3D-Printed Antibacterial Scaffolds for the Regeneration of Alveolar Bone in Severe Periodontitis.

Current clinical treatment of periodontitis alleviates periodontal symptoms and helps to keep the disease under control for extended periods. Despite this, a significant destruction of the tooth's underlying bone tissue often takes place progressively. Herein, we present a two-way therapeutic approach for local delivery of antibacterial agents and bone tissue regeneration, incorporating ~1% w/w tetracycline hydrochloride (TCH) into a 3D-printed scaffold composed of poly(ε-caprolactone) (PCL). Samples were assessed for their morphological, physicochemical, pharmacokinetic, and antibacterial properties. Furthermore, osteoprecursor cells (MC3T3-E1) were employed to evaluate the osteoinductive potential of the drug-loaded scaffolds. Cell proliferation, viability, and differentiation were determined on all cell-seeded scaffolds. At the end of the culture, PCL-TCH scaffolds promoted abundant collagen organic matrix, demonstrating augmented alkaline phosphatase (ALP) activity and areas of accumulated mineralised bone tissue, despite their belayed cell proliferation. Based on the observed effectiveness of the PCL-TCH scaffolds to inhibit Staphylococcus aureus, these constructs could serve as an alternative bioactive implant that supports bacterial inhibition and favours a 3D microenvironment for bone tissue regeneration in severe periodontitis.

Occurrence of Luteolin in the Greek Flora, Isolation of Luteolin and Its Action for the Treatment of Periodontal Diseases.

Higher plants possess the ability to synthesize a great number of compounds with many different functions, known as secondary metabolites. Polyphenols, a class of flavonoids, are secondary metabolites that play a crucial role in plant adaptation to both biotic and abiotic environments, including UV radiation, high light intensity, low/high temperatures, and attacks from pathogens, among others. One of the compounds that has received great attention over the last few years is luteolin. The objective of the current paper is to review the extraction and detection methods of luteolin in plants of the Greek flora, as well as their luteolin content. Furthermore, plant species, crop management and environmental factors can affect luteolin content and/or its derivatives. Luteolin exhibits various biological activities, such as cytotoxic, anti-inflammatory, antioxidant and antibacterial ones. As a result, luteolin has been employed as a bioactive molecule in numerous applications within the food industry and the biomedical field. Among the different available options for managing periodontitis, dental care products containing herbal compounds have been in the spotlight owing to the beneficial pharmacological properties of the bioactive ingredients. In this context, luteolin's anti-inflammatory activity has been harnessed to combat periodontal disease and promote the restoration of damaged bone tissue.

Branched Poly(ε-caprolactone)-Based Copolyesters of Different Architectures and Their Use in the Preparation of Anticancer Drug-Loaded Nanoparticles.

Limitations associated with the use of linear biodegradable polyesters in the preparation of anticancer nano-based drug delivery systems (nanoDDS) have turned scientific attention to the utilization of branched-chain (co-)polymers. In this context, the present study evaluates the use of novel branched poly(ε-caprolactone) (PCL)-based copolymers of different architectures for the preparation of anticancer nanoparticle (NP)-based formulations, using paclitaxel (PTX) as a model drug. Specifically, three PCL-polyol branched polyesters, namely, a three-arm copolymer based on glycerol (PCL-GLY), a four-arm copolymer based on pentaerythritol (PCL-PE), and a five-arm copolymer based on xylitol (PCL-XYL), were synthesized via ring-opening polymerization and characterized by proton nuclear magnetic resonance (1H-NMR), gel permeation chromatography (GPC), intrinsic viscosity, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier-transform infrared (FT-IR) spectroscopy and cytotoxicity. Then, PTX-loaded NPs were prepared by an oil-in-water emulsion. The size of the obtained NPs varied from 200 to 300 nm, while the drug was dispersed in crystalline form in all formulations. High encapsulation efficiency and high yields were obtained in all cases, while FTIR analysis showed no molecular drug polymer. Finally, in vitro drug release studies showed that the studied nanocarriers significantly enhanced the dissolution rate and extent of the drug.

