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

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

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)

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

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

Taste masked thin films printed by jet dispensing

Taste masking of bitter active substances is an emerging area in the pharmaceutical industry especially for paediatric/geriatric medications. In this study we introduce the use of jet – dispensing as a taste masking technology by printing mucosal thin films of three model bitter substances, Cetirizine HCl, Diphenylhydramine HCl and Ibuprofen. The process was used to dispense aqueous drugs/polymer solutions at very high speed where eventually the drugs were embedded in the polymer matrix. The in vivo evaluation of jet – dispensed mucosal films showed excellent taste masking for drug loadings from 20 - 40%. Jet dispensing was proved to make uniform, accurate and reproducible thin films with excellent content uniformity

Controllable degradation kinetics of POSS nanoparticle-integrated poly(ε-caprolactone urea)urethane elastomers for tissue engineering applications.

Biodegradable elastomers are a popular choice for tissue engineering scaffolds, particularly in mechanically challenging settings (e.g. the skin). As the optimal rate of scaffold degradation depends on the tissue type to be regenerated, next-generation scaffolds must demonstrate tuneable degradation patterns. Previous investigations mainly focussed on the integration of more or less hydrolysable components to modulate degradation rates. In this study, however, the objective was to develop and synthesize a family of novel biodegradable polyurethanes (PUs) based on a poly(ε-caprolactone urea)urethane backbone integrating polyhedral oligomeric silsesquioxane (POSS-PCLU) with varying amounts of hard segments (24%, 28% and 33% (w/v)) in order to investigate the influence of hard segment chemistry on the degradation rate and profile. PUs lacking POSS nanoparticles served to prove the important function of POSS in maintaining the mechanical structures of the PU scaffolds before, during and after degradation. Mechanical testing of degraded samples revealed hard segment-dependent modulation of the materials' viscoelastic properties, which was attributable to (i) degradation-induced changes in the PU crystallinity and (ii) either the presence or absence of POSS. In conclusion, this study presents a facile method of controlling degradation profiles of PU scaffolds used in tissue engineering applications

Fabrication of controlled-release budesonide tablets via desktop (FDM) 3D printing

The aim of this work was to explore the feasibility of using fused deposition modelling (FDM) 3D printing (3DP) technology with hot melt extrusion (HME) and fluid bed coating to fabricate modified-release budesonide dosage forms. Budesonide was sucessfully loaded into polyvinyl alcohol filaments using HME. The filaments were transfomed into capsule-shaped tablets (caplets) containing 9 mg budesonide using a FDM 3D printer; the caplets were then overcoated with a layer of enteric polymer. The final printed formulation was tested in a dynamic dissolution bicarbonate buffer system, and two commercial budesonide products, Cortiment® (Uceris®) and Entocort®, were also investigated for comparison. Budesonide release from the Entocort® formulation was rapid in conditions of the upper small intestine while release from the Cortiment® product was more delayed and prolonged. In contrast, the new 3D printed caplet formulation started to release in the mid-small intestine but release then continued in a sustained manner throughout the distal intestine and colon. This work has demonstrated the potential of combining FDM 3DP with established pharmaceutical processes, including HME and film coating, to fabricate modified release oral dosage forms

Thermal Behavior of Benzoic Acid/lsonicotinamide Binary Cocrystals

A comprehensive study of the thermal behavior of the 1:1 and 2:1 benzoic acid/isonicotinamide cocrystals is reported. The 1:1 material shows a simple unit cell expansion followed by melting upon heating. The 2:1 crystal exhibits more complex behavior. Its unit cell first expands upon heating, as a result of C–H···π interactions being lengthened. It then is converted into the 1:1 crystal, as demonstrated by significant changes in its X-ray diffraction pattern. The loss of 1 equiv of benzoic acid is confirmed by thermogravimetric analysis–mass spectrometry. Hot stage microscopy confirms that, as intuitively expected, the transformation begins at the crystal surface. The temperature at which conversion occurs is highly dependent on the sample mass and geometry, being reduced when the sample is under a gas flow or has a greater exposed surface area but increased when the heating rate is elevated

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