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