Electrospinning as a novel approach to oral delivery – what effect does the drug have on spinnability?

Abstract

Abstract Background: The development of drug loaded nanofibers for oral delivery is becoming of great interest within the pharmaceutical field for the last decade. This due to their distinct size and structure. In addition, they can be formulated from a wide range of polymers materials that have different properties which allows the development of a wide variety of drug delivery design that are appropriate to target different target sites and present a wide range of drug release mechanism. There is a range of different procedures for generating these nanofibers, however, the simplest process which does not require sophisticated sample preparation methods and is gaining particular interest is for the production of drug loaded nanofibers is the electrospinning process. This process allows the production of nanofibers by using electrostatic forces to generate fibres from a polymer solution. What makes it more suitable to use over other methods is that it can make produce fibres with controlled size and morphology, which is of great importance to improve the efficiency of drug formulations. There are a number of published researches found to electrospine drug loaded polymers for different purposes. For example, to formulate modified release formulations and/ or for taste masking the bitter taste of the drugs. Nonetheless, as this process became of great interest there is sufficient amount of research that have been done to investigate the effect of the solution properties and the processing parameters on the spinnability and the quality of the fibres produced. However, there is lack of investigation on the effect of the addition of drug on the spinnability and the quality of the fibres produced. Thus, this study drives it's need from the lack of investigation in this matter. Aim: The key aim of this project is to examine the effect of the addition of drug on the electrospinning process, the morphology and sizes of fibres produced. Method: Two polymers and two forms of ibuprofen were used to carry out this investigation. Firstly, the effect of the addition of ibuprofen sodium on the hydrophilic polymer polyvinylpyrrolidone (PVP) is examined. Secondly, the effect of individually adding both the salt and the base forms of ibuprofen on the spinnability of the amphiphilic organic polymer Poly (Lactide/Glycolide) (PLGA) is also examined. PVP solutions were made at 50% w/v of PVP in ethanol. Ibuprofen sodium was added to the solutions at 1%, 5%, 10%, 20% and 30% w/w (relative to the dry weight of PVP). PLGA solution, in the other hand, were prepared at 40% 4 w/v of PLGA in Acetone. Both sodium ibuprofen and ibuprofen were used to load PLGA solutions, which were prepared in the same way as the drug loaded PVP solutions. When electrospinning these solutions they were pumped by a syringe pump at a flow rate of 1mL/hr and an applied voltage between 18 and 20 kV. The temperature ranged from 22 to 25 ̊C and the relative humidity ranged between 30-44 %. These process parameters and the total polymer concentration are kept constant throughout the project in order to minimise the variance and to be able to identify the effect of the addition of drug on these parameters. These constant parameters are the optimum parameters that gave rise to the formation of a stable tyler cone and allowed the production of drug-free fine uniform fibres for both polymers used. The effect of adding ibuprofen sodium and ibuprofen on the spinnability of the polymers is examined in comparison to the drug-free polymers solutions. The viscosity and the electrical conductivity of the drug free formulation and the drug loaded formulations were measured, as they were expected to be affected by the addition of the drug. The morphology and the sizes of the electrospun fibres was characterised by SEM. Findings: The addition of drug to the polymer solutions was observed