Amino acids in oral drug delivery:salts, ion-pairs and transcriptomics

Oral drug delivery is considered the most popular route of delivery because of the ease of administration, availability of a wide range of dosage forms and the large surface area for drug absorption via the intestinal membrane. However, besides the unfavourable biopharmaceutical properties of the therapeutic agents, efflux transporters such as Pglycoprotein (P-gp) and multiple resistance proteins (MRP) decrease the overall drug uptake by extruding the drug from the cells. Although, prodrugs have been investigated to improve drug partitioning by masking the polar groups covalently with pre-moieties promoting increased uptake, they present significant challenges including reduced solubility and increased toxicity. The current work investigates the use of amino acids as ion-pairs for three model drugs: indomethacin (weak acid), trimethoprim (weak base) and ciprofloxacin (zwitter ion) in an attempt to improve both solubility and uptake. Solubility was studied by salt formation while creating new routes for uptake across the membranes via amino acids transporter proteins or dipeptidyl transporters was the rationale to enhance absorption. New salts were prepared for the model drugs and the oppositely charged amino acids by freeze drying and they were characterised using FTIR, 1HNMR, DSC, SEM, pH solubility profile, solubility and dissolution. Permeability profiles were assessed using an in vitro cell based method; Caco-2 cells and the genetic changes occurring across the transporter genes and various pathways involved in the cellular activities were studied using DNA microarrays. Solubility data showed a significant increase in drug solubility upon preparing the new salts with the oppositely charged counter ions (ciprofloxacin glutamate salt exhibiting 2.9x103 fold enhancement when compared to the free drug). Moreover, permeability studies showed a 3 fold increase in trimethoprim and indomethacin permeabilities upon ion-pairing with amino acids and more than 10 fold when the zwitter ionic drug was paired with glutamic acid. Microarray data revealed that trimethoprim was absorbed actively via OCTN1 transporters while MRP7 is the main transporter gene that mediates its efflux. The absorption of trimethoprim from trimethoprim glutamic acid ion-paired formulations was affected by the ratio of glutamic acid in the formulation which was inversely proportional to the degree of expression of OCTN1. Interestingly, ciprofloxacin glutamic acid ion-pairs were found to decrease the up-regulation of ciprofloxacin efflux proteins (P-gp and MRP4) and over-express two solute carrier transporters; (PEPT2 and SLCO1A2) suggesting that a high aqueous binding constant (K11aq) enables the ion-paired formulations to be absorbed as one entity. In conclusion, formation of ion-pairs with amino acids can influence in a positive way solubility, transfer and gene expression effects of drugs

Building a community of practice for engaging pharmacy students to learn in a collaborative research environment

Conventional research project supervision is not always compatible with current challenges facing Higher Education, such as students’ diverse backgrounds, increasing demands and multidisciplinary research interests. Additionally, research students may experience isolation at different stages of research. To help students coping with these challenges, approaches such as progress reports, departmental presentations and co-supervision have been introduced. Community of practices (CoP) are alternative approaches that if successfully adopted may improve the students’ learning experience. These communities were developed as knowledge-based social structures between groups of people sharing goals and interests. Considering the importance of CoPs as a strategy to engage students and researchers to work collaboratively; this study aims to investigate the impact of a formal CoP on the students’ learning experience at different levels of study

Nano-engineering chitosan particles to sustain the release of promethazine from orodispersables

The acceleration of solid dosage form product development can be facilitated by the inclusion of excipients that exhibit poly-/multi-functionality with reduction of the time invested in multiple excipient optimisations. Because active pharmaceutical ingredients (APIs) and tablet excipients present diverse densification behaviours upon compaction, the involvement of these different powders during compaction makes the compaction process very complicated. The aim of this study was to assess the macrometric characteristics and distribution of surface charges of two powders: indomethacin (IND) and arginine (ARG); and evaluate their impact on the densification properties of the two powders. Response surface modelling (RSM) was employed to predict the effect of two independent variables; Compression pressure (F) and ARG percentage (R) in binary mixtures on the properties of resultant tablets. The study looked at three responses namely; porosity (P), tensile strength (S) and disintegration time (T). Micrometric studies showed that IND had a higher charge density (net charge to mass ratio) when compared to ARG; nonetheless, ARG demonstrated good compaction properties with high plasticity (Y=28.01MPa). Therefore, ARG as filler to IND tablets was associated with better mechanical properties of the tablets (tablet tensile strength (σ) increased from 0.2±0.05N/mm2 to 2.85±0.36N/mm2 upon adding ARG at molar ratio of 8:1 to IND). Moreover, tablets' disintegration time was shortened to reach few seconds in some of the formulations. RSM revealed tablet porosity to be affected by both compression pressure and ARG ratio for IND/ARG physical mixtures (PMs). Conversely, the tensile strength (σ) and disintegration time (T) for the PMs were influenced by the compression pressure, ARG ratio and their interactive term (FR); and a strong correlation was observed between the experimental results and the predicted data for tablet porosity. This work provides clear evidence of the multi-functionality of ARG as filler, binder and disintegrant for directly compressed tablets

Microfabrication of net shape zirconia/alumina nanocomposite micro parts

Recently, there are growing demands in manufacturing of net shape micro parts for wide range of applications due to the increasing interest in miniaturization. In this paper, the fabrication of tetragonal phase zirconia/alumina (YSZ/Al2O3) nanocomposite micro-parts with high quality is presented. The fabrication process is based on soft lithography and colloidal powder dispersion. Experimental results showed that by optimizing the soft lithography and the dispersion process, it was possible to produce high-resolution micro-parts with well dispersed alumina. The X-ray diffraction results had confirmed the important role of the alumina particles in eliminating the emergence of monoclinic phase while the microstructures reveal a pure tetragonal phase. In addition, the sintered YSZ/Al2O3 micro parts achieved micro hardness with 20% superior to the pure YSZ sintered micro-parts with the addition of 5% alumina

Pharmaceutical excipients and drug metabolism : a mini-review

Conclusions from previously reported articles have revealed that many commonly used pharmaceutical excipients, known to be pharmacologically inert, show effects on drug transporters and/or metabolic enzymes. Thus, the pharmacokinetics (absorption, distribution, metabolism and elimination) of active pharmaceutical ingredients are possibly altered because of their transport and metabolism modulation from the incorporated excipients. The aim of this review is to present studies on the interaction of various commonly-used excipients on pre-systemic metabolism by CYP450 enzymes. Excipients such as surfactants, polymers, fatty acids and solvents are discussed. Based on all the reported outcomes, the most potent inhibitors were found to be surfactants and the least effective were organic solvents. However, there are many factors that can influence the inhibition of CYP450, for instance type of excipient, concentration of excipient, type of CYP450 isoenzyme, incubation condition etc. Such evidence will be very useful in dosage form design, so that the right formulation can be designed to maximize drug bioavailability, especially for poorly bioavailable drugs

Effect of non-cross-linked calcium on characteristics, swelling, drug release and mucoadhesion of calcium alginate beads

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Investigation of efficient adsorbents using transient analysis of adsorption chillers with Simulink

With the availability of waste heat from various power stations and industrial processes, adsorption cooling systems offer advantages compared to mechanical vapour compression systems. The dynamic modelling of such system is very important as it predicts the system performance with time in terms of bed temperature, pressure, cooling capacity and coefficient of performance. Therefore there is a need for a robust simulation platform that can be used to predict the system dynamic performance under various operating conditions and accommodate design changes efficiently. This work exploits Simulink software capabilities to develop such simulation platform and investigate the effects of using different adsorbent materials and cycle times on cooling capacity and coefficient of performance. Results showed that such platform is very effective in comparative studies. Results showed that water/silica gel produce more cooling capacity compared to ethanol/activated carbon adsorbents at short cycle time, while Maxsorb has better performance at longer cycle time as its cooling capacity increases with adsorption time

Fatty acid microemulsion for the treatment of neonatal conjunctivitis : quantification, characterisation and evaluation of antimicrobial activity

Fatty acids (FAs) are used by many organisms as defence mechanism against virulent bacteria. The high safety profile and broad spectrum of activity make them potential alternatives to currently used topical antibiotics for the treatment of eye infections in neonates. The current study utilised a Design of Experiment approach to optimise the quantification of five fatty acids namely; lauric acid, tridecanoic acid, myristoleic acid, palmitoleic acid and α-linolenic acid. The significance of the influence of the experimental parameters such as volume of catalyst, volume of n-hexane, incubation temperature, incubation time and the number of extraction steps on derivatisation was established by statistical screening with a factorial approach. Derivatisation was confirmed using attenuated total reflectance infrared (ATR) and 1H NMR spectrum. A gas chromatographic method (GC-FID) was developed and validated according to ICH guidelines for the identification and quantification of fatty acids. The results were found to be linear over the concentration range studied with coefficient of variation greater than 0.99 and high recovery values and low intra-day and inter-day variation values for all FAs. Then, different α-linolenic acid-based microemulsions (MEs) were prepared using Tween 80 as surfactant, polyethylene glycol 400 (PEG 400) as co surfactant and water as aqueous phase. The developed GC method was used to quantify the FA content in ME formulations. The results indicated that the developed GC method is very effective to quantify the FA content in the ME formulations. The antimicrobial efficacy of FA-based MEs were tested against Staphylococcus aureus. It was concluded that the FA-based MEs have strong antimicrobial effect against S. aureus

Thermal energy storage using metal–organic framework materials

Metal–organic framework (MOF) materials are new adsorbent materials that have high surface area and pore volume and hence high adsorption uptake. The previous exceptional properties make this class of materials have a great potential in many applications like cooling, gas separation and energy storage. However, there is very limited information on the performance of metal–organic framework materials in energy storage applications and their performance compared to conventional adsorbents. This paper aims to present an experimental characterisation of CPO-27(Ni) MOF material for water adsorption and to investigate its viability for energy storage. CPO-27(Ni) (known as MOF-74(Ni)), which is a MOF material that has high water adsorption capabilities of 0.47 gH2O gads−1 and hydrothermally stable and can be supplied in large quantities. Firstly, the material water adsorption isotherms were predicated using Materials Studio software via the material structure information and then compared to the experimentally measured isotherms. The experimentally measured isotherms and kinetics were used to model a double bed adsorption system for energy storage application using Simulink–Matlab software coupled with Nist RefProp thermophysical routines. Finally, the performance of CPO-27(Ni) was then compared with silica gel. The CPO-27(Ni) was found to outperform silica gel at long half cycle time (more than 30 min) at low evaporating temperature making it suitable for energy storage applications. The energy stored in the condenser and the adsorption bed was found to be dependent mostly on the regeneration and the cooling temperatures. The potential of the energy recovered from the adsorption bed can be double the one recovered from the condenser. Also, the energy recovery during condensation and adsorption was found to be independent of the reactor conductance except at small conductance ratio. Finally, the adsorption unit cooling water flow strategy was found to affect the amount of the energy recovered as recirculating the cooling water through the adsorption bed and then condenser was found to decrease the recovered energy from the condenser by 4%