Preparation and Evaluation of Siderol Amorphous Solid Dispersions: Selection of Suitable Matrix/Carrier.

The present study investigates the preparation of amorphous solid dispersions (ASD) for the ent-kaurane diterpenoid siderol (SDR). Initially, evaluation of the pure drug (isolated from Sideritis scardica) revealed that the API is a non-stable glass former, and hence the selection of a suitable ASD's matrix/carrier needs special attention. For this reason, four commonly used polymers and copolymers, namely poly(vinylpyrrolidone), copovidone, hydroxypropyl cellulose, and Soluplus® (SOL), were screened via film casting and crystal growth rate measurements. Amongst them, SOL showed the highest SDR's crystal growth rate reduction, and, since it was also miscible with the drug, it was selected for further testing. In this direction, SDR-SOL ASDs were successfully prepared via melt-quench cooling. These formulations showed full API amorphization, while good physical stability (i.e., a stable SDR amorphous dispersions) were obtained after storage for several months. Finally, evaluation of molecular interactions (with the aid of ATR-FTIR spectroscopy) showed strong H-bonds between SOL and SDR, while the use of molecular dynamics (MD) simulations unraveled the nature of these interactions. Therefore, based on the findings of the present work, SOL seems to be an appropriate matrix/carrier for the preparation of SDR ASDs, although further studies are needed in order to explore its full potentials.

High-Drug-Loading Amorphous Solid Dispersions via In Situ Thermal Cross-Linking: Unraveling the Mechanisms of Stabilization.

This article takes a step forward in understanding the mechanisms involved during the preparation and performance of cross-linked high-drug-loading (HDL) amorphous solid dispersions (ASDs). Specifically, ASDs, having 90 wt % poorly water-soluble drug indomethacin (IND), were prepared via in situ thermal cross-linking of poly(acrylic acid) (PAA) and poly(vinyl alcohol) (PVA) and thoroughly evaluated in terms of physical stability and in vitro supersaturation. Results showed that HDL ASDs having excellent active pharmaceutical ingredient (API) amorphous stability and prolonged in vitro supersaturation were prepared by fine tuning the cross-linking procedure. Unraveling of the processes involved during ASD's formation shed light on the significant role of the cross-linking conditions (i.e., temperature and time), the physicochemical properties of the API, and the hydrolysis level of the cross-linker as key factors in modulating ASD's stability. In-depth analysis of the prepared systems revealed the (1) reduction of API's molecular motions within the cross-linked polymeric networks (through API's strong spatial confinement), (2) the structural changes in the prepared cross-linked matrices (induced by the high API drug loading), and (3) the tuning of the cross-linking density via utilization of low-hydrolyzed PVA as the major mechanisms responsible for ASD's exceptional performance. Complementary analysis by means of molecular dynamics simulations also highlighted the vital role of strong drug-polymer intermolecular interactions evolving among the ASD components. Overall, the impression of the complexity of in situ cross-linked ASDs has been reinforced with the excessive variation of parameters investigated in the current study, offering thus insights up to the submolecular level to lay the groundwork and foundations for the comprehensive assessment of a new emerging class of HDL amorphous API formulations.

Development of Water-Soluble Electrospun Fibers for the Oral Delivery of Cannabinoids.

Cannabidiol (CBD) and cannabigerol (CBG) are two active pharmaceutical ingredients, derived from cannabis plant. In the present study, CBD and CBG were formulated with polyvinyl(pyrrolidone) (PVP) and Eudragit L-100, using electrohydrodynamic atomization (electrospinning). The produced fibers were smooth and uniform in shape, with average fiber diameters in the range of 700-900 nm for PVP fibers and 1-5 µm for Eudragit L-100 fibers. The encapsulation efficiency for both CB and CBG was high (over 90%) for all formulations tested. Both in vitro release and disintegration tests of the formulations in simulated gastric fluids (SGF) and simulated intestinal fluids (SIF) indicated the rapid disintegration and dissolution of the fibers and the subsequent rapid release of the drugs. The study concluded that the electrospinning process is a fast and efficient method to produce drug-loaded fibers suitable for the per os administration of cannabinoids.

