Oral transmucosal delivery of domperidone from immediate release films produced via hot-melt extrusion technology

Abstract

The objective of the study was to prepare and characterize the domperidone (DOM) hot-melt extruded (HME) buccal films by both in vitro and in vivo techniques. The HME film formulations contained PEO N10 and/or its combination with HPMC E5 LV or Eudragit RL100 as polymeric carriers, and PEG3350 as a plasticizer. The blends were co-processed at a screw speed of 50 rpm with the barrel temperatures ranging from 120-160°C utilizing a bench top co-rotating twin-screw hot-melt extruder using a transverse-slit die. The HME films were evaluated for drug content, drug excipient interaction, in vitro drug release, mechanical properties, in vivo residence time, in vitro bioadhesion, swelling and erosion, ex vivo permeation from HME films and the selected optimal formulation was subjected for bioavailability studies in healthy human volunteers. The extruded films demonstrated no drug excipient interaction and excellent content uniformity. The selected HME film formulation (DOM2) exhibited a tensile strength (0.72 Kg/mm(2)), elongation at break (28.4% mm(2)), in vivo residence time (120 min), peak detachment force (1.55 N), work of adhesion (1.49 mJ), swelling index (210.2%), erosion (10.5%) and in vitro drug release of 84.8% in 2 h. Bioavailability from the optimized HME buccal films was 1.5 times higher than the oral dosage form and the results showed statistically significant (p < 0.05) difference. The ex vivo-in vivo correlation was found to have biphasic pattern and followed type A correlation. The results indicate that HME is a viable technique for the preparation of DOM buccal-adhesive films with improved bioavailability characteristics.

Oral transmucosal drug delivery for pediatric use

“…Subsequently the mixture is cast onto a substrate surface and the solvent is allowed to evaporate, leading to the formation of a drug-containing polymeric film. Alternatively, hotmelt extrusion is another method to prepare an oral film [104][105][106][107]. It has the advantage of avoiding the use of organic solvent but is not suitable for thermo-labile compounds [108].…”

Orodispersible films: Towards drug delivery in special populations

“…Hot melt extrusion (HME) offers the advantage of a solvent-free process for ODF manufacturing (Palem et al, 2016(Palem et al, , 2013Park et al, 2015;Repka et al, 2003). Yet, poor availability of suitable polymers and high temperatures may pose stability issues to the active (Hoffmann et al, 2011).…”

Development of an antifungal denture adhesive film for oral candidiasis utilizing hot melt extrusion technology

“…However, few researchers have demonstrated that HME techniques are a viable method to prepare novel, scalable delivery systems via extruded films. Indeed, very few oral transmucosal systems are currently available in the market [18]. …”