Applications of AFM in pharmaceutical sciences

Atomic force microscopy (AFM) is a high-resolution imaging technique that uses a small probe (tip and cantilever) to provide topographical information on surfaces in air or in liquid media. By pushing the tip into the surface or by pulling it away, nanomechanical data such as compliance (stiffness, Young’s Modulus) or adhesion, respectively, may be obtained and can also be presented visually in the form of maps displayed alongside topography images. This chapter outlines the principles of operation of AFM, describing some of the important imaging modes and then focuses on the use of the technique for pharmaceutical research. Areas include tablet coating and dissolution, crystal growth and polymorphism, particles and fibres, nanomedicine, nanotoxicology, drug-protein and protein-protein interactions, live cells, bacterial biofilms and viruses. Specific examples include mapping of ligand-receptor binding on cell surfaces, studies of protein-protein interactions to provide kinetic information and the potential of AFM to be used as an early diagnostic tool for cancer and other diseases. Many of these reported investigations are from 2011-2014, both from the literature and a few selected studies from the authors’ laboratories

Hot-melt extrusion (HME) formulations of Albendazole for increasing dissolution properties

Hot-Melt-Extrusion (HME) is a flexible process that uses high temperature and pressure conditions to pump raw materials such as an Active Pharmaceutical Ingredient (API) and a pharmaceutical grade polymer through a barrel. The material is conveyed and mixed using intermeshing co-rotating twin-screws and then pushed through a die to form a well-shaped strand. Due to the high mixing degree provided by the twin-screws, the drug is transformed from crystalline to amorphous form. The use of twin-screw extruders is currently being implemented within continuous manufacturing platforms (Crowley, 2007)

A novel hot-melt extrusion formulation of albendazole for increasing dissolution properties

The main aim of the research focused on the production of hot-melt extrusion (HME) formulations with increased dissolution properties of albendazole (ABZ). Therefore, HME was applied as a continuous manufacturing technique to produce amorphous solid dispersions of the poorly water soluble drug ABZ combined with the polymer matrix polyvinylpyrrolidone PVP K12. HME formulations of ABZ – PVP K12 comprised a drug content of 1%, 5% and 10% w/w. The main analytical characterisation techniques used were Scanning Electron Microscopy (SEM), Micro-computed Tomography (µ-CT), X-Ray Powder Diffraction (XRPD), Differential Scanning Calorimetry (DSC) and dissolution profile studies. The application of SEM, XRPD and DSC evidenced drug physical transformation from crystalline to amorphous state and therefore, the achievement of an amorphous solid dispersion. The introduction of a novel technique, µ-CT, to characterise the internal structure of these materials revealed key information regarding materials distribution and void content. Dissolution profile studies evidenced a high increase in drug release profile compared to pure ABZ. These promising results can lead to a great enhancement of the oral bioavailability of ABZ dosage forms. Therefore, HME is a potential continuous manufacturing technique to overcome ABZ poor solubility properties and lead to a significant increase in the therapeutic effect

An investigation into fused filament fabrication for pharmaceutical manufacturing

In a modern world, what is the best way to deliver medicines to the patient? Human beings are an extremely diverse species with many different factors that can influence the behaviour of a drug within the body. Children are a perfect example of such variety. Doses are often prescribed based on body weight, and can vary greatly from infants to adolescents. With current ‘traditional’ manufacture of oral dose pharmaceuticals, generally only a limited number of doses are produced, leading to difficulties with appropriate dosing. The ability to manufacture personalised doses for these patients would be of great benefit both practically and financially, and may even lead to ‘point of care’ manufacture

Inkjet printing of insulin microneedles for transdermal delivery

Inkjet printing technology was used to apply insulin polymeric layers on metal microneedles for transdermal delivery. A range of various polymers such as gelatin (GLN), polyvinyl caprolactame-polyvinyl acetate-polyethylene glycol (SOL), poly(2-ethyl-2-oxazoline) (POX) and trehalose (THL) were assessed for their capacity to form thin uniform and homogeneous layers that preserve insulin intact. Atomic force microscopy (AFM) showed homogeneous insulin–polymer layers without any phase separation while SOL demonstrated the best performance. Circular discroism (CD) analysis of rehydrated films showed that insulin’s alpha helices and β–sheet were well preserved for THL and SOL. In contrast, GLN and POX insulin layers revealed small band shifts indicating possible conformational changes. Insulin release in Franz diffusion cells from MNs inserted into porcine skin showed rapid release rates for POX and GLN within the first 20 min. Inkjet printing was proved an effective approach for transdermal delivery of insulin in solid state

Spectrum of autoimmune bullous diseases in northern Greece. A 4-year retrospective study and review of the literature

Bullous Diseases Unit at the 2nd Department of Dermatology and Venereology, Aristotle University of Thessaloniki was founded with the aim to provide the optimal diagnostic approach and treatment of patients with autoimmune bullous diseases (AΙBD).  We processed all AIBD files of patients diagnosed from 2011 to 2014 in order to record all epidemiological data and therapeutic manipulations during monitoring. 57 patients were diagnosed with intraepidermal and 62 with subepidermal bullous diseases. There were 51 cases (89%) of pemphigus vulgaris (PV) and 6 (11%) of pemphigus foliaceus (PF), whereas 45 (73%) patients were diagnosed with bullous pemphigoid (BP), 9 (14%) with mucous membrane pemphigoid (MMP), 3 (5%) with pemphigoid gestationis (PG), 3 (5%) with linear IgA dermatosis (LAD), 1 (2%) with epidermolysis bullosa aquisita (EBA), and 1 patient with an undefined subepidermal AIBD. The mean age of patients within the pemphigus spectrum was 57 years. In the pemphigoid spectrum, the mean age was 72 years. Comorbidities were reported with increasing frequency, as well as treatment options other than systemic corticosteroids, such as adjuvant immunosuppressive agents, which were used to achieve complete remission. This is a report from a tertiary AIBD Referral Center in northern Greece. Our data from a 4-year period contribute to the completion of the global geographic incidence map of AIBD.  </p