Product transfer from lab-scale to pilot-scale of quetiapine fumarate orodispersible films using quality by design approach

Bulbul E. O., Mesut B., Cevher E., Oztas E., Ozsoy Y.

JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, vol.54, 2019 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 54
  • Publication Date: 2019
  • Doi Number: 10.1016/j.jddst.2019.101358
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Keywords: Scale-up, Continuous manufacturing, Orodispersible film, Quetiapine fumarate, Quality by design, ATYPICAL ANTIPSYCHOTICS, FORMULATION, DELIVERY, DRUGS, HYDROCHLORIDE, NANOPARTICLES, PLASTICIZERS, MANUFACTURE
  • Istanbul University Affiliated: Yes


In this study, transfer from lab-scale non-continuous production to pilot-scale continuous production of orodispersible films was provided using solvent casting method under the framework of quality by design. Non-continuous production was carried out with petri dishes and continuous production was carried out with a coating machine. Films containing hydroxypropyl methylcellulose E5 as film forming polymer, polyethylene glycol 400 and propylene glycol as plasticizers, quetiapine fumarate as drug were formulated. Viscosity of the polymer dispersions, weight, thickness and disintegration time of the films were compared for the transfer of production. pH, moisture content, mechanical properties, folding endurance, uniformity of dosage units, dissolution, stability studies were also performed in pilot-scale orodispersible films. Finally, cytotoxicity studies were performed to determine cell viability. The study showed the possibility of producing F2-p-65/70 (pilot-scale film formulation containing 10 mg propylene glycol, dried at 65 degrees C and 70 degrees C) and F4-p-65/70 (pilot-scale film formulation containing 15 mg propylene glycol, dried at 65 degrees C and 70 degrees C), as the most suitable for further studies. Thus, a promising improvement has been achieved for schizophrenic patients by the production of quetiapine fumarate loaded orodispersible films and the process of scale-up in films has been demonstrated.