Compatibility of Drotaverine Hydrochloride with Ibuprofen and Ketoprofen Nonsteroidal Anti-Inflammatory Drugs Mixtures

Abstract

Formulations with two or more active pharmaceutical ingredients (APIs) are a researched trend due to their convenient use compared with multiple medications. Moreover, drug-drug combinations may have a synergistic effect. Drotaverine hydrochloride (D-HCl) is commonly used for its antispasmodic action. The combination of a spasmolytic and an analgesic drug such as ibuprofen (Ibu) or ketoprofen (Ket) could become the answer for the treatment of localized pain. D-HCl:Ibu and D-HCl:Ket drug-drug interactions leading to the formation of eutectic compositions with increased bioavailability, obtained by mechanosynthesis, a green, solvent-free method was explored for the first time. The compatibility of Ibuprofen, Ketoprofen, and Drotaverine Hydrochloride was investigated using differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier-Transform Infrared spectroscopy (FTIR). Solid-liquid equilibrium (SLE) phase diagrams for the binary systems of active pharmaceutical ingredients were developed and the Tammann diagrams were designed to determine the eutectic compositions. The excess thermodynamic functions GE for the pre-, post-, and eutectic compositions were obtained using the computed activity coefficients data. Results show that drotaverine-based pharmaceutical forms for pain treatment may be obtained at 0.9 respectively 0.8 molar fractions of ibuprofen and ketoprofen which is advantageous because the maximum allowed daily dose of Ibu is about 6 times higher than those of D-HCl and Ket. The obtained eutectics may be a viable option for the treatment of pain associated with cancer therapy.

Measurements of Binary Solid–Liquid Equilibrium of Anticancer Drug p-Toluenesulfonamide with Benzamide, Isonicotinamide, or Salicylamide

“…Leitner et al 24 studied SLE in three binary systems containing paracetamol, with phenylephrine hydrochloride, tramadol hydrochloride, and ibuprofen, respectively. Soare et al 25 reported SLE data for the binary systems of ibuprofendrotaverine hydrochloride and ketoprofen-drotaverine hydrochloride. Zemańkováet al 26 experimentally determined the SLE of four binary systems, including naproxen-indomethacin, naproxen-ibuprofen, naproxen-probucol, and indomethacinparacetamol.…”

The Effect of Drotaverine on Gastrointestinal Motility and Heart Rate Variability in Normal, Resting Horses

“…In humans, drotaverine can suppress spasm-associated pain and is successfully used in the symptomatic treatment of various conditions such as gastrointestinal, urinary, biliary, vasomotor diseases associated with smooth muscle spasms [1,11], it has a cytostatic effect [12] and improves cognitive function [13]. It is available without prescription in many countries of Central and Eastern Europe (Poland [11,[14][15][16], Hungary [17], Estonia, Croatia, Latvia [4], Romania [18,19]), Africa (Nigeria [20]) and Asia (India [21][22][23], Russia [24], China [25] under several brand names.…”

Development of a Chromatographic Technique for Quantification of Drotaverine Hydrochloride and Diclofenac Potassium

“…The spasmolytic activity of this drug act by inhibiting the phosphodiesterase-4. It shows clinical importance in various disease associated with smooth muscle spam [1][2][3] . The phenylacetic acid derivative, Diclofenac Potasium (DICLO) is classified as a non-steroidal anti-inflammatory medication acts by inhibiting cyclooxygenase enzyme, which is the key enzyme responsible for the synthesis of prostaglandins (PGs).…”