Miscibility and Solubility of Caffeine and Theophylline in Hydroxypropyl Methylcellulose

Abstract

As amorphization may improve the solubility and bioavailability of a drug substance, the aim of this work was to assess to what extent the crystallinity of caffeine (CAF) and theophylline (TF) can be reduced by homogenization with a polymeric excipient. To realize this purpose, the physical mixtures of both methylxanthines with hydroxypropyl methylcellulose (HPMC) were examined using differential scanning calorimetry (DSC), hot-stage microscopy (HSM), Fourier-transform infrared (FTIR) and Raman spectroscopy. Moreover, phase diagrams for the physical mixtures were calculated using theoretical data. Results of DSC experiments suggested that both CAF and TF underwent amorphization, which indicated proportional loss of crystallinity for methylxanthines in the mixtures with HPMC. Additionally, HSM revealed that no other crystalline or amorphous phases were created other than those observed for CAF and TF. FTIR and Raman spectra displayed all the bands characteristic for methylxanthines in mixtures with HPMC, thereby excluding changes in their chemical structures. However, changes to the intensity of the bands created by hydrogen bonds imply the formation of hydrogen bonding in the carbonyl group of methylxanthines and the methyl polymer group. This is consistent with data obtained using principal component analysis. The findings of these studies revealed the quantities of methylxanthines which may be dissolved in the polymer at a given temperature and the composition at which methylxanthines and polymer are sufficiently miscible to form a solid solution.

Improvement in Inhalation Properties of Theophylline and Levofloxacin by Co-Amorphization and Enhancement in Its Stability by Addition of Amino Acid as a Third Component

“…This profile suggests that water desorption and crystal transformation of LEV were induced by heating, and T m was 229.3 ± 2.3 °C. These heat flow profiles agreed with previously reported results. , The XRPD patterns of THE and LEV were not changed in the profiles of the PMs (Figure S1), suggesting the absence of crystal transformation. However, the thermal profiles were changed following physical mixing.…”

Starch Alcogels, Aerogels, and Aerogel-like Xerogels: Adsorption and Release of Theophylline

“…It indicates that starches adsorb theophylline from ethanol. We suppose that this is due to a better affinity of theophylline to starch as compared to ethanol, as confirmed by the values of solubility parameters of theophylline 33 (23.53 MPa 1/2 ), starch 34 (24 MPa 1/2 ), and ethanol 35 (26.5 MPa 1/2 ). Experimental loading capacities of starch alcogels (eq 2) are presented in Figure 3a.…”

The Importance of Dissolution Tests to Evaluate Quality of Dietary Supplements: Case Study of Controlled Release Caffeine Capsules

“…Caffeine is a weak acid with pKa of 14.0 and lipophilicity (octanol-water partition coefficient, LogP) of 0.1 (17). Its water solubility is 11.0 mg/mL, being classified as class I (high solubility and high permeability) according to the Biopharmaceutical Classification System (18).…”