The development of novel colon targeted drug delivery systems

Oral delivery of multi-drug formulations to the colon offers many advantages to the patients suffering from diseases such as inflammatory bowel disease, including improved drug bioavailability and patients’ compliance. The purpose of this project was to develop colon targeted multi-drug delivery nanosystems for oral administration using electrohydrodynamic processes. Electrospinnability of enteric polymer, hydroxypropylmethylcellulose acetate succinate (HPMCAS), was affected by the formulation and environmental factors. Beaded HPMCAS fibers were obtained, when relative humidity was controlled. Three model drugs (5-aminosalicylic acid, hydrocortisone, paracetamol) were mixed with the HPMCAS electrospinning feed solution to produce multidrug loaded nano-fibers. The drug release behaviour of electrospun multi-drug formulation did not fulfil the enteric requirements, as more than 10% of each drug was released within 2 hours in gastric pH, even though the polymeric matrices did not dissolve. The lack of enteric properties was also observed in electrospun single-drug loaded formulations. To deliver 5-aminosalicylic acid (5-ASA) into the colon without any drug loss in stomach, spherical 5-ASA loaded zein nanoparticles (NPs) were prepared by nanoprecipitation in order to incorporate them into the HPMCAS fibers. Single-step particle-in-fiber incorporation by co-axial electrospinning was not feasible. Therefore, a layered formulation (NPs in between two layers of HPMCAS fibers) was prepared instead. However, the layers of HPMCAS fibers did not protect the 5-ASA from diffusion into the acidic buffer. As the rapid drug release was anticipated to be due to the high surface areas of the electrospun fibers, significantly thicker extrudates were employed as an alternative to reduce the drug release rate. Single-drug loaded extrudates containing the same drug-polymer ratios as the single-drug loaded fibers were prepared at three different diameters. In-vitro dissolution data showed the surface to volume ratio of the formulation and the physico-chemical properties of the drugs are key factors influencing the enteric properties of the HPMCAS formulations