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

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

3D printed implantable drug delivery devices for women’s health: Formulation challenges and regulatory perspective

Modern pharmaceutical interventions are shifting from traditional “one-size-fits-all” approaches toward tailored therapies. Following the regulatory approval of Spritam®, the first marketed drug manufactured using three-dimensional printing (3DP) technologies, there is a precedence set for the use of 3DP in the manufacture of pharmaceutical products. The involvement of 3DP technologies in pharmaceutical research has demonstrated its capabilities in enabling the customisation of characteristics such as drug dosing, release characteristics and product designs on an individualised basis. Nonetheless, research into 3DP implantable drug delivery devices lags behind that for oral devices, cell-based therapies and tissue engineering applications. The recent efforts and initiatives to address the disparity in women’s health is overdue but should provide a drive for more research into this area, especially using new and emerging technologies as 3DP. Therefore, the focus of this review has been placed on the unique opportunity of formulating personalised implantable drug delivery systems using 3DP for women’s health applications, particularly passive implants. An evaluation of the current landscape and key formulation challenges for achieving this is provided supplemented with critical insight into the current global regulatory status and its outlook

Crystallisation in printed droplets: understanding crystallisation of d-mannitol polymorphs

Crystallisation of mannitol in the confinement of inkjet printed droplets was studied; the effects of droplet size and the presence of a foreign surface were investigated in comparison to the commonly used manufacturing technique of spray drying. Only the metastable polymorphs (α and δ) were observed in printed droplets with predominance of the α polymorph with increasing the droplet size, except for the smallest droplets generated (�100 pL) where the stable β polymorph was observed. The β polymorph was also predominant in spray-dried samples, with metastable forms appearing upon the addition of a polymer (Eudragit). We propose a dependence of the crystallisation of mannitol polymorphs on either the presence or absence of a surface to favour either the stable or the metastable polymorphs. These findings expand the experimental work that could be conducted to understand the crystallisation behaviour in droplets. By proposing heterogeneous nucleation to favour the formation of the metastable polymorphs while homogeneous nucleation favouring the stable β polymorph, one might understand why the same manufacturing method such as spray drying would produce one polymorph when processed alone but another when present in a formulation. This is of great importance to the pharmaceutical industry to aid in understanding the implications of crystallisation in manufacturing processes such as spray drying

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

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

Damage limitation: comparing the impact of polymers on bleached hair, when applied within or as post-bleach treatments

Hair bleaching causes undesirable chemical and structural changes to the cortex, the most prominent process being the oxidation of the disulphide bonds of the amino acid cystine and the creation of cysteic acid. It is known that this process affects mostly the Keratin Associated Proteins (KAP) which are amorphous and sulphur-rich. A major secondary effect is the overall destabilisation of the cortex structure within which the crystalline Intermediate Filaments’ (IF) proteins are supported by KAP. An overall decrease in the proportion of ordered protein structure, reduction of mechanical strength and the denaturation temperature of hair have been used to quantify the degree of damage. The cuticle also undergoes oxidative damage during bleaching which causes reduced thickness and increased surface roughness. Mitigating and counteracting these changes in the hair surface and internal structure have been a prime objective of the haircare industry. Such action would be expected to deliver immediate sensory benefits perceivable by the consumer. This project was to compared the impact of three actives said to deliver structural benefits to bleached hair. Their impact was evaluated in two conditions: when applied with the bleaching cream (WB) and after bleaching (AT)

Current and Prospective Applications of 3D Printing in Cosmetics: A Literature Review

3D printing (3DP) is a manufacturing technology that produces 3D objects from a design file using layer-by-layer deposition of material. It has already found applications in the healthcare and pharmaceutical industries, while its use in the field of topical delivery has been extensively studied in the last two decades. The aim of this study is to provide a comprehensive overview of the 3DP-based developments in topical delivery, with special emphasis on its current and potential use in the cosmetic field. This review covers the principles and main types of 3DP technology, production and characteristics of two key 3DP skin delivery platforms (patches and microneedles—MNs), as well as topical active materials used, focusing on those for cosmetic application

3D printing of medicines: Engineering novel oral devices with unique design and drug release characteristics

YesThree dimensional printing (3DP) was used to engineer novel oral drug delivery devices, with specialised design configurations loaded with multiple actives, with applications in personalised medicine. A filament extruder was used to obtain drug-loaded - paracetamol (acetaminophen) or caffeine - filaments of polyvinyl alcohol with characteristics suitable for use in fused-deposition modelling 3D printing. A multi-nozzle 3D printer enabled fabrication of capsule-shaped solid devices, containing paracetamol and caffeine, with different internal structures. The design configurations included a multilayer device, with each layer containing drug, whose identity was different from the drug in the adjacent layers; and a two-compartment device comprising a caplet embedded within a larger caplet (DuoCaplet), with each compartment containing a different drug. Raman spectroscopy was used to collect 2-dimensional hyper spectral arrays across the entire surface of the devices. Processing of the arrays using direct classical least squares component matching to produce false colour representations of distribution of the drugs showed clearly the areas that contain paracetamol and caffeine, and that there is a definitive separation between the drug layers. Drug release tests in biorelevant media showed unique drug release profiles dependent on the macrostructure of the devices. In the case of the multilayer devices, release of both drugs was simultaneous and independent of drug solubility. With the DuoCaplet design it was possible to engineer either rapid drug release or delayed release by selecting the site of incorporation of the drug in the device, and the lag-time for release from the internal compartment was dependent on the characteristics of the external layer. The study confirms the potential of 3D printing to fabricate multiple-drug containing devices with specialized design configurations and unique drug release characteristics, which would not otherwise be possible using conventional manufacturing methods.The full-text of this article will be released for public view at the end of the publisher embargo on 10 Oct 2016

Metastable crystalline phase formation in deep eutectic systems revealed by simultaneous synchrotron XRD and DSC

The phase behaviour of various deep eutectic systems was analysed using concurrent synchrotron powder X-ray diffraction and differential scanning calorimetry. Deep eutectic systems containing the pharmaceuticals metacetamol, 2-ethoxybenzamide or benzamide as binary mixtures with phenol revealed new crystalline phases melting either before or with crystals of phenol, highlighting their lower stabilities. Furthermore, in the phenol:2-ethoxybenzamide system it was shown that multiple metastable phases can form, highlighting the potential for the separation of a hierarchy of crystal structures with differing stabilities from eutectic systems. Through these experiments, we strengthen the idea that eutectic systems can be described by understanding the formation and stabilities of metastable co-crystalline structures. These novel results lead to a deeper understanding of the structure and thermodynamics of deep eutectic solvents, with relevance for analagous systems across materials science