Dysphagia is a disorder recognised by the WHO and defined as difficulty swallowing solid food and liquids. Carolina Acosta Romero, researcher in mechanochemistry and reactive extrusion, AIMPLAS, discusses easy swallowing solutions for dysphagia.
AIMPLAS CHARO PASCUAL
Swallowing, or deglutition, is a neuromuscular process of voluntary and involuntary movements that involves 26 different muscles of the mouth, pharynx, larynx and oesophagus, together with innervation from the central nervous system and peripheral nervous system so that the pharynx can perform swallowing, breathing and phonatory functions, all within a matter of milliseconds. Swallowing disorders are caused by structural or functional impairment of one or more swallowing phases. Impairment is structural when a motor/muscular difficulty limits the patient’s ability to swallow (mechanical or obstructive dysphagia) and is functional when neuronal activation of the swallowing reflex is impaired (neurological dysphagia).
Recent data indicate that swallowing difficulties associated with dysphagia affect 8% of the Spanish population, which represents more than three million people.
While dysphagia is most prevalent among people over 75 years of age and patients with neurological problems (multiple sclerosis, Alzheimer’s; around 85% of patients with swallowing problems have Alzheimer’s), the disorder actually affects people of all ages. According to reports from the World Gastroenterology Organization, it is estimated that 1 in 17 people in the world will suffer from some form of dysphagia in their lifetime.
Dysphagia occurs in more than 40% of people who have suffered a stroke or head and neck cancer. Likewise, certain syndromes and pathologies affecting the paediatric and neonatal age group involve a series of physiological and/or anatomical alterations that can lead to dysphagia, with an estimated prevalence of 30-80% of the ailment in children with developmental disorders.
The prevalence of dysphagia and associated malnutrition in patients hospitalised for COVID-19 surprised many professionals, given that swallowing difficulties not only occurred in 50% of hospitalised patients, but one in three patients presented with dysphagia up to six months after discharge.
The specific consequences and complications of dysphagia include malnutrition, loss of muscle mass and weight, sarcopenia and dehydration, as well as a higher incidence of respiratory superinfections, aspiration pneumonia, reintubation in post-ICU patients, prolongation of hospitalisation, and even mortality.
In line with the consequences of inadequately treated dysphagia, the prevalence of this disorder and its effects in patients results in prolongation of hospitalisation and a significant increase in associated healthcare costs, as reported in the study by Julia Álvarez et al.
In this context, besides providing increased support for working groups that develop intervention methods for patients with swallowing disorders, solutions should also be developed for administration of medication and food supplements for these patients. When patients are treated using a “simultaneous, early and universal approach to dysphagia and nutritional risk, their clinical evolution improves”.
The DEGLUMED Project seeks to provide solutions for people with swallowing problems when they take medication and food supplements (nutraceuticals). These solutions are designed for the elderly, as well as children and other population groups with swallowing difficulties. Many drugs are available in solid oral dosage forms such as tablets and capsules. However, some people find these drugs difficult to swallow. The taste also affects patients’ ability to swallow medication and can cause them to reject and spit it out (which may or may not be detected when the drug is taken).
In order to facilitate swallowing, proposed solutions include training both carers and patients to identify best swallow positions, as well as assess the safest diet for the patient, according International Dysphagia Diet Standardization Initiative (IDDSI) standardisation. On the other hand, solutions include designing dispensers that place the tablet in a suitable position for easier swallowing, using coatings that make tablets slide more, modifying oral intake formats, such as orodispersible (ODS) films that quickly dissolve on the tongue.
Although ODS format is well known, it has been virtually unused in any commercial products on the market, which means that there is a niche for this solution to the problem. In addition, the production of these films is mainly carried out using discontinuous processes such as casting, where solvents must first be prepared to obtain the film.
3D Printing
The DEGLUMED Project initiative, funded by the Valencian Institute for Business Competitiveness (IVACE), focuses on the design of easy-to-swallow formats for medicines and nutraceuticals. DEGLUMED is therefore developing ODS films in a one-step process by using hot melt extrusion and pharmaceutical compounding to save energy, provide greater drug reproducibility and bioavailability, avoid solvent consumption and enable the development of complex formulations.
This project contributes to the European Commission’s environmental policies as part of efforts to implement cleaner production technologies that reduce energy and raw material consumption.
DEGLUMED is also committed to personalised medicine, which addresses the challenges of common drugs that are not effective as treatment for many patients, and rising healthcare costs due to an ageing population and the increased prevalence of chronic diseases.
Figure 1
The technology used in this project makes it possible to produce films in a single step and obtain filament if required for subsequent FDM printing (fused deposition modelling) or to use pellets for direct printing with 3D printers prepared to work with this format. The advantages of this technology include personalisation, the ability to print complex structures by combining different materials, savings on materials (when the process is fine-tuned, material loss is practically nil), versatility, and short production series at affordable costs.
During project development, food-grade polymers were selected to ensure rapid, correct dilution, together with excipients such as plasticisers to adapt the dissolving behaviour of the active ingredient and product wettability. Different formulations were therefore assessed to find products with greater active ingredient bioavailability while laboratory-scale process conditions were determined (see Figure 1).
Figure 2
Different formulations were evaluated, and the design of experiments (DOE) was defined using B vitamins cyanocabalamin (B12) and riboflavin (B2), as well as natural extracts used as nutraceuticals as active pharmaceutical ingredients (APIs) to obtain ODS films and pellets for subsequent printing (Figure 2).
Laboratory-scale tests were used to assess disintegration in artificial saliva (Figure 3) and therefore assess the dissolution kinetics and final texture, taking into account the classification of liquids and foods in terms of the physiological rationale involved in oral processing indicated by the IDDSI. The project is also collaborating with different institutes and universities in the community to validate the laboratory results obtained.
Based on the results obtained at laboratory scale, the project is now in the pilot scale-up phase with preliminary processing tests at 300-500 g/h, which will lead to processing at 5 kg/h at the AIMPLAS cleanroom facilities.
The ultimate aim of the project is therefore to generate new knowledge on processing continuous formulations for the pharmaceutical/nutraceutical sectors and to promote the development of new formats that provide greater personalisation in the administration of medicines and food supplements and the creation of new health products.
Figure 3
Besides producing more precise doses of medication for each patient, the technology makes it possible to create ODS films and filaments in a single step for use in fused deposition modelling (FDM) or as pellets for direct printing on printers designed to work with this format. Due to the type of technology used, the project enhances the effectiveness of active ingredients and their release.
AIMPLAS is carrying out this research in collaboration with companies that handle project applications, including the production of medicines, food supplements, health products and cosmetics, as well as specialists in 3D printing products and services. Specifically, the companies participating in the project are Especialidades Farmacéuticas Centrum (Asacpharma), Labinderb, Marenostrum and IT3D.
This project is financed by IVACE through ERDF funds from the European Union within the Valencian Community ERDF Operational Programme (2021-2027). This funding is targeted at technology centres in the Valencian Community to develop non-economic R&D projects in collaboration with companies in 2022.