Determination and modeling of caffeine solubility in N-methyl-2-pyrrolidone + propylene glycol mixtures

Highlights

• Solubility of caffeine solubility in NMP + PG at different temperatures.

• Correlation/back-calculation of the solubility data by some cosolvency models.

• Calculation of thermodynamic parameters by using the van’t Hoff and Gibbs equations.

Abstract

The thermodynamics and solubilization behavior of caffeine in non-aqueous binary mixtures of N-methyl-2-pyrrolidone (NMP) and propylene glycol (PG) at temperatures ranged from 293.2 to 313.2 K are measured using a shake-flask method and the obtained solubility data are mathematically represented by using some cosolvency models (e.g. Jouyban-Acree, Jouyban-Acree-van’t Hoff, the mixture response surface, the double log–log and the modified Wilson) and their accuracy is investigated by computation of the mean relative deviations (MRD%) for back-calculated data. The density values of caffeine saturated solutions are determined and represented by Jouyban-Acree equation. Moreover, the apparent thermodynamic parameters of the caffeine dissolution process in the binary mixture of NMP and PG are computed using the Gibbs and van’t Hoff equations at mean harmonic temperature and discussed.

Introduction

Caffeine (3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione, Fig. 1) is a naturally occurring compound that is categorized as a psychoactive drug and mild stimulant [1]. Caffeine enhances visuospatial reasoning, memory and reaction time task performance in the elderly [2]. It is a factor in people's well-being, good physical performance and positive mood due to the secretion of dopamine in the brain [3], [4]. Caffeine is available as ampoule, tablet, gum, and capsule in the pharmaceutical market. It is also naturally found in the fruits, leaves and seeds of > 63 plant species worldwide including cocoa, Yaupon Holly, guarana and yerba mate. Diet pills and cosmetic manufacturers are considered the largest consumers of caffeine. Moreover, it is also employed in manufacturing body wash, lip balm, soap and facial scrub [5]. Various methodologies have been developed to extract caffeine from its natural sources such as water extraction, supercritical carbon dioxide extraction and organic solvent extraction. The extraction is performed by simply adding a portion of solvent to the liquid which contains dissolved caffeine. However, water is the most widely used liquid in the liquid–liquid extraction procedure, the use of organic solvents also has a special place and wide consumption [5]. Moreover, it is proved that coffee and beverages without caffeine is associated with many unique health benefits, including increased longevity and decreased risk of multiple cancers and chronic diseases. So, decaffeination can be a useful procedure for these productions. The conventional decaffeination process is extracting caffeine with an organic solvent that is based on the solubility property of caffeine or their ingredients in the used solvents. Knowing caffeine solubility can be helpful for these procedures and with the more information database available about caffeine solubility, pharmacists, chemists, and engineers will be able to make the right decision about the best solvent/antisolvent system for caffeine extraction [6], [7].

So far, the solubility profile of caffeine has been studied in monosolvents of chloroform, ethyl acetate, ethanol, carbon tetrachloride, water, dichloromethane, methanol and acetone at 298–323 K [8], 1-propanol, ethyl acetate, ethanol, methanol at 288.15 to 328.15 K [9], aqueous mixture of polyethylene glycol 400 at 298.2 K [10], dioxane at 298.2 K [11], and N,N-dimethylformamide (DMF) at 298.2 K [12] and non-aqueous mixtures of (carbitol + ethanol), (N-methyl-2-pyrrolidone (NMP) + ethanol), (NMP + 2-propanol), (NMP + 1-propanol), and (NMP + ethylene glycol) that are our previous works. But there is no report for the solubility of caffeine in the binary mixture of NMP and propylene glycol (PG). Caffeine is available in two crystalline forms (i,e. anhydrous and mono hydrated) that the used form of caffeine in the current study is anhydrous. NMP as a cosolvent in this work is categorized in class 2 of residual solvents with limited usage in drug substances, excipients, and drug products [13].

To provide a solubility database for caffeine in the cosolvency systems, the goals of this study are to (1) investigate the solubility and density of caffeine saturated solutions in the mixed solutions of NMP and PG at different temperatures; (2) correlate the data with reported cosolvency models; and (3) calculate the apparent thermodynamic properties for caffeine dissolution process in the mixed solvents of NMP and PG.