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Reversible addition-fragmentation chain transfer (RAFT)-mediated dispersion polymerization induced self-assembly (PISA) of boronic acid (BA)-substituted acrylamides is established. The first PISA on unprotected BA-substituted monomer yields spherical nanoparticles (NPs) that undergo room-temperature transitions to higher order morphologies upon dilution with the dispersion solvent. PISA with the BA pinacol ester-derivative yields spherical NPs, worms, and vesicles.

Ceramic materials are increasingly used in micro-electro-mechanical systems (MEMS) as they offer many advantages such as high-temperature resistance, high wear resistance, low density, and favourable mechanical and chemical properties at elevated temperature. However, with the emerging of additive manufacturing, the use of ceramics for functional and structural MEMS raises new opportunities and challenges. This paper provides an extensive review of the manufacturing processes used for ceramic-based MEMS, including additive and conventional manufacturing technologies. The review covers the micro-fabrication techniques of ceramics with the focus on their operating principles, main features, and processed materials. Challenges that need to be addressed in applying additive technologies in MEMS include ceramic printing on wafers, post-processing at the micro-level, resolution, and quality control. The paper also sheds light on the new possibilities of ceramic additive micro-fabrication and their potential applications, which indicates a promising future.

Since the FDA approval of Spritam, there has been a growing interest in the application of 3D printing in pharmaceutical science. 3D printing is a method of manufacturing involving the layer-by-layer deposition of materials to create a final product according to a digital model. There are various techniques used to achieve this method of printing including the SLS, SLA, FDM, SSE and PB-inkjet printing. In biomanufacturing, bone and tissue engineering involving 3D printing to create scaffolds, while in pharmaceutics, 3D printing was applied in drug development, and the fabrication of drug delivery devices. This paper aims to review the use of some 3D printing techniques in the fabrication of oral solid dosage forms. FDM, SLA SLS, and PB-Inkjet printing processes were found suitable for the fabrication of oral solid dosage forms, though a great deal of the available research was focused on fused deposition modelling due to its availability and flexibility. Process parameters as well as strategies to control the characteristics of printed dosage forms are analysed and discussed. The review also presents the advantages and possible limitations of 3D printing of medicines.

The study aimed to develop two types of dry powder inhaler (DPI) formulations containing glucagon-like peptide-1(7-36) amide (GLP-1): carrier-free (drug alone, no excipients) and carrier-based DPI formulations for pulmonary delivery of GLP-1. This is the first study focusing on the development of excipient free GLP-1 DPI formulations for inhaled therapy in Type 2 diabetes. The aerosolisation performance of both DPI formulations was studied using a next generation impactor and a DPI device (Handihaler®) at flow rate of 30 L min

Background Diabetes is a widely spread chronic disease affecting about 463 million people in 2019. It is defined as chronic hyperglycemia caused by either an impaired action or an abnormal secretion of insulin. New diabetes medications based on glucose-sensitive delivery systems can offer better control of blood glucose levels without the need to worry about the patient diet control or the frequency of exercising. Such delivery systems are comprised of glucose-sensitive moieties such as glucose oxidase, Phenylboronic acid derivatives and Concanavalin A. These systems can be administered via different routes such as subcutaneous injections, implants, oral, transdermal and nasal. This systematic review discussed the most suitable insulin delivery system in terms of efficiency to maintain blood glucose levels in normal range, and safety in animals upon administration. Method The search was conducted using different databases such as Web of Knowledge, Pubmed, Europe PMC, Wiley Online Library, and Science direct. Results A total of 313 studies were collected and 64 studies were included after screening using inclusion and exclusion criteria based on PICOS model. The results indicated that subcutaneous implants incorporated with glucose oxidase are the most suitable and were able to maintain normal blood glucose for up to 1738 h with a single administration. This was followed by PBA intraperitoneal implant, then oral GOx. Toxicity studies were conducted for all these dosage forms indicating good biocompatibility. Conclusion The GOx subcutaneous implant was found to be the most efficient and safe insulin delivery systems offering prolonged control of glucose in diabetic patients.

