Development and optimization of oral film formulations

The aim of this study is to develop the orodispersible film formulations of quetiapine fumarate within Quality by Design (QbD) framework for suitable industrial production by applying scale-up process. In some condition such as geriatric, pediatric, dysphagia like patients, fear of choking and unavailability of water, the swallowing of capsules and tablets may become difficult. To overcome from these types of problem, new type of drug delivery system has been designed. Orodispersible film is a new dosage form in which is prepared by using polymers with suitable excipients. Quetiapine fumarate, which is used as an active substance in this study, is a novel antipsychotic agent which elicits response in both positive and negative symptoms of schizophrenia and bipolar disorder. Orodispersible films were prepared using HPMC E5 as polymer, polyethylene glycol 400 and propylene glycol as plasticizer, xylitol as sweetener, peppermint oil as flavoring and blue coloring agent. First, films were manufactured in laboratory scale by solvent casting method. Laboratory scale films were selected according to their gel viscosity, weight uniformity, thickness, and disintegration time characteristics, then produced in a pilot scale manufacturing machine. Weight uniformity, thickness, pH, moisture content, tensile strength, elongation, folding endurance, disintegration test, content uniformity, dissolution rate, cytotoxicity and stability studies of the final film formulations were performed. Critical parameters were determined with QbD approach and a design area was created by using Minitab 18 program. As a result of the studies carried out from the laboratory scale to the pilot scale within QbD framework was shown, Fnm-29-65 film formulation, which has the highest tensile strength (3.650 ± 0.47 N/cm2), suitable elongation (5.427 ± 0.19 %), disintegration time (120.00 ± 2.28 sec), content uniformity (98.66 ± 1.32 %) and dissolution rate (in 10 min, 87.69 ± 4.65 %) properties has been determined as the ideal formulation. Key Words: Oral film, Orodispersible film, Scale up, Quality by design, Quetiapine fumarate.