Experimental, Thermodynamic, and Molecular Modeling Evaluation of Amorphous Simvastatin-Poly(vinylpyrrolidone) Solid Dispersions.

A crucial step for the selection of proper amorphous solid dispersion (ASD) matrix carriers is the in-depth assessment of drug/polymer physicochemical properties. In this context, the present study extends the work of previously published attempts by evaluating the formation of simvastatin (SIM)-poly(vinylpyrrolidone) (PVP) ASDs with the aid of thermodynamic and molecular modeling. Specifically, the implementation of both Flory-Huggins lattice theory and molecular dynamics (MD) simulations was able to predict the miscibility between the two components (a finding that was experimentally verified via differential scanning calorimetry (DSC) and hot stage polarized microscopy), while a complete temperature-concentration phase-transition profile was constructed, leading to the identification of the thermodynamically metastable and unstable ASD zones. Furthermore, as in the case of previously published reports, the analysis of the ASDs via Fourier transform infrared spectroscopy did not clarify the type and extent of observed molecular interactions. Hence, in the present study, a computer-based MD simulation model was developed for the first time in order to gain an insight into the properties of the observed interactions. MD amorphous assemblies of SIM, PVP, and their mixtures were initially developed, and the calculated glass transition temperatures were in close agreement with experimentally obtained results, indicating that the developed models could be considered as realistic representations of the actual systems. Furthermore, molecular interactions evaluation via radial distribution function and radius of gyration analysis revealed that increasing SIM content results in a significant PVP chain shrinkage, which eventually leads to SIM-SIM amorphous intermolecular interactions, leading to the formation of amorphous drug zones. Finally, MD-based results were experimentally verified via DSC.

Quality Risk Management and Quality by Design for the Development of Diclofenac Sodium Intra-articular Gelatin Microspheres.

The aim of the present study was to evaluate the development of an intra-articular nonsteroidal anti-inflammatory drug gelatin microsphere formulation based on quality risk management and quality by design approaches. Specifically, after setting the quality target product profile and the critical quality attributes, risk assessment was performed by constructing Ishikawa fishbone diagrams based on preliminary hazard analysis. A Plackett-Burman screening experimental design was applied in order to identify the factors (previously classified by risk assessment analysis as having high risk of failure) having a statistically significant impact on the formation of gelatin microspheres. Particle size, polydispersity index, and drug loading were used as responses, while diclofenac sodium was selected as a model drug. All drug-loaded gelatin microspheres were prepared by emulsion-crosslinking process. Screening results showed that gelatin type, surfactant type and quantity, oil phase type, emulsification speed, and glutaraldehyde's concentration had a statistically significant impact on microsphere's final and intermediate critical quality attributes. A design space was then constructed based on central composite design overlaying contour plots, while verification experiments for the optimum suggested formulation (derived from a set control strategy) showed good agreement between the predicted and the experimentally observed results. In addition, the physicochemical characterization of the optimum formulation showed the formation of significant molecular interactions between the drug and the gelatin matrix, leading to the complete amorphization of diclofenac within the microsphere structure, while dissolution release experiments showed a biphasic release profile which extended the drug's release for up to 30 days, governed by a Fickian diffusion release mechanism.

Development of a new esomeprazole delayed release gastro-resistant pellet formulation with improved storage stability.

