Spray Drying Process Challenges and Considerations for Inhaled Biologics- A Review.

Spray drying presents numerous advantages over other drying technologies, particularly for inhaled biologics because of the fine-tuned particle attributes requirements. To fully leverage these benefits, it is crucial to address several process challenges and considerations throughout the end-to-end spray-drying process, including stages prior to, during, and post- drying. This review provides a detailed overview of the challenges associated with spray-drying of biologics along with the aspects of protein degradation.

The Degradation Chemistry of Farglitazar and Elucidation of the Oxidative Degradation Mechanisms.

The chemical degradation of farglitazar (1) was investigated using a series of controlled stress testing experiments. Farglitazar drug substance was stressed under acidic, natural pH, basic, and oxidative conditions in solution. In the solid state, the drug substance was stressed with heat, high humidity, and light.

Phase Behavior of Tapered Diblock Copolymers from Self-Consistent Field Theory.

Tapered diblock copolymers are similar to AB diblock copolymers, but the sharp junction between the A and B blocks is replaced with a gradient region in which composition varies from mostly A to mostly B along its length. The A side of the taper can be attached to the A block (normal) or the B block (inverse). We demonstrate how taper length and direction affect the phase diagrams and density profiles using self-consistent field theory.

Morphologies of ABC triblock terpolymer melts containing poly(cyclohexadiene): effects of conformational asymmetry.

We have synthesized linear ABC triblock terpolymers containing poly(1,3-cyclohexadiene), PCHD, as an end block and characterized their morphologies in the melt. Specifically, we have studied terpolymers containing polystyrene (PS), polybutadiene (PB), and polyisoprene (PI) as the other blocks. Systematically varying the ratio of 1,2- /1,4-microstructures of poly(1,3-cyclohexadiene), we have studied the effects of conformational asymmetry among the three blocks on the morphologies using transmission electron microscopy (TEM), small-angle X-ray scattering (SAXS), and self-consistent field theory (SCFT) performed with PolySwift++.

Elucidating the pathways of degradation of denagliptin.

Stress testing or forced degradation studies of denagliptin (1) tosylate in solution and solid-state, its blends with excipients, and capsules were conducted in order to elucidate degradation pathways, aid formulation development, and generate data to support regulatory filings. In solution, denagliptin was stressed in acid, water, and base using organic cosolvents. In the solid-state, denagliptin was stressed under heat, humidity, and light.

Hybrid particle-field simulations of polymer nanocomposites.

We present a theoretical framework and computer simulation methodology for investigating the equilibrium structure and properties of mesostructured polymeric fluids with embedded colloids or nanoparticles. The method is based on a field-theoretic description of the fluid in which particle coordinates and chemical potential field variables are simultaneously updated. The fluid model can contain polymers of arbitrary chemical and architectural complexity, along with particles of all shapes, sizes, and surface treatments.

Introducing variable cell shape methods in field theory simulations of polymers.

We propose a new method for carrying out field-theoretic simulations of polymer systems under conditions of prescribed external stress, allowing for shape changes in the simulation box. A compact expression for the deviatoric stress tensor is derived in terms of the chain propagator, and it is used to monitor changes in the box shape according to a simple relaxation scheme. The method allows fully relaxed, stress free configurations to be obtained even in nontrivial morphologies, and it enables the study of morphology transitions induced by external stresses.

Field-theoretic simulations of polymer solutions: finite-size and discretization effects.

In this work we analyze the finite-size and discretization effects that occur in field-theoretic polymer simulations. Following our previous work, we study these effects for a polymer solution in the canonical ensemble confined to a slit (with nonadsorbing walls) of width L, and focus on the behavior of two quantities: the chemical potential mu, and the correlation length xi. Our results show that the finite-size effects disappear for both quantities once the lateral size of the system L is larger than approximately 2xi.

Composite mesostructures by nano-confinement.

In a physically confined environment, interfacial interactions, symmetry breaking, structural frustration and confinement-induced entropy loss can play dominant roles in determining molecular organization. Here we present a systematic study of the confined assembly of silica-surfactant composite mesostructures within cylindrical nanochannels of varying diameters. Using exactly the same precursors and reaction conditions that form the two-dimensional hexagonal SBA-15 mesostructured thin film, unprecedented silica mesostructures with chiral mesopores such as single- and double-helical geometries spontaneously form inside individual alumina nanochannels.

Mass spectral fragmentation reactions of angiotensin-converting enzyme (ACE) inhibitors.

A variety of mass spectrometric techniques have been employed in the study of a series of structurally similar compounds used in the treatment of hypertension. The compounds, known collectively as angiotensin-converting enzyme (ACE) inhibitors, all share the amino acid residue proline or some variant thereof, as a common structural element. The gas phase fragmentation behavior of these compounds has been explored systematically using various instruments and techniques.

Continuous polydispersity in a self-consistent field theory for diblock copolymers.

An efficient algorithm is presented for numerically evaluating a self-consistent field theoretic (SCFT) model of an AB diblock copolymer that incorporates continuous polydispersity in one of the blocks. An interesting segregation effect is found in which chains of intermediate molecular weight are concentrated at domain interfaces. This model of continuous polydispersity is also implemented in the random phase approximation (RPA) to study the order-disorder transition and predicts that the stability of the disordered, homogeneous phase decreases as the polydispersity in one of the blocks increases.