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.
Highlights
Accepted: 29 October 2021The use of polymorphous or amorphous forms, organic salts, co-crystals or solid dispersions usually improves the bioavailability of poorly water-soluble active ingredients [1]
N where the number number of ofdrug drugsubstance substancelattice lattice sites, defined as the volume of drug where nn is is the sites, defined as the volume of drug subsubstance molecule occupied by a polymer chain and χ is the drug substance–polymer stance molecule occupied by a polymer chain and χ is the drug substance–polymer interinteraction parameter
The measurements performed reveal that the miscibility of ingredients and formation of solid solution are effective in the partial reduction of methylxanthine crystallinity when mixed with hydroxypropyl methylcellulose (HPMC)
Summary
The use of polymorphous or amorphous forms, organic salts, co-crystals or solid dispersions usually improves the bioavailability of poorly water-soluble active ingredients (drug substances) [1]. Amorphization is advantageous because the creation of an amorphous form leads to the creation of extremely small particles. [2,3,4] The solubility of this form is usually profitable because no energy is needed to break the crystal lattice. Solid dispersions (SDs) of drug substances with polymeric excipients are an attractive way to improve the solubility and bioavailability of active substances [2,3]. The drug substance is dispersed at a molecular level in a solid, usually polymeric matrix [3,4].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
