Formulation and Assessment of Taste-masked Electrospun Fibre Mats for Paediatric Drug Delivery

Since the Paediatric Regulation came into force by the European Medicines Agency in 2007, the drive to formulate age-appropriate dosage forms has been accelerated. The aim of this thesis was to develop new approaches for paediatric formulation design through the optimisation of novel taste-masking and taste-assessment methods. Electrospinning was demonstrated to be a suitable taste-masking technology, producing fibre mats that can be further formulated into easy to swallow oral films. The electrospinning of Eudragit E PO, a taste-masking polymer, was optimised using Quality by Design principles and in particular Design of Experiment. To further enhance the taste-masking capability of the electrospun mat, co-axial electrospinning was utilised using another taste-masking polymer, Kollicoat Smartseal. The use of both polymers successfully taste-masked chlorpheniramine maleate, a known bitter anti-histamine. This was demonstrated using an electronic biosensor tasting system or E-tongue. The E-tongue was used to assess the bitterness threshold of this model drug but also of other standard bitter drugs for benchmarking. In addition, it was used to taste-assess various formulations which aided in ranking and deselecting formulations. Electrospun fibre mats can be further processed into a number of different dosage forms for final presentation to the patient. The fibre mats were designed to be presented as an oral film. A water-soluble outer layer was added to the films using multi-axial electrospinning. A human panel was conducted to investigate the mouthfeel and overall acceptability of electrospun PVA films versus solvent-cast PVA films. The electrospun films were found to be as acceptable as the standard solvent-cast films, a very promising result for clinical translation. PVA and PVP were electrospun with the previously optimised polymers using tri-axial and tetra-axial electrospinning. The taste of the multi-axial electrospun fibre mats were assessed and it was found that adding a water-soluble outer layer reduces the taste-masking ability. Thus, it was found that electrospinning of a bitter drug using hydrophobic taste-masking polymers is very promising in the formulation of paediatric oral films

Palatability assessment of oral dosage forms for companion animals: A systematic review

The challenging administration of poorly palatable oral dosage forms to companion animals has fostered sub-optimal treatment outcomes for animals and thus a need for highly palatable treatments. Pharmaceutical companies are creating formulations to answer this need, but lack of a standardised procedure renders palatability assessment complicated and hinders comparison between studies. The gold standard in assessing voluntary acceptance is to utilise an acceptance test and/or preference test but slight variations as to how these are conducted can be observed between studies. This systematic review aims to examine palatability assessment methods and how palatability of oral dosage forms influences acceptability of medicines in companion animals. Solid oral dosage forms are well tolerated by dogs but very poorly by cats. Cats accept pastes more readily although this dosage form seems more suited for short-term forced administration and owner convenience. Liquid formulations seem to be well tolerated in cats but poorly in dogs. Meat-based flavours yield high palatability. The shape and colour of dosage forms also seem to impact palatability. Methodology can induce bias and must therefore be adapted to the animals and dosage forms tested. It seems there is a lack of evidence relating to formulation parameters that yield high palatability in companion animals. Additional studies and revised guidelines from the European Medicines Agency on palatability testing of veterinary medicinal products are therefore required. This review provides insight as to which dosage form, flavours and physical aspect generate increased palatability and which methodological parameters should be altered or monitored to avoid bias

Drug Delivery Applications of Coaxial Electrospun Nanofibres in Cancer Therapy

Cancer is one of the most serious health problems and the second leading cause of death worldwide, and with an ageing and growing population, problems related to cancer will continue. In the battle against cancer, many therapies and anticancer drugs have been developed. Chemotherapy and relevant drugs are widely used in clinical practice; however, their applications are always accompanied by severe side effects. In recent years, the drug delivery system has been improved by nanotechnology to reduce the adverse effects of the delivered drugs. Among the different candidates, core–sheath nanofibres prepared by coaxial electrospinning are outstanding due to their unique properties, including their large surface area, high encapsulation efficiency, good mechanical property, multidrug loading capacity, and ability to govern drug release kinetics. Therefore, encapsulating drugs in coaxial electrospun nanofibres is a desirable method for controlled and sustained drug release. This review summarises the drug delivery applications of coaxial electrospun nanofibres with different structures and drugs for various cancer treatments

