Complex Drug Delivery Systems Research Articles

Advances in 4D Bio-Printing Technology for Enhanced Drug Delivery Systems

This mini-review covers the premise of how 4D bio-printing constitutes the next step out of the realm of 3D bio-printing by establishing time as a functional dimension. While structures derived from 3D bio-printing are static, 4D-bio-printed structures have time to change shape by responding to a certain external stimulus such as temperature or light. This review of materials and processes for use in 4D bio-printing looks at how this will improve drug delivery systems. With this technology, the systems can now be designed so that they not only administer drugs in a controlled manner but also adjust to meet the needs of the concerned patient. Such adaptability opens avenues for further personalized medicine, whereby treatments are more tailored to the patient's specific needs. Development of complex drug delivery systems - Bio-printing in 4D brings hope to deliver formulations that had been difficult to realize earlier. These include multi-chamber devices or bio-erodible materials that degrade the safety feature once the therapeutic payload has been delivered to the body. Thus, 4D bio-printing offers a possibility for more effective treatments and better health results in defeating some of the potential shortcomings in the traditional drug delivery approaches. The potential this technology brings in terms of versatility towards personalized medicine portends a considerable influence over the future of healthcare through adaptive, patient-specific solutions.

A Review on Rotary Tablet Machines and Recent Advancements in Tableting Technologies and Tablet Design

Rotary tablet machines have been instrumental in the manufacturing of solid oral dosage forms, enabling accurate dosing, stability during storage, and convenient administration. This review comprehensively discusses the fundamental components, operating principles, and manufacturing methods associated with rotary tablet machines. Furthermore, it delves into recent groundbreaking advancements in tableting technologies, with a particular emphasis on three-dimensional (3D) printing technology for personalized drug manufacturing. 3D printing, also known as additive manufacturing, has emerged as a game-changer in the pharmaceutical industry, allowing for the production of personalized 3D-printed drugs through computer-aided model design. This technology offers significant advantages over traditional manufacturing processes, including the ability to create complex drug delivery systems, achieve intricate release profiles, and rapidly produce small batches of drugs tailored to individual patient needs. In addition to 3D printing, the review highlights recent innovations in tablet design, such as tablet-in-tablet, multilayer tablets, tablet-in-capsule, and microchip-embedded tablets. These advancements have the potential to enhance drug delivery, improve patient compliance, and optimize therapeutic outcomes

Raman spectroscopic imaging – practical applications in industrial pharmacy and medical diagnostics: a review.

Currently, Raman imaging as a non-destructive technique providing knowledge on structural characterization of the investigated samples is gaining more and more interest among industrial formulation and process scientists. In the pharmaceutical sector, the creation of novel products and formulations necessitates flexible and adaptable analysis, and increasingly also imaging capabilities. In this paper, the attention is directed toward the research progress, that has occurred in the application of non-invasive Raman chemical imaging techniques in industrial pharmacy and medical diagnostics in recent years. This work aims to explore the potential of Raman imaging as a knowledge discovery method for the non-destructive evaluation of pharmaceutical formulations as well as human cells to support medical diagnostics in clinical practice. A review of the latest scientific papers indicates that the applications of Raman imaging in pharmaceutical sciences and medical diagnostics are diverse and far-reaching from ensuring the quality of pharmaceutical formulations to studying complex drug delivery systems, monitoring manufacturing processes, and medical diagnostics of cancers and other diseases. As technology continues to evolve, the integration of Raman imaging into pharmaceutical and clinical practices is expected to expand, providing new insights and solutions to the challenges faced by the pharmaceutical industry and medical diagnostics.

Assembled pH-Responsive Gastric Drug Delivery Systems Based on 3D-Printed Shells.