Versão submetida é uma versão do autor antes de formatada pela revista. Pode ser depositada em repositório institucional. Feedback on student work is a key mechanism for improving learning in Higher Education (HE) and can be provided in a variety of forms. Recently, many institutions have moved to the provision of electronic feedback, although evidence for the effectiveness of this is mixed. While many studies evaluating the students’ perception of feedback are now available, there is little evidence of contrasting perceptions of its value according to different disciplines. This work aims to evaluate the relationship between students’ expectations and perception of feedback, especially electronic, and the disciplinary area of study in HE. Students (n=1017) across different courses from a post-1992 university in the UK were surveyed and categorized into five disciplinary clusters: Science, Technology, Engineering and Mathematics; Business and Accounting; Art and Design; Media and Languages; and Psychology and Social Care. Perceived relevance as well as the most pertinent features and expectations of the quality of electronic feedback for students varies according to disciplinary cluster and thus closely aligns with a specific cluster’s learning and teaching practices. The findings of this study may help institutions to reflect on the role of electronic feedback as part of their ongoing assessment practice and how teaching in the different disciplines may result in different understandings of the value of electronic feedback. info:eu-repo/semantics/publishedVersion

Quantitative analysis using proton NMR (1H qNMR) has been employed in various areas such as pharmaceutical analysis (e.g., dissolution study), vaccines, natural products analysis, metabolites, and macrolide antibiotics in agriculture industry. However, it is not routinely used in the quantification of saccharides in dry powder inhaler (DPI) formulations. The aim of this study was to develop a 1H NMR method for the quantification of saccharides employed in DPI formulations. Dry powders as DPI carriers were prepared by spray drying (SD) and spray freeze drying (SFD) using three saccharides: namely D-mannitol, D-sorbitol and D-(+)-sucrose. The calibration curves constructed for all three saccharides demonstrated linearity with R2 value of 1. The 1H qNMR method produced accurate (relative error %: 0.184–3.697) and precise data with high repeatability (RSD %: 0.517–3.126) within the calibration curve concentration range. The 1H qNMR method also demonstrated significant sensitivity with low values of limit of detection (0.058 mM for D-mannitol, 0.045 mM for D-(+)-sucrose, and 0.056 mM for D-sorbitol) and limit of quantitation (0.175 mM for D-mannitol, 0.135 mM for D-(+)-sucrose, and 0.168 mM for D-sorbitol). Pulmonary deposition via impaction experiments of the three saccharides was quantified using the developed method. It was found that SFD D-mannitol (68.99%) and SFD D-(+)-sucrose (66.62%) exhibited better delivered dose (total saccharide deposition in throat and all impactor stages) than SD D-mannitol (49.03%) and SD D-(+)-sucrose (57.70%) (p

Intensive self-monitoring of blood glucose levels by patients with diabetes achieves optimal glucose control, hence reducing the likelihood of complications.This is a prospective, cross-sectional study targeting adults with diabetes through community pharmacies and patient groups in Central and West London over a period of 10 weeks.In all, 195 adults with diabetes were included in the analysis of the results. When monitoring adherence was examined, 43.4% (n=33/76) of participants with type 1 diabetes reported that their health care professionals had asked them to monitor their blood glucose levels between 3 and 4 times per day; however, 10% of this group was not following their health-care professionals' directions. Participants with type 2 diabetes were asked the same question; 42.9% (n=51/119) were asked to monitor their blood glucose between 3 and 4 times a day, but only 2.5% (n=3/119) were following their health-care professionals' directions. When questioned about their reasons for poor adherence, the cohort indicated that it was due to the painful (29.2%, n=57/195), uncomfortable (33.8%, n=66/195) or inconvenient (36.9%, n=72/195) nature of testing. In addition, 75.3% (n=147/195) of the participants expressed their desire for a noninvasive monitoring device, and 74.3% (n=145/195) said they would be satisfied to use one of the preselected advanced technologies to monitor their blood glucose levels.The favoured advanced technology, selected by 49.7% (n=97/195) of participants, was the wristband. Statistical significance was seen between the type of diabetes and the device selected; patients with type 1 diabetes preferred contact lenses (p0.05) and tattoos (p0.0001), whereas participants with type 2 diabetes preferred earlobe sensors (p0.0001) and saliva analyzers (p0.0001). Participants' gender, age and ethnicity also influenced device selection.

