DESIGN AND DEVELOPMENT OF AN ORODISPERSIBLE FILM AS A NEW DRUG DELIVERY FILM-SYSTEM TO DYSPHAGIC PATIENTS

Purpose: Oral route is generally the most preferable route of drug administration even though is not always accessible due to specific pathological conditions. The onset of swallowing difficulties may be a situation where oral solid medicines are not manageable. A quite new technology in the pharmaceutical field is focused on the development of orodispersible films (ODFs) as a good alternative to conventional solid forms (i.e., tablets or capsules).1,2 The aim of this work is to develop an ODF using electrospinning technique3 in order to tune a proper drug delivery film-system (DDFS) able to facilitate drug administration to dysphagic patients. Electrospinning apparatus allows to produce a nanofibers’ matrix disintegrating into the mouth. Specifications reported in European Pharmacopoeia 8th edition (Eu.Ph.)4 about orodispersible tablets are generally used as reference because there is still not a clear description on ODFs characterization methods. Methods: The spinning solutions were prepared by dissolving two polymers polyvinylpyrrolidone K90 (PVP K90) 5% w/w and polyethylene oxide 300k Da (PEO 300k) 5% w/w in water under magnetic stirring. This blend was chosen for producing a placebo film after a selection of several polymers and electrospinning conditions to achieve proper film properties about disintegration time and handling. Additionally, a DDFS was prepared by adding pravastatin sodium 1% w/w in the placebo mixture. The electrospinning process was carried out applying the following parameters: voltage 15kV, 20cm needle-collector distance and flow-rate 0.5mL/hour in placebo system and drug-loaded system. Surface morphology and dimensions of nanofibers were revealed and measured using a JSM-5900LV scanning electron microscope (SEM). Disintegration tests were performed on squared pieces (2cm*2cm) of each produced film to evaluate the complete disappearance of the film when a proper volume (3-5mL) of artificial saliva (phosphate buffer solution pH 6.0) was added into a Petri dish to simulate oral cavity conditions. Disintegration time was recorded and tests were performed in triplicate. Results: SEM pictures showed that nanofibers appeared straight and elongated in the entire mat. Their dimensions ranged within 445.50 ± 39.68nm and 439.60 ± 33.49nm in placebo film and in DDFS, respectively. Fiber size and fiber distribution looked homogeneous in all mat. Detection of cationic sodium related to pravastatin and determined by elemental analysis, confirmed the presence of the drug in the DDFS. Disintegration of the films resulted into 120 and 60-75 seconds in placebo film and in DDFS, respectively, in accordance with specifications reported in Eu.Ph. for orodispersible tablets. In fact, Eu.Ph. establishes that tablets should disintegrates into the mouth within 3 minutes. Then, these results demonstrated a possible relationship existing between fiber dimension and speed of disintegration of the mat: decreasing diameter size, films revealed a quicker time for disappearance in the mouth. Mats exhibited a quite good manipulation and handling properties to guarantee a suitable administration on the tongue. Conclusions: Orodispersible films may be considered promising drug delivery systems especially for patients who present specific alterations in deglutition process. ODFs may offer a valid alternative to conventional forms and the switch between the two forms may assure drug therapy compliance.