Gastric acid secretion is closely associated with the development and treatment of chronic gastritis, gastric ulcers, and reflux esophagitis. However, gastric acid secretion is affected by complex physiological and pathological factors, and real-time detection and control are complicated and expensive. A gastric delivery system for antacids and therapeutics in response to low pH in the stomach holds promise for smart and personalized treatment of stomach diseases. In this study, pH-responsive modular units were used to assemble various modular devices for self-regulation of pH and drug delivery to the stomach. The modular unit with a release window of 50 mm2 could respond to pH and self-regulate within 10 min, which is related to its downward floatation and internal gas production. The assembled devices could stably float downward in the medium and detach sequentially at specific times. The assembled devices loaded with antacids exhibited smart pH self-regulation under complex physiological and pathological conditions. In addition, the assembled devices loaded with antacids and acid suppressors could multi-pulse or prolong drug release after rapid neutralization of gastric acid. Compared with traditional coating technology, 3D printing can print the shell layer by layer, flexibly adjust the internal and external structure and composition, and assemble it into a multi-level drug release system. Compared with traditional coating, 3D-printed shells have the advantage of the flexible adjustment of internal and external structure and composition, and are easy to assemble into a complex drug delivery system. This provides a universal and flexible strategy for the personalized treatment of diseases with abnormal gastric acid secretion, especially for delivering acid-unstable drugs.

Assembly properties of complex drug delivery systems

The interaction of materials within the context of a formulation and its manufacturing process can have a defining impact on a parenteral drug product performance. Therefore, establishment of methodologies to investigate the interactions of drug substance with itself and other components can be a critical aspect of developing a product and understanding its potential failure modes. This paper will discuss some of the methodologies used to investigate assembly properties of different delivery systems, including separation techniques combined with on-line multiple detectors, and nanoscale imaging. Examples where the data are combined with modelling the morphology demonstrate the strength of combining multiple experiments with calculations to provide deeper insight into functionality for e.g. polymeric nanoparticles and drug dendrimer conjugates.

Development of Essential Oil Delivery Systems by 'Click Chemistry' Methods: Possible Ways to Manage Duchenne Muscular Dystrophy.

Recently, rare diseases have received attention due to the need for improvement in diagnosed patients' and their families' lives. Duchenne muscular dystrophy (DMD) is a rare, severe, progressive, muscle-wasting disease. Today, the therapeutic standard for treating DMD is corticosteroids, which cause serious adverse side effects. Nutraceuticals, e.g., herbal extracts or essential oils (EOs), are possible active substances to develop new drug delivery systems to improve DMD patients' lives. New drug delivery systems lead to new drug effects, improved safety and accuracy, and new therapies for rare diseases. Herbal extracts and EOs combined with click chemistry can lead to the development of safer treatments for DMD. In this review, we focus on the need for novel drug delivery systems using EOs as the therapy for DMD and the potential use of click chemistry for drug delivery systems. New EO complex drug delivery systems may offer a new approach for improving muscle conditions and mental health issues associated with DMD. However, further research should identify the potential of these systems in the context of DMD. In this review, we discuss possibilities for applying EOs to DMD before implementing expensive research in a theoretical way.

Ultrasound-mediated multifunctional magnetic microbubbles for drug delivery of celastrol in VX2 liver transplant tumors.

Celastrol (CST) has positive pharmacological effects on various cancers, but clinical application is limited because of poor water solubility and systemic toxicity. Ferric oxide (Fe3O4) has a large specific surface area and can be functionalized by inorganic modification to form complex magnetic drug delivery systems. Herein, Fe3O4 was surface-modified with citric acid and polyethylene glycol (PEG) (via) the Mitsunobu reaction and then covalently bound to CST. Finally, magnetic microbubbles (MMBs) containing perfluoropropane (C3F8) and Fe3O4-PEG2K-CST particles were constructed with poly(lactic-co-glycolic acid) (PLGA) as the shell membrane. In vitro studies showed that ultrasound-mediated MMBs exhibited improved inhibition of VX2 cell proliferation compared to inhibition achieved using MMBs without ultrasound mediation, blank MMBs, or free CST. In ultrasound mode, MMBs have favorable imaging properties. After the application of a high mechanical index, MMBs collapse through the cavitation effect, releasing their internal Fe3O4-PEG2K-CST. The CST is then delivered to the tumor microenvironment under acidic conditions. In magnetic resonance imaging T2 mode, a specific hypointense signal was observed in the tumor area compared with that before treatment, whereas no significant change occurred in the signal intensity of the surrounding organs. After treatment, pathological examination of tumor-bearing rabbit tissues showed that iron elements accumulated in several apoptosis cells in the tumor area, with no apparent abnormalities found in other areas. Thus, ultrasound-mediated MMBs could significantly improve the drug uptake of solid tumors and inhibit tumor growth with favorable biological safety.

Fused Deposition Modelling 3D-Printed Gastro-Retentive Floating Device for Propranolol Hcl Tablets.

Three-dimensional printing has revolutionized drug manufacturing and has provided a solution to the limitations associated with the conventional manufacturing method by designing complex drug delivery systems with customized drug release profiles for personalized therapies. The present investigation aims to design a gastric floating tablet with prolonged gastric floating time and sustained drug release profile. In the present study, a gastro retentive floating device (GRFD) was designed and fabricated using a fused deposition modelling (FDM)-based 3D printing technique. This device acts as a multifunctional dosage form exhibiting prolonged gastric retention time and sustained drug release profile with improved oral bioavailability in the upper gastrointestinal tract. Commercial polyvinyl alcohol (PVA) and polylactic acid (PLA) filaments were used to design GRFD, which was comprised of dual compartments. The outer sealed compartment acts as an air-filled chamber that imparts buoyancy to the device and the inner compartment is filled with a commercial propranolol hydrochloride immediate-release tablet. The device is designed as a round-shaped shell with a central opening of varying size (1 mm, 2 mm, 3 mm, and 4 mm), which acts as a drug release window. Scanning electron microscope (SEM) images were used to determine morphological characterization. The in vitro buoyancy and drug release were evaluated using the USP type II dissolution apparatus. All the designed GRFDs exhibit good floating ability and sustained drug release profiles. GRFDs fabricated using PLA filament show maximum buoyancy (>24 h) and sustained drug release for up to 10 h. The floating ability and drug release from the developed devices were governed by the drug release window opening size and the filament material affinity towards the gastric fluid. The designed GRFDs show great prospects in modifying the drug release characteristics and could be applied to any conventional immediate-release product.

Semi-solid extrusion 3D-printing of eucalypt extract-loaded polyethylene oxide gels intended for pharmaceutical applications

In pharmaceutics, 3D printing is considered as a promising future technology for fabricating more complex patient-specific drug delivery systems (DDSs). An anti-staphylococcal herbal preparation, “Chlorophyllipt”, is produced mainly in a liquid form by the pharmaceutical industry in Ukraine, and it is composed of an ethanolic eucalypt extract (EE). Since staphylococcal infections have become a true challenge for the health care in all over the world, it would be relevant and justified to develop the aqueous gels of the present EE applicable for the 3D printing of the corresponding solid DDSs. The aim of the present study was to develop a novel polyethylene oxide (PEO) gel loaded with EE for a semi-solid extrusion (SSE) 3D printing and to print the corresponding oral solid DDSs with different sizes and shapes. For SSE 3D printing, we prepared and tested total ten (10) different aqueous PEO gel formulations loaded with EE. Prior to 3D printing, the physical appearance, homogeneity, injection force and viscosity of the gels were investigated. The EE-PEO gels were printed to lattice- and round-shaped solid DDSs with the head speed of 0.5 mm/s, and the weight (mass uniformity) and effective surface area of the printed systems were determined. The most feasible EE-PEO gel for SSE 3D printing comprised of 10 mg/ml of EE, 30 mg/ml of eumulgin and 20 mg/ml of ascorbic acid in a 20-% aqueous PEO gel. The key process parameters of the SSE 3D printing were identified and verified. The printing quality of EE-PEO DDSs were very good, thus showing compatibility of a plant extract and carrier polymer. Such 3D-printed antimicrobial DDSs can be used for example in the treatment of skin wounds and infections of the oral cavity.

Polymer-Based Hydrogels Applied in Drug Delivery: An Overview.

Polymer-based hydrogels are hydrophilic polymer networks with crosslinks widely applied for drug delivery applications because of their ability to hold large amounts of water and biological fluids and control drug release based on their unique physicochemical properties and biocompatibility. Current trends in the development of hydrogel drug delivery systems involve the release of drugs in response to specific triggers such as pH, temperature, or enzymes for targeted drug delivery and to reduce the potential for systemic toxicity. In addition, developing injectable hydrogel formulations that are easily used and sustain drug release during this extended time is a growing interest. Another emerging trend in hydrogel drug delivery is the synthesis of nano hydrogels and other functional substances for improving targeted drug loading and release efficacy. Following these development trends, advanced hydrogels possessing mechanically improved properties, controlled release rates, and biocompatibility is developing as a focus of the field. More complex drug delivery systems such as multi-drug delivery and combination therapies will be developed based on these advancements. In addition, polymer-based hydrogels are gaining increasing attention in personalized medicine because of their ability to be tailored to a specific patient, for example, drug release rates, drug combinations, target-specific drug delivery, improvement of disease treatment effectiveness, and healthcare cost reduction. Overall, hydrogel application is advancing rapidly, towards more efficient and effective drug delivery systems in the future.

Transdermal Drug Delivery System

A transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into systemic circulation. Often, this promotes healing to an injured area of the body. An advantage of a transdermal drug delivery route over other types of medication delivery such as oral, topical, intravenous, intramuscular, etc. is that the patch provides a controlled release of the medication into the patient, usually through either a porous membrane covering a reservoir of medication or through body heat melting thin layers of medication embedded in the adhesive. Transdermal drug delivery offers controlled release of the drug into the patient, it enables a steady blood level profile, resulting in reduced systemic side effects and, sometimes, improved efficacy over other dosage forms. The main objective of transdermal drug delivery system is to deliver drugs into systemic circulation through skin at predetermined rate with minimal inter and intrapatient variations. Transdermal drugs are self- contained, discrete dosage form. It delivers a drug through intact skin at a controlled rate into the systemic circulation. Delivery rate is controlled by the skin or membrane in the delivery system. It is a sophisticated complex drug delivery system which is difficult to formulate. It requires specialized manufacturing process/equipment. The materials of construction, configuration and combination of the drug with the proper cosolvent, excipient, penetration enhancer, and membrane are carefully selected and matched to optimize adhesive properties and drug delivery requirements. Several transdermal products and applications include hormone replacement therapy, management of pain, angina pectoris, smoking cessation and neurological disorders such as Parkinson's disease. Formulated to deliver the drug at optimized rate into the systemic circulation should adhere to the skin for the expected duration should not cause any skin irritation and/or sensitization, enhancing bioavailability via bypassing first pass metabolism, minimizing pharmacokinetic peaks and troughs, improving tolerability and dosing increasing patient compliance in continuous delivery. This review article provides an overview of TDDS, its advantages over conventional dosage forms, Limitations, various components of Transdermal patches, types of Transdermal patches, methods of preparation and Ideal requirements for TDDS, regulatory issues over transdermal drug delivery, its physicochemical methods of evaluation, therapeutic uses and recent advances in transdermal drug delivery system.1

Nanotherapy for bone repair: milk-derived small extracellular vesicles delivery of icariin

Icariin (ICA) played an important role in the treatment of inflammatory bone defects. However, pharmacokinetic studies have shown that its poor bioavailability limited its application. In this context, we isolated bovine milk-derived sEV and prepared sEV-ICA to improve the osteogenic effect of ICA. In this study, we successfully constructed sEV-ICA. sEV-ICA was found to have significantly higher osteogenic efficiency than ICA in cell culture and cranial bone defect models. Mechanistically, bioinformatics analysis predicted that signal transducers and activators of transcription 5 (STAT5a) may bind to the GJA1 promoter, while luciferase activity assays and chromatin immunoprecipitation (ChIP) experiments confirmed that STAT5a directly binded to the GJA1 promoter to promote osteogenesis. We proved that compared with ICA, sEV-ICA showed a better effect of promoting bone repair in vivo and in vitro. In addition, sEV-ICA could promote osteogenesis by promoting the combination of STAT5a and GJA1 promoter. In summary, as a complex drug delivery system, sEV-ICA constituted a rapid and effective method for the treatment of bone defects and could improve the osteogenic activity of ICA.

