and oxalate capsules, respectively, even though the same t max (48 min) was observed. However, dosage tuning can bring the bioavailability of our salts into that of the hydrochloride salt, with the advantage of nonhygroscopicity and higher chemical stability.

show abstract

Section: Resultsmentioning

confidence: 99%

New Multicomponent Crystal Forms of Adiphenine with Low Hygroscopicity

Ribeiro

Silva

Neto

et al. 2022

Crystal Growth & Design

View full text Add to dashboard Cite

show abstract

“…They have also been used to form hydrogels [19], shown to partition into phospholipid membranes [20], and used as additives in personal cleansing products [21]. Ali, et al modified a C18 liquid chromatography column with a Glutamic acid-based surfactant and were able to separate ten short-chain aliphatic carboxylic acids [22]. Finally, the Glutamic acid-containing headgroup can be further functionalized by connecting other amino acids to the surfactant's carboxylate functional groups to produce surfactant molecules with branched amino acid headgroups.…”

Section: Introductionmentioning

confidence: 99%

“…Finally, the Glutamic acid-containing headgroup can be further functionalized by connecting other amino acids to the surfactant's carboxylate functional groups to produce surfactant molecules with branched amino acid headgroups. carboxylic acids [22]. Finally, the Glutamic acid-containing headgroup can be further functionalized by connecting other amino acids to the surfactant's carboxylate functional groups to produce surfactant molecules with branched amino acid headgroups.…”

Section: Introductionmentioning

confidence: 99%

An Investigation of the Effect of pH on Micelle Formation by a Glutamic Acid-Based Biosurfactant

Mayer,

Rauscher,

Fritz

et al. 2024

Colloids and Interfaces

View full text Add to dashboard Cite

NMR spectroscopy, molecular modeling, and conductivity experiments were used to investigate micelle formation by the amino acid-based surfactant tridecanoic L-glutamic acid. Amino acid-based biosurfactants are green alternatives to surfactants derived from petroleum. NMR titrations were used to measure the monomeric surfactant’s primary and gamma (γ) carboxylic acid pKa values. Intramolecular hydrogen bonding within the surfactant’s headgroup caused the primary carboxylic acid to be less acidic than the corresponding functional group in free L-glutamic acid. Likewise, intermolecular hydrogen bonding caused the micellar surfactant’s γ carboxylic functional group to be less acidic than the corresponding monomer value. The binding of four positive counterions to the anionic micelles was also investigated. At pH levels below 7.0 when the surfactant headgroup charge was −1, the micelle hydrodynamic radii were larger (~30 Å) and the mole fraction of micelle-bound counterions was in the 0.4–0.7 range. In the pH range of 7.0–10.5, the micelle radii decreased with increasing pH and the mole fraction of micelle bound counterions increased. These observations were attributed to changes in the surfactant headgroup charge with pH. Above pH 10.5, the counterions deprotonated and the mole fraction of micelle-bound counterions decreased further. Finally, critical micelle concentration measurements showed that the micelles formed at lower concentrations at pH 6 when the headgroup charge was predominately −1 and at higher concentrations at pH 7 where headgroups had a mixture of −1 and −2 charges in solution.

show abstract