This study describes the development of a new esomeprazole (ESO) delayed release gastro-resistant formulation with improved storage stability. A three-step (drug-, sub(seal)- and enteric-) coating process was employed with the aid of a fluid bed coater. Several formulation factors (namely, size and quantity of starting non-pareil sugar spheres, binder quantity during drug-layering, sub(seal)-coating polymer type, and quantity and enteric coating quantity) were evaluated and the whole process was modeled with the aid of feed-forward back-propagation artificial neural networks (ANNs). Results showed that the selection of small-sized starting spheres (45/60 mesh size) leads to pellet agglomeration, while as sub(seal)-coating weight gain increases a reduction in ESO dissolution rate is observed. The enteric-coating applied (Eudragit L30D-55) showed good gastro-resistant performance in both 0.1 N HCl and pH 4.5 media, while immediate release profiles with more than 85% of ESO being released in less than 30 min were obtained. The effect of cellulose-based sub(seal)-coating polymers, (namely, hydroxypropyl cellulose and hydroxypropylmethyl cellulose) on formulation's storage stability at 40 ± 2 °C/75 ± 5%RH indicated that only hydroxypropylmethyl cellulose was able to stabilize ESO delayed-release formulations in terms of assay, dissolution, impurities, and gastro-resistance performance. Finally, scanning electron microscopy (SEM) analysis revealed smooth and homogeneous external surface/coating layers in all three levels (drug-, sub(seal)-, and enteric- coating), while x-ray diffraction showed no polymorphic transformations.

Chitosan Nanoparticles with Encapsulated Natural and UF-Purified Annatto and Saffron for the Preparation of UV Protective Cosmetic Emulsions.

The aim of the present work is to evaluate the preparation of sunscreen emulsions based on chitosan (CS) nanoparticles with annatto, ultrafiltrated (UF) annatto, saffron, and ultrafiltrated saffron. Ionic gelation was used for the preparation of chitosan nanoparticles, while their morphological characteristics and physicochemical properties were evaluated via Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM), and dynamic light scattering (DLS). Results showed that the prepared nanoparticles ranged from ~150 to ~500 nm and had a spherical or irregular shape. In the case of annatto and UF annatto, due to the formation of H-bonds, the sunscreen agents were amorphously dispersed within CS nanoparticles, while in the case of saffron and UF saffron, crystalline dispersion was observed. All encapsulated materials had good thermal stability as well as color stability. In a further step, sunscreen emulsions were prepared based on the formed CS-sunscreen nanoparticles and evaluated for their stability in terms of pH and viscosity, along with their ultraviolet (UV) radiation protection ability in terms of sun protection factor (SPF). All prepared emulsions showed low cytotoxicity and good storage stability for up to 90 days, while minimum sunscreen protection was observed with SPF values varying from 2.15 to 4.85.

Development of a New Aprepitant Liquisolid Formulation with the Aid of Artificial Neural Networks and Genetic Programming.

In the present study, liquisolid formulations were developed for improving dissolution profile of aprepitant (APT) in a solid dosage form. Experimental studies were complemented with artificial neural networks and genetic programming. Specifically, the type and concentration of liquid vehicle was evaluated through saturation-solubility studies, while the effect of the amount of viscosity increasing agent (HPMC), the type of wetting (Soluplus® vs. PVP) and solubilizing (Poloxamer®407 vs. Kolliphor®ELP) agents, and the ratio of solid coating (microcrystalline cellulose) to carrier (colloidal silicon dioxide) were evaluated based on in vitro drug release studies. The optimum liquisolid formulation exhibited improved dissolution characteristics compared to the marketed product Emend®. X-ray diffraction (XRD), scanning electron microscopy (SEM) and a novel method combining particle size analysis by dynamic light scattering (DLS) and HPLC, revealed that the increase in dissolution rate of APT in the optimum liquisolid formulation was due to the formation of stable APT nanocrystals. Differential scanning calorimetry (DSC) and attenuated total reflection FTIR spectroscopy (ATR-FTIR) revealed the presence of intermolecular interactions between APT and liquisolid formulation excipients. Multilinear regression analysis (MLR), artificial neural networks (ANNs), and genetic programming (GP) were used to correlate several formulation variables with dissolution profile parameters (Y 15min and Y 30min) using a full factorial experimental design. Results showed increased correlation efficacy for ANNs and GP (RMSE of 0.151 and 0.273, respectively) compared to MLR (RMSE = 0.413).

