An Unconventional Route for Synthesis and Solid-State Processing of Low-Entangled Ultra-High Molecular Weight Isotactic Polypropylene.

Introducing the reverse micelle formation during polymerization, and thus avoiding the catalyst support, aggregated single crystals of ultra-high molecular weight isotactic polypropylene having spherical morphology are obtained. The ease in flowability of the spherical nascent morphology, having a low-entangled state in the non-crystalline region of the single crystals in the semi-crystalline polymer, allows the sintering of the nascent polymer in the solid state without melting. Thus maintains a low-entangled state, and facilitates the translation of macroscopic forces to macromolecular length scale, without melting, leading to the formation of uniaxially drawn objects having unprecedented properties that can be used in the development of one component, high-performance, easy-to-recycle composites. Thus having the potential of replacing difficult-to-recycle hybrid composites.

Understanding solid-state processing of pharmaceutical cocrystals via milling: Role of tablet excipients.

Discovery of novel cocrystal systems and improvement of their physicochemical properties dominates the current literature on cocrystals yet the required end-product formulation is rarely addressed. Drug product manufacturing includes complex API solid state processing steps such as milling, granulation, and tableting. These all require high mechanical stress which can lead to solid-state phase transformations into polymorphs and solvates, or lead to dissociation of cocrystals into their individual components. Here we measured the effect of tablet excipients on solid-state processing of a range of pharmaceutical cocrystal formulations. Our findings were rationalised using Density Functional Theory (DFT) calculations of intermolecular binding energies of cocrystal constituents and co-milling excipients. A 1:1 stoichiometric ratio of API Theophylline (THP) and co-former 4-Aminobenzoic acid (4ABA) was co-milled with five different excipients: hydroxypropylmethylcellulose (HPMC), polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), lactose, and microcrystalline cellulose (MCC). The experiments were carried out in 10 and 25 ml milling jars at 30 Hz for different milling times. Co-milled samples were characterised for formation of cocrystals and phase transformation using powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). Our data shows that co-milling in the presence of PEG, HMPC or lactose yields purer cocrystals, supported by the calculated stronger excipient interactions for PVP and MCC. We identify a suitably-prepared THP-4ABA pharmaceutical cocrystal formulation that is stable under extended milling conditions.