Search

Alzheimer’s disease is a brain disorder characterized by a gradual decline in memory, thinking, behavior, and social skills. Galantamine hydrobromide is a reversible competitive cholinesterase inhibitor used for managing Alzheimer’s disease. Its oral administration, however, is accompanied by unwanted side effects, such as gastrointestinal disturbances, nausea, and vomiting. These side effects could be avoided by the incorporation of galantamine into nanoparticles. The present study describes the preparation and characterization of HPMC-based fast-dissolving oral films with galantamine-loaded chitosan nanoparticles. Galantamine-loaded chitosan nanoparticles were prepared using the ionotropic gelation method. High values for loading efficiency were established. DLS was used to evaluate the particle size and the Z-potential. The polymer used in this study for the preparation of the fast-dissolving oral films was HPMC, and PEG 400 was used as a plasticizer. The quality of the prepared films was evaluated based on the following criteria: flexibility, spreading ability, adhesiveness, non-sticky and easily peeled, and appearance. The thickness, folding endurance, and disintegration times of the prepared films were determined. In vitro dissolution studies were conducted in order to establish the drug release rate from the films.

The paediatric population is composed of several very different subgroups, each with its own specific characteristics. For this reason, children cannot be considered “small adults”. The development of formulations suitable for children is a complex process, as it must consider the physiological changes that occur during childhood and the impact they have on the absorption of drugs. Sildenafil citrate is a drug with a narrow therapeutic index used in paediatrics to treat pulmonary hypertension. In the present work, technological approaches for extemporaneous preparation of paediatric oral forms containing sildenafil citrate for personalized therapy in children were studied. The prepared formulations were tested for physical and microbiological stability, in-use stability, and determination of active substance content. All tested oral formulations remained unchanged in terms of appearance during the entire period of stability monitoring at the selected storage conditions – room temperature 25 °C ± 5 °C and in a refrigerator at 5 °C ± 2 °C. The established pH values suggest that the formulations remained chemically stable during the stability study. The content of sildenafil citrate in all prepared oral formulations remained above 95% w/v. The microbiological quality of the prepared compositions was confirmed. Rational strategies for preparation of extemporaneous formulations were proposed based on the analysis of experimental data.

3D printing is an innovative technology for building three-dimensional objects by laying down successive layers of material under the control of a computer software. It is entering pharmacy mainly because of its revolutionary potential to provide individualized dosage forms that meet the needs of each patient, due to the possibility to produce objects of many different sizes and shapes. An important aspect of personalized 3D tablets is the possibility to include several active substances in one dosage form, which would reduce the daily number of medications and the frequency of their administration and improve patient compliance. Another advantage of 3D printing is the possibility of producing small batches or even individual drugs for each patient. Despite the many advantages, 3D printing has several technological challenges to overcome before it becomes widely applicable in pharmacy. Five basic technologies are currently applied in pharmaceutical practice: powder-based printing, selective laser sintering, stereolithography, extrusion moulding printing, and electrohydrodynamic 3D printing. This article reviewed development, research focus, and prospects of each technology respectively.

Aripiprazole (ARZ) is a medication used for the treatment of various diseases such as schizophrenia, bipolar disorder, major depressive disorder, autism, and Tourette’s syndrome. Despite its therapeutic benefits, ARZ is characterized by a poor water solubility which provoked the development of various delivery systems in order to enhance its solubility. In the present work, a nanoscale drug delivery system based on N,N-dimethylacrylamide (DMAA) and β-cyclodextrin triacrylate (β-CD-Ac3) as potential aripiprazole delivery vehicles was developed. The nanogels were synthesized by free radical polymerization of DMAA in the presence of β-CD-Ac3 as a crosslinking agent and then loaded with ARZ via host-guest inclusion complexation. The blank- and drug-loaded nanogels were evaluated using different methods. Fourier transform infrared (FTIR) spectroscopy was employed to confirm the incorporation of β-CD moieties into the polymer network. Dynamic light scattering (DLS) was used to study the size of the developed systems. The samples exhibited a monomodal particle size distribution and a relatively narrow dispersity index. The hydrodynamic diameter (Dh) of the gels varied between 107 and 129 nm, with a tendency for slightly larger particles as the β-CD-Ac3 fraction increased. Loading the drug into the nanocarrier resulted in slightly larger particles than the blank gels, but their size was still in the nanoscopic range (166 to 169 nm). The release profiles in PBS were studied and a sustained release pattern with no significant burst effect was observed. A cytotoxicity assessment was also conducted to demonstrate the non-toxicity and biocompatibility of the studied polymers.

