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Characterization of Cimetidine-Piroxicam Coprecipitate Interaction Using Experimental Studies and Molecular Dynamic Simulations

The crystalline states of cimetidine and piroxicam, when coprecipitated from solvents containing 1:1 mole ratio, were transformed to amorphous states as observed using powder X-ray diffraction (PXRD). Amorphous forms of drugs generally exhibit higher water solubility than crystalline forms. It is therefore interesting to investigate the interactions that cause the transformation of both the crystalline drugs. Intermolecular interactions between the drugs were determined using Fourier-transform infrared spectroscopy (FTIR) and solid-state 13C CP/MAS NMR. Molecular dynamic (MD) simulation was performed for the first time for this type of study to indicate the specific groups involved in the interactions based on radial distribution function (RDF) analyses. RDF is a useful tool to describe the average density of atoms at a distance from a specified atom. FTIR spectra revealed a shift of the C≡N stretching band of cimetidine. The 13C CP/MAS NMR spectra indicated downfield shifts of C11, C15 and C7 of piroxicam. RDF analyses indicated that intermolecular interactions occurred between the amide oxygen atom as well as the pyridyl nitrogen of piroxicam and H-N3 of cimetidine. The hydrogen atom (O–H) at C7 interacts with the N1 of cimetidine. Since the MD simulation results are consistent with, and complementary to the experimental analyses, such simulations could provide a novel strategy for investigating specific interacting groups of drugs in coprecipitates, or in amorphous mixtures.

Monte Carlo simulation of the structure of mono- and bidisperse polyethylene nanocomposites

The structure of bidisperse polyethylene (PE) nanocomposite mixtures of 50:50 (by mole) of long and short chains of C160H322/C80H162 and C160H322/C40H82 filled with spherical nanoparticles were investigated by a coarse-grained, on lattice Monte Carlo method using rotational isomeric state theory for short-range and Lennard-Jones for long-range energetic interactions. Simulations were performed to evaluate the effect of wall-to-wall distance between fillers (D), polymer-filler interaction (w) and polydispersity (number of short chains in the mixture) on the behavior of the long PE chains. The results indicate that long chain conformation statistics remain Gaussian regardless of the effects of confinement, interaction strength and polydispersity. The various long PE subchain structures (bridges, dangling ends, trains, and loops) are influenced strongly by confinement whereas monomer-filler interaction and polydispersity did not have any impact. In addition, the average number of subchain segments per filler in bidisperse PE nanocomposites decreased by about 50% compared to the nanocomposite system with monodisperse PE chains. The presence of short PE chains in the polymer matrix leads to a reduction of the repeat unit density of long PE chains at the interface suggesting that the interface is preferentially populated by short chains.

Molecular simulation and experimental studies of the miscibility of chitosan/poly(ethylene oxide) blends

The miscibility of chitosan/poly(ethylene oxide) (CS/PEO) blends was investigated by a combination of experiment and molecular simulation. Results from X-ray diffraction (WAXD) and thermal analysis (DSC) suggest that the maximum miscibility was seen at the PEO weight fraction (wPEO) =0.2; the optimum stoichiometric ratio for CS and PEO functional groups. The change in vibrational frequencies from infrared spectra was attributed to the specific interaction between PEO ether oxygen with the amino and hydroxyl groups of CS. Radial distribution functions (RDF) from MD simulation suggest that all CS functional groups (NH2, C3-OH, and C6-OH) can interact with PEO ether groups for which NH2 has the highest activity. For CS hydroxyl groups, a more significant contribution of C6-OH rather than C3-OH groups that interact with PEO ether oxygen was observed. The interaction parameter (χ) determined from MD simulation was in good agreement with that of the DSC experiment (χCS-PEO = -0.21). Based on a comparison between χ and χcritical, CS/PEO blend was predicted to be miscible for wPEO <0.58 with a maximum at wPEO =0.2. In addition, the order parameter from the mesoscale simulation was employed to monitor the phase separation in these blends. From MesoDyn simulation, the miscibility was decreased with increasing PEO content, and miscible CS/PEO blends were obtained only with wPEO <0.58, in good agreement with MD simulation and experiment.

A multiscale simulation model for poly(ethylene oxide)

An overview of the recent development of a multiscale simulation of amorphous polymeric materials at the bulk density is presented. Poly(ethylene oxide), (PEO), (CH3O-[CH2-CH2-O]nCH3) was selected to illustrate the method. The model starts from an ab initio quantum chemistry to obtain the statistical weights of polymer conformation based on the rotational isomeric state (RIS) theory. PEO chains were then mapped to a coarse-grained model using the modified RIS model onto the second nearest neighbor diamond (2nnd) lattice. The average non-bonded interactions were treated by the discretized Lennard-Jones (LJ) potential. Bulk PEO melts with molecular weight up to 8000 g/mol was generated and equilibrated. The on-lattice properties such as molecular size and conformational statistics agree well with the theory. Fully atomistic amorphous PEO models can be obtained by the reverse-mapping procedure to recover the missing atoms. After an energy minimization step, properties including torsional angle distribution, solubility parameter and static neutron scattering structure factor are in good agreement with experimental results.

Mesoscale simulation and experimental studies of self-assembly behavior of a PLA-PEG-PLA triblock copolymer micelle for sustained drug delivery

Dissipative Particle Dynamic simulation (DPD) was employed to investigate PLA-PEG-PLA copolymer micelles to gain more understanding at the molecular level in addition to experimental studies. Critical micelle concentration (cmc), micelle size and small molecule encapsulation of these triblock copolymer micelles with different hydrophobic/hydrophilic (LA/EG) block ratios (2.56, 4.88 and 7.25 with fixed PEG length = 23 monomer units) were determined. Only the appropriated LA/EG block ratio (4.88 and 7.25) can induce the formation of spherical micelle in a dilute solution. The cmc and micelle size were decreased and increased, respectively, as a function of the LA/EG block ratio. Upon adding small solubilizate molecules, a larger micelle size was formed. Then, PLA-PEG-PLA with the same LA/EG block ratios as DPD simulation were synthesized and the micelle solution was prepared. Pyrene was used as the molecular probe to find the cmc by fluorescence spectroscopy. Light scattering was applied to determine the hydrodynamic radius (RH) of these micelles. The cmc and RH were decreased and increased, respectively, with LA/EG ratio, qualitatively similar to the trends as simulation results. The behavior of these copolymer micelles to encapsulate the small solubilizate molecules was also studied by fluorescence technique. The partition coefficients of pyrene between the water phase and the micelle core were increased with a higher LA/EG block ratio similar to results from the simulation.

Dynamics of polypropylene chains in their binary blends of different stereochemical sequences studied by Monte Carlo simulations

The conformational and dynamic properties of polypropylene (PP) for both pure melts and blends with different chain tacticity were investigated by Monte Carlo simulation of isotactic (iPP), atactic (aPP) and syndiotactic (sPP) polypropylenes. The simulation of coarse-grained PP models was performed on a high coordination lattice incorporating short- and long-range intramolecular interactions from the rotational isomeric state (RIS) model and Lennard-Jones (LJ) potential function of propane pairs, respectively. The dynamics of chains in binary PP/PP mixture were investigated with the composition of C150H302 with different chain taciticity. The diffusion rates of PP with different stereochemistry are generally in the order as: iPP > aPP ≫ sPP. For PP/PP blends with 50:50 wt% binary mixtures, immiscibility was observed when sPP was introduced into the mixtures. The diffusion rate of iPP and aPP became slower after mixing, while sPP diffuses significantly faster in the binary mixtures. The mobility of PP chains depends on both intramolecular (molecular size and chain stiffness) and intermolecular (chain packing) interactions. The effect of intramolecular contribution is greater than that of intermolecular contribution for iPP and aPP chains in binary mixtures. For sPP chain, intermolecular interaction has greater influence on the dynamics than intramolecular contribution.

Similarities and differences in the rapid crystallization induced in n-tetracontane by an instantaneous deep quench of the free-standing nanofiber and free-standing thin film

The crystallization of a confined short polyethylene chain, n-tetracontane, quenched from the melt has been investigated by a dynamic Monte Carlo method on a hight coordination lattice. The periodic boundary conditions force the formation of a free-standing nanofiber exposed to a vacuum. After the deep quench, the nanofiber adopts a configuration dominated by extended chains aligned parallel to the fiber axis. The vicinity of the fiber axis is less dense, and less well ordered, than portions of the fiber located further from the fiber axis. Annealing finds that this low-density region inside the fiber is not as easily removed as is the grain boundary that usually develops inside a free-standing thin film upon rapid crystallization.

