Production and Characterization of Hot-Melt Extruded Films Containing Clotrimazole

Abstract

Hot-melt extrusion technology (HME) was used to prepare muco-adhesive matrix films containing 10% w/w clotrimazole (CT) intended for local drug delivery applications for the oral cavity. This study was aimed at the production and characterization of these drug delivery systems for the prophylaxis and treatment of oral candidiasis. The film system's formulation contained hydroxypropyl cellulose and poly(ethylene oxide) as polymeric carriers, the bioadhesive polycarbophil, and other excipients. The CT formulation was processed at a temperature range of 125-130 degrees C utilizing a Killion extruder (Model KLB-100) equipped with a 6-inch flex-lip die. The films were evaluated for postextrusion drug content, physical and chemical content uniformity, drug release, thermal and crystalline behavior, and bioadhesive strength. The extruded films demonstrated excellent content uniformity and a postprocessing drug content of 93.3% (+/- 1.0). The degradation product, (o-chlorophenyl)diphenyl methanol, was also identified and quantitated using high performance liquid chromatography. The films were determined to exhibit desirable and consistent release properties and bioadhesive strength (p < 0.05). The results of this study indicate that HME is a viable technique for the preparation of muco-adhesive films containing clotrimazole for oral candidiasis.

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).…”

Pharmaceutical Applications of Hot-Melt Extrusion: Part II

“…Repka et al extensively investigated hot-melt extrusion techniques as effective tools for preparing transmucosal drug delivery systems. These researchers characterized hot-melt extruded hydroxypropyl cellulose or polyethylene oxide, which contained clotrimazole, a drug used for oral candidiasis therapy (Prodduturi et al, 2004Repka et al, 2003). The film was processed at a temperature range of 125-130°C utilizing a Killion extruder (ModelKLB-100) equipped with a 6-inch flex-lip die.…”

“…Hot-melt extrusion (HME) is a manufacturing process widely used in plastics industry, and has significant potential as a continuous pharmaceutical process. During hot-melt extrusion of pharmaceutical dosage forms, a blend of active ingredient, thermoplastic polymeric carrier, and other processing aids, including plasticizers and antioxidants, is heated and softened inside the extruder and then pressurized through a die into granules, cylinders, or films (Crowley et al, 2004b;Crowley et al, 2002;Munjal et al, 2006a;Repka et al, 2005;Repka et al, 2003;Young Cr, 2005;Young, 2003;Zheng et al, 2004).…”

Immunization with PspA Incorporated into a Poly(Ethylene Oxide) Matrix Elicits Protective Immunity against Streptococcus pneumoniae

“…This shows that PspA in the matrix is recognized by the immune system and that the immune response is similar to that in mice immunized with PspA on alum and is not a local response. The laminated-film system has been used to study the prophylaxis and treatment of oral candidiasis by incorporating clotrimazole in the film system and the delivery of dental analgesia such as lidocaine (19,20). To our knowledge, this study is the first to investigate the efficacy of pneumococcal immunization via a laminated-film system.…”

“…rPspA/Rx1 was incorporated into hot-melt extrusion matrices composed of poly(ethylene oxide). This process has been shown to be a viable technique for delivery of drugs (20). A volume of polymer slurry was mixed with 500 g of rPspA/Rx1 such that a 5-mm disk of the final material would contain approximately 30 g of rPspA/Rx1 using an extruder that produced a single sheet or film of polymerized matrix.…”