Advances in Formulation and Manufacturing Strategies for the Delivery of Therapeutic Proteins and Peptides in Orally Disintegrating Dosage Forms

Therapeutic proteins and peptides (TPPs) are increasingly favoured above small drug molecules due to their high specificity to the site of action and reduced adverse effects resulting in increased use of these agents for medical treatments and therapies. Consequently, there is a need to formulate TPPs in dosage forms that are accessible and suitable for a wide range of patient groups as the use of TPPs becomes increasingly prevalent in healthcare settings worldwide. Orally disintegrating dosage forms (ODDF) are formulations that can ensure easy-to-administer medication to a wider patient population including paediatrics, geriatrics and people in low-resource countries. There are many challenges involved in developing suitable pharmaceutical strategies to protect TPPs during formulation and manufacturing, as well as storage, and maintenance of a cold-chain during transportation. This review will discuss advances being made in the research and development of pharmaceutical and manufacturing strategies used to incorporate various TPPs into ODDF systems

Exploring co-crystallisation as a technique for taste-masking of nevirapine

The bitter taste of pharmaceuticals majorly impacts patient adherence. Co-crystallisation has been proposed as a novel way for taste masking using sweetener-based co-formers, while other co-formers also have a positive effect. We hypothesise that the sweetness of the co-formers is not the key factor but rather the molecular aggregation between the drug and co-former in solution, i.e., the stronger the interaction, the better the taste masking effect. Here, we explore the solution aggregation between the bitter-tasting drug nevirapine and five co-formers by 1H NMR spectroscopy. The co-formers benzoic acid, salicylic acid and maleic acid show strong interaction with nevirapine, while glutaric acid and saccharin have weak and no interaction, respectively. The taste of the resulting co-crystal, as assessed by the electrical taste sensing system e-tongue, reveals that the bitterness of nevirapine has been covered with the co-crystal benzoic acid, maleic acid and glutaric acid but not saccharin or salicylic acid. From the taste results we deduct that both solution aggregation and the taste of the pure co-former play an important role in taste masking. It is likely that a large variety of co-formers can be used to cover bitter drugs and we show that the investigation of molecular aggregation in solution can help screen the co-formers before any in vitro or in vivo taste test

Medical and pharmacy students’ perspectives of remote synchronous interprofessional education sessions

Background Interprofessional education (IPE) at university level is an essential component of undergraduate healthcare curricula, as well as being a requirement of many associated regulatory bodies. In this study, the perception of pharmacy and medical students’ of remote IPE was evaluated. Methods A series of IPE sessions took place via Zoom and students’ feedback was collected after each session. Both qualitative and quantitative data were collected and analysed. Results 72% (23/32) of medical students strongly agreed that the sessions had helped to improve their appreciation of the role of pharmacists, whereas 37% (22/59) of pharmacy students strongly agreed, reporting a median response of ‘somewhat agreeing’, that their appreciation of the role of general practitioners had improved. This difference was found to be statistically significant (p = 0.0143). Amongst students who responded, 55% (53/97) identified remote teaching as their preferred mode of delivery for an IPE session. Conclusions The survey demonstrated that the students valued the development of their prescribing skills as well as the ancillary skills gained, such as communication and teamwork. Remote IPE can be a practical means of improving medical and pharmacy students’ understanding of each other’s professional roles, as well as improving the skills required for prescribing

Formulation and Characterisation of Carbamazepine Orodispersible 3D-Printed Mini-Tablets for Paediatric Use

