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Tesi etd-03242015-215337

Thesis type
Tesi di laurea magistrale LM5
Ophthalmic Inserts prepared either by Extrusion or by Freeze-Drying : Technological and Biopharmaceutical Characterization
Corso di studi
relatore Dott. Monti, Daniela
correlatore Prof. Chetoni, Patrizia
Parole chiave
  • In vitro release
  • Amylo starch
  • Hot-melt extrusion
  • DSC
  • Freeze-drying
  • Fluocinolone acetonide
  • Vancomycin
Data inizio appello
Riassunto analitico
The main goal of this thesis is the development of an ophthalmic biodegradable insert containing fluocinolone acetonide (FA), to apply in the posterior segment of the eye. The inserts under study were prepared using the hot-melt extrusion technique (HME). In a previous study, an insert based on hydroxypropyl cellulose (HPC-FA) was selected as the best with respect to a wide range of devices tested. New inserts containing amylo-maize starch N-400 (AMYLO), corn starch (CS) or corn starch with magnesium stearate (CS-MS) were prepared. All inserts were added of 3% FA (AMYLO-FA, CS-FA and CS-MS-FA, respectively). Swelling and dissolution properties of the new inserts were analysed in isotonic buffer saline (PBS) by a visual examination. During the examination time (up to 12 days), AMYLO-FA produced no changes in terms of dissolution and gel-like transformation in addition to an initial hydration and light swelling compared to the inserts containing CS; so it has appeared the most suitable for further studies. <br>The physicochemical characteristics of the selected inserts (HPC-FA and AMYLO-FA) were determined by a) in vitro drug release and by b) differential scanning calorimetry (DSC). Drug release performance of AMYLO-FA and HPC-FA inserts was comparatively evaluated using Gummer-type diffusion cells up to 52h, maintaining the sink conditions (continuous receiving phase replacement), to evaluate the device influence on the FA release independently to the surrounding environment. During the time observed, HPC-FA released the drug too quickly (89% of drug released) for our goal unlike AMYLO-FA that showed a remarkable reduction of FA release (36.13%). The test on AMYLO-FA was continued for 8 days and a slow but continuous release was obtained to reach 63.66% of FA at the end of the experiment. A controlled drug delivery with zero order kinetics could be hypothesized when AMYLO-FA release process reached the steady-state. The release rate of FA from AMYLO-FA insert was also determined when the receiving phase (PBS) was totally replaced every 24h and 48h simulating the biological conditions: vitreous humor turnover is considered stagnant. For both performed experiment protocols FA release from AMYLO-FA insert was linear during the 25-day sampling period but the release rate decreased by half for sampling 48 hours. Then it would seem that the release of the drug from the device was mainly influenced and driven by the receiving environment rather than from the insert. <br>The DSC analysis of AMYLO-FA (as physical mixture and extruded) suggested that no polymer-drug interaction occurred using the HME and this means that the release of the drug might depend only on the modified polymer structure. <br>The second part of this thesis aimed at tuning up cylindrical matrices by freeze-drying for administration of vancomycin (VA) in the precorneal area to produce a sustained release of drug and consequently to reduce the number of applications. The matrices prepared contained hydroxypropyl methylcellulose (HPMC) and VA in ratio 0.25 to 1 and were subjected to a) in vitro release study and b) DSC analysis. HPMC-VA matrix released the drug very slowly for our goal, may be due to a drug-polymer interaction during the freeze-drying process. DSC analysis of lyophilized matrix and the single components would suggest this hypothesis. <br>