3D printing of LEGO® like designs with tailored release profiles for treatment of sleep disorder.

3D printed LEGO®-like designs are an attractive approach for the development of compartmental delivery systems due to their potential for dose personalisation through the customisation of drug release profiles. Additive manufacturing technologies such as Fused Deposition Modelling (FDM) are ideal for the printing of structures with complex geometries and various sizes. This study is a paradigm for the fabrication of 3D printed LEGO® -like tablets by altering the design of the modular units and the filament composition for the delivery of different drug substances. By using a combination of placebo and drug loaded compartments comprising of immediate release (hydroxypropyl cellulose) and pH dependant polymers (hypromellose acetate succinate) we were able to customise the release kinetics of melatonin and caffeine that can potentially be used for the treatment of sleep disorders. The LEGO® -like compartments were designed to achieve immediate release of melatonin followed by variable lag times and controlled release of caffeine.

Comparative taste-masking evaluation of microencapsulated bitter drugs using Smartseal 30D and ReadyMix for paediatric dosage forms.

The taste of drug substances plays a key role in the development of paediatric formulations with suitable organoleptic properties. The aim of the study was to evaluate the taste masking effectiveness of Smartseal 30D and ReadyMix on a range of bitter drug substances such as diphenhydramine HCl (DPD), ibuprofen lysine (IBU-LS), and phenylephrine HCl (PPH) for the development of paediatric dosage forms. The drugs were microencapsulated in the polymer carriers at 10-20% loadings using spray-drying processing. Spray drying of drug formulations was optimized in terms of percent yield and encapsulation efficiency followed by physicochemical characterization in order to identify the drugs' physical state in the polymer microparticles. The in vivo taste masking efficiency was evaluated using human test panel and showed noticeable reduction of drug's bitterness at all loadings in comparison to the bulk substances.

Bioconjugated solid lipid nanoparticles (SLNs) for targeted prostate cancer therapy.

Prostate cancer is one of the prominent causes of cancer mortality in men all over the world and a challenge to treat. In this study, transferrin (Tf) bioconjugated solid lipid nanoparticles (SLNs) were developed and loaded with curcumin (CRC) for active targeting of prostate cancer cells. Curcumin is an anticancer agent, but its clinical applications are impeded due to the poor water solubility and bioavailability. Prepared blank Tf-SLNs showed minimal cytotoxicity while Tf-CRC-SLNs demonstrated significant in-vitro anti-proliferative activity compared to CRC-SLNs alone. Cellular uptake of Tf-CRC-SLNs were found to be significantly higher (p < 0.05/=0.01) compared to unconjugated SLNs or pure drug alone. Bioconjugated Tf-CRC-SLNs also showed improved early apoptotic and late apoptotic or early necrotic populations (6.4% and 88.9% respectively) to CRC-SLNs and CRC solution. Most importantly, in-vivo studies with Tf-CRC-SLNs in mice bearing prostate cancer revealed significant tumour regression (392.64 mm3 after 4 weeks, p < 0.001) compared to the control group. The findings of this work encourage future investigations and further in-vivo clinical studies on the potential of bioconjugated SLNs for cancer cure.

An investigation into the formations of the internal microstructures of solid dispersions prepared by hot melt extrusion.

Hot melt extrusion (HME) is a widely used manufacturing process for pharmaceutical solid dispersions. The complexity of the HME formulations and the number of excipients used in the process are increasing with the advancement of the relevant knowledge. However, one of the areas that is still significantly lacking understanding is the control of internal microstructure of extrudates. Internal microstructure, consisting of voids, in hot melt extruded amorphous solid dispersions is often observed without the causes having been systemically investigated in the literature. In this study, we investigated a range of factors that demonstrated their impacts on the formation of the voids. These include the effect of the types of the materials (i.e. drug, polymer and additive) used in the formulation, the quantity of the drug and the additives used, the key extrusion processing parameters, the type of extruder, and the drying of the raw materials prior to extrusion. The results indicate that the appropriate viscosity and the presence of phase-separated particulates are essential for the formation of the voids. The particulates act as nuclei for the entrapped gas bubbles and the viscosity of the mixture during extrusion governs the collapse/escape of the bubbles. To minimise void formation, the results of this study indicate that slow screw speed, low moisture content of the raw materials, fewer particulates and the addition of lubricants, such as low melting lipid excipients, could be beneficial. This study systematically examines the mechanism of void formation in HME extrudates and generates new strategies that can be used to manage such void formations.