Solution pH is an important factor during drug formulation and processing. Changes in pH present challenges. Regulation of pH is typically managed by using a buffer system, which must have a suitable pKa. The pKa value of buffers depends on temperature, pressure and ionic strength. In addition, the pKa value can also be affected by the polarity of the solvent, e.g., by the addition of a co-solvent. Theoretical considerations and accessible experimental data were used to understand how the pKa values of pharmaceutically relevant buffers depend on these factors. Changes in temperature also affect the buffer pKa. Carboxylic acid moieties were least affected by changes in temperature. Buffers containing amino groups were most affected by changes in temperature, and the pKa decreased as temperature was increased. It was possible to predict accurately how buffer pKa varies with temperature, based on changes in enthalpy and heat capacity for the ionization reactions. Changes in pressure had a limited effect on buffer pKa for pressures <100 MPa. At higher pressures, buffer pKa varied by up to 0.5 pH units. Altering the ionic strength or polarity of the solvent influenced buffer pKa slightly. However, it is possible to keep both the ionic strength and the polarity of the solvent constant during drug formulation and processing.

In drug formulations, cyclodextrins are used to increase aqueous solubility and chemical stability of drugs via formation of inclusion complexes. For ionizable drug molecules, the complexation strength depends on pH. Increased ionization leads to a more soluble drug, but also results in destabilization of cyclodextrin complexes. Therefore, formulation scientists aim to find a balance between increased drug solubility and high complexation strength. In this work, a theoretical expression for the dependency between the stability constant and pH is presented, allowing the accurate prediction of the stability constant at any pH. The theoretical expression requires three out of four input parameters; the pKa of the free guest molecule, the pKa of the complex, and the stability constants for the neutral and fully ionized complex. Stability constants for β-cyclodextrin and ibuprofen complexes were determined by isothermal titration calorimetry at seven pH values (2.5-5.5) and four temperatures (15-55˚C). All these measured stability constants complied with the theoretical expression. Ten additional data sets from the literature comprising eight different drug molecules and three different cyclodextrins confirmed the ability of the theoretical expression to account for the observed pH-dependence of stability constants.

Complex formation between cyclodextrins and ionizable guest molecules depends on pH.The neutral species of an ionizable guest molecule in general has the highest affinity for the cyclodextrin cavity, but ionized species will also be able to form complexes with cyclodextrins. This work presents a theoretical expression for the relationship between the stability constant and pH for interaction between neutral cyclodextrins and ionizable guest molecules with multiple pKa values. Input parameters for the theoretical expression are pKa values of the guest molecule and stability constants for the complex at specific pH values. The pH profile of the stability constant for a complex depends on the acidbase properties of the guest and the closeness of the pKa values, and examples of pH profiles for polyprotic acids, bases and amphoteric guests are shown. Empirical data sets from the literature were used to confirm the accuracy of the theoretical expression, and Monte Carlo simulations were used to validate that the theoretical expression yield a good fit to empirical data. Lastly, an experimental protocol was suggested, and a freely available graphical user interface is presented to facilitate easy use of the theoretical expression.

Two types of poly(heterocycle) Langmuir-Blodgett films have been fabricated: (1) copolymers of pyrrole and 3-alkylpyrrole (3-hexadecylpyrrole and octadecylpyrrole) LB films; (2) mixtures of poly(3-alkylthiophene) and stearic acid LB films. The orientation of single-layer and multilayer films on platinum substrates has been studied by near edge X-ray absorption fine structure (NEXAFS) spectroscopy, which also provides information about interaction between the aromatic groups and the metallic substrate. The alkyl-substituted pyrrole monomers form highly ordered multilayer LB films with the hydrocarbon chains perpendicular to the substrate, while the LB films of copolymers of pyrrole and alkyl-substituted pyrrole are more disordered. In the case of mixtures of poly(3-alkylthiophene) and stearic acid LB films, the hydrocarbon chains of the stearic acid molecules are highly ordered. The poly(3alkylthiophene) components, on the other hand, exhibit random orientation of the thiophene moieties. The orientation of the hydrocarbon chain of the poly(3-alkylthiophene) varies with the chain length, from random to highly ordered along the surface normal of the substrate, as the chain length changes from 4 to 18 carbon units.

Usnic acid has anti-cancer activity, however, low solubility and toxicity limit the potential. To investigate biological activity of usnic acid derivatives, enantiopure derivatives were synthesised by reacting usnic acid with ethylenediamine, which yielded one dimer product ((+)-1), and two tetra cyclic compounds ((+)-2 and (-)-2). The products were characterised with NMR, and evaluated in vitro in human colon cancer cell line Caco-2 by cell count, phase-contrast microscopy, MTT-assay, measurement of DNA content and cell cycle distribution. All compounds tested showed cytostatic effect in Caco-2 cells, but each compound had a distinct effect. Compound (+)-1 showed anti-proliferative activity by increasing the percentage of cells in S-phase with 25 % compared to the control. Compounds (+)-2 and (-)-2 induced paraptosis, but only compound (+)-2 modulated cell cycle distribution