Off-label prescribing is widespread among pediatricians, and it is unlikely that this trend will soon be bound by a uniform legal framework. This is necessitated by the fact that there are four variables: the patient’s health condition, the physician’s experience and knowledge, the legislative measures (laws, directives, guidelines, and recommendations), and finally, the pharmaceutical industry. There is considerable concern worldwide about the use of off-label medicines in children. We may call it an enormous global problem that is much talked about and written about; however, we should not forget that the goal around which everyone should unite is the patient’s life. For healthcare providers, the most important thing will always be the health and preservation of the patient’s life, particularly when it comes to children with life-threatening conditions in neonatal and pediatric intensive care units (NICU and PICU). The study aimed to examine the prevalence of off-label drug use in pediatrics. Literature research was conducted, and we included studies from 2012 to 2022 that evaluated off-label drug prevalence in various pediatric patient populations.

Cannabidiol (CBD) is a promising drug candidate with pleiotropic pharmacological activity, whose low aqueous solubility and unfavorable pharmacokinetics have presented obstacles to its full clinical implementation. The rational design of nanocarriers, including niosomes for CBD encapsulation, can provide a plausible approach to overcoming these limitations. The present study is focused on exploring the feasibility of copolymer-modified niosomes as platforms for systemic delivery of CBD. To confer steric stabilization, the niosomal membranes were grafted with newly synthesized amphiphilic linear or star-shaped 3- and 4-arm star-shaped copolymers based on polyglycidol (PG) and poly(ε-caprolactone) (PCL) blocks. The niosomes were prepared by film hydration method and were characterized by DLS, cryo-TEM, encapsulation efficacy, and in vitro release. Free and formulated cannabidiol were further investigated for cytotoxicity and pro-apoptotic and anti-inflammatory activities in vitro in three human tumor cell lines. The optimal formulation, based on Tween 60:Span60:Chol (3.5:3.5:3 molar ration) modified with 2.5 mol% star-shaped 3-arm copolymer, is characterized by a size of 235 nm, high encapsulation of CBD (94%), and controlled release properties. Niosomal cannabidiol retained the antineoplastic activity of the free agent, but noteworthy superior apoptogenic and inflammatory biomarker-modulating effects were established at equieffective exposure vs. the free drug. Specific alterations in key signaling molecules, implicated in programmed cell death, cancer cell biology, and inflammation, were recorded with the niosomal formulations.

Three-dimensional (3D) printing has emerged as a new promising technique for the production of personalized dosage forms and medical devices. Polyvinyl alcohol is prominently used as a source material to produce 3D-printed medicines via fused deposition modeling (FDM)—a technology that combines hot melt extrusion and 3D printing. A preliminary screening of three grades of PVA indicated that partially hydrolyzed PVA with a molecular weight (MW) of 31,000–50,000 and plasticized with sorbitol was most suitable for 3D printing. Paracetamol was used as a model drug. The materials and the produced filaments were characterized by X-ray powder diffraction (XRPD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The complex viscosity (η*) of the polymer melts was determined as a function of the angular frequency (ω) at the printing temperature to assess their printability. Three-dimensional printlets with a 40% infill exhibited an immediate release of the API, while tablets with a higher infill were prone to a prolonged release regardless of the filament drug loading. A factorial design was used to give more insight into the influence of the drug-loading of the filaments and the tablet infill as independent variables on the production of 3D printlets. The Pareto chart confirmed that the infill had a statistically significant effect on the dissolution rate after 45 min, which was chosen as the response variable.

Dexamethasone (DXM) is a highly potent and long-acting synthetic glucocorticoid with anti-inflammatory, anti-allergic, and immunosuppressive effects. However, the systemic application of DXM can cause undesirable side effects: sleep disorders, nervousness, heart rhythm disorders, heart attack, and others. In the present study, multicomponent polymer networks were developed as potential new platforms for the dermal application of dexamethasone sodium phosphate (DSP). First, a copolymer network (CPN) comprising hydrophilic segments of different chemical structures was synthesized by applying redox polymerization of dimethyl acrylamide onto poly(ethylene glycol) in the presence of poly(ethylene glycol) diacrylate (PEGDA) as a crosslinker. On this basis, an interpenetrating polymer network structure (IPN) was obtained by introducing a second network of PEGDA-crosslinked poly(N-isopropylacrylamide). Multicomponent networks obtained were characterized by FTIR, TGA, and swelling kinetics in different solvents. Both CPN and IPN showed a high swelling degree in aqueous media (up to 1800 and 1200%, respectively), reaching the equilibrium swelling within 24 h. Additionally, IPN showed temperature-responsive swelling in an aqueous solution as the equilibrium swelling degree decreased considerably with an increase in the temperature. In order to evaluate the networks’ potential as drug carriers, swelling in DSP aqueous solutions of varied concentration was investigated. It was established that the amount of encapsulated DSP could be easily controlled by the concentration of drug aqueous solution. In vitro DSP release was studied in buffer solution (BS) with pH 7.4 at 37 °C. The results obtained during DSP loading and release experiments proved the feasibility of the developed multicomponent hydrophilic polymer networks as effective platforms for potential dermal application.

Natural alkaloid galantamine is widely used for the treatment of mild to moderate Alzheimer’s dementia. Galantamine hydrobromide (GH) is available as fast-release tablets, extended-release capsules, and oral solutions. However, its oral delivery can cause some unwanted side effects, such as gastrointestinal disturbances, nausea, and vomiting. Intranasal administration is one possible way to avoid such unwanted effects. In this work, chitosan-based nanoparticles (NPs) were studied as potential GH delivery vehicles for nasal application. The NPs were synthesized via ionic gelation and studied using dynamic light scattering (DLS) as well as by spectroscopic and thermal methods. The GH-loaded chitosan–alginate complex particles were also prepared as a way to modify the release of GH. The high loading efficiency of the GH was confirmed for both types of particles, at 67% for the GH-loaded chitosan NPs and 70% for the complex chitosan/alginate GH-loaded particles. The mean particle size of the GH-loaded chitosan NPs was about 240 nm, while the sodium alginate coated chitosan particles loaded with GH were expectedly bigger, with a mean particle size of ~286 nm. GH release profiles in PBS at 37 °C were obtained for both types of NPs, and it was found that the GH-loaded chitosan NPs allowed the prolonged release of the incorporated drug for a period of 8 h, while the complex GH-loaded chitosan/alginate NPs released the incorporated GH faster. The stability of the prepared GH-loaded NPs was also demonstrated after 1 year of storage at 5 °C ± 3 °C.

Nowadays, modern pharmaceutical investigations are directed toward the design and production of drug delivery systems for achieving prolonged and controlled drug delivery. In this respect, the use of interpenetrating polymer networks (IPNs) is an opportunity in the preparation of polymer drug delivery systems with desired characteristics. This paper describes the synthesis and characterization of novel poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) and polyacrylamide (PAAm)-based IPNs with different compositions and their application as diclofenac sodium delivery systems. The prepared IPNs were shown to possess phase-separated structures at the nano level, as revealed by SEM and TM-DSC. The IPNs’ composition was shown to determine the swelling behavior of these novel materials, and the inclusion of the charged IPN component (PDMAEMA) has changed the water molecules type diffusion from Fickian to non-Fickian, as revealed by the swelling kinetics study. Loading efficiency of diclofenac sodium and diclofenac sodium content in the polymer network was evaluated, and in vitro drug release experiments were carried out in order to estimate the ability of the obtained IPNs to control the release of the water-soluble drug.