Marek Pyda

PAMAM dendrimers as solubilizers and hosts for 8-methoxypsoralene enabling transdermal diffusion of the guest

PAMAM dendrimers form host-guest complexes with 8-methoxypsoralene (8-MOP) - the photosensitizer for PUVA therapy. The stoichiometry of complexes was studied by (1)H NMR spectroscopy in solution and by differential scanning calorimetry in neat mixtures containing 8-MOP and dendrimers of generations G2.5, G3, G3.5, and G4. The dendrimers showed solubilization effect for 8-MOP resulting in increase of 8-MOP concentration in methanol up to 15 molecules of 8-MOP per G2.5 and G3 and 30 molecules of 8-MOP per G3.5, and G4. Isolation of oily host-guest complexes containing 3 or 7 molecules of 8-MOP per G3 and G4, respectively corroborate well with DSC results; glass transition temperature of neat host-guest complexes increases with number of host molecules in comparison with G3 or G4, until the capacity of host is exceeded. The oily host-guest complexes of stoichiometry 3:1 and 7:1 of 8-MOP to G3 and G4, respectively are well soluble in water. The 3:1 host-guest complexes diffused slowly through polyvinyldifluoride and pig ear skin membranes, when released from o/w emulsion. The host-guest complex 8-MOP-G3 was proposed as convenient formulation for psoralene skin administration in PUVA therapy.

Bisoprolol and Bisoprolol-Valsartan Compatibility Studied by Differential Scanning Calorimetry, Nuclear Magnetic Resonance and X-Ray Powder Diffractometry

PurposeThe objective of this study was to evaluate the thermal behavior of crystalline and amorphous bisoprolol fumarate and its compatibility with amorphous valsartan. This pharmacologically relevant drug combination is a potential candidate for fixed-dose combination formulation.MethodsDSC and TMDSC were used to examine thermal behavior of bisoprolol fumarate. SSNMR and XRPD were applied to probe the solid state forms. The thermal behavior of physical mixtures with different concentrations of bisoprolol and valsartan were examined by DSC and TMDSC, and the observed interactions were investigated by XRPD, solution- and solid-state NMR.ResultsThe phase transitions from thermal methods and solid-state NMR spectra of crystalline and amorphous bisoprolol fumarate are reported. Strong interactions between bisoprolol fumarate and valsartan were observed above 60 C, resulting in the formation of a new amorphous material. Solution- and solid-state NMR provided insight into the molecular nature of the incompatibility.ConclusionsA combined analysis of thermal methods, solution- and solid-state NMR and XRPD experiments allowed the investigation of the conformational and dynamic properties of bisoprolol fumarate. Since bisoprolol fumarate and valsartan react to form a new amorphous product, formulation of a fixed-dose combination would require separate reservoirs for bisoprolol and valsartan to prevent interactions. Similar problems might be expected with other excipients or APIs containing carboxylic groups.

Thermal Properties and Thermodynamics of Poly( l -lactic acid)

Thermal properties and thermodynamics of poly(l-lactic acid) PLLA at nonequilibrium and equilibrium states and during reversing and nonreversing processes are presented, based on the apparent heat-flow and heat capacity (C p ). The experimental, apparent heat capacity results from measurements by adiabatic calorimetry, standard differential scanning calorimetry, and temperature-modulated differential scanning calorimetry are interpreted in terms of microscopic molecular motion in the entire temperature range. The low-temperature, below the glass transition, experimental heat capacity of solid state is linked to the vibrational motion. The heat capacity of the liquid state of PLLA is linked additional to the vibrational, also to the conformational, and anharmonic motions or estimated from an empirical addition scheme based on contributions of the constituent chain-segments of polymers. Once calculated, solid C p (vibration) and liquid C p (liquid) heat capacities are established so they can serve as two reference baselines for the quantitative thermal analysis of nonequilibrium semicrystalline poly(lactic acid). Knowing heat capacities (C p (vibration), C p (liquid)) and transitions parameters, the integral functions such as the enthalpy (H), entropy (S) and free enthalpy (Gibbs function) (G) for equilibrium conditions are calculated and used as a reference for analysis. All recommended results for PLLA, are collected and organized as part of the ATHAS Data Bank. Examples of the qualitative and quantitative thermal analysis of amorphous and semicrystalline poly(lactic acid) are presented to characterize phases and phase transitions such as glass transition, enthalpy relaxation, cold crystallization/cystallization, reorganization and melting, as well as amount of phase: crystallinity, mobile and rigid amorphous fraction on the ATHAS scheme (Advanced Thermal Analysis System).

Dermatological Application of PAMAM – Vitamin Bioconjugates and Host-Guest Complexes – Vitamin C Case Study

Stoichiometry of reaction describes the quantitative relationships among substances as they participate in chemical reactions. Furthermore the term stoichiometry is used to describe the quantitative relationship among elements in compounds. This is also valid in the quantitative description of so-called weak complexes formed between molecules through non-covalent and non-ionic interactions. They generally arise from hydrogen bonding or Van der Waals interactions and are very common in biological chemistry, like in the case of enzyme-substrate, enzyme-inhibitor, or enzyme-coenzyme complexes. In less specific systems, stoichiometry may be referred to the number of small molecules interacting with one macromolecule to form complex structure. Depending on the interaction type between the components of the complex they are often desribed as host (macromolecule, H) – guest (small molecule, g) complexes. The host-guest complexes can sometimes be isolated as compounds of defined strochiometry, however their dissolution always leads to establishing an equilibrium between complexes and free guest, according to the scheme: