Bioadhesive Films Research Articles

Physical Characterization of a New Skin Bioadhesive Film

Physical properties (roughness, gloss, mechanical, surface topography and adhesive) of a bioadhesive film for the transdermal delivery of drugs and its interactions with a skin model surface were studied. Roughness is a measurement of the small-scale variations in the height of a physical surface. No significant differences in Ra between the "x" and "y" dimensions for both the skin model and patch were detected, due to uniformity in their production. Scanning electron microscope pictures showed small particles projected from the film. Those particles resulted in increasing roughness and surface area. For the patch, gloss values measured at 20 degrees were 6.0 +/- 0.9 and at 60 degrees , 32.2 +/- 2.2 gloss units, respectively, indicating a semi-gloss material. Concerning the mechanical properties, the tensile strength of the film resulted four- to sevenfold greater than the peel force from the model skin used, indicating the suitability of the film for skin application. The adhesion to skin model depended on the amount of water used for film application and on the elapsed time between film application and removal. Finally, the model skin that was invented by Charkoudian can be used as an alternative to costly and highly variable human skin substrates since it possesses human topography.

Ex vivo evaluation of bioadhesive films for buccal delivery of fentanyl

The goals of this work were (i) to develop bioadhesive films for the buccal delivery of fentanyl, and (ii) to evaluate their performance in vitro using the pig esophageal model. Films were made with polyvinylpyrrolidone (PVP) of two different molecular weights: PVP K30 and PVP K90. Delivery of fentanyl was determined across full-thickness mucosa and across heat-separated epithelium (where the permeability barrier was shown to be located). The influence of film pH was investigated, and it was found that fentanyl permeation increased with increasing pH (i.e., when a higher percentage of the unionized fraction of drug was present). However, at the pH values studied, fentanyl was predominantly ionized suggesting that transport pathways offering a hydrophilic, or polar, environment across the mucosa were available. The transport rates achieved from the PVP films providing the highest delivery suggest that a buccal system of only 1–2 cm2 in surface area could achieve a therapeutic effect equivalent to a 10 cm2 transdermal patch, with a much shorter lag-time.

Bioadhesive monolayer film for the in vitro transdermal delivery of sumatriptan

The work presented here aims to develop a bioadhesive monolayer film containing sumatriptan as adjuvant for the treatment of headache pain in a severe migraine attack. Permeation experiments were performed from the films prepared and from the respective solution, to evaluate the relevant permeation parameters. The effect of the penetration enhancers Transcutol, 2-pyrrolidone, and polyethylene glycol 600 was evaluated. The results obtained show that Transcutol and 2-pyrrolidone decreased sumatriptan permeation from solution, whereas a modest increase was produced by polyethylene glycol 600. The enhancers produced the same effects when they were included in the film. Compared to solution, the film showed a higher sumatriptan flux in the early times of the experiment. When the film was applied in occlusive conditions the profiles were much higher, indicating the importance of patch drying. Concerning skin retention, the bioadhesive film produced a reduction of the amount of sumatriptan remaining in the skin, but this can be advantageous in the control of drug input, since it reduces the reservoir effect in the skin and allows for an immediate interruption of drug input when the patch is removed.

New transdermal bioadhesive film containing oxybutynin: In vitro permeation across rabbit ear skin

Oxybutynin is used extensively in the treatment of patients with overactive bladder. The aim of this work was to realize and test in vitro a new transdermal bioadhesive film containing oxybutynin. Transdermal films were prepared by dissolving in water an adhesive (Plastoid ®), a film-forming polymer (polyvinyl alcohol), a plasticizer (sorbitol) and the drug. The mixture was then spread on siliconized paper and oven-dried. Permeation experiments were conducted in Franz-type diffusion cells using rabbit ear skin as barrier. The donor compartment contained a water solution, the prepared film (with or without backing) or the commercial patch (Oxytrol ®). The experiments were performed for 24 h. Oxybutynin showed good permeation characteristics across the skin. When the film was applied in occlusive conditions the release profiles were much higher than in non-occlusive conditions, reaching 50% of drug permeated after 24 h. Compared to the commercial patch Oxytrol ®, the film was more efficient suggesting that a smaller area or a lower drug loading could be employed. The results obtained show that the bioadhesive film can be a promising and innovative therapeutic system for the transdermal administration of oxybutynin.

