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

Andreia-Cristina Soare,Ioana Stanculescu,Viorica Meltzer,Claudiu Colbea,Elena Pincu

doi:10.3390/ma15031244

Andreia-Cristina Soare, Ioana Stanculescu + Show 3 more

Open Access

https://doi.org/10.3390/ma15031244

Copy DOI

Journal: Materials	Publication Date: Feb 8, 2022
Citations: 3	License type: CC BY 4.0

Affiliation: University of Bucharest

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.

Highlights

Nowadays, multiple medications are an issue that the pharmaceutical industry tries to address by developing new formulations containing two or more active pharmaceutical ingredients (APIs) that act simultaneously and synergistically, eventually without having adverse effects on the body
Pharmaceutical cocrystals may potentiate the physicochemical and mechanical properties of the substances [3], bioavailability [4], solubility [4,5] or stability [3,6] as well as in vivo activity [1], while a eutectic mixture behaves like a single pure substance having a melting temperature lower than that of the components which is correlated with increased bioavailability [7]
Mechanosynthesis, a simple, rapid, and ecological method was used for the preparation of the binary systems of APIs

Summary

Introduction

Multiple medications are an issue that the pharmaceutical industry tries to address by developing new formulations containing two or more active pharmaceutical ingredients (APIs) that act simultaneously and synergistically, eventually without having adverse effects on the body. An optimal formulation of this kind can be achieved by forming cocrystals or eutectic mixtures [1,2]. Pharmaceutical cocrystals may potentiate the physicochemical and mechanical properties of the substances [3], bioavailability [4], solubility [4,5] or stability [3,6] as well as in vivo activity [1], while a eutectic mixture behaves like a single pure substance having a melting temperature lower than that of the components which is correlated with increased bioavailability [7]. Ibuprofen (RS)-2-(4-(2-methylpropyl) phenyl) propionic acid (Figure 1a) and Ketoprofen (RS) 2-(3-benzophenyl)-propionic acid (Figure 1b) are propionic acid derivatives

Objectives

Methods

Results

Conclusion