Release Of Active Pharmaceutical Ingredients Research Articles

Polymer- and Lipid-Based Nanostructures Serving Wound Healing Applications: A Review.

Management of hard-to-heal wounds often requires specialized care that surpasses the capabilities of conventional treatments. Even the most advanced commercial products lack the functionality to meet the needs of hard-to-heal wounds, especially those complicated by active infection, extreme bleeding, and chronic inflammation. The review explores how supramolecular nanovesicles and nanoparticles-such as dendrimers, micelles, polymersomes, and lipid-based nanocarriers-can be key to introducing advanced wound healing and monitoring properties to address the complex needs of hard-to-heal wounds. Their potential to enable advanced functions essential for next-generation wound healing products-such as hemostatic functions, transdermal penetration, macrophage polarization, targeted delivery, and controlled release of active pharmaceutical ingredients (antibiotics, gaseous products, anti-inflammatory drugs, growth factors)-is discussed via an extensive overview of the recent reports. These studies highlight that the integration of supramolecular systems in wound care is crucial for advancing toward a new generation of wound healing products and addressing significant gaps in current wound management practices. Current strategies and potential improvements regarding personalized therapies, transdermal delivery, and the promising critically evaluated but underexplored polymer-based nanovesicles, including polymersomes and proteinosomes, for wound healing.

Formulation and Release of Active Pharmaceutical Ingredients Using a Supramolecular Self-Healing Two-Component Gel.

A two-component low-molecular-weight gelator (LMWG) formed from a modified amino acid and an aldehyde was formulated with active pharmaceutical ingredients (APIs). Basic APIs (propranolol, atropine) can be mixed with the LMWG prior to gel assembly while acidic APIs (naproxen, rosuvastatin) inhibit assembly by disrupting the LMWG imine bond and were loaded by diffusion after gel assembly. For diffusion-loaded gels, the API in the liquid-like phase was rapidly released, with the remainder, interacting with gel fibres, retained in the gel. Rosuvastatin release was particularly low with Saturation Transfer Difference (STD) NMR indicating interactions between the aromatic ring and the self-assembled gel network. Propranolol also interacted with the gel via its aromatic unit, and its release led to gel erosion. Using agarose as a polymer gelator additive reinforced the gel, restricting erosion. In contrast, atropine was readily released over a period of hours - it is primarily in the liquid-like phase with STD NMR indicating no interactions with the gel network. The atropine-loaded gel retained its thixotropic properties. Overall, APIs must be carefully chosen to optimise formulation/release. Of the APIs investigated, atropine has most potential for further development. Atropine has applications in treating myopia, and our results suggest potential ophthalmic applications of supramolecular gels.

Zeolites – tabletting ibuprofen with and without zeolites as an excipient

Abstract Introduction Drug delivery via the oral route is a patient and industry-preferred approach. However, maintaining plasma concentrations of the active pharmaceutical ingredient (API) within the therapeutic window can be challenging with immediate-release (IR) tablets. To avoid the plasma peaks and troughs associated with IR tablets, sustained release (SR) formulations have been investigated. Zeolites are microporous aluminosilicate minerals that represent a novel tabletting material with the potential for modifying drug release due to their unique adsorption and ion exchange properties1. Aim This study will investigate the potential for inclusion of zeolites within orally disintegrating tablets (ODTs) and assessment of their ability to modify API release. Methods In-house, 50%w/w ibuprofen (IBU)-loaded ODTs (IHODTs) were prepared from Pearlitol® Flash, magnesium (Mg) stearate and 2 different zeolites (CP814C and CP814E), incorporated at 5%w/w each, using a manual tablet press. Formulations were prepared and mixed for 10 minutes in a cube mixer prior to direct compression (DC) into tablets. Physical characteristics of the tablets were assessed by hardness and friability measurements. Tablet quality was assessed by disintegration and dissolution analysis to British Pharmacopeia (BP) standards2. Release profiles were assessed against various models to determine the effect of zeolites on the release of IBU. Formulations were further examined and characterised using scanning electron microscopy (SEM) and energy-dispersive x-ray (EDX) spectroscopy. An ethics evaluation was completed, and the study was identified as not having any ethical considerations by the University of South Wales. Results The mean weight of blank ODTs was found to be 225.3mg, with a mean thickness of 3.65mm, diameter of 8.10mm, hardness of 43.9±9.2N (mean±SD, n=5) and friability of 0.2±0.2% (mean±SD, n=3). The hardness of IHODTs was found to be 59.98±1.6N, reducing to 54.9±4.3N and 43.4±0.7N (mean±SD, n=3) with the inclusion of CP814C and CP814E, respectively. The friability of IHODTs containing zeolites was 1.76±0.4% and 1.91±0.9N (mean±SD, n=3), for CP814C and CP814E, respectively; conforming to BP specification2. The disintegration time for all in-house tablets, both with and without a zeolite included, was found to be an order of magnitude greater than commercial ODTs (CT) controls, but all remained within the BP specification2. The release of IBU from IHODTs and CTs showed good correlation to the first-order release model (R2 = 0.96 and 0.98, respectively), indicating IR behaviour. Similarly, the release of IBU from IHODTs containing zeolites was shown to correlate best with the first-order release model, R2 = 0.91 for CP814C and R2 = 0.90 for CP814E, respectively. SEM analysis suggested a homogeneous blend of components within IHODTs, whilst EDX analysis indicated the presence of silicon and aluminium from zeolites, and Mg and carbon from Mg stearate and IBU, respectively. Discussion / Conclusion This study investigated the effect of zeolite inclusion on the release properties of ODTs containing IBU. Although the quality of ODTs containing zeolites was not compromised, this study suggests that inclusion of a zeolite by DC only, does not significantly modify the release profile. Future studies are required to ascertain whether zeolites can achieve SR from ODTs using alternative API loading approaches, such as solvent loading1.

New Insights on the Burst Release Kinetics of Spray-Dried PLGA Microspheres.

Spray drying is one of the leading manufacturing methods for active pharmaceutical ingredients (APIs) owing to its rapid, single-step, and cost-effective nature. It also has the capacity to generate microspheres capable of controlled release of APIs including biomolecules and vaccines. However, one of the key challenges of spray-dried formulations especially with poly(lactic-co-glycolic acid) (PLGA)-based controlled-release injectables is burst release, where a significant fraction of the API is released prematurely within a short period of time following administration, leading to detrimental impact on the performance and quality of end products. This study uses a model API, bovine serum albumin (BSA) protein, to identify the sources of burst release that may affect the kinetics and performance of long-acting injectable microsphere formulations. Spray-dried microspheres with various formulations (i.e., variable BSA/PLGA ratios) were characterized in terms of their morphology, particle size, surface area, thermal properties, moisture content, as well as chemical compositions and their distributions to investigate the impact of spray drying on the burst release phenomenon. The results suggest that a relatively high initial release (85%) observed is mainly attributed to the protein distribution close to the particle surface. Morphology analysis provided evidence that the microspheres retained their spherical structure during the burst release phase. X-ray photoelectron spectroscopy, hard X-ray photoelectron spectroscopy, and argon cluster sputtering-assisted time-of-flight secondary ion mass spectrometry analysis suggest an enrichment of PLGA on particle surfaces with buried BSA protein. The statistically significant difference in particle size and surface area between three different formulations may be responsible for an initial variation in release but did not seem to alter the overall burst release profile. Considering the suggested source of burst release, the two-fluid spray-drying method, characterized by a single liquid feed delivering a preprepared emulsion, generated matrix-type microspheres with a surface layer of PLGA, as evidenced by surface analysis. The PLGA surface layer proved to be prone to degradation and pore formation, allowing for faster diffusion of BSA out of the microspheres, resulting in a burst release. Increasing the polymer concentration did not seem to halt this process.

Formulation of Dual-Functional Nonionic Cetomacrogol Creams Incorporated with Bacteriophage and Human Platelet Lysate for Effective Targeting of MDR P. aeruginosa and Enhanced Wound Healing.

Successful development of phage-based therapeutics and their utility predominantly depend on the mode and route of phage administration. Topical and site-directed phage application evokes minimal immune clearance and allows more phage-host adsorption, thereby ensuring higher phage efficacy. However, a notable drawback of conventional topical phage applications is the absence of sustained release. Occlusive emollients guarantee the controlled release of active pharmaceutical ingredients (APIs), thereby facilitating administration, preventing moisture loss, and acting as a skin barrier. In this study, we developed phage and human platelet lysate (h-PL) incorporated cetomacrogol-based creams for combined phage therapy and wound healing. The base material for phage immobilization was formulated by emulsifying paraffin and sterile water with cetomacrogol (emulsifying agent). Specifically, we incorporated a Pseudomonas aeruginosa-infecting lytic phage vB_PaeM_M12PA in the formulation and characterized its genome in this study. Cetomacrogol, a nonionic PEG (polyethylene glycol) based ether, rendered phage stability and allowed initial burst release followed by continuous controlled release of phages from the embedding matrix in the initial 6-8 h. Rheological studies showed that the material has elastic properties with storage moduli (G') values ranging from 109.51 ± 2.10 to 126.02 ± 3.13 kPa, indicating frequency-independent deformation. Platelet lysates in the cream acted as wound healing agents, and in vitro evaluation of cell migration and wound healing capacity of h-PL showed a significant enhancement by the sixth hour compared to untreated groups. The phage-incorporated cream showed sustained phage release in solid media and a significant reduction in bacterial growth in liquid cultures. In vivo wound healing studies in 6-week-old Wistar rats with full-thickness excision wounds and subsequent histopathological studies showed that the formulation enhanced wound healing and tissue restoration efficiency. In conclusion, the study unveils a promising approach for integrated phage therapy and wound healing strategies.

The Effectiveness of Vitamin E Soft Capsules as an Antioxidant

Antioxidants inhibit the oxidation of other molecules and play an important role in maintaining a healthy body. Antioxidants are found in fruits, vegetables, all parts of plants, and are present in the body as enzymes or products of metabolism. Vitamin E refers to a large number of natural or synthetic compounds, with alpha-tocopherol being the most active and widely distributed form in nature. Alpha-tocopherol is the most active antioxidant form of vitamin E and serves as the primary lipophilic antioxidant in plasma, membranes, and tissues. The most important function of vitamin E is its antioxidant capability, counteracting free radical attacks that can damage cells and cause various degenerative diseases. Additionally, antioxidants help reduce the effects of photoaging on the skin, potentiate anti-aging and anti-inflammatory activity, increase the rate of wound healing, and help maintain healthy eyes and the immune system. One form of vitamin E dosage form is a soft capsule which has several advantages, including the ease of filling the Active Pharmaceutical Ingredient (API) in liquid form, higher production capacity and formulation uniformity compared to gelatin tablets or hard capsules. Soft capsule preparations also have rapid API release, which can result in achieving therapeutic blood levels more quickly and achieving greater bioavailability. This study aims to evaluate soft capsule dosage forms in enhancing the effectiveness of vitamin E as an antioxidant. The research utilizes review articles sourced from national and international journals, as well as scientific journals. The results show that vitamin E supplementation in soft capsules can increase its effectiveness as an antioxidant.

Comparative Evaluation of Dissolution Performance in a USP 2 Setup and Alternative Stirrers and Vessel Designs: A Systematic Computational Investigation.

The dissolution testing method described in the United States Pharmacopeia (USP) Chapter ⟨711⟩ is widely used for assessing the release of active pharmaceutical ingredients from solid dosage forms. However, extensive use over the years has revealed certain issues, including high experimental intervariability observed in specific formulations and the settling of particles in the dead zone of the vessel. To address these concerns and gain a comprehensive understanding of the hydrodynamic conditions within the USP 2 apparatus, computational fluid dynamic simulations have been employed in this study. The base design employed in this study is the 900 mL USP 2 vessel along with a paddle stirrer at a 50 rpm rotational speed. Additionally, alternative stirrer designs, including the hydrofoil, pitched blade, and Rushton impeller, are investigated. A comparison is also made between a flat-bottom tank and the USP round-bottom vessel of the same volume and diameter. Furthermore, this work examines the impact of various parameters, such as clearance distance (distance between the bottom of the impeller and bottom of the vessel), number of impeller blades, impeller diameter, and impeller attachment angle. The volume-average shear rate (Stv), fluid velocity (Utv), and energy dissipation rates (ϵtv) represent the key properties evaluated in this study. Comparing the USP2 design and systems with the same stirrer but flat-bottom vessel reveals more homogeneous mixing compared to the USP2 design. Analyzing fluid flow streamlines in different designs demonstrates that hydrofoil stirrers generate more suspension or upward movement of fluid compared to paddle stirrers. Therefore, when impellers are of a similar size, hydrofoil designs generate higher fluid velocities in the coning area. Furthermore, the angle of blade attachment to the hub influences the fluid velocity in the coning area in a way that the 60° angle design generates more suspension than the 45° angle design. The findings indicate that the paddle stirrer design leads to a heterogeneous shear rate and velocity distributions within the vessel compared with the other designs, suggesting suboptimal performance. These insights provide valuable guidance for the development of improved in vitro dissolution testing devices, emphasizing the importance of optimized design considerations to minimize hydrodynamic variability, enhance dissolution characterization, and reduce variability in dissolution test results. Ultimately, such advancements hold potential for improving in vitro-in vivo correlations in drug development.

Development of an emulsion composition with fennel and caraway essential oils for use in the combined therapy of ulcerative colitis

The aim of the study is to develop the composition of an emulsion containing essential oils of Fennel and Caraway seeds for use in the symptomatic complex therapy of ulcerative colitis with the aim of eliminating functional intestinal disorders. Materials and methods. The objects of the study were samples of emulsions containing active pharmaceutical ingredients (essential oils of Fennel and Caraway), purified water, oils (refined sunflower oil, refined olive oil, refined sesame oil), emulsifiers (polyethylene glycol 40 hydrogenated castor oil, polysorbate 80, polyethylene glycol 100 stearate, acacia gum, guar gum, xanthan gum, soya lecithin), viscosity regulator - apple pectin and flavouring agents (food additives with cherry and tarragon flavour). Organoleptic properties, stability, rheological parameters, pH, particle size determination by microscopy, and a taste test were carried out with model emulsion samples. Research to establish the optimal technological parameters was carried out in parallel. Results. The main parameters of the technological process have been established, which allow to obtain an emulsion with evenly distributed particles: 15 minutes at maximum speed. The concentration of emulsifiers at which the emulsions are stable was selected. It was found that the samples containing polyethylene glycol 100 stearate, gums, and soy lecithin have satisfactory organoleptic properties. The sample with soy lecithin emulsifier differs from the others in its ability to form microemulsions, but it has low viscosity. To improve the rheological properties, apple pectin was added to the emulsion. The taste test showed that among vegetable oils, refined sesame oil has a more neutral taste, and the flavouring additive "Tarkhun" balances the taste better. The release of active pharmaceutical ingredients (APIs) from the emulsion base was confirmed by thin-layer chromatography. Conclusions. A microemulsion with essential oils based on refined sesame oil, soy lecithin, with the addition of viscosity and flavour correctors was developed. The obtained emulsion has satisfactory organoleptic properties and conforms to the requirements for emulsion quality indicators

Hydrogel formats to model potential drug interactions occurring at the subcutaneous injection site

We have previously developed an in vitro instrument, termed subcutaneous injection site simulator (SCISSOR), that can be used to monitor release properties of an active pharmaceutical ingredient (API) and formulation components of a medicine designed for SC injection. Initial studies to validate the SCISSOR instrument applications used a simple hyaluronic acid (HA) hydrogel to monitor early release events. We now report a type of cross-linked HA that can, when combined with HA, provide a hydrogel (HA-XR) with optical clarity and rheological properties that remain stable for at least 6 days. Incorporation of 0.05–0.1 mg/mL of collagens isolated from human fibroblasts (Col F), bovine type I collagen (Col I), chicken collagen type II (Col II), or chondroitin sulphate (CS) produced HA or HA-XR hydrogel formats with optical clarity and rheological properties comparable to HA or HA-XR alone. HA + Col F hydrogel had a much greater effect on release rates of 70 kDa compared to 4 kDa dextran, while Col F incorporated into the HA-XR hydrogel accentuated differences in release rates of prandial and basal forms of insulin as well as decreased the release rate of denosumab. A hydrogel format of HA + Col I was used to examine the complex events for bevacizumab release under conditions where a target ligand (vascular endothelial growth factor) can interact with extracellular matrix (ECM). Together, these data have demonstrated the feasibility of using a cross-linked HA format to examine API release over multiple days and incorporation of specific ECM elements to prepare more biomimetic hydrogels that allow for tractable examination of their potential impact of API release.

The landscape of small-molecule prodrugs.

Prodrugs are derivatives with superior properties compared with the parent active pharmaceutical ingredient (API), which undergo biotransformation after administration to generate the API in situ. Although sharing this general characteristic, prodrugs encompass a wide range of different chemical structures, therapeutic indications and properties. Here we provide the first holistic analysis of the current landscape of approved prodrugs using cheminformatics and data science approaches to reveal trends in prodrug development. We highlight rationales that underlie prodrug design, their indications, mechanisms of API release, the chemistry of promoieties added to APIs to form prodrugs and the market impact of prodrugs. On the basis of this analysis, we discuss strengths and limitations of current prodrug approaches and suggest areas for future development.

Co-Assembly of Cancer Drugs with Cyclo-HH Peptides: Insights from Simulations and Experiments.

Peptide-based nanomaterials can serve as promising drug delivery agents, facilitating the release of active pharmaceutical ingredients while reducing the risk of adverse reactions. We previously demonstrated that Cyclo-Histidine-Histidine (Cyclo-HH), co-assembled with cancer drug Epirubicin, zinc, and nitrate ions, can constitute an attractive drug delivery system, combining drug self-encapsulation, enhanced fluorescence, and the ability to transport the drug into cells. Here, we investigated both computationally and experimentally whether Cyclo-HH could co-assemble, in the presence of zinc and nitrate ions, with other cancer drugs with different physicochemical properties. Our studies indicated that Methotrexate, in addition to Epirubicin and its epimer Doxorubicin, and to a lesser extent Mitomycin-C and 5-Fluorouracil, have the capacity to co-assemble with Cyclo-HH, zinc, and nitrate ions, while a significantly lower propensity was observed for Cisplatin. Epirubicin, Doxorubicin, and Methorexate showed improved drug encapsulation and drug release properties, compared to Mitomycin-C and 5-Fluorouracil. We demonstrated the biocompatibility of the co-assembled systems, as well as their ability to intracellularly release the drugs, particularly for Epirubicin, Doxorubicin, and Methorexate. Zinc and nitrate were shown to be important in the co-assembly, coordinating with drugs and/or Cyclo-HH, thereby enabling drug-peptide as well as drug-drug interactions in successfully formed nanocarriers. The insights could be used in the future design of advanced cancer therapeutic systems with improved properties.

Use of Magnetic Resonance Imaging for Visualization of Oral Dosage Forms in the Human Stomach: A Scoping Review.

Oral dosage forms are the most widely and frequently used formulations to deliver active pharmaceutical ingredients (APIs), due to their ease of administration and noninvasiveness. Knowledge of intragastric release rates and gastric mixing is crucial for predicting the API release profile, especially for immediate release formulations. However, knowledge of the intragastric fate of oral dosage forms in vivo to date is limited, particularly for dosage forms administered when the stomach is in the fed state. An improved understanding of gastric food processing, dosage form location, disintegration times, and food effects is essential for greater understanding for effective API formulation design. In vitro standard and controlled modeling has played a significant role in predicting the behavior of dosage forms in vivo. However, discrepancies are reported between in vitro and in vivo disintegration times, with these discrepancies being greatest in the fed state. Studying the fate of a dosage form in vivo is a challenging process, usually requiring the use of invasive methods, such as intubation. Noninvasive, whole body imaging techniques can however provide unique insights into this process. A scoping review was performed systematically to identify and critically appraise published studies using MRI to visualize oral solid dosage forms in vivo in healthy human subjects. The review identifies that so far, an all-purpose robust contrast agent or dosage form type has not been established for dosage form visualization and disintegration studies in the gastrointestinal system. Opportunities have been identified for future studies, with particular focus on characterizing dosage form disintegration for development after the consumption food, as exemplified by the standard Food and Drug Administration (FDA) high fat meal.

Miniaturized screening and performance prediction of tailored subcutaneous extended-release formulations for preclinical in vivo studies

Microencapsulation of active pharmaceutical ingredients (APIs) for preparation of long acting injectable (LAI) formulations is an auspicious technique to enable preclinical characterization of a broad variety of APIs, ideally independent of their physicochemical and pharmacokinetic (PK) characteristics. During early API discovery, tunable LAI formulations may enable pharmacological proof-of-concept for the given variety of candidates by tailoring the level of plasma exposure over the duration of various timespans. Although numerous reports on small scale preparation methods for LAIs utilizing copolymers of lactic and glycolic acid (PLGA) and polymers of lactic acid (PLA) highlight their potential, application in formulation screening and use in preclinical in vivo studies is yet very limited. Transfer from downscale formulation preparation to in vivo experiments is hampered in early preclinical API screening by the large number of API candidates with simultaneously very limited available amount in the lower sub-gram scale, lack of formulation stability and deficient tunability of sustained release.We hereby present a novel comprehensive platform tool for tailored extended-release formulations, aiming to support a variety of preclinical in vivo experiments with ranging required plasma exposure levels and timespans. A novel small-scale spray drying process was successfully implemented by using an air brush based instrument for preparation of PLGA and PLA based formulations. Using Design of Experiments (DoE), required API amount of 250 mg was demonstrated to suffice for identification of dominant polymer characteristics with largest impact on sustained release capability for an individual API. BI-3231, a hydrophilic and weakly acidic small compound with good water solubility and permeability, but low metabolic stability, was used as an exemplary model for one of the many candidates during API discovery. Furthermore, an in vitro to in vivo correlation (IVIVC) of API release rate was established in mice, which enabled the prediction of in vivo plasma concentration plateaus after single subcutaneous injection, using only in vitro dissolution profiles of screened formulations.By tailoring LAI formulations and their doses for acute and sub-chronic preclinical experiments, we exemplary demonstrate the practical use for BI-3231. Pharmacological proof-of-concept could be enabled whilst circumventing the need of multiple administration as result of extensive hepatic metabolism and simultaneously superseding numerous in vivo experiments for formulation tailoring.

Tailoring the use of excipients in bottom-up production of naproxen crystal suspensions via membrane technology

Long-acting crystal suspensions of active pharmaceutical ingredients (API) mostly comprised of an API, a suspension media (water) and excipients and provide sustained API release over time. Excipients are crucial for controlling particle size and to achieve the stability of the API crystals in suspension. A bottom-up process was designed to produce long-acting crystal suspensions whilst investigating the excipient requirements during the production process and the subsequent storage. PVP K30 emerged as the most effective excipient for generating stable naproxen crystals with the desired size of 1 to 15 μm, using ethanol as solvent and water as anti-solvent. Calculations, performed based on the crystal properties and assuming complete PVP K30 adsorption on the crystal surface, revealed lower PVP K30 requirements during storage compared to initial crystal generation. Consequently, a membrane-based diafiltration process was used to determine and fine-tune PVP K30 concentration in the suspension post–crystallization. A seven-stage diafiltration process removed 98 % of the PVP K30 present in the suspension thereby reducing the PVP-to-naproxen ratio from 1:2 to 1:39 without impacting the stability of naproxen crystals in suspension. This work provides insights into the excipient requirements at various production stages and introduce the membrane-based diafiltration for precise excipient control after crystallization.

REVIEW PENGARUH PENGGUNAAN SURFAKTAN PADA KARAKTERISTIK SEDIAAN ORODISPERSIBLE FILM (ODF) OBAT BERKELARUTAN RENDAH DALAM AIR: SIFAT DISINTEGRASI DAN DISOLUSI

Orodispersible film (ODF) is a drug delivery gaining widespread acceptance because it disintegrates quickly and can be self-administered. ODF has the advantage of increasing the active pharmaceutical ingredient (API) effectiveness by rapid dissolution in the oral cavity after direct contact with saliva. One of the components of ODF that influences the physical characteristics and dissolution of low-soluble drugs in water is surfactant. This material acts as a wetting or dispersing agent so the film can quickly disintegrate and release API. The method used is searching for international journal data using the Google Scholar. The surfactants reported to have been used in the ODF formulation are L-arginine, poloxamer 407, tween 80, and sodium dodecyl sulfate. In general, surfactant usage significantly affects the disintegration behavior of the film and API release. This behavior is caused by reducing the interfacial tension between phases by surfactants, which causes increased solid surface wetting and helps speed up the film disintegration and API dissolution from the ODF matrix. The conclusion is that surfactant usage with the appropriate type and concentration will help improve the ODF quality, especially in the disintegration properties of the dosage form and API dissolution.

Electrospun Nanofibers: Shaping the Future of Controlled and Responsive Drug Delivery.

Electrospun nanofibers for drug delivery systems (DDS) introduce a revolutionary means of administering pharmaceuticals, holding promise for both improved drug efficacy and reduced side effects. These biopolymer nanofiber membranes, distinguished by their high surface area-to-volume ratio, biocompatibility, and biodegradability, are ideally suited for pharmaceutical and biomedical applications. One of their standout attributes is the capability to offer the controlled release of the active pharmaceutical ingredient (API), allowing custom-tailored release profiles to address specific diseases and administration routes. Moreover, stimuli-responsive electrospun DDS can adapt to conditions at the drug target, enhancing the precision and selectivity of drug delivery. Such localized API delivery paves the way for superior therapeutic efficiency while diminishing the risk of side effects and systemic toxicity. Electrospun nanofibers can foster better patient compliance and enhanced clinical outcomes by amplifying the therapeutic efficiency of routinely prescribed medications. This review delves into the design principles and techniques central to achieving controlled API release using electrospun membranes. The advanced drug release mechanisms of electrospun DDS highlighted in this review illustrate their versatility and potential to improve the efficacy of medical treatments.

Nanomaterial payload delivery to central nervous system glia for neural protection and repair

Central nervous system (CNS) glia, including astrocytes, microglia, and oligodendrocytes, play prominent roles in traumatic injury and degenerative disorders. Due to their importance, active pharmaceutical ingredients (APIs) are being developed to modulate CNS glia in order to improve outcomes in traumatic injury and disease. While many of these APIs show promise in vitro, the majority of APIs that are systemically delivered show little penetration through the blood–brain barrier (BBB) or blood-spinal cord barrier (BSCB) and into the CNS, rendering them ineffective. Novel nanomaterials are being developed to deliver APIs into the CNS to modulate glial responses and improve outcomes in injury and disease. Nanomaterials are attractive options as therapies for central nervous system protection and repair in degenerative disorders and traumatic injury due to their intrinsic capabilities in API delivery. Nanomaterials can improve API accumulation in the CNS by increasing permeation through the BBB of systemically delivered APIs, extending the timeline of API release, and interacting biophysically with CNS cell populations due to their mechanical properties and nanoscale architectures. In this review, we present the recent advances in the fields of both locally implanted nanomaterials and systemically administered nanoparticles developed for the delivery of APIs to the CNS that modulate glial activity as a strategy to improve outcomes in traumatic injury and disease. We identify current research gaps and discuss potential developments in the field that will continue to translate the use of glia-targeting nanomaterials to the clinic.