Management of Brain Cancer and Neurodegenerative Disorders with Polymer-Based Nanoparticles as a Biocompatible Platform.

The blood-brain barrier (BBB) serves as a protective barrier for the central nervous system (CNS) against drugs that enter the bloodstream. The BBB is a key clinical barrier in the treatment of CNS illnesses because it restricts drug entry into the brain. To bypass this barrier and release relevant drugs into the brain matrix, nanotechnology-based delivery systems have been developed. Given the unstable nature of NPs, an appropriate amount of a biocompatible polymer coating on NPs is thought to have a key role in reducing cellular cytotoxicity while also boosting stability. Human serum albumin (HSA), poly (lactic-co-glycolic acid) (PLGA), Polylactide (PLA), poly (alkyl cyanoacrylate) (PACA), gelatin, and chitosan are only a few of the significant polymers mentioned. In this review article, we categorized polymer-coated nanoparticles from basic to complex drug delivery systems and discussed their application as novel drug carriers to the brain.

Selenium-ruthenium complex blocks H1N1 influenza virus-induced cell damage by activating GPx1/TrxR1.

Background: Influenza A (H1N1) virus is an acute respiratory infectious disease that causes massive morbidity and mortality worldwide. As an essential trace element, selenium is widely applied in the treatment of various diseases because of its functions of enhancing immune response, antioxidant and antiviral mutation. In this study, we constructed the selenium-containing metal complex drug delivery system Ru(biim)(PhenSe)2 (RuSe), and investigated the anti-influenza virus efficacy and the potential antiviral mechanism for RuSe. Methods: The inhibitory effect of RuSe on influenza-mediated apoptosis was examined by cell count assay, cell cycle assay, Annenxin-V assay, TUNEL-DAPI assay and reactive oxygen species level determination. Virulence assay, PCR and neuraminidase inhibition assay revealed the inhibition of RuSe on influenza virus. At the level of animal experiments, two animal models were used to clarify the role of RuSe through HE staining, immunohistochemical staining, cytokine determination, selenium metabolism determination and selenium protein expression level determination. Results: The results of this study confirm that RuSe enhances the expression levels of selenium proteins GPx1 and TrxR1 by regulating selenium metabolism, thereby inhibiting viral replication and assembly and regulating virus-mediated mitochondria-related apoptosis. On the other hand, animal experiments show that RuSe can reduce lung tissue inflammation and inhibit lung tissue cell apoptosis in mice, and improve the survival state of mice. In addition, RuSe significantly improves the low immune response of Se-deficient mice by regulating selenium metabolism, and effectively alleviated lung fibrosis and lung tissue apoptosis in Se-deficient mice. Conclusions: This study suggests that RuSe provides a promising new approach for the clinical treatment of influenza virus.

Macrophage Membrane-Coated Liposomes as Controlled Drug Release Nanocarriers for Precision Treatment of Osteosarcoma

Osteosarcoma has a relatively high incidence rate among primary malignant tumors, and the survival rate is low. Clinically, surgical resection and chemotherapy are mainly used, which are difficult to utilize to treat metastatic or recurrent osteosarcoma. The combination of chemotherapy and immunotherapy can achieve a better tumor treatment effect. M1 macrophages (M1 Mø) can kill tumor cells and have tumor-targeting and phagocytosis ability, which are an ideal tool for tumor-targeted drug delivery. However, as carriers, living cells have the disadvantages of uncontrollable size, poor tissue permeability, and poor stability. In this study, the M1 macrophage membrane (M1M) was used as the carrier and loaded with MMP-2 (matrix metalloproteinase-2)-sensitive drug-loaded liposomes (GL) to prepare a complex nanovesicle drug delivery system M1M (GL/DOX/TPI-1), with a tumor active targeting function, for combined chemical and immune therapy from doxorubicin (DOX) and tyrosine phosphatase inhibitor 1 (TPI-1). The complex nanovesicles not only retain the tumor-targeting ability from the M1 macrophage membrane but also have the advantages of controllable size, responsive drug release, and high stability. The results of in vivo efficacy test show that the drug delivery system realizes active targeted enrichment in osteosarcoma tissue. Under the response of MMP-2, the internally encapsulated antitumor drugs DOX and TPI-1 from the system are released. This drug delivery system combined with chemical and immune treatment can effectively achieve the aim of the treatment of osteosarcoma.

Balance of Macrophage Activation by a Complex Coacervate-Based Adhesive Drug Carrier Facilitates Diabetic Wound Healing.

Uncontrolled and sustained inflammation disrupts the wound-healing process and produces excessive reactive oxygen species, resulting in chronic or impaired wound closure. Natural antioxidants such as plant-based extracts and natural polysaccharides have a long history in wound care. However, they are hard to apply to wound beds due to high levels of exudate or anatomical sites to which securing a dressing is difficult. Therefore, we developed a complex coacervate-based drug carrier with underwater adhesive properties that circumvents these challenges by enabling wet adhesion and controlling inflammatory responses. This resulted in significantly accelerated wound healing through balancing the pro- and anti-inflammatory responses in macrophages. In brief, we designed a complex coacervate-based drug carrier (ADC) comprising oligochitosan and inositol hexaphosphate to entrap and release antioxidant proanthocyanins (PA) in a sustained way. The results from in vitro experiments demonstrated that ADC is able to reduce LPS-stimulated pro-inflammatory responses in macrophages. The ability of ADC to reduce LPS-stimulated pro-inflammatory responses in macrophages is even more promising when ADC is encapsulated with PA (ADC-PA). Our results indicate that ADC-PA is able to polarize macrophages into an M2 tissue-healing phenotype via up-regulation of anti-inflammatory and resolution of inflammatory responses. Treatment with ADC-PA around the wound beds fine-tunes the balance between the numbers of inducible nitric oxide synthase-positive (iNOS+) and mannose receptor-negative (CD206-) M1 and iNOS-CD206+ M2 macrophages in the wound microenvironment compared to controls. Achieving such a balance between the numbers of iNOS+CD206- M1 and iNOS-CD206+ M2 macrophages in the wound microenvironment has led to significantly improved wound closure in mouse models of diabetes, which exhibit severe impairments in wound healing. Together, our results demonstrate for the first time the use of a complex coacervate-based drug delivery system to promote timely resolution of the inflammatory responses for diabetic wound healing by fine-tuning the functions of macrophages.

Characterization of the Interaction of Polymeric Micelles with siRNA: A Combined Experimental and Molecular Dynamics Study.

The simulation of large molecular systems remains a daunting challenge, which justifies the exploration of novel methodologies to keep computers as an ideal companion tool for everyday laboratory work. Whole micelles, bigger than 20 nm in size, formed by the self-assembly of hundreds of copolymers containing more than 50 repeating units, have until now rarely been simulated, due to a lack of computational power. Therefore, a flexible amphiphilic triblock copolymer (mPEG45-α-PLL10-PLA25) containing a total of 80 repeating units, has been emulated and synthesized to embody compactified nanoconstructs of over 900 assembled copolymers, sized between 80 and 100 nm, for siRNA complexing purposes. In this study, the tailored triblock copolymers containing a controlled number of amino groups, were used as a support model to address the binding behavior of STAT3-siRNA, in the formation of micelleplexes. Since increasingly complex drug delivery systems require an ever more optimized physicochemical characterization, a converging description has been implemented by a combination of experimentation and computational simulations. The computational data were advantageous in allowing for the assumption of an optimal N/P ratio favoring both conformational rigidifications of STAT3-siRNA with low competitive phenomena at the binding sites of the micellar carriers. These calculations were consistent with the experimental data showing that an N/P ratio of 1.5 resulted in a sufficient amount of complexed STAT3-siRNA with an electrical potential at the slipping plane of the nanopharmaceuticals, close to the charge neutralization.

Phase-Field Model for Drug Release of Water-Swellable Filaments for Fused Filament Fabrication.

This paper treats the drug release process as a phase-field problem and a phase-field model capable of simulating the dynamics of multiple moving fronts, transient drug fluxes, and fractional drug release from swellable polymeric systems is proposed and validated experimentally. The model can not only capture accurately the positions and movements of the distinct fronts without tracking the locations of fronts explicitly but also predict well the release profile to the completion of the release process. The parametric study has shown that parameters including water diffusion coefficient, drug saturation solubility, drug diffusion coefficient, initial drug loading ratio, and initial porosity are critical in regulating the drug release kinetics. It has been also demonstrated that the model can be applied to the study of swellable filaments and has wide applicability for different materials. Due to explicit boundary position tracking being eliminated, the model paves the way for practical use and can be extended for dealing with geometrically complex drug delivery systems. It is a useful tool to guide the design of new controlled delivery systems fabricated by fused filament fabrication.

Formation of disaggregated polymer microspheres by a novel method combining pulsed voltage electrospray and wet phase inversion techniques

Polymer microspheres with controlled sizes have attracted interest due to their potential use in medical field. Therefore it is of great importance to be able to produce a large number of disaggregated microspheres with a narrow diameter distribution. This work describes the successful elaboration of the method combining electrospray and wet phase inversion for the manufacturing of such polymer microspheres with mean diameters of 2 – 15 µm. Their recovery and drying are easy and they can be directly applied afterwards. The method is universal enough to produce microspheres from various polymers (polycaprolactone, polyethersulfone) and different solvents (dimethylformamide, N-methylpyrrolidone). It was noticed on the basis of microscopic images and using the nitrogen adsorption–desorption method that the specific surface of the microspheres differs depending on the polymer and solvent used. The work introduces additional parameters resulting from the use of pulsed voltage in the electrospray (pulse frequency f and duration τ) which results in better process control. As an example of the use of microspheres as drug carriers, they were loaded with rhodamine and its release was tested. Such microspheres could be dispersed in polymer solution and used in extrusion-based techniques (electrospinning, 3D printing) to form novel complex drug delivery systems.

Raman Imaging as a powerful tool to elucidate chemical processes in a matrix: Medicated chewing gums with nicotine

Extruded medicated chewing gum is a convenient but complex drug delivery system. Description of gum ingredient distribution and interactions in literature is sparse, but fundamental in product characterization and stability prediction. Although Raman spectroscopy has been used for such characterization of numerous dosage forms, its applicability to medicated chewing gum has not been studied until now. The objective was to investigate the applicability of confocal Raman imaging on chewing gum for identification and distribution of excipients and the model drug nicotine, including changes occurring during shelf life. A sample preparation protocol was composed to present an even surface of a gum cross section without altering the gum matrix texture. High-resolution Raman maps were obtained by Non Negative Least Squares (NNLS) analysis for a reference gum and gums stored for 6 months at mild (25 °C/60% RH) and accelerated (40 °C/75% RH) conditions. Additional Empty Modelling™ analysis confirmed the results of NNLS. The NNLS analysis located nicotine and the following excipients: gum base, calcium carbonate, sorbitol, xylitol, sodium carbonate, sodium bicarbonate and talc in distinct domains of the reference sample. Changes of the sample stored at accelerated conditions was discovered as sodium carbonate was not observed in this sample. Additionally, stereo light microscopy showed changes in product appearance and high-performance liquid chromatography confirmed formation of the oxidation product nicotine-1′-N-oxide in this sample. The gum formulation and its ingredients displayed characteristic Raman spectra, proving Raman imaging as a useful method for characterizing medicated chewing gums, including changes occurring during stability testing.