Unidirectional Drug Release Research Articles

Permeability of triamcinolone acetonide, released from mucoadhesive films, through a buccal mucosa-mimetic barrier: Permeapad™

ObjectivesThe permeability of triamcinolone acetonide (TA), from bilayer mucoadhesive buccal films, through a biomimetic membrane, Permeapad™, was investigated employing Franz diffusion cell. The delivery systems composition and ethyl cellulose (EC) backing layer, on drug permeability, were assessed. MethodsThree TA-loaded films were tested; hydroxypropyl methylcellulose (HPMC K4M; bilayer [F1] and monolayer), HPMC K4M/Polyvinylpyrrolidone (PVP): 90/10 [F2], and HPMC K15M film [F3]. All films contained propylene glycol (PG-plasticiser). TA solution alone was used as a control. TA permeability via a Permeapad™ barrier, simulating buccal mucosa, was assessed over 8 h using a Franz diffusion cell. TA permeated into the receptor compartment, released in the donor compartment, and located on/within the Permeapad™ barrier were analysed using UV-spectrophotometer. Results45.7 % drug retention within the Permeapad™ barrier was delivered from F1 (highest). F1, F2, and F3 significantly improved the TA’s permeability through Permeapad™, compared to TA solution alone (e.g., 8.5 % TA-solution, 21.5 %-F1), attributed to the synergy effect of HPMC and propylene glycol acting as penetration enhancers. F1 displayed a significant increase in drug permeability (receptor compartment; 21.5 %) compared to F3 (17.0 %). PVP significantly enhanced drug permeability (27.5 %). Impermeable EC backing layer controlled unidirectional drug release and reduced drug loss into the donor compartment (e.g., ∼28 % for monolayer film to ∼10 % for bilayer film, F1). SignificanceThe mucoadhesive films demonstrated improved TA permeability via Permeapad™. The findings suggest that these bilayer mucoadhesive films, particularly F1, hold promise for the effective topical treatment of oral mucosa disorders, such as recurrent aphthous stomatitis and oral lichen planus.

Biodegradable Local Chemotherapy Platform with Prolonged and Controlled Release of Doxorubicin for the Prevention of Local Tumor Recurrence.

Local recurrence after surgical and therapeutic treatment remains a significant clinical problem in oncology. Recurrence may be due to imperfections in existing therapies, particularly chemotherapy. To improve antitumor activity and prevent local cancer recurrence while keeping toxicity at acceptable levels, we have developed and demonstrated a biodegradable local chemotherapy platform that provides controlled and prolonged drug release. The platform consists of a polycaprolactone (PCL) substrate, which provides the structural integrity of the platform and the predominant unidirectional drug release, and a thin multilayer coating (∼200 nm) containing doxorubicin (DOX). The coating is an electrostatic complex obtained by the layer-by-layer (LbL) assembly and consists of natural polyelectrolytes [poly-γ-glutamic acid (γ-PGA) and chitosan (CS) or poly-l-lysine (PLL)]. To improve the release stability, an ionic conjugate of DOX and γ-PGA was prepared and incorporated into the multilayer coating. By varying the structure of the coating by adding empty (without DOX) bilayers, we were able to control the kinetics of drug release. The resulting platforms contained equal numbers of empty bilayers and DOX-loaded bilayers (15 + 15 or 30 + 30 bilayers) with a maximum loading of 566 ng/cm2. The platforms demonstrated prolonged and fairly uniform drug release for more than 5 months while retaining antitumor activity in vitro on ovarian cancer cells (SKOV-3). The empty platforms (without DOX) showed good cytocompatibility and no cytotoxicity to human fibroblasts and SKOV-3 cells. This study presents the development of a local chemotherapy platform consisting of a PCL-based substrate which provides structural stability and a biodegradable polyelectrolyte layered coating which combines layers containing a polyanion ionic complex with DOX with empty bilayers to ensure prolonged and controlled drug release. Our results may provide a basis for improving the efficacy of chemotherapy using drug delivery systems.

Flexible Coatings Facilitate pH-Targeted Drug Release via Self-Unfolding Foils: Applications for Oral Drug Delivery.

Ingestible self-configurable proximity-enabling devices have been developed as a non-invasive platform to improve the bioavailability of drug compounds via swellable or self-unfolding devices. Self-unfolding foils support unidirectional drug release in close proximity to the intestinal epithelium, the main drug absorption site following oral administration. The foils are loaded with a solid-state formulation containing the active pharmaceutical ingredient and then coated and rolled into enteric capsules. The coated lid must remain intact to ensure drug protection in the rolled state until targeted release in the small intestine after capsule disintegration. Despite promising results in previous studies, the deposition of an enteric top coating that remains intact after rolling is still challenging. In this study, we compare different mixtures of enteric polymers and a plasticizer, PEG 6000, as potential coating materials. We evaluate mechanical properties as well as drug protection and targeted release in gastric and intestinal media, respectively. Commercially available Eudragit® FL30D-55 appears to be the most suitable material due to its high strain at failure and integrity after capsule fitting. In vitro studies of coated foils in gastric and intestinal media confirm successful pH-triggered drug release. This indicates the potential advantage of the selected material in the development of self-unfolding foils for oral drug delivery.

Comprehensive review of materials, applications, and future innovations in biodegradable esophageal stents.

Esophageal stricture (ES) results from benign and malignant conditions, such as uncontrolled gastroesophageal reflux disease (GERD) and esophageal neoplasms. Upper gastrointestinal endoscopy is the preferred diagnostic approach for ES and its underlying causes. Stent insertion using an endoscope is a prevalent method for alleviating or treating ES. Nevertheless, the widely used self-expandable metal stents (SEMS) and self-expandable plastic stents (SEPS) can result in complications such as migration and restenosis. Furthermore, they necessitate secondary extraction in cases of benign esophageal stricture (BES), rendering them unsatisfactory for clinical requirements. Over the past 3decades, significant attention has been devoted to biodegradable materials, including synthetic polyester polymers and magnesium-based alloys, owing to their exceptional biocompatibility and biodegradability while addressing the challenges associated with recurring procedures after BES resolves. Novel esophageal stents have been developed and are undergoing experimental and clinical trials. Drug-eluting stents (DES) with drug-loading and drug-releasing capabilities are currently a research focal point, offering more efficient and precise ES treatments. Functional innovations have been investigated to optimize stent performance, including unidirectional drug-release and anti-migration features. Emerging manufacturing technologies such as three-dimensional (3D) printing and new biodegradable materials such as hydrogels have also contributed to the innovation of esophageal stents. The ultimate objective of the research and development of these materials is their clinical application in the treatment of ES and other benign conditions and the palliative treatment of malignant esophageal stricture (MES). This review aimed to offer a comprehensive overview of current biodegradable esophageal stent materials and their applications, highlight current research limitations and innovations, and offer insights into future development priorities and directions.

Unidirectional drug release from 3D printed personalized buccal patches using FDM technology

Oromucosal delivery of active ingredients of drugs provides a superior administration route for the treatment of oral diseases, due to avoidance of the first pass effect. In the present work, in view of the characteristics of large differences between oral ulcer symptoms and different lesion sizes, dexamethasone acetate unidirectional drug release buccal patches has been prepared based on Fused Deposition Modelling (FDM). Unidirectional drug release was achieved by covering the top and side with ethyl cellulose. Polyvinyl alcohol as a drug carrier, xylitol as a plasticizer. First, the protection effect of different thicknesses of the protective layer is investigated to determine the thickness of the protective layer. Co-extrusion printing method was adapted, utilizing blank filament to regulate preparations with different areas' drug loading. The results show that co-extrusion had no significant impact on the overall patches' drug release and adhesion properties. The physicochemical properties of the patches were also characterized. Evaluation of irritation is showed that these patches do not cause irritation to the oral mucosa of rats. Pharmacodynamic evaluation results showed that the preparation could promote the reduction of ulcer area. The results showed that FDM printing is a convenient and practical approach in manufacturing buccal patches.

Development and Characterization of Gel-Based Buccoadhesive Bilayer Formulation of Nifedipine.

A promising controlled drug delivery system has been developed based on polymeric buccoadhesive bilayered formulation that uses a drug-free backing layer and a polymeric hydrophilic gel buccoadhesive core layer containing nifedipine. The DSC thermogravimetric analysis confirms the drug's entrapment in the gel layer and reveals no evidence of a potential interaction. Various ratios of bioadhesive polymers, including HPMC K100, PVP K30, SCMC, and CP 934, were combined with EC as an impermeable backing layer to ensure unidirectional drug release towards the buccal mucosa. The polymeric compositions of hydrophilic gel-natured HPMC, SCMC, and CP formed a matrix layer by surrounding the core nifedipine during compression. Preformulation studies were performed for all of the ingredients in order to evaluate their physical and flow characteristics. Ex vivo buccoadhesive strength, surface pH, swelling index, in vitro and in vivo drug release, and ex vivo permeation investigations were performed to evaluate the produced gel-based system. Rapid temperature variations had no appreciable impact on the substance's physical properties, pharmacological content, or buccoadhesive strength during stability testing using actual human saliva. It was clear from a histological examination of the ex vivo mucosa that the developed system did not cause any irritation or inflammation at the site of administration. The formulation NT5 was the best one, with a correlation coefficient of 0.9966. The in vitro and in vivo drug release profiles were well correlated, and they mimic the in vitro drug release pattern via the biological membrane. Thus, the developed gel-based formulation was found to be novel, stable, and useful for the targeted delivery of nifedipine.

Antibacterial food packaging capable of sustained and unidirectional release carvacrol/thymol nanoemulsions for pork preservation

Pork is highly susceptible to microbial spoilage and oxidative deterioration. In this work, an active packaging film capable of sustained and unidirectional release natural antimicrobials was developed to prolong the shelf life of chilled pork. Thymol&carvacrol nanoemulsions (TH&CA NEs) with two active constituents were prepared by low-energy spontaneous emulsification method and showed excellent antioxidant and antibacterial abilities. A trilayer film composed of loading, adhesive and barrier layers were fabricated using polyquaternium-10 (PQ-10)&carboxymethyl chitosan (CMC) microgels (denoted as PC), mixed solution of PQ-10 and zein (Z), and zein solution as raw material of each layer by layer-by-layer casting method. TH&CA@PC-PZ-Z packaging films were obtained by adding dropwise TH&CA NEs onto PC loading layer of PC-PZ-Z film and showed good interlaminar bonding strength, suitable water retention, satisfactory biological safety, as well as great antioxidant and antibacterial activities. In addition, most of TH&CA NEs in TH&CA@PC-PZ-Z films could be released from PC loading layer in a sustainable way for at least 7 days due to the block of Z barrier layer. The preservation effects of TH&CA@PC-PZ-Z films on chilled pork were further investigated in comparison with a plastic fresh-keeping film made by low-density polyethylene (LDPE). Results showed that TH&CA@PC-PZ-Z films could effectively retard lipid and protein oxidation and inhibit microbial growth during 11 days storage, thereby prolonged the shelf-life of chilled pork. We believe that the sustainable and unidirectional drug release film can be developed as a promising packaging film in preserving fresh meat products.

The Influence of Shape Parameters on Unidirectional Drug Release from 3D Printed Implants and Prediction of Release from Implants with Individualized Shapes.