This review intends to act as an overview of fructose malabsorption (FM) and its role in the aetiology of diseases including, but not limited to, irritable bowel syndrome (IBS) and infantile colic and the relationship between fructose absorption and the propagation of some cancers. IBS results in a variety of symptoms including stomach pains, cramps and bloating. Patients can be categorised into two groups, depending on whether the patients’ experiences either constipation (IBS-C) or diarrhoea (IBS-D). FM has been proposed as a potential cause of IBS-D and other diseases, such as infantile colic. However, our knowledge of FM is limited by our understanding of the biochemistry related to the absorption of fructose in the small intestine and FM’s relationship with small intestinal bacterial overgrowth. It is important to consider the dietary effects on FM and most importantly, the quantity of excess free fructose consumed. The diagnosis of FM is difficult and often requires indirect means that may result in false positives. Current treatments of FM include dietary intervention, such as low fermentable oligo-, di-, monosaccharides and polyols diets and enzymatic treatments, such as the use of xylose isomerase. More research is needed to accurately diagnose and effectively treat FM. This review is designed with the goal of providing a detailed outline of the issues regarding the causes, diagnosis and treatment of FM.

Three-dimensional (3D) printing is a recent technology, which gives the possibility to manufacture personalised dosage forms and it has a broad range of applications. One of the most developed, it is the manufacture of oral solid dosage and the four 3DP techniques which have been more used for their manufacture are FDM, inkjet 3DP, SLA and SLS. This systematic review is carried out to statistically analyze the current 3DP techniques employed in manufacturing oral solid formulations and assess the recent trends of this new technology. The work has been organised into four steps, (1) screening of the articles, definition of the inclusion and exclusion criteria and classification of the articles in the two main groups (included/excluded); (2) quantification and characterisation of the included articles; (3) evaluation of the validity of data and data extraction process; (4) data analysis, discussion, and conclusion to define which technique offers the best properties to be applied in the manufacture of oral solid formulations. It has been observed that with SLS 3DP technique, all the characterisation tests required by the BP (drug content, drug dissolution profile, hardness, friability, disintegration time and uniformity of weight) have been performed in the majority of articles, except for the friability test. However, it is not possible to define which of the four 3DP techniques is the most suitable for the manufacture of oral solid formulations, because the selection is affected by different parameters, such as the type of formulation, the physical-mechanical properties to achieve. Moreover, each technique has its specific advantages and disadvantages, such as for FDM the biggest challenge is the degradation of the drug, due to high printing temperature process or for SLA is the toxicity of the carcinogenic risk of the photopolymerising material.

Various studies have explored potential therapeutic applications of capsaicin in human medicine, for example in pain, obesity, cancer, cardiovascular and respiratory disease. The aim of this scoping review was to identify and chart available evidence on therapeutic applications of capsaicin in humans using any mode of capsaicin delivery to treat conditions of the respiratory system.Electronic bibliographic databases (Web of Science, PubMed, Medline, ScienceDirect, Embase, Scopus) were searched from inception to 2021 to identify experimental studies reporting clinical outcomes of therapeutic applications of capsaicin. Studies with or without control group published in peer-reviewed journals were included. Animal studies, studies of human cell lines, and physiological proof of concept studies were excluded. Reviewer pairs independently double-screened 2799 search results for inclusion.Twenty-three original studies were included. Capsaicin has been investigated for the treatment of non-allergic rhinitis (n = 15), nasal polyposis (n = 3), allergic rhinitis (n = 2), unexplained chronic cough (n = 2), and prevention of aspiration pneumonia (n = 1). Modes of delivery included intranasal application (nasal spray, soaked pads, solution), inhalation, ingestion, and aural ointment. Seventeen studies reported positive effects of capsaicin on clinical outcomes for rhinitis, nasal polyposis, chronic cough, and pneumonia. Sixteen studies reported on the safety of capsaicin, with no reports of significant adverse events and overall fair to good patient acceptability.While the evidence identified in this review has limited implications for clinical practice, studies support the general safety of capsaicin as administered in these studies and highlight emerging strands of research and clinical hypotheses which warrant further examination.

Porous biomedical implants hold great potential in preventing stress shielding while improving bone osseointegration and regeneration. In this paper, a novel approach is introduced to control the porosity of 316L stainless steel implants by using canister-free hot isostatic pressing (CF-HIPing). The proposed approach uses cold isostatic pressing (CIPing) to generate powder compacts with various particle sizes, followed by CF-HIPing. 316L stainless steel samples with controlled porosity, and mechanical and biological properties were successfully achieved. The results showed a significant increase in the samples’ porosity with increasing powder size. Porous structures with a strength of 108–360 MPa, Vickers hardness of 25–49 HV and elastic modulus between 17 and 50 GPa were produced using a particle size range of 5–50 μm. The effect of samples with various porosities on the in vitro response of mouse pre-osteoblastic cells in terms of toxicity and proliferation was studied. All samples showed that they had a minimal toxic effect on the osteoblasts. Samples with low porosity, prepared using a particle size of 5 μm, were believed to hinder the transport of nutrients and oxygen to the cells and hence had lower proliferation. In addition, samples prepared using a particle size range of 16–50 μm were associated with an increased proliferation and are therefore expected to improve the rate of bone osseointegration.

Diabetes mellitus is one of the long-known chronic diseases. Today, over 400 million people have been diagnosed with diabetes, yet curing it is still a challenge. Over the decades, the approaches of treating diabetes mellitus have evolved and polymeric materials have played an integral part in developing and manufacturing anti-diabetic medications. However, injection of insulin remains a conventional therapy for the treatment of diabetes. Oral administration is generally the most preferred route; yet, physiological barriers lead to a challenge in the formulation development for oral delivery of antidiabetic peptide and protein drugs. This present review focuses on the role of different types of biodegradable polymers (e.g., synthetic and natural) that have been used to develop micro and nanoparticles based formulations for anti-diabetic drugs (Type 1 and Type 2) and how the various encapsulation strategies impact its therapeutic effect, including pharmacokinetics studies, drug release profiles, and efficacy of the encapsulated drugs. This review also includes studies of different dosage forms such as oral, nasal, inhalation, and sublingual for the treatment of diabetes that have been investigated using synthetic and natural biodegradable polymers in order to develop an alternative route to subcutaneous route for better control of serum glucose levels.

Despite following global guidelines to manage diabetes, inadequate blood glucose control is reported especially with oral hypoglycemics. This poses a major failure, leaving insulin as the only choice for several diabetic patients. Nonetheless, continuous use of subcutaneous insulin has led to poor compliance due to undesirable side effects. As a result, alternative approaches of insulin delivery were explored. Glucose-sensitive technology, a novel approach under extensive research, bears a promising future in diabetes management. It is based on natural and synthetic moieties which are able to sense glucose in their surroundings. In addition to glucose detection, these molecules also bind with glucose efficiently. In this chapter, three main glucose-sensitive moieties namely glucose oxidase, concanavalin A, and phenylboronic acid have been discussed in detail. In addition, this chapter summarizes the mechanism of action of three systems when incorporated into a formulation along with the advantages and limitations associated with their use.

In the cosmeceutical field, it is essential to develop topical delivery systems which would allow drugs to create a depot and permeate within the skin. The aim of the present study was to develop composite nanofibers of polyvinyl alcohol/quercetin/essential oils using the electrospinning technique, and assess their efficiency in acne alleviation. Quercetin was chosen due to its anti-inflammatory, anti-oxidant, and antibacterial activities. Nanofibers were characterized for their morphology, ex-vivo deposition/permeation, physical/mechanical integrity, thermal properties, and chemical characteristics. In addition, the anti-bacterial efficacy was tested on Propionibacterium acne (P. acne), and a cytotoxicity assay was carried out. Lastly, an experimental clinical trial was conducted on acne patients, where the percentage reduction of inflammatory, non-inflammatory and total acne lesions was taken as evaluation criterion. Results showed that quercetin was successfully loaded into the nanofibers which were homogenously dispersed. They showed a reasonable skin deposition percentage of 28.24% ± 0.012, a significantly higher antibacterial efficacy against Propionibacterium acne than quercetin alone, and were utterly safe on skin fibroblastic cells. Upon clinical examination on acne patients, the nanofibers showed 61.2%, 14.7%, and 52.9% reduction of inflammatory, comedonal, and total acne lesions respectively, suggesting a promising topical anti-acne delivery system.

There is an immense research interest to utilise contact lens (CLs) as a popular platform for ocular drug delivery. However, CLs are the major predisposing factors of bacterial keratitis which is commonly caused by adhesion of microbes such as Pseudomonas aeruginosa and Staphylococcus epidermidis. The aim of the current study is to explore the effect of surfactants; Poloxamer 188, Polysorbate 80 and Tetronic® 90R4 (at 0.25% - 3% v/v) on the characteristics of CLs and on the adhesion abilities of Pseudomonas aeruginosa to the lenses' surfaces. CLs were formulated using a hydrophilic monomer; 2-hydroxyethyl methacrylate (HEMA) together with silicone-based polymer such as Poly dimethyl siloxane (PDMS) or 3,3,3-trifluoropropylsilane (FSA) then lenses were polymerized under UV light. The formulated CLs with surfactants were found to have an increased equilibrium water content (EWC) due to hydrophilic moiety present in surfactants. A relationship was deduced between EWC and surface contact angle of lenses containing surfactants; where an increased EWC was associated with a decrease in contact angle reflecting a more hydrophilic surfaces of CLs. Apart from the 3% Polysorbate 80 (p < .0001) CLs, all other formulations had light transmission values over 80%. Lenses with surfactants were found to have lower bacterial ATP concentration than lenses without surfactants. Poloxamer 188 in FSA lenses reduced bacterial adhesion from 4.22 × 10-4 ± 1.30 × 10-4 pM to 1.03 × 10-4 ± 4.86 × 10-5 pM, a reduction by 75.59% when compared to the control lenses (p = .002). Moreover, 1% Tetronic® 90R4 in PDMS showed a reduction by 57.17% in ATP concentration. Polysorbate 80 in FSA exhibited the least bacterial adhesion with an average bacterial ATP concentration of 3.85 × 10-5 ± 2.61 × 10-5 pM; i.e 90.88% less bacterial ATP than control lenses (p = .001). Bioluminescence studies demonstrated a decrease in Pseudomonas aeruginosa adhesion to CLs containing surfactants without impairing the optical and mechanical characteristics of the lenses.

Dental implantation was introduced as a restorative procedure to reinstate the teeth functions and put the patient in normal contour, comfort, speech and health. Dental implants have been used over the centuries and the production techniques have been developed over the years. One of the advanced technologies is additive manufacturing (AM) which enables high degree of freedom ability to produce complex shaped and customized parts similar to human teeth. AM facilitates the production of complex geometric structure without the need of preparing expensive tools, hence it is more cost effective and time saving process. The current chapter provides an overview of AM as a promising technology for near net shape production of dental in preparing customised dental implants. The chapter also explore the anatomy and mechanical properties of human teeth together with the requirements for the design of teeth implants. The chapter survey the current AM technologies used for dental implant, clinical implications and highlights the future trend of AM in the development of near net shaped dental implants.

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. Electronic supplementary material The online version of this article (doi:10.1007/s13346-016-0338-3) contains supplementary material, which is available to authorized users.

Orally disintegrating tablets (ODTs) or orodispersible tablets are solid dosage forms that disintegrate within 3 minutes in the mouth into a paste that can be easily swallowed. ODTs have improved over the past years, in an attempt to produce a safe and efficient substitute to the conventional oral dosage forms, particularly for dysphagia patients. Since its introduction in the market in the 1980s, ODTs expanded rapidly and achieved revenues over $3 billion in 2006 and sustaining 20% annual growth. It is therefore evident that ODTs carry good commercial value, however there is potential for improvement. Current sustained-release technologies may be exploited and incorporated into an ODT to provide greater therapeutic value by reducing the need for multiple daily dosing regimens and improving patient adherence. A number of technologies such as polymer coated nanoparticles, stimuli-responsive polymers and ion-exchange resins have emerged to produce robust, sustained release orally disintegrating tablets (SR-ODT). The purpose of this review is to highlight these various approaches and techniques and how they have been utilised in an ODT formulation to extend differentiated line, market exclusivity and patent life. The review also explores future perspective and the potential challenges that SR-ODTs will face.

Oral modified-release multiparticulate dosage forms, which are also referred to as oral multiple-unit particulate systems, are becoming increasingly popular for oral drug delivery applications. The compaction of polymer-coated multiparticulates into tablets to produce a sustained-release dosage form is preferred over hard gelatin capsules. Moreover, multiparticulate tablets are a promising solution to chronic conditions, patients’ adherence, and swallowing difficulties if incorporated into orodispersible matrices. Nonetheless, the compaction of multiparticulates often damages the functional polymer coat, which results in a rapid release of the drug substance and the subsequent loss of sustained-release properties. This review brings to the forefront key formulation variables that are likely to influence the compaction of coated multiparticulates into sustained-release tablets. It focusses on the tabletting of coated drug-loaded pellets, microparticles, and nanoparticles with a designated section on each. Furthermore, it explores the various approaches that are used to evaluate the compaction behaviour of particulate systems.