Mechanical Characterization and Drug Permeation Properties of Tetracaine-loaded Bioadhesive Films for Percutaneous Local Anesthesia

ABSTRACTIn the development of bioadhesive patch devices for percutaneous local anesthesia, the tensile properties of the films produced after the casting of the gel intermediates is of key importance to the clinical compliance of the product, and its effective delivery of the local anesthetic agent. A range of bioadhesive patches were formulated and their mechanical and in vitro permeation properties determined. Altering formulation significantly altered the mechanical properties of films. The tensile properties of the films could be modified to allow concomitant benefits in the mechanical and drug permeation properties of the films, ensuring that patches not only exerted clinically beneficial effects, but are also mechanically robust. Tetracaine was found to plasticize films and while this effect was weak, it was significant both statistically and potentially also in the effect it has on the clinical use of these devices. Drug release from tetracaine patches demonstrate the same trends as found previously across polydimethylsiloxane films. By altering the formulation of the patch device, the drug release from the device to the skin is readily and accurately controlled, and was not solely a function of the stratum corneum barrier properties but additionally of the formulation.

Release and permeation kinetics of caffeine from bioadhesive transdermal films

The aim of this work was to investigate, in vitro, the kinetics of release and permeation of caffeine, chosen as model drug, from bioadhesive transdermal films. These films are not self-adhesive but become adhesive when applied to wet skin. Permeation experiments were performed from films with different drug loadings using rabbit ear skin as barrier. In order to characterize the release kinetics of caffeine from the film, a polyethylene membrane, impregnated with isopropyl myristate was employed. The data obtained in the present work suggest that caffeine release from transdermal bioadhesive films was controlled either by the permeability characteristics of the skin or by the film itself, depending on drug loading. When drug loading is low (ie, caffeine is dissolved in the polymers constituting the film), the control resides in the skin. When caffeine loading exceeds its solubility in the film, the permeation profile is not linear, but shows a sort of burst effect in the early times of permeation, probably owing to the presence of solid drug and/or to a certain degree of "conserved supersaturation" in the solid phase.

Evaluation of bioadhesive performance of chitosan derivatives as films for buccal application

The purpose of this work is to evaluate the buccal bioadhesive performance of film.s made by four different chitosan derivatives: chitosan chloride (CL., 13 ), chitosan glutamate (G., 13 ), 5-methyl-pyrrolidinone chitosan (MP) and a partially reacetylated chitosan (RC). Films were prepared by casting and ionically cross-linked by tripolyphosphate (TPP) using increasing TPP:chitosan molar ratio (20:1-200:1). A rapid and simple in vitro test based on use of buccal cell suspension was modified to assess bioadhesion of solid dosage forms and it proved able to discriminate between bioadhesion properties of films made by different chitosans and with different TPP:chitosan molar ratios. All films, with the exception of the MP films, have biphasic bioadhesion profile, showing a bioadhesiveness drop over a fixed amount of TPP which depends on the type of chitosan. This comparative study has enabled G 213 and MP to be chosen as the most promising chitosan derivatives aimed at optimizing the designing of controlled drug delivery via buccal bioadhesive films.

Bioadhesive Transdermal Film Containing Caffeine

The aim of this work was to investigate in vitro the transdermal permeation of caffeine from a new bioadhesive film, using rabbit ear skin as a barrier. The effects of film composition and of the presence of penetration enhancers in the formulation were studied. The obtained fluxes were compared with those shown by commercial formulations. The results obtained indicate that the bioadhesive film gave rise to a higher transdermal permeation compared to a commercial gel and to a saturated solution of caffeine in water. Additionally, the film did not present the typical time lag of solution and gel. Another peculiar feature of the film is that the percentage of permeated active substance is much higher than that obtained from commercial formulations. Finally, it was possible to modulate caffeine permeation from the film by adding different enhancers/solvents.

Influence of plasticizer type and storage conditions on properties of poly(methyl vinyl ether‐co‐maleic anhydride) bioadhesive films

AbstractPoly(methyl vinyl ether‐co‐maleic anhydride) formed films from aqueous formulations with characteristics that are ideal as a basis for producing a drug‐containing bioadhesive delivery system when plasticized with a monohydroxyl functionalized plasticizer. Hence, films containing a novel plasticizer, tripropylene glycol methyl ether (TPME), maintained their adhesive strength and tensile properties when packaged in aluminized foil for extended periods of time. Films plasticized with commonly used polyhydric alcohols, such as the glycerol in this study, underwent an esterification reaction that led to polymer crosslinking, as shown in NMR studies. These revealed the presence of peaks in the ester/carbonyl region, suggesting that glyceride residue formation had been initiated. Given the polyfunctional nature of glycerol, progressive esterification would result in a polyester network and an accompanying profound alteration in the physical characteristics. Indeed, films became brittle over time with a loss of both the aqueous solubility and bioadhesion to porcine skin. In addition, a swelling index was measurable after 7 days, a property not seen with those films containing TPME. This change in bioadhesive strength and pliability was independent of the packaging conditions, rendering the films that contain glycerol as unsuitable as a basis for topical bioadhesive delivery of drug substances. Consequently, films containing TPME have potential as an alternative formulation strategy. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 91: 1576–1589, 2004

Bioadhesive film for the transdermal delivery of lidocaine: in vitro and in vivo behavior

The aim of this work was to study, in vitro and in vivo, the behavior of a skin bioadhesive film containing lidocaine. The film characterization included drug transport studies through skin in vitro and in vivo tape stripping with and without iontophoresis. We studied the effect of drug loading in order to identify the release mechanism. Finally, the release rate was compared with a lidocaine commercial gel, to assess the therapeutic value. From the data obtained it can be concluded that the monolayer film acts as a water-permeable transdermal/dermal patch on application to the skin. The permeation kinetics across the skin was not linear, but the patch acted as a matrix controlling drug delivery. Additionally, the permeation rate increased with drug loading. The in vivo experiments with tape stripping indicated that the presence of water during film application is essential to achieve not only the proper adhesion but also an effective accumulation. The application of electric current to the patch can further increase the amount of drug accumulated in the stratum corneum.

Regulating aspects of biosoluble and insoluble film release systems containing protein proteinase inhibitor

New types of potent aprotinin-containing medicinal polymer films are elaborated for topical applications. The higher the temperature of drying, the lower the steam absorption, the film swelling, and the velocity of aprotinin in vitro release. The presence of antimicrobials having the basic functional groups contributed to compacting the structure of the films and retention of aprotinin in them. The velocity of aprotinin release from the films is regulated by adding different polymers. Inclusion of polyvinylpirrolidone in the film resulted in acceleration and increase of aprotinin release. This was probably because of increasing the film swelling by a factor of 1.7. Additional retention of the inhibitor in films was achieved by inclusion of sodium alginate and cellulose powder capable of binding aprotinin. Soluble bioadhesive films derived from a copolymer of acrylamide, N-vinyl-pirrolidone, ethyl acrylate (M r 30,000-600,000) and aprotinin were obtained and analyzed. Kinetics of aprotinin release from biosoluble films was studied under various conditions. The duration of aprotinin release was comparable with duration of gradual dissolution of the matrix. Bioavailability of aprotinin from soluble films was linear with time.

Moisture-activated, electrically conducting bioadhesive interfaces for biomedical sensor applications

An electrically conducting interface for biomedical sensors, formed by casting and drying a polymer blend containing poly(methyl vinyl ether–maleic anhydride), glycerin as plasticizer, polyvinylpyrrolidone as viscosity builder and sodium chloride as the conducting electrolyte, is described. The resulting flexible bioadhesive film can adhere to a biological substrate under adverse conditions such as high humidity or when the biological substrate is immersed in water or a physiological fluid. The technology allows the design, for example, of an electrode for the monitoring of foetal heart rate and other physiological and analytical sensors. The effect on interface bioadhesion of varying both the composition of the polymer blend and the ambient moisture conditions on storage were investigated in respect of bioadhesion to a model substrate (wet neonate porcine skin) and the mechanical behaviour of the the interface. Optimum bioadhesive performance was obtained from films formulated from blends (pH 5) containing copolymer–plasticizer (2 + 1) and 5% m/m polyvinylpyrrolidone. Moisture conditions on storage had a significant effect on both the subsequent bioadhesive performance and the mechanical properties of the stored films. Formulation and hydration interactions were identified using 2 × 2 factorial design experiments. Data analysis was by a two-way ANOVA with repeated measures.

Moisture‐activated, electrically conducting bioadhesive hydrogels as interfaces for bioelectrodes: Effect of film hydration on cutaneous adherence in wet environments

AbstractThe water contents of bioadhesive polymeric films of poly(methylvinyl ether–maleic anhydride) copolymer, stored at two humidities and at two temperatures, have been determined by continuous gravimetry. The water contents of the films increased under storage conditions of increasing humidity. The bioadhesion of these films was assessed using an in vitro bioadhesive tester previously validated in our laboratory. Water uptake during the bioadhesive test was taken into account and the final water content of films recorded as a “corrected equilibrium water content” (CEWC). A good quality second‐order polynomial relationship between bioadhesion and the CEWC of films stored at both 23 and 35°C was developed using standard curve fitting analyses. A 2 × 2 factorial design experiment revealed that there was a synergistic relationship between temperature and percentage relative humidity with regard to their effect on the bioadhesion of polymeric films, presumably due to their combined effect on film water content. These findings have implications for both the storage and packaging of hydrophilic polymeric films. © 1995 John Wiley & Sons, Inc.

A bioadhesive patch cervical drug delivery system for the administration of 5-fluorouracil to cervical tissue

A novel bioadhesive cervical patch drug delivery is described, containing 5-fluorouracil for the treatment of cervical intraepithelial neoplasia (CIN). The patch was of bilaminar design, with a drug-loaded bioadhesive film cast from a gel containing 2% (w/w) Carbopol® 981 plasticised with 1% (w/w) glycerin. The casting solvent was ethanol/water 30:70, chosen to give a non-fissuring film with an even particle size distribution. The film, which was mechanically stable on storage under ambient conditions, was bonded directly to a backing layer formed from thermally-cured polyvinyl chloride emulsion. Bioadhesive strength was independent of drug loading in the bioadhesive matrix over the range investigated but was influenced by both the plasticiser concentration in the casting gel and the thickness of the final film. Release of 5-fluorouracil from the bioadhesive layer into an aqueous sink was rapid but was controlled down to an undetectable level through the backing layer. The latter characteristic was desirable to prevent drug spill from the device onto vaginal epithelium in vivo. Despite the relatively hydrophilic nature of 5-fluorouracil, substantial drug release through human cervical tissue samples was observed over approximately 20 h. Drug release, which was clearly tissue rather than device dependent, may have been aided by a shunt diffusion route through aqueous pores in the tissue. The bioadhesive and drug release characteristics of the 5-fluorouracil cervical patch indicated that it would be suitable for further clinical investigation as a drug treatment for CIN.

Design of an apparatus incorporating a linear variable differential transformer for the measurement of type III bioadhesion to cervical tissue

The design and initial evaluation of a bioadhesive strength testing apparatus are reported. Measurement of adhesive strength is mediated via a linear variable differential transformer (LVDT). The apparatus, constructed from Perspex, consists of a movable platform with a pedestal to which the bioadhesive formulation is attached. Tissue is secured to a second, upper pedestal linked to the LVDT via a sensor. During the test procedure the platform is moved downwards at a predetermined rate controlled by the motor drive logic board. As movement occurs to the upper pedestal this can be detected by the output from the LVDT which is recorded potentiometrically. The force generated is measured by a previously calibrated spring contained within the sensor housing. Different calibrated springs can be used to increase OT decrease the sensitivity of the apparatus. Initial evaluation of the testing device was performed on a range of candidate bioadhesive film formulations. The effects on bioadhesion of varying the initial applied weight, mucus surface density, film thickness and film hydration were investigated. Excellent bioadhesion was achieved with the application of a dry sodium carboxymethylcellulose/ sodium carbopol film to cervical tissue with a surface mucus layer.