3D Printing of Progesterone-Loaded Intrauterine System Using Vat Photopolymerisation

Three-dimensional printing (3DP) provides the opportunity to personalise different dosage forms and therapeutic regimen where conventional manufacturing processes might not be applicable. Limited work has been done to investigate using 3DP for personalising hormonal intrauterine systems (IUSs). The aim of this work was to prepare 3DP IUS containing progesterone using vat photopolymerisation (VPP) technique. The device was successfully printed and showed a slow release in phosphate buffer (pH 7.4). VPP has the advantages of better printing resolution producing smoother surfaces, and the elimination of the pre-printing process of hot melt extrusion (HME) needed for fused deposition modelling (FDM) method. To the author’s knowledge, this is the first report of using VPP for printing hormone-loaded IUSs

Rapid preparation of pharmaceutical co-crystals with thermal ink-jet printing

Thermal ink-jet printing (TIJP) is shown to be a rapid (minutes) method with which to prepare pharmaceutical co-crystals; co-crystals were identified in all cases where the co-formers could be dissolved in water and/or water/ethanol solutions

Intravesical combination therapies for non-muscle invasive bladder cancer: Recent advances and future directions

Bladder cancer is the 10th most frequently diagnosed cancer worldwide with 5-year survival rate around 70%. The current first-line treatment for non-muscle invasive bladder cancer is transurethral resection of bladder tumours followed by intravesical Mycobacterium Bovis Bacillus Calmette-Guérin (BCG) immunotherapy. However, tumor recurrence rate is still high ranging from 31% to 78% within five years. To avoid radical cystectomy, intravesical combination therapies have been developed as salvage treatments to overcome BCG failure. Recent advances in diagnostics thanks to tumor molecular profiling and in treatment such as development of immunotherapies provides more treatment options beyond BCG treatment. This also goes hand-in hand with formulation advances to deliver these new therapies where traditional drug delivery systems might not be suitable, which in turn is completed by challenges to deliver drugs via the intravesical route. In this article the aim was to provide an in-depth analysis of the current developments of intravesical combination therapies, ranging from relatively simple combinations of mixing existed intravesical therapeutic agents (immunotherapies and chemotherapies) to the combined formulations containing advanced gene therapies and targeted therapies, with special focus on therapies that have made it to the clinical trial stage. In addition, recent attempts to utilize device-assisted treatments and novel drug delivery platforms are included. This review also highlights the limitations that still need to be overcome such as the inadequate studies on newly explored drug carriers and proposes potential directions for future work to overcome BCG-failure

Simultaneous differential scanning calorimetry – synchrotron X-ray powder diffraction : a powerful technique for physical form characterisation in pharmaceutical materials

© 2016 American Chemical Society. We report a powerful new technique: hyphenating synchrotron X-ray powder diffraction (XRD) with differential scanning calorimetry (DSC). This is achieved with a simple modification to a standard laboratory DSC instrument, in contrast to previous reports which have involved extensive and complex modifications to a DSC to mount it in the synchrotron beam. The high-energy X-rays of the synchrotron permit the recording of powder diffraction patterns in as little as 2 s, meaning that thermally induced phase changes can be accurately quantified and additional insight on the nature of phase transitions obtained. Such detailed knowledge cannot be gained from existing laboratory XRD instruments, since much longer collection times are required. We demonstrate the power of our approach with two model systems, glutaric acid and sulfathiazole, both of which show enantiotropic polymorphism. The phase transformations between the low and high temperature polymorphs are revealed to be direct solid-solid processes, and sequential refinement against the diffraction patterns obtained permits phase fractions at each temperature to be calculated and unit cell parameters to be accurately quantified as a function of temperature. The combination of XRD and DSC has further allowed us to identify mixtures of phases which appeared phase-pure by DSC

Are oxygen and sulfur atoms structurally equivalent in organic crystals?

New guidelines for the design of structurally equivalent molecular crystals were derived from structural analyses of new cocrystals and polymorphs of saccharin and thiosaccharin, aided by a computational study. The study shows that isostructural crystals may be obtained through an exchange of >C?O with >C?S in the molecular components of the solids, but only if the exchanged atom is not involved in hydrogen bonding

A Simultaneous X-ray Diffraction-Differential Scanning Calorimetry Study into the Phase Transitions of Mefenamic Acid

In this study, the polymorphic transitions of mefenamic acid (MA) were studied by synchrotron X-ray powder diffraction combined with differential scanning calorimetry (XRD-DSC). The initial material was found to be phase-pure form I which, when heated, produces two endotherms that can be observed by DSC at 162.72 and 219.55°C. The former was found to correspond to a solid–solid enantiotropic transition from form I to a mixture of forms II and III. The latter is the melting point of form II. As form I is heated, significantly greater unit-cell expansion is seen in the a direction than in b and c, which can be explained by the stronger intermolecular interactions in the bc plane. Refinements of the reported MA structures against the patterns collected during heating revealed that at 175°C there exists a mixture of forms I, II and III, whereas only forms II and III remain at 205°C. However, reflections are observed at both temperatures which cannot be fitted with the known forms of MA. It is hypothesized that a new form of MA is produced upon heating. The stability of MA after the enantiotropic transition temperature is II > III > I, which differs from the previously reported II > I > III

Sustained antimicrobial activity and reduced toxicity of oxidative biocides through biodegradable microparticles

The spread of antibiotic-resistant pathogens requires new treatments. Small molecule precursor compounds that produce oxidative biocides with well-established antimicrobial properties could provide a range of new therapeutic products to combat resistant infections. The aim of this study was to investigate a novel biomaterials-based approach for the manufacture, targeted delivery and controlled release of a peroxygen donor (sodium percarbonate) combined with an acetyl donor (tetraacetylethylenediamine) to deliver local antimicrobial activity via a dynamic equilibrium mixture of hydrogen peroxide and peracetic acid. Entrapment of the pre-cursor compounds into hierarchically structured degradable microparticles was achieved using an innovative dry manufacturing process involving thermally induced phase separation (TIPS) that circumvented compound decomposition associated with conventional microparticle manufacture. The microparticles provided controlled release of hydrogen peroxide and peracetic acid that led to rapid and sustained killing of multiple drug-resistant organisms (methicillin-resistant Staphylococcus aureus and carbapenem-resistant Escherichia coli) without associated cytotoxicity in vitro nor intracutaneous reactivity in vivo. The results from this study demonstrate for the first time that microparticles loaded with acetyl and peroxygen donors retain their antimicrobial activity whilst eliciting no host toxicity. In doing so, it overcomes the detrimental effects that have prevented oxidative biocides from being used as alternatives to conventional antibiotics