The bacterial species Neisseria gonorrhoeae (N. gonorrhoeae) and Staphylococcus aureus (S. aureus) are amongst the main microorganisms that cause ophthalmia neonatorum. The current treatment involves the use of various antibiotics such as ciprofloxacin, cephalosporin, ceftriaxone and cefotaxime. However, this treatment strategy is becoming more ineffective due to the antibiotic resistance in N. gonorrhoeae. The current study explores the potential use of fatty acid based microemulsions (ME) to prevent N. gonorrhoeae and S. aureus infections in new-borns’ eyes without harmful side effects such as corneal or conjunctiva irritation. Pseudo-ternary phase diagrams were constructed to evaluate microemulsion regions and six different α-linolenic acid based microemulsions were prepared. The prepared formulations were characterized for α-linolenic acid content, size, transparency, zeta potential, Polarized light Microscopy, antimicrobial activity and ex vivo ocular toxicity. The mean droplet size of the ME formulations was in the range of 190.4 to 350.5 nm and polydispersity index (PDI) values were in the range of 0.102 to 0.561. All formulations were found stable upon storage for at least 8 weeks. In addition, self-diffusion coefficients determined by nuclear magnetic resonance (NMR) reflected that the diffusability of water increased at higher than 30% w/w water, while that of fatty acids and surfactants was in reverse. The antimicrobial efficacy of microemulsions was determined against N. gonorrhoeae and S. aureus. It was concluded that all microemulsions have strong antimicrobial effects against N. gonorrhoeae and S. aureus. Finally, bovine corneal opacity permeability (BCOP) and hen’s egg chorioallantoic (HET-CAM) tests results showed that all microemulsion formulations were not strong ocular irritants.

Orally dispersing tablets (ODTs), also known as orodispersibles, were first introduced into the market in 1980s to overcome dysphagia problems amongst pediatrics and geriatrics. Despite their abilities to avoid swallowing difficulties, frequency of dosing stood as a barrier for these formulations. The aim of the current study is to produce and optimize a sustained release orally disintegrating tablets (SR-ODT), with the aid of chitosan. A design of experiment (DoE) was first performed using Minitab to determine the effect of five independent variables on three dependent responses when producing the nanoparticles using ionotopic gelation. The variables studied were (tripolyphosphate concentration TPP, chitosan concentration CS, acetic acid concentration, chitosan: tripolyphosphate ratios and stirring time) and the responses were (particle size, surface charge and encapsulation efficiency). A formulation with optimum particle size, surface charge and encapsulation efficiency was prepared and further coated with polyvinylpyrolidine (PVP), polyethylene glycol (PEG) and polyethylene co-acrylic acid (PEAA). Minitab studies revealed that the nanoparticles' particle size was affected by most of the independent variables except stirring time and the ratios of CS to TPP. The optimized nanoparticles showed particle size of 153.8±14nm, surface charge of 31.4±0.9mV and encapsulation efficiency of 99.7±0.06%. The DSC showed that PMZ was solubilized within chitosan nanoparticle, whereas SEM images indicated that all the samples were spherical in shape with smooth surface and had similar size to that measured by DLS. After coating and dispersing into the tablets' matrices, the tablets were evaluated to determine their friability, disintegration time and tensile strength. All tablets were at an appropriate friability (less than 1%) and had tensile strength above 2.5N/mm(2). Besides, all the tablets managed to disintegrate within 40s whilst sustaining the drug release over 24h.

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 = 28.01 MPa). Therefore, ARG as filler to IND tablets was associated with better mechanical properties of the tablets (tablet tensile strength (r) increased from 0.2 ± 0.05 N/mm2 to 2.85 ± 0.36 N/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 (r) 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.

The fast development in materials science has resulted in the emergence of new pharmaceutical materials with superior physical and mechanical properties. Low-substituted hydroxypropyl cellulose is an ether derivative of cellulose and is praised for its multi-functionality as a binder, disintegrant, film coating agent and as a suitable material for medical dressings. Nevertheless, very little is known about the compaction behaviour of this polymer. The aim of the current study was to evaluate the compaction and disintegration behaviour of four grades of L-HPC namely; LH32, LH21, LH11, and LHB1. The macrometric properties of the four powders were studied and the compaction behaviour was evaluated using the out-of-die method. LH11 and LH22 showed poor flow properties as the powders were dominated by fibrous particles with high aspect ratios, which reduced the powder flow. LH32 showed a weak compressibility profile and demonstrated a large elastic region, making it harder for this polymer to deform plastically. These findings are supported by AFM which revealed the high roughness of LH32 powder (100.09 ± 18.84 nm), resulting in small area of contact, but promoting mechanical interlocking. On the contrary, LH21 and LH11 powders had smooth surfaces which enabled larger contact area and higher adhesion forces of 21.01 ± 11.35 nN and 9.50 ± 5.78 nN, respectively. This promoted bond formation during compression as LH21 and LH11 powders had low strength yield.

In this study, solid dispersions of prednisolone (PRD) and bovine serum albumin (BSA) were prepared by spray drying and freeze drying methods using a PRD:BSA solution [20:1 molar ratio (MR)]. PRD-BSA dispersed mixtures were characterized by scanning electron microscopy (SEM), and powder X-ray diffraction (XRD), and differential scanning calorimetry (DSC). PRD-BSA physical and dispersed mixtures showed significantly higher solubility in water than that of unprocessed drug. Enhancement factor of six was obtained in both physical mixture and solid dispersion solubility studies. In-vitro dissolution and release studies under physiological conditions showed an immediate release of PRD from the solid dispersions, with almost 90% of the drug dissolved in the first 10 min. PRD was immediately released from BSA binding complex. This study demonstrates the potential for the use of BSA to enhance the solubility and dissolution rate, hence bioavailability, of the unionizable drugs.

In spite of significant improvements in micro-replication techniques, methods to fabricate well-defined net shape microstructures are still in a developing stage. Soft lithography has the capability to manufacture complex micro- and nanostructures. Although it is considered a robust technique, a major limitation is related to the distortion encountered in the fabricated structures during the drying process. In the present work, a manufacturing technology has been developed that emerges the benefits of soft lithography and micro-electrical discharge machining (μ-EDM) to produce stainless steel precise micro-components for micro-implantable devices. The micro-parts produced by soft lithography were subsequently surface processed via μ-EDM in order to improve the surface quality. In addition to this, it was found that μ-EDM drastically improved the surface roughness of stainless steel micro-components from Ra = 3.4 μm to Ra = 0.43 μm.

Unlike materials subtractive technologies, additive manufacturing (AM) works on producing near-net-shape components according to a specific design at which the synthesis is achieved layer by layer. Additive manufacturing allows design freedom, making design-driven manufacturing a reality. However, its poor surface quality is considered as one of the key challenges that are worth to overcome. The main objective of this chapter is to report a comprehensive overview of the techniques used to improve the surface finish and their advancements of products made by metal additive manufacturing (AM) technologies and to highlight experimental processes and data. Powder bed fusion (PBF) and direct laser deposition (DLD) are the main processes covered in this review. The chapter starts with the literature review and introduction to the main metal AM processes and their surface roughness limitations, the effect of their parameters and the effect of the laser re-melting on the surface quality. Next, it is followed by a number of surface finishing techniques such as laser polishing, chemical and electropolishing. Experimental results of post-surface finishing of AM parts by microelectrical discharge machining are also presented.

Assessment of oral drug bioavailability is an important parameter for new chemical entities (NCEs) in drug development cycle. After evaluating the pharmacological response of these new molecules, the following critical stage is to investigate their in vitro permeability. Despite the great success achieved by prodrugs, covalent linking the drug molecule with a hydrophobic moiety might result in a new entity that might be toxic or ineffective. Therefore, an alternative that would improve the drug uptake without affecting the efficacy of the drug molecule would be advantageous. The aim of the current study is to investigate the effect of ion-pairing on the permeability profile of a model drug: indomethacin (IND) to understand the mechanism behind the permeability improvement across Caco-2 monolayers. Arginine and lysine formed ion-pairs with IND at various molar ratios 1:1, 1:2, 1:4 and 1:8 as reflected by the double reciprocal graphs. The partitioning capacities of the IND were evaluated using octanol/water partitioning studies and the apparent permeabilities (P app) were measured across Caco-2 monolayers for the different formulations. Partitioning studies reflected the high hydrophobicity of IND (Log P = 3) which dropped upon increasing the concentrations of arginine/lysine in the ion pairs. Nevertheless, the prepared ion pairs improved IND permeability especially after 60 min of the start of the experiment. Coupling partitioning and permeability results suggest a decrease in the passive transcellular uptake due to the drop in IND portioning capacities and a possible involvement of active carriers. Future work will investigate which transport gene might be involved in the absorption of the ion paired formulations using molecular biology technologies. © 2014 Elsevier B.V. All rights reserved.