Physicochemical characterization of nimodipine-polyethylene glycol solid dispersion systems.

This study investigates the solid-solid interactions between nimodipine (NIM) and polyethylene glycol (PEG) of different mean molecular weights (PEG 2000, 4000 and 6000), in solid dispersion systems, applying differential scanning calorimetry (DSC), Fourier-Transform infrared spectroscopy, powder X-ray diffraction (PXRD), hot stage microscopy (HSM) and theoretical modeling by the Flory-Huggins (FH) solution theory. Phase diagrams constructed with the aid of DSC and FH solution theory showed sensitivity on the estimated values of the FH interaction parameter (χ). When χ is considered a constant number (χ = α, α ≠ 0), formation of a eutectic mixture is predicted in the 70-80% w/w PEG concentration region, while when χ was considered as a function of concentration and temperature (χ = f(φ,Τ)), the model predicts the formation of monotectic systems. Construction of more precise phase diagrams by HSM to the aid of Kofler's "contact preparation" method confirmed the monotectic nature of the examined systems. Studies on NIM's re-crystallization process in the solid dispersions revealed a strong dependence of the crystallization rate, as well as the resulting crystal form, on the mean molecular weight and concentration of PEG: NIM crystallization rates decrease as PEG's MW increases, while NIM mod II crystals predominate in dispersions prepared at temperatures above NIM's liquidus and growth of NIM mod I prevailing in PEG-rich samples.

Evaluation of Suitable Polymeric Matrix/Carriers during Loading of Poorly Water Soluble Drugs onto Mesoporous Silica: Physical Stability and In Vitro Supersaturation.

The application of mesoporous carriers in formulations of amorphous solid dispersions (ASDs) has been suggested to enhance the stability of amorphous drugs. However, mesoporous carriers do not demonstrate satisfactory inhibitory effects on the precipitation of active pharmaceutical ingredients (APIs), and the inclusion of an appropriate polymer within ASDs becomes imperative to maintaining drug supersaturation. The aim of this study was to evaluate ternary olanzapine (OLN) ASDs with Syloid 244FP and to find an appropriate polymeric carrier. The polymer's selection criteria were based on the physical stability of the ASDs and the release rate of the drug from the systems. The polymers investigated were hydroxypropylmethyl cellulose (HPMC) and copovidone (coPVP). The formation of ASDs was achievable in all investigated cases, as demonstrated by the complete lack of crystallinity confirmed through both powder X-ray diffraction (pXRD) analysis and differential scanning calorimetry (DSC) for all developed formulations. The solvent shift method was employed to evaluate the ability of the studied carriers to inhibit the precipitation of supersaturated OLN. coPVP emerged as a more suitable precipitation inhibitor compared with HPMC and Syloid 244 FP. Subsequently, in vitro dissolution studies under non-sink conditions revealed a higher degree of supersaturation in ternary systems where coPVP was used as a polymeric carrier, as these systems exhibited, under the examined conditions, up to a 2-fold increase in the released OLN compared with the pure crystalline drug. Moreover, stability studies conducted utilizing pXRD demonstrated that ternary formulations incorporating coPVP and Syloid 244 FP maintained stability for an extended period of 8 months. In contrast, binary systems exhibited a comparatively shorter stability duration, indicating the synergistic effect of coPVP and Syloid 244 FP on the physical stability of the amorphous API. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) studies showed that the development of stronger molecular interactions can be provided as an explanation for this synergistic effect, as the formation of robust H-bonds may be considered responsible for inhibiting the precipitation of the supersaturated API. Therefore, the incorporