Development and Characterizations of Pullulan and Maltodextrin-Based Oral Fast-Dissolving Films Employing a Box-Behnken Experimental Design

Kiramat Ali Shah; Binbin Gao; Robia Kamal; Anam Razzaq; Sun Qi; Qiu-Ning Zhu; Song Lina; Linyu Huang; Grainne Cremin; Haroon Iqbal; Farid Menaa; Jing-Hao Cui

doi:10.3390/ma15103591

Development and Characterizations of Pullulan and Maltodextrin-Based Oral Fast-Dissolving Films Employing a Box-Behnken Experimental Design

Materials (Basel). 2022 May 18;15(10):3591. doi: 10.3390/ma15103591.

Authors

Affiliations

¹ College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
² Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland (RCSI), D02YN77 Dublin, Ireland.
³ The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China.
⁴ Department of Internal Medicine and Nanomedicine, California Innovations Corporation, San Diego, CA 92037, USA.

Abstract

Migraine is a neurological disorder characterized by severe headaches, visual aversions, auditory, and olfactory disorders, accompanied by nausea and vomiting. Zolmitriptan (ZMT^®) is a potent 5HT1B/1D serotonin receptor agonist frequently used for the treatment of migraine. It has erratic absorption from the gastrointestinal tract (GIT), but its oral bioavailability is low (40-45%) due to the hepatic metabolism. This makes it an ideal candidate for oral fast dissolving formulations. Hence, the current study was undertaken to design and develop oral fast-dissolving films (OFDFs) containing ZMT for migraine treatment. The OFDFs were formulated by the solvent casting method (SCM) using Pullulan (PU) and maltodextrin (MDX) as film-forming agents and propylene glycol (PG) as a plasticizer. The strategy was designed using Box-Behnken experimental design considering the proportion of PU:MDX and percentage of PG as independent variables. The effectiveness of the OFDF's was measured based on the following responses: drug release at five min, disintegration time (D-time), and tensile strength (TS). The influence of formulation factors, including percent elongation (%E), thickness, water content, moisture absorption, and folding endurance on ZMT-OFDFs, were also studied. The results showed a successful fabrication of stable ZMT-OFDFs, with surface uniformity and amorphous shape of ZMT in fabricated films. The optimized formulation showed a remarkable rapid dissolution, over 90% within the first 5 min, a fast D-time of 18 s, and excellent mechanical characteristics. Improved maximum plasma concentration (C max) and area under the curve (AUC 0-t) in animals (rats) treated with ZMT-OFDFs compared to those treated with an intra-gastric (i-g) suspension of ZMT were also observed. Copolymer OFDFs with ZMT is an exciting proposition with great potential for the treatment of migraine headache. This study offers a promising strategy for developing ZMT-OFDFs using SCM. ZMT-OFDFs showed remarkable rapid dissolution and fast D-time, which might endeavor ZMT-OFDFs as an auspicious alternative approach to improve patient compliance and shorten the onset time of ZMT in migraine treatment.

Keywords: Zolmitriptan; drug delivery; maltodextrin; oral fast-dissolving film; propylene glycol; pullulan.

Grants and funding

81173005/Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) and the National Natural Science Foundation (81173005) in China.