Heli Paukkonen, 2018
Abstract
"The main role of excipients is to ensure the safety and efficacy of the whole pharmaceutical formulation throughout its shelf-life and administration. Formulation design and development as well as material testing are the key components for successful drug delivery. This is becoming increasingly complicated as new active pharmaceutical ingredients typically have poor solubility and/or bioavailability. Due to this, there is an ever increasing need to explore new excipients and material combinations as innovative formulation solutions are required. Furthermore, modified release formulations are needed to control the release rates and to adjust the desired therapeutic effects, raising even more demand for effective formulations. The main aim of this thesis was to evaluate the performance of plant based materials nanofibrillar cellulose (NFC) and anionic carboxylated nanofibrillar cellulose (ANFC) as pharmaceutical excipients for modified release formulations and bioadhesive films. These materials are widely available from renewable sources; biocompatible with relatively low toxicity combined with high mechanical strength and large surface area available for encapsulation. NFC and ANFC, together with HFBII protein, were used as emulsion stabilizers for encapsulation and release of poorly water-soluble drugs. The synergistic stabilization mechanism achieved with these biopolymers improved emulsions stability with extremely low concentrations. In another study, ANFC hydrogels were evaluated as matrix reservoirs for diffusion controlled drug release. Their rheological and drug release properties were shown to be preserved after freeze-drying and reconstruction. The ANFC hydrogels controlled the release kinetics of small molecular weight drugs moderately, whereas significant control was obtained in the case of large proteins. In a comparative study, three new grades of microcrystalline cellulose (MCC) hydrogels were evaluated for diffusion controlled drug release. MCC matrices efficiently controlled the release of both large and small compounds, indicating great potential for drug release applications in a similar manner to the ANFC hydrogels. Bioadhesive NFC and ANFC based films were prepared by incorporating bioadhesive polymers mucin, pectin and chitosan into the film structure. The bioadhesive properties of the films combined with good mechanical and hydration properties, together with low toxicity makes them a feasible option for buccal drug delivery applications. In conclusion, NFC and ANFC were shown to be versatile excipients applicable for several types of dosage forms. In the future, it is seen that these materials may be used systematically as functional excipients for modified release dosage form."
Heli Paukkonen, Nanofibrillar cellulose for encapsulation and release of pharmaceuticals, University of Helsinki, Finland, 2018.