The Effect of Inkjet Printing over Polymeric Films as Potential Buccal Biologics Delivery Systems.

The buccal mucosa appears as a promissory route for biologic drug administration, and pharmaceutical films are flexible dosage forms that can be used in the buccal mucosa as drug delivery systems for either a local or systemic effect. Recently, thin films have been used as printing substrates to manufacture these dosage forms by inkjet printing. As such, it is necessary to investigate the effects of printing biologics on films as substrates in terms of their physical and mucoadhesive properties. Here, we explored solvent casting as a conventional method with two biocompatible polymers, hydroxypropyl methylcellulose, and chitosan, and we used electrospinning process as an electrospun film fabrication of polycaprolactone fibers due to its potential to elicit mucoadhesion. Lysozyme was used as biologic drug model and was formulated as a solution for printing by thermal inkjet printing. Films were characterized before and after printing by mechanical and mucoadhesive properties, surface, and ultrastructure morphology through scanning electron microscopy and solid state properties by thermal analysis. Although minor differences were detected in micrographs and thermograms in all polymeric films tested, neither mechanical nor mucoadhesive properties were affected by these differences. Thus, biologic drug printing on films was successful without affecting their mechanical or mucoadhesive properties. These results open way to explore biologics loading on buccal films by inkjet printing, and future efforts will include further in vitro and in vivo evaluations.

Effect of surfactants and drug load on physico-mechanical and dissolution properties of nanocrystalline tadalafil-loaded oral films.

The aim of the present work was to prepare tadalafil (TDF) nanocrystals-loaded oral polymeric films (OFs) and investigate the effect of hydrophilic surfactants and drug loads on the physico-mechanical and dissolution properties. The nanosuspensions of TDF were prepared by high shear homogenization. HPMC based placebo casting film gel was prepared and mixed with TDF nanosuspensions. Films were casted using an automated film applicator and dried at 60°C for 45min. Particle size (PS), polydispersity index (PDI), and zeta potential (ZP) of TDF nanosuspensions were measured in a Zetasizer. The films were characterized using SEM, AFM, DSC, TGA and PXRD. The mechanical properties and in vitro drug release were determined using standard methods. TDF existed in crystalline form and the particles remained in the nano-range in redispersed films. TDF nanocrystals were embedded in the polymeric matrix and the drug loaded films were rough on the surface. Mechanical properties of the films varied with changes in drug load and surfactant. Significant changes in the disintegration times were noticed in films containing surfactants compared to surfactant-free films. About 80% of the drug release was observed between 3 and 30min. TPGS showed better TDF release from the films at different drug loads. CHEMICAL COMPOUNDS: Hydroxy propyl methyl cellulose (PubChem CID: 57503849); Glycerol (PubChem CID: 753); Pluronic F-68 (PubChem CID: 24751); Vitamin E TPGS (PubChem CID: 71406).

Challenges and Future Prospects for the Delivery of Biologics: Oral Mucosal, Pulmonary, and Transdermal Routes.

Biologic products are large molecules such as proteins, peptides, nucleic acids, etc., which have already produced many new drugs for clinical use in the last decades. Due to the inherent challenges faced by biologics after oral administration (e.g., acidic stomach pH, digestive enzymes, and limited permeation through the gastrointestinal tract), several alternative routes of administration have been investigated to enable sufficient drug absorption into systemic circulation. This review describes the buccal, sublingual, pulmonary, and transdermal routes of administration for biologics with relevant details of the respective barriers. While all these routes avoid transit through the gastrointestinal tract, each has its own strengths and weaknesses that may be optimal for specific classes of compounds. Buccal and sublingual delivery enable rapid drug uptake through a relatively permeable barrier but are limited by small epithelial surface area, stratified epithelia, and the practical complexities of maintaining a drug delivery system in the mouth. Pulmonary delivery accesses the highly permeable and large surface area of the alveolar epithelium but must overcome the complexities of safe and effective delivery to the alveoli deep in the lung. Transdermal delivery offers convenient access to the body for extended-release delivery via the skin surface but requires the use of novel devices and formulations to overcome the skin's formidable stratum corneum barrier. New technologies and strategies advanced to overcome these challenges are reviewed, and critical views in future developments of each route are given.

Effect of plasticizers on the physico-mechanical properties of pullulan based pharmaceutical oral films.

The effect of different plasticizers (glycerol, vitamin E TPGS and triacetin) and their concentrations on the physico-mechanical properties of pullulan based oral films was studied. A full factorial (32) design of experiments was used. Elastic modulus, tensile strength, elongation at break and disintegration time were selected as response variables. Modulated differential scanning calorimeter (MDSC) was used for determining glass transition temperature (Tg) of pullulan films. The surface morphology of films was evaluated by SEM, while ATR-FTIR was used to obtain a molecular level understanding of polymer-plasticizer interactions. The DoE analysis allowed for the modelling of tensile strength and elongation at break. The highest elongations were observed in glycerol at 20% w/w. Majority of the films disintegrated within one minute without significant differences. ATR-FTIR spectra of pullulan alone and different plasticizer blend films show characteristic molecular interactions. The present study concluded that glycerol is suitable plasticizer compared to others for manufacturing pullulan based oral films.

Inkjet Printing of Proteins: an Experimental Approach.

Peptides and proteins represent a promissory group of molecules used by the pharmaceutical industry for drug therapy with great potential for development. However, the administration of these molecules presents a series of difficulties, making necessary the exploration of new alternatives like the buccal route of administration to improve drug therapy compliance. Although drop-on demand printers have been explored for small molecule drugs with promising results, the development of delivery systems for peptides and proteins through inkjet printing has seen little development. Therefore, the aim of this study was to assess the feasibility of using a thermal inkjet printing system for dispensing lysozyme and ribonuclease-A as model proteins. To address the absorption limitations of a potential buccal use, a permeation enhancer (sodium deoxycholate) was also studied in formulations. We found that a conventional printer successfully printed both proteins, exhibiting very high printing efficiency. Furthermore, the protein structure was not affected and minor effects were observed in the enzymatic activity after the printing process. In conclusion, we provide evidence for the usage of an inexpensive, easy to use, reliable, and reproducible thermal inkjet printing system to dispense proteins solutions for potential buccal application. Our research significantly contributes to present an alternative for manufacturing biologics delivery systems, with emphasis in buccal applications. Next steps of developments will be aimed at the use of new materials for printing, controlled release, and protection strategies for proteins and peptides.

Overview and Future Potential of Buccal Mucoadhesive Films as Drug Delivery Systems for Biologics.

The main route of administration for drug products is the oral route, yet biologics are initially developed as injectables due to their limited stability through the gastrointestinal tract and solubility issues. In order to avoid injections, a myriad of investigations on alternative administration routes that can bypass enzymatic degradation and the first-pass effect are found in the literature. As an alternative site for biologics absorption, the buccal route presents with a number of advantages. The buccal mucosa is a barrier, providing protection to underlying tissue, but is more permeable than other alternative routes such as the skin. Buccal films are polymeric matrices designed to be mucoadhesive properties and usually formulated with permeability enhancers to improve bioavailability. Conventionally, buccal films for biologics are manufactured by solvent casting, yet recent developments have shown the potential of hot melt extrusion, and most recently ink jet printing as promising strategies. This review aims at depicting the field of biologics-loaded mucoadhesive films as buccal drug delivery systems. In light of the literature available, the buccal epithelium is a promising route for biologics administration, which is reflected in clinical trials currently in progress, looking forward to register and commercialize the first biologic product formulated as a buccal film.