Evaluation of different substrates for inkjet printing of rasagiline mesylate.

The main goal of the present study was to evaluate applicability of the different model substrates, namely orodispersible films (ODFs), porous copy paper sheets, and water impermeable transparency films (TFs) in preparation of the inkjet-printed drug-delivery systems. Rasagiline mesylate (RM) was used as a low-dose active pharmaceutical ingredient (API). Flexible doses of the drug in a single unit were obtained by printing several subsequent layers on top of the already printed ones, using an off-the-shelf consumer thermal inkjet (TIJ) printer. The produced drug-delivery systems were subjected to microscopic and chemical analysis together with solid-state characterization and content uniformity studies. The results revealed that RM recrystallized on the surface of ODFs and TFs, and the printed crystals were arranged in lines. No drug crystals were detected after printing on the surface of the copy paper due to absorption of the ink into the matrix of the substrate. The best linear correlation between the dose of the drug and the number of the printing layers was obtained for the porous copy paper. The other two substrates showed poor linearity and unacceptable standard deviations of the printed drug substance due to limited absorption of the API ink into the carrier. The shear stress between the substrate, the print head, and the paper feeding rollers caused smearing of the drug that had been surface-deposited during the earlier printing cycles. In conclusion, this study indicates that the edible substrates with absorption properties similar to copy paper are favorable for successful preparation of drug-delivery systems by TIJ printers.

Drug-printing by flexographic printing technology--a new manufacturing process for orodispersible films.

Orodispersible films (ODFs) are intended to disintegrate within seconds when placed onto the tongue. The common way of manufacturing is the solvent casting method. Flexographic printing on drug-free ODFs is introduced as a highly flexible and cost-effective alternative manufacturing method in this study. Rasagiline mesylate and tadalafil were used as model drugs. Printing of rasagiline solutions and tadalafil suspensions was feasible. Up to four printing cycles were performed. The possibility to employ several printing cycles enables a continuous, highly flexible manufacturing process, for example for individualised medicine. The obtained ODFs were characterised regarding their mechanical properties, their disintegration time, API crystallinity and homogeneity. Rasagiline mesylate did not recrystallise after the printing process. Relevant film properties were not affected by printing. Results were comparable to the results of ODFs manufactured with the common solvent casting technique, but the APIs are less stressed through mixing, solvent evaporation and heat. Further, loss of material due to cutting jumbo and daughter rolls can be reduced. Therefore, a versatile new manufacturing technology particularly for processing high-potent low-dose or heat sensitive drugs is introduced in this study.

Advances in orodispersible films for drug delivery.

INTRODUCTION: Orodispersible films for oral delivery are gaining popularity. Whereas breath-fresheners and over-the-counter products have already become quite common in the US, the first prescription drug films were introduced into the EU and US markets only very recently. Already considered as a unique Rx (prescription drug) dosage form by the FDA (oral soluble film), such products are not substitutable by conventional oral dosage forms. The official term defined by the European Medicines Agency is orodispersible film (ODF). AREAS COVERED: This review gives an overview on the benefits of ODFs, typical excipients and products already available on the market. ODFs are defined and differentiated from other films and dosage forms. Possible manufacturing methods are described. As ODFs are not yet listed in one of the pharmacopoeias, possible methods for characterization and quality control are discussed. Required characteristics, advantages and disadvantages are elaborated. Biopharmaceutical considerations are provided because such films can also be used to enhance bioavailability of a drug. EXPERT OPINION: The magnitude of variants of ODF technology and the advantages over conventional dosage forms promise more applications and more marketed products with ODFs in the near future. Therefore, the authorities have to publish a monograph for ODFs as soon as possible to standardize characterization methods and quality specifications.

Rapidfilm: an innovative pharmaceutical form designed to improve patient compliance.

The aim of the research was to assess the bioequivalence between Rapidfilm, a new patented delivery system, versus the traditional orodispersible tablet (ODT). A randomized, two-way, single dose, crossover, bioequivalence study was conducted in 24 fasting, healthy volunteers with two formulations of ondansetron (Ondansetron Rapidfilm vs. Zofran Zydis Lingual ODT by GlaxoSmithKline GmbH & Co. KG). Plasma samples were analysed by a validated LC-MS/MS method during a collection period of 24 h post-dosing. The analysis of variance (ANOVA) on the targeted pharmacokinetic parameters did not show any significant difference between the two formulations and 90% confidence intervals (CIs) fell within the common acceptance range of 80-125%, satisfying the bioequivalence criteria. These results allow Rapidfilm to claim the same panel of indications of the conventional immediate release oral solid dosage forms, but offering several advantages also over the ODT: it can result in higher patient convenience for several applications.

Loading of tetanus toxoid to biodegradable nanoparticles from branched poly(sulfobutyl-polyvinyl alcohol)-g-(lactide-co-glycolide) nanoparticles by protein adsorption: a mechanistic study.

PURPOSE: Mucosal delivery of vaccine-loaded nanoparticles (NP) is an attractive proposition from an immunologic perspective. Although numerous NP preparation methods are known, sufficient antigen loading of NP remains a challenge. The aim of this study was to evaluate adsorptive loading of NP with a negatively charged surface structure using tetanus toxoid (TT) as a model vaccine. METHODS: Blank NP, consisting of poly(sulfobutyl-polyvinyl alcohol)-g-(lactide-co-glycolide), as well as poly(lactide-co-glycolide) NP were prepared by a solvent displacement technique. The use of polymers with different degrees of substitution resulted in NP with different negative surfaces charges. Adsorption of TT to NP was performed varying to NP surface properties, protein equilibrium concentration, and loading conditions. RESULTS: The protein adsorption was controlled by NP surface properties, and maximum TT adsorption occurred at highly negatively charged NP surfaces. Results from isothermal titration calorimetry and zeta-potential measurement suggest an adsorption process governed by electrostatic interactions. The adsorption followed the Langmuir isotherm in the concentration ranges studied. TT withstood this gentle loading procedure in a nonaggregated, enzyme-linked immunoabsorbant assay-active form. CONCLUSION: The results demonstrate that negatively charged NP consisting of poly(sulfobutyl-polyvinyl alcohol)-g-(lactide-co-glycolide) are suitable for adsorptive loading with TT and may have potential for mucosal vaccination.