One of the main challenges to paediatric drug administration is swallowing difficulties, hindering the acceptability of the medicine and hence clinical outcomes. This study aims at developing a child-appropriate dosage form, the orodispersible mini-tablet (ODMT), using the model drug carbamazepine (CBZ). This dosage form was prepared and 3D-printed via a semi-solid extrusion technique. Design of Experiment methods were applied for optimising the formulation. The formulation with 40% (w/w) of SSG (superdisintegrant) and 5% (w/w) of PVP K30 (binder) was selected and loaded with CBZ. The drug-loaded tablets were characterised by a mean hardness of 18.5 N and a disintegrating time of 84 s, along with acceptable friability. The mean drug loading ratio of the tablets was tested as 90.56%, and the drug release rate in 0.1 M HCl reached 68.3% at 45 min. Excipients showed proper compatibility with the drug in physical form analysis. Taste assessment via an E-tongue was also conducted, where the drug did not show bitter taste signals at a low concentration in the taste assessment, and the sweetener also blocked bitterness signals in the testing. To this end, ODMTs were found to be potential candidates for child-appropriate dosage forms delivering CBZ

Utilising Co-Axial Electrospinning as a Taste-Masking Technology for Paediatric Drug Delivery

The present study describes the use of two taste-masking polymers to fabricate a formulation of chlorpheniramine maleate for paediatric administration. Co-axial electrospinning was utilized to create layered nanofibres; the two polymers, Eudragit® E PO and Kollicoat® Smartseal, were alternated between the core and the shell of the system in order to identify the optimum taste-masked formulation. The drug was loaded in the core on all occasions. It was found that the formulation with Kollicoat® Smartseal in the core with the drug, and Eudragit® E PO in the shell showed the most effective taste-masking compared to the other formulations. These fibres were in the nano-range and had smooth morphology as verified by scanning electron microscopy. Solid-state characterization and thermal analysis confirmed that amorphous solid dispersions were formed upon electrospinning. The Insent E-tongue was used to assess the taste-masking efficiency of the samples, and it was found that this formulation was undetectable by the bitter sensor, indicating successful taste-masking compared to the raw version of the drug. The E-tongue also confirmed the drug’s bitterness threshold as compared to quinine HCl dihydrate, a parameter that is useful for formulation design and taste-masking planning

Exploring co-crystallisation as a technique for taste-masking of nevirapine

The bitter taste of pharmaceuticals majorly impacts patient adherence. Co-crystallisation has been proposed as a novel way for taste masking using sweetener-based co-formers, while other co-formers also have a positive effect. We hypothesise that the sweetness of the co-formers is not the key factor but rather the molecular aggregation between the drug and co-former in solution, i.e., the stronger the interaction, the better the taste masking effect. Here, we explore the solution aggregation between the bitter-tasting drug nevirapine and five co-formers by 1H NMR spectroscopy. The co-formers benzoic acid, salicylic acid and maleic acid show strong interaction with nevirapine, while glutaric acid and saccharin have weak and no interaction, respectively. The taste of the resulting co-crystal, as assessed by the electrical taste sensing system e-tongue, reveals that the bitterness of nevirapine has been covered with the co-crystal benzoic acid, maleic acid and glutaric acid but not saccharin or salicylic acid. From the taste results we deduct that both solution aggregation and the taste of the pure co-former play an important role in taste masking. It is likely that a large variety of co-formers can be used to cover bitter drugs and we show that the investigation of molecular aggregation in solution can help screen the co-formers before any in vitro or in vivo taste test

Engineering artesunate-loaded micelles using spray drying for pulmonary drug delivery

Novel d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) micelles containing the anti-cancer drug artesunate (ART) were developed in a dry powder form for inhalation for the treatment of lung cancer. Targeted delivery to the lungs via inhalation presents a challenge, and the current study involved the development, characterization, and cytotoxicity determination of the dry powder formulations. TPGS micelles encapsulating ART were successfully prepared using thin-film hydration method, followed by the preparation of a dry powder formulation through spray-drying, which included lactose and leucine as carrier molecules. Characterization of the dry powder formulation using Sympatec laser diffraction particle size analyzer and a next generation impactor. The analysis showed a unimodal particle size distribution with a mean particle size of 3.27 μm and a fine particle fraction of 31%, respectively. Artesunate-loaded micelle dry powder formulation demonstrated higher cytotoxicity against the A549 adenocarcinomic human alveolar basal epithelial cell line when compared to currently used cancer therapies docetaxel and doxorubicin. Overall, this study demonstrates that spray-dried micelles containing artesunate have the potential to be used as a dry powder formulation for inhalation in the treatment of lung cancer