Dissolvable Films Research Articles

RESULTS OF A REPEAT DOSE STUDY ON THE PHARMACOKINETICS OF A SUBLINGUAL FILM USING A NOVEL PRODRUG OF EPINEPHRINE (DESF)

<h3>Introduction</h3> DESF is the first and only orally delivered epinephrine product candidate in clinical development and has the same target indication as that for Epinephrine injection in the emergency treatment of Type 1 allergic reactions. A pre-clinical study was conducted to compare the pharmacokinetic profiles of epinephrine following administration of DESF via one or two dissolvable films in miniature swine. <h3>Methods</h3> A total of 20 male Yucatan miniature swine were used for this study. Animals were separated into two groups and received either one or two doses of DESF 12 mg 10 minutes apart. Following dose administration, the animals had pharmacokinetic (PK) blood samples obtained at multiple time-points, with Oral Mucositis Assessment Scale (OMAS) scores performed at pre-dose, 4 hours, and 24 hours post-dose. <h3>Results</h3> No mortality/moribundity occurred during the study. The group receiving a single dose had an expected lower mean Cmax (11.1 vs 24.7 ng/ml) and AUC (738.5 vs 1314 ng/ml*min) than the group receiving repeated doses. The Cmax ratio and AUC ratio were similar at 2.23 and 1.78, respectively. Tmax was established at around 30 min. for the single dose group and at around 40 min. for those receiving a repeat dose. The overall PK profiles showed similar patterns between the two groups. <h3>Conclusion</h3> DESF demonstrates dose proportional PK when a second dose is administered 10 minutes after the first done. These results suggest that a different treatment delivery modality for epinephrine is possible and could address significant unmet need in patients.

Trends in food sensory science

Trends in food sensory science

Centrifugally automated Solid-Phase Extraction of DNA by immiscible liquid valving and chemically powered centripetal pumping of peripherally stored reagents

This paper presents two flow-control technologies for use on centrifugal Lab-on-a-Disc systems. The first, immiscible liquid valving, selectively blocks microfluidic channels using a high-density liquid fluorocarbon (FC-40). Used with a specific channel geometry, the FC-40 can permit liquid to enter a chamber but prevents it flowing back along the same path and so acts as “liquid” check-valve. The same liquid can be combined with a water-dissolvable film to provide an extremely robust liquid routing structure. The second technology uses CO2 gas, created by wetting of commodity baking powder by water, to centripetally pump liquid from the periphery of the disc to the centre of the disc. The technologies are combined with valving schemes based on strategically placed, solvent-selective dissolvable films (DFs) to demonstrate repeated pumping of a liquid sample from the edge of the disc to the centre of the disc. The flow-control technologies are then combined to demonstrate fully automated Solid-Phase Extraction (SPE) of DNA with reagent storage on the periphery of the disc. We report an extraction efficiency of 47% measured relative to commercial spin-columns.

Development of Oral Dissolvable Films of Diclofenac Sodium for Osteoarthritis Using Albizia and Khaya Gums as Hydrophilic Film Formers.

Oral dissolvable films (ODFs) of diclofenac sodium intended for osteoarthritis were prepared using Albizia and Khaya gums as hydrophilic film formers. The physicochemical properties of the gums were characterized and the gums were used to prepare diclofenac sodium ODFs (~50 mg/4 cm2 film) by solvent casting. The two gums showed satisfactory film forming properties. The physicomechanical properties, drug-excipient compatibility, and in vitro drug release of the films in phosphate buffer pH 6.8 were studied. Khaya gum had higher extraction yield, moisture content, insoluble matter and true density while Albizia gum showed greater swelling capacity, solubility, and minerals content. The ODFs were thin, soft, and flexible with smooth glossy surfaces and possessed satisfactory physicomechanical properties. FTIR studies showed that no interaction occurred between the drug and the gums. The ODFs disintegrated in <45 s achieved >75% drug release within 7 min with dissolution efficiencies of ~83–96%. Drug releases from F2, F3, F4, F5, and F6 were similar to F1 (p > 0.05; f1 < 15 and f2 ≥ 50) while F7 differed markedly from F1 (p < 0.001; f1 > 15 and f2 < 50). Drug release followed the Higuchi kinetic model which is indicative of Fickian drug diffusion.

Printing medicines as orodispersible dosage forms: Effect of substrate on the printed micro-structure

We present our recent advancements in developing a viable manufacturing process for printed medicine. Our approach involves using a non-contact printing system that incorporates both piezoelectric- and solenoid valve-based inkjet printing technologies, to deliver both active and inactive pharmaceutical materials onto medical-graded orodispersible films. By using two complimentary inkjet technologies, we were able to dispense an extensive range of fluids, from aqueous drug solutions to viscous polymer coating materials. Essentially, we demonstrate printing of a wide range of formulations for patient-ready, orodispersible drug dosage forms, without the risk of drug degradation by ink heating and of substrate damages (by contact printing). In addition, our printing process has been optimized to ensure that the drug doses can be loaded onto the orally dissolvable films without introducing defects, such as holes or tears, while retaining a smooth surface texture that promotes patient adherence and allows for uniform post-coatings. Results show that our platform technology can address key issues in manufacturing orodispersible drug dosage forms and bring us closer to delivering personalized and precision medicine to targeted patient populations.

Correlation between temperature-dependent dissolution of poly(N-vinylcaprolactam)/poly(N-l-(1-hydroxymethyl)propylmethacrylamide) layer-by-layer films and cloud point of mixed solutions of the two polymers in the presence of chloride salts

We studied the effect of chloride salts on the dissolution behavior of layer-by-layer (LbL) films of two thermosensitive polymers. Poly(N-vinylcaprolactam) (PVCL) and poly(N-l-(1-hydroxymethyl)propylmethacrylamide) (P(l-HMPMAm)) were used to assemble a LbL film in water at 33°C. We found that the dissolution temperature (Td) of the LbL film in a solution of 0.5M chloride salts was lower than that in water. Furthermore, the effect of chloride salts on the Td of films was positively correlated with the effect of chloride salts on the cloud points of the mixed solutions. These experimental results indicate that the stability of the LbL films of two thermosensitive homopolymers can be increased in chloride salt solutions. Other researchers have found that some polyelectrolyte LbL films are stable in water but dissolve in a solution containing high concentrations of salts. The effect of salts on polyelectrolyte LbL films and the effect of salts on LbL films of the thermosensitive polymers are opposite. The opposite effects could be attributed to the different characteristics – some films are ionic and the others are non-ionic. These dissolvable films of non-ionic polymers could have potential for biological applications.

Novel probiotic dissolvable carboxymethyl cellulose films as oral health biotherapeutics: in vitro preparation and characterization

Objectives: Oral health is influenced by the mouth's resident microorganisms. Dental caries and periodontitis are oral disorders caused by imbalances in the oral microbiota. Probiotics have potential for the prevention and treatment of oral disorders. Current formulations, including supplements and foods, have limitations for oral delivery including short storage time, low residence time in the mouth, effects on food consistency, and low patient compliance. Oral thin films (OTFs) may be efficient in delivering probiotics to the mouth. This research aims to develop a novel carboxymethyl cellulose (CMC)-probiotic-OTF to deliver probiotics for the treatment/prevention of oral disorders.Methods: CMC-OTFs were developed with varying CMC concentration (1.25 – 10 mg/mL), weight (5 – 40 g), thickness (16 – 262 μm), hygroscopicity (30.8 – 78.9 mg/cm2 film), and dissolving time (135 – 600 s). The 10 g 5 mg/mL CMC-OTF was selected and used to incorporate Lactobacillus fermentum NCIMB 5221 (6.75 × 108 cells/film), a probiotic with anti-inflammatory potential for periodontitis treatment and capable of inhibiting microorganisms responsible for dental caries and oral candidiasis.Results: The CMC-OTF maintained probiotic viability and antioxidant activity following 150 days of storage with a production of 549.52 ± 26.08 μM Trolox equivalents.Conclusion: This research shows the successful development and characterization of a novel probiotic-CMC-OTF with potential as an oral health biotherapeutic.

Centrifugo-pneumatic valving utilizing dissolvable films

In this article we introduce a novel technology that utilizes specialized water dissolvable thin films for valving in centrifugal microfluidic systems. In previous work (William Meathrel and Cathy Moritz, IVD Technologies, 2007), dissolvable films (DFs) have been assembled in laminar flow devices to form efficient sacrificial valves where DFs simply open by direct contact with liquid. Here, we build on the original DF valving scheme to leverage sophisticated, merely rotationally actuated vapour barriers and flow control for enabling comprehensive assay integration with low-complexity instrumentation on "lab-on-a-disc" platforms. The advanced sacrificial valving function is achieved by creating an inverted gas-liquid stack upstream of the DF during priming of the system. At low rotational speeds, a pocket of trapped air prevents a surface-tension stabilized liquid plug from wetting the DF membrane. However, high-speed rotation disrupts the metastable gas/liquid interface to wet the DF and thus opens the valve. By judicious choice of the radial position and geometry of the valve, the burst frequency can be tuned over a wide range of rotational speeds nearly 10 times greater than those attained by common capillary burst valves based on hydrophobic constrictions. The broad range of reproducible burst frequencies of the DF valves bears the potential for full integration and automation of comprehensive, multi-step biochemical assay protocols. In this report we demonstrate DF valving, discuss the biocompatibility of using the films, and show a potential sequential valving system including the on-demand release of on-board stored liquid reagents, fast centrifugal sedimentation and vigorous mixing; thus providing a viable basis for use in lab-on-a-disc platforms for point-of-care diagnostics and other life science applications.

Dissolvable films of silk fibroin for ultrathin conformal bio-integrated electronics

Electronics that are capable of intimate, non-invasive integration with the soft, curvilinear surfaces of biological tissues offer important opportunities for diagnosing and treating disease and for improving brain/machine interfaces. This article describes a material strategy for a type of bio-interfaced system that relies on ultrathin electronics supported by bioresorbable substrates of silk fibroin. Mounting such devices on tissue and then allowing the silk to dissolve and resorb initiates a spontaneous, conformal wrapping process driven by capillary forces at the biotic/abiotic interface. Specialized mesh designs and ultrathin forms for the electronics ensure minimal stresses on the tissue and highly conformal coverage, even for complex curvilinear surfaces, as confirmed by experimental and theoretical studies. In vivo, neural mapping experiments on feline animal models illustrate one mode of use for this class of technology. These concepts provide new capabilities for implantable and surgical devices.