The local treatment of diseases by drug-eluting implants is a promising tool to enable successful therapy under potentially reduced systemic side effects. Especially, the highly flexible manufacturing technique of 3D printing provides the opportunity for the individualization of implant shapes adapted to the patient-specific anatomy. It can be assumed that variations in shape can strongly affect the released amounts of drug per time. This influence was investigated by performing drug release studies with model implants of different dimensions. For this purpose, bilayered model implants in a simplified geometrical shape in form of bilayered hollow cylinders were developed. The drug-loaded abluminal part consisted of a suitable polymer ratio of Eudragit® RS and RL, while the drug-free luminal part composed of polylactic acid served as a diffusion barrier. Implants with different heights and wall thicknesses were produced using an optimized 3D printing process, and drug release was determined in vitro. The area-to-volume ratio was identified as an important parameter influencing the fractional drug release from the implants. Based on the obtained results drug release from 3D printed implants with individual shapes exemplarily adapted to the frontal neo-ostial anatomy of three different patients was predicted and also tested in an independent set of experiments. The similarity of predicted and tested release profiles indicates the predictability of drug release from individualized implants for this particular drug-eluting system and could possibly facilitate the estimation of the performance of customized implants independent of individual in vitro testing of each implant geometry.

Microscopic Cascading Devices for Boosting Mucus Penetration in Oral Drug Delivery—Micromotors Nesting Inside Microcontainers (Small 15/2023)

Microscopic Cascading Devices In article number 2206330, Tijana Maric and co-workers present cascade drug delivery microdevices comprise of micromotors and microcontainers to deliver a model drug and move through porcine mucosa. The conceptual device combines the advantages of unidirectional drug release achieved by microcontainers orientation and the dynamic motion properties of micromotors.

Evaluation in pig of an intestinal administration device for oral peptide delivery

The bioavailability of peptides co-delivered with permeation enhancers following oral administration remains low and highly variable. Two factors that may contribute to this are the dilution of the permeation enhancer in the intestinal fluid, as well as spreading of the released permeation enhancer and peptide in the lumen by intestinal motility. In this work we evaluated an Intestinal Administration Device (IAD) designed to reduce the luminal dilution of drug and permeation enhancer, and to minimize movement of the dosage form in the intestinal lumen. To achieve this, the IAD utilizes an expanding design that holds immediate release mini tablets and places these in contact with the intestinal epithelium, where unidirectional drug release can occur. The expanding conformation limits movement of the IAD in the intestinal tract, thereby enabling drug release at a single focal point in the intestine. A pig model was selected to study the ability of the IAD to promote intestinal absorption of the peptide MEDI7219 formulated together with the permeation enhancer sodium caprate. We compared the IAD to intestinally administered enteric coated capsules and an intestinally administered solution. The IAD restricted movement of the immediate release tablets in the small intestine and histological evaluation of the mucosa indicated that high concentrations of sodium caprate were achieved. Despite significant effect of the permeation enhancer on the integrity of the intestinal epithelium, the bioavailability of MEDI7219 was of the same order of magnitude as that achieved with the solution and enteric coated capsule formulations (2.5-3.8%). The variability in plasma concentrations of MEDI7219 were however lower when delivered using the IAD as compared to the solution and enteric coated capsule formulations. This suggests that dosage forms that can limit intestinal dilution and control the position of drug release can be a way to reduce the absorptive variability of peptides delivered with permeation enhancers but do not offer significant benefits in terms of increasing bioavailability.

Patches as Polymeric Systems for Improved Delivery of Topical Corticosteroids: Advances and Future Perspectives.

Mucoadhesive polymer patches are a promising alternative for prolonged and controlled delivery of topical corticosteroids (CS) to improve their biopharmaceutical properties (mainly increasing local bioavailability and reducing systemic toxicity). The main biopharmaceutical advantages of patches compared to traditional oral dosage forms are their excellent bioadhesive properties and their increased drug residence time, modified and unidirectional drug release, improved local bioavailability and safety profile, additional pain receptor protection, and patient friendliness. This review describes the main approaches that can be used for the pharmaceutical R&D of oromucosal patches with improved physicochemical, mechanical, and pharmacological properties. The review mainly focuses on ways to increase the bioadhesion of oromucosal patches and to modify drug release, as well as ways to improve local bioavailability and safety by developing unidirectional -release poly-layer patches. Various techniques for obtaining patches and their influence on the structure and properties of the resulting dosage forms are also presented.