Monte Carlo simulation of the stability and structure of polyethylene oxide nanodroplet with different solvent qualities

Monte Carlo simulation for poly(ethylene oxide), PEO, was applied to study the effect of solvent quality on the stability and structure of PEO nanodroplets in the poor solvent regime. The Hamiltonian included intrachain and non-bonded interactions. The intrachain interactions were based on an extended rotational isomeric state (RIS) model, and the non-bonded interactions were based on a discretized form of the Lennard-Jones (LJ) potential. The solvent was included implicitly into the simulations by manipulating the attractive portion of the long-range interactions. The results of the simulations clearly showed that as the solvent became poorer, the nanodroplet became denser, and their interfacial thickness decreased. These changes led to PEO chains assuming more compact conformations to enable better packing in the bulk region of the nanodroplets. The average shape of the nanodroplets changed from spherical to ellipsoidal as the solvent quality decreased. This shape anisotropy was attributed to chains assuming compact conformations while trying to pack more efficiently in the bulk region. The chain end bead distribution was strongly influenced by the solvent quality. As the solvent became poorer, a greater proportion of the end beads were excluded from the bulk region because of the need to achieve better packing. Simulations also suggested the formation of a layered structure as the solvent quality decreased.

Monte Carlo simulation study of the effect of chain tacticity on demixing of polyethylene/polypropylene blends

The molecular origin of the demixing behavior for 50: 50 (wt/wt) polyethylene/polypropylene (PE/PP) with different tacticity of PP at the melts (473 K) was investigated by Monte Carlo simulation of coarse-grained polymer model. Isotactic (iPP), atactic (aPP) and syndiotactic (sPP) polypropylenes were used for blending with PE. Coarse-graining polymer chains were represented by 50 beads, corresponding to C100H202 and C150H302 for PE and PP, respectively. The simulation was performed on a high coordination lattice incorporating short-range intramolecular interactions from the Rotational Isomeric State (RIS) model and long-range intermolecular interactions Lennard-Jones (LJ) potential function of ethane and propane units. Chain dimensions, the characteristic ratio (C n ) and self-diffusion coefficient (D) of PE in the blends are sensitive to the stereochemistry of PP chains. Compared with neat PE melts, PE dimension was relatively unchanged in PE/iPP and PE/aPP blends but slightly decreased in PE/sPP blends. PP dimension was increased in PE/iPP and PE/aPP mixture but decreased in PE/sPP blend in comparison with neat PP melts. In addition, diffusion of PE and PP chains in PE/PP mixture was decreased and increased, respectively, compared to the pure melts. Interchain pair correlation functions were used to detect the immiscibility of the blends. The tendency of demixing of PE/aPP and PE/iPP blends were weaker than that of PE/sPP blend.

Effect of stereochemical sequence on the dynamics of atactic polypropylene melt

AbstractDynamic Monte Carlo (DMC) simulation was used to study the dynamics of a series of coarse-grained atactic polypropylene (aPP) model chains (C192H578) in the melt state at 473 K. Model chains with meso diads factions, Pm, set at 0.25, 0.5, and 0.75 but with different meso and racemo diads sequences were studied. It was observed that aPP chains with an alternate meso and racemo diads sequence exhibited the highest mobility (or diffusivity) among all stereochemical sequences studied. Additionally, chains with long consecutive sequences of diads of the same type exhibited lower mobility than those with more random stereochemical sequences. The differences in the intramolecular and intermolecular interactions resulting from differences in diad sequences contributed to the observed differences in dynamics. In particular, intramolecular interactions play a more dominant role for aPP chains containing low fractions of meso diads or none at all (i.e., all racemo diads (Pm=0.0) or syndiotactic chains). On the other hand, in the cases of Pm values close to 1.0 (i.e., isotactic chains), intermolecular interactions play a more dominant role than the intramolecular interactions.