The aim of this study was to investigate the use of bovine serum albumin (BSA) as a solubility enhancer for indometacin (IND) as a model drug. IND-BSA solid dispersions were prepared by both spray drying and freeze drying techniques using IND:BSA solution (20:1 Molar Ratio (MR)) and IND:BSA suspension (100:1 MR). The solid state of IND in solid dispersions was characterised by SEM, DSC and XRD. The aqueous solubility of IND in the presence of increased amounts of BSA was evaluated. Additionally, IND dissolution and release profiles were evaluated. IND in solid dispersions with BSA showed significantly higher solubility in water than that of the physical mixture of both. Enhancement factors of 24,000 and 100,000 were obtained for the solid dispersion formulated in 20:1 MR and 100:1 MR, respectively. Dissolution studies in-vitro indicated a significant increase in the dissolution rate of IND from solid dispersions compared to that of the free drug, with almost 95% of the drug dissolved in the first 5 min. Furthermore, an immediate release of IND from BSA solid dispersions was shown. The potential use of albumin as solubility enhancer for poorly soluble drugs, particularly, for immediate release volume-limited dosage forms is reported.

Background 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. Methods Six months qualitative evaluation study. Participants included two PhD, five Master, and two undergraduate students (level 6) from the School of Pharmacy at a British University. Participants were asked to interact face-to-face and online using Diigo as a virtual learning environment to share and discuss problems and questions related to their on-going work, including the finding of research articles. Qualitative data were gathered from two focus groups and an in-depth thematic analysis of the online interactions was carried out. Results All participants at undergraduate and Master level felt that their learning experience was boosted by the sharing of knowledge and resources. Closer look at the data reveal that most of the production and interactions were made by the largest group (i.e., Master students). This group believed that Diigo helped them in building up their research knowledge by sharing information online, which also enriched their face-to-face (f2f) discussions. In contrast, PhD students felt that the CoP did not significantly help them to develop their knowledge. Conclusions The development of a small CoP helps students to gain knowledge and improves their research productivity by sharing experience and skills. The CoP was effectively supported by Diigo, which provided a good platform for data’ sharing and a culture of collaboration. The CoP had an overall positive impact on the students’ learning experience and research.

Drug resistance was first identified in cancer cells that express proteins known as multidrug resistance proteins that extrude the therapeutic agents out of the cells resulting in alteration of pharmacokinetics, tissue distribution, and pharmacodynamics of drugs. To this end studies were carried out to investigate the role of pharmacological inhibitors and pharmaceutical excipients with a primary focus on P-glycoprotein (P-gp). The aim of this study was to investigate holistic changes in transporter gene expression during permeability upon formulation of indomethacin as solid dispersion. Initial characterization studies of solid dispersion of indomethacin showed that the drug was dispersed within the carrier in amorphous form. Analysis of permeability data across Caco-2 monolayers revealed that drug absorption increased by 4-fold when reformulated as solid dispersion. The last phase of the work involved investigation of gene expression changes of transporter genes during permeability. The results showed that there were significant differences in the expression of both ATP-binding cassette (ABC) transporter genes as well as solute carrier transporter (SLC) genes suggesting that the inclusion of polyethylene glycol as well as changes in molecular form of drug from crystalline to amorphous have a significant bearing on the expression of transporter network genes resulting in differences in drug permeability. © 2011 Informa UK, Ltd.

Orally disintegrating tablets (ODTs) offer many advantages over the conventional oral dosage forms in terms of convenience and ease of use. Over the last decade, substantial advances in the formulation of ODTs have been achieved in academia and industry that resulted in the emerging of a large number of patents. The aim of this review is to summarise the most recent patents in ODT formulations and highlight their motivations, inventive steps and significances in the development of ODT formulations. Five major techniques have been applied in manufacturing of ODTs, namely conventional tablet press, moulding, freeze drying, tablet loading and pulverization, with majority of the patents dedicated to the use of conventional tablet pressing. The patents have addressed various issues concerning the manufacturing of robust and practical ODT formulations by disclosing new manufacturing techniques, advantageous materials, and innovative formulation steps. However, future developments are required to reduce the cost and widening the application of the new manufacturing techniques, while simplifying and shortening the formulation steps will be crucial in the well established ones.