Biodegradable Polymer Composites of Metal Organic Framework-5 (MOF-5) for the Efficient and Sustained Delivery of Cephalexin and Metronidazole

The sustained and controlled delivery of antimicrobial drugs has been largely studied using nanomaterials, like metal organic frameworks (MOFs), and various polymers. However, not much attention has been given to combining MOFs and biodegradable polymers towards the potentially more sustained release of active pharmaceutical ingredients. Herein, we report a comparative study of two widely used antimicrobial drugs, cephalexin and metronidazole, from zinc-based MOF-5 incorporated into biodegradable polycaprolactone (PCL) and poly-lactic glycolic acid (PLGA) composites. Cephalexin and metronidazole were separately loaded into MOF-5 post-synthetically, followed by their integration into biodegradable PLGA and PCL composites. The pristine MOF-5 and the loaded MOFs were thoroughly characterised using Fourier-transformed infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and powder X-ray diffraction (PXRD). Ultraviolet-visible (UV-Vis) spectroscopy studies were carried out to assess the release of the drugs in PBS for up to 72 h, showing a cumulative release of 24.95 wt% and 27.84 wt% for cephalexin and metronidazole, respectively. The antibacterial properties of the pristine MOF, pure drugs, drug-loaded MOFs and the loaded composites were assessed against Gram-positive and Gram-negative bacterial strains, Staphylococcus aureus or Staphylococcus epidermidis and Escherichia coli or Acinetobacter baumanii, respectively. A cephalexin-loaded MOF-5 composite of PCL (PCL-ceph@MOF-5) showed the best efficiency for the controlled release of drugs to inhibit the growth of the bacteria compared to the other composites. This study demonstrates that the combination of MOFs with biodegradable polymers can provide an efficient platform for the sustained release of antimicrobial drugs and can be a promising tool to manage antimicrobial resistance (AMR).

Comparison of Hydroxypropyl Methylcellulose and Alginate Gel Films with Meloxicam as Fast Orodispersible Drug Delivery.

The aim of the study was the preparation and comparison of two types of orodispersible gel films (ODF) by the solvent casting method. Natural polymers: sodium alginate (ALG) or hydroxypropyl methylcellulose (HPMC) were used as the gel film formers, and Kollidon or microcrystalline cellulose was used as the disintegrant. Meloxicam (MLX), the drug used to treat rheumatic diseases for children and adults, was proposed as the active pharmaceutical ingredient (API). The influence of the polymer and disintegrant on the properties of ODF was investigated. The evaluation of prepared gel films was based on appearance description, mass uniformity measurement, disintegration time, API content, film wettability, and water content. Also, the dissolution test was prepared in a basket apparatus using artificial salvia (pH = 6.8) as the medium. The obtained API release profiles were analyzed for the similarity factors (f2) with the DDSolver software. The results showed that independently of the polymer or disintegrant, using the solvent casting method, gel films have a similar appearance and active substance content close to the theoretical value and water content of less than 10%. Only the type of polymer influences the release profiles of MLX. However, the disintegration time was longer than 30 s, which makes the films non-fast-dissolving drug delivery systems. This means that for the ODF system, further evaluation is required, and some changes in the composition of the film have to be done.

Composites of N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide with Polymers: Effect of Crystallinity on Solubility and Stability.

This work aimed to develop and characterize a water-soluble, high-release active pharmaceutical ingredient (API) composite based on the practically water-insoluble API N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide (GML-3), a substance with antidepressant and anxiolytic action. This allows to ensure the bioavailability of the medicinal product of combined action. Composites obtained by the method of creating amorphous solid dispersions, where polyvinylpyrrolidone (PVP) or Soluplus® was used as a polymer, were studied for crystallinity, stability and the release of API from the composite into purified water. The resulting differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), and dissolution test data indicate that the resulting composites are amorphous at 1:15 API: polymer ratios for PVP and 1:5 for Soluplus®, which ensures the solubility of GML-3 in purified water and maintaining the supercritical state in solution.