FORMULATION AND EVALUATION OF CILNIDIPINE MUCOADHESIVE BUCCAL FILM BY SOLVENT CASTING TECHNIQUE FOR THE TREATMENT OF HYPERTENSION

Objective: Buccal drug delivery is the most suited route for local as well as systemic delivery of drugs. Cilnidipine is an L/N type dihydropyridine 4th generation calcium channel blocker (CCB), which decreases hypertension by blocking the N-type calcium channel to attenuate vascular sympathetic neurotransmission. It has high first-pass metabolism leading to low bioavailability. Hence the present research work was undertaken to formulate mucoadhesive buccal film of Cilnidipine with an objective to enhance therapeutic efficacy, bioavailability and was developed to administer into the unconscious and less-co-operative patients. Methods: Cilnidipine buccal films were prepared by a solvent-casting technique using various concentrations of mucoadhesive-polymers such as Hydroxyl propyl methylcellulose (HPMC) E15 and K4M and ethyl-cellulose as backing-layer, which acts like a patch providing unidirectional drug release. Prepared films were evaluated for their weight variation, thickness, surface-pH, swelling-index, drug content uniformity, in vitro residence time, folding endurance, tensile strength, in vitro release and permeability studies. Results: The infra-red (IR) spectra showed no interaction, and Physico-chemical characteristics were found within the limit. Swelling of the film increases with increasing concentration of polymers and %drug content of all formulations found to be in the range of 92.13%±0.94% to 97.92%±0.35%. The formulation F5, showed a promising tensile strength, folding endurance and in vitro drug release of about 95.18±0.03%, thus can be selected as an optimized formulation of mucoadhesive buccal film. Conclusion: The formulation of Cilnidipine mucoadhesive buccal film was found to be satisfactory and reasonable.

Functionalized polymeric patch for localized oxaliplatin delivery to treat gastric cancer

Localized delivery of chemotherapeutic agents allows extended drug exposure at the target site, thereby reducing systemic toxicity. We report the development of functionalized polymeric patch with unidirectional drug release to treat gastric cancer. The oxaliplatin-loaded patch was prepared by incorporating sodium carboxymethyl cellulose, hydroxypropyl cellulose and polyvinylpyrrolidone. The patch was functionalized by coating with transferrin-poly(lactic-co-glycolic acid) conjugate on one side of the patch for cancer targeting. The other side of the patch was coated with ethylcellulose (EC) to restrict the release of oxaliplatin. The physical and mechanical properties of oxaliplatin-loaded patches were characterized. Mucoadhesion studies using excised rat stomach tissue have shown that the functionalized side of the patch has significantly (p < 0.05) greater mucoadhesion strength compared with EC coated side of the patch. The in vitro and ex vivo (stomach sac and open-membrane model) studies revealed greater permeation of oxaliplatin across the stomach tissue when adhered to the functionalized and non-functionalized side of the patch compared with EC coated side. It was found that the growth inhibition with oxaliplatin solution was not significantly greater compared with corresponding concentrations of oxaliplatin-loaded patch in AGS and Caco-2 cell models. The in vivo studies were performed in mice, where indocyanine green-loaded patch encapsulated in a gelatin capsule was orally administered. The near-infrared (NIR) optical imaging revealed adherence of the patch on the mucosal side of the stomach tissue for up to 6 h. In conclusion, the functionalized polymeric patch loaded with oxaliplatin can be a potential localized delivery system to target gastric cancer.

Hyaluronic-benzydamine oromucosal films outperform conventional mouth rinse in ulcer healing

Oral mucositis is an ulcerative inflammation that is commonly encountered in patients receiving radio- and chemotherapy as an acute side effect. Local benzydamine (Bnz) application suppresses inflammation, while hyaluronic acid (HA) aids ulcer healing. In this study, Bnz-HA, a triple-layer oromucosal film, was developed for fast localized treatment of oral mucositis, compared to conventional formulations, with the aim to prolong Bnz retention onto the affected area and enhance its therapeutic efficacy by HA incorporation. The Bnz-HA films comprised a mucoadhesive-layer, containing HA and HPMC 4000, that adheres to the oral mucosa and controls Bnz release from the middle drug-layer, which was, in turn, adhered to a backing-layer containing Eudragit RS and allowing unidirectional drug release. Similarly, Bnz films were prepared omitting the HA addition. The films were characterized for their mucoadhesion, swelling capacity and in vitro drug release. The extent and duration of ulcer healing after 5 days film application were recorded in vivo using oral ulcer rabbit model. Bnz-HA and Bnz films showed strong mucoadhesion, maximum swelling after 2 h and a controlled drug release over 12 h. However, the incorporation of HA in Bnz-HA films significantly enhanced ulcer healing, outperforming the Bnz film and Tantum-Verde® mouth rinse. Conclusively, Bnz-HA films control Bnz release, reduce the dosing frequency and achieve rapid ulcer healing, hence being a promising delivery system outperforming conventional oral rinse.

Artificial vascular implants with unidirectional drug release and mechanical properties imitating natural blood vessels

Small-diameter artificial vessels require a combination of a range of material properties, including high strength, compliance, sutureability, and kink resistance in specific situations. We combined electrospinning technology with thermally induced separation technology to prepare composite three-layer artificial vessels using a PCL/gelatin co-blended material and a hybrid hydrogel enhanced gel structure to achieve high strength, flexibility and kink resistance, as well as excellent water tightness. The electrospun fibers in the artificial vessel provide mechanical stability, while the gelatin blended material enhances hydrophilicity. The results show that the three-layer composite structure is well bonded together, provides sufficient rupture strength and sutureability, and exhibits arterial-like compliance and resistance to kinking. The hydrogel layer drug release rate can also be adjusted by adjusting the PCL/gelatin co-blended layer ratio. This composite vascular scaffold is expected to play an important role in tissue engineering.

Unidirectional drug release from 3D printed mucoadhesive buccal films using FDM technology: In vitro and ex vivo evaluation

Oromucosal delivery of active pharmaceutical ingredients provides an attractive alternative route of administration, due to avoidance of the first pass effect and improved patient compliance. In the current work, fused deposition modelling (FDM) 3D printing was investigated as an additive manufacturing approach for poly(vinyl alcohol)-based mucoadhesive films, enabling unidirectional drug release. For this purpose, chitosan was incorporated as a permeation and mucoadhesion enhancer whereas ethylcellulose and commercial wafer sheets were evaluated as backing layers. The formulated films were initially assessed for structural integrity and dose uniformity. Solid-state characterization of the films, including thermal methods (DSC, TGA), diffraction (XRPD) and Raman spectroscopy, was implemented to characterize the physicochemical properties of the produced polymeric filaments and buccal films. The mechanical properties of the products were investigated by instrumented indentation and tensile tests. Evaluation of buccal films was assessed in vitro, to study the effect of backing-layer type on hydration capacity of the films, diffusion of the drug throughout the restricting layer and release profiles in simulated saliva. The ex vivo performance of the manufactured products, associated with the presence of chitosan, was investigated by textural analysis for mucoadhesion properties, whereas permeation studies and histological studies were performed across porcine buccal epithelium. The results demonstrated that FDM printing is a timesaving and versatile approach in the context of manufacturing multi-layered mucoadhesive buccal films, providing unidirectional release properties.

Ex vivo intestinal perfusion model for investigating mucoadhesion of microcontainers.

Micro fabricated delivery systems have shown promise in increasing oral bioavailability of drugs. Micrometer-sized polymeric devices (microcontainers) have the potential to facilitate unidirectional drug release directly into the intestinal mucosa whereby, drug absorption can be enhanced. The aim of this study was to develop an ex vivo model to investigate mucosal adhesion and orientation of microcontainers. Furthermore, to investigate how microcontainers with varying height, shape and material behave in regards to mucoadhesion and orientation. Microcontainers were placed at the top of an inclined piece of porcine small intestine. The tissue was perfused with biorelevant medium followed by microscopic examination to observe the orientation and amount of microcontainers on the tissue. The mucoadhesion of the microcontainers were evaluated based on the observed position on the tissue after being exposed to flow. When comparing the varying types of microcontainers, good adhesion was in general observed since most of the microcontainers were located in the beginning of the intestine. Microcontainers fabricated from the epoxy-based photoresist SU-8 had a slightly better adherence than those fabricated from poly-ɛ-caprolactone (PCL). The orientation of the microcontainers appeare to be dictated mainly by the height. In general, the model showed promising results in evaluating mucoadhesion and orientation.

A multilayered sheet-type device capable of sustained drug release and deployment control.

Minimally invasive delivery of a sustained drug release device to the body is a promising approach for treating chronic conditions such as retinal diseases. Herein, we describe a sheet-type device capable of sustained drug release and deployment control after being applied to the body through a small opened hole via a syringe-type injector. Such device consists of a four-layered structure of thin photopolymerized sheets, which are in turn made of different ratios of a mixture of polyethylene glycol dimethacrylate (PEGDM) and triethylene glycol dimethacrylate (TEGDM). A layer containing a model drug, i.e., fluorescein, was sandwiched between a controlled release and guard layer to achieve sustained unidirectional drug release. A deployment layer was then attached onto the guard layer to control the curvature of the device following deployment. The sheet-type device was sufficiently flexible to be rolled up and could be inserted into a syringe-type injector. When the device was injected into the subconjunctival space of a rabbit eye through a small opened hole, it unfolded to fit the eyeball curvature. Moreover, homogenates of the choroid/retinal pigment epithelium (RPE) as well as the retina exhibited fluorescence during 4weeks after implantation, confirming that the drug could be delivered to the retina by using the device. This developed sheet-type device offers the possibility of achieving minimally invasive transplantation into diseased tissues and organs, and could provide improved therapeutic modalities as well as reduce possible side effects.

Additive Manufacturing of Microreservoir Devices for Oral Drug Delivery Using an Acculas BA-30 Micro-Stereolithography Instrument: A Feasibility Study

Within the research and the development of protective carrier platforms intended for oral drug delivery, polymeric microreservoir devices with sizes around 300 μm have been proposed as a delivery system capable of unidirectional drug release. So far, microreservoir devices have been fabricated with simple shapes by means of high-throughput fabrication methods. In this feasibility study, state-of-the-art micro-stereolithography 3D printing is used for the fabrication of various microreservoir geometries. Scanning electron microscopy characterization and conducted resolution tests demonstrated the capability of the used technology and unveils challenges and opportunities associated with the proposed fabrication process.

Preparation and characterization of gastrointestinal wafer formulations

Many active pharmaceutical ingredients (API) have a very poor or highly variable bioavailability after oral administration. One possibility to overcome this problem might be found in the application of mucoadhesive dosage forms like gastrointestinal wafers. However, a currently unsolved challenge is the control of the adhesion of the wafer to the intestinal mucus. One suggested solution might be the combination of gastrointestinal wafers and expanding systems. Such a combination requires thin and elastic wafers which are further characterized by an unidirectional drug release. In this study gastrointestinal, twolayered wafers containing a water-insoluble backing layer and a drug-loaded, mucoadhesive layer were fabricated by casting solvent technique. The backing layer consists of Ethocel™ Standard 10 Premium and the mucoadhesive layer was prepared using a mixture of Methocel™ E15 Premium LV, polyvinyl alcohol and Macrogol 400. The wafers were characterized regarding their appearance, mechanical properties and dissolution profiles as well as the influence of backing layer thickness on drug transfer and their ability of unidirectional drug release. The wafers with backing layer thickness of 500μg Ethocel™/cm2 presented adequate mechanical properties, a drug transfer about 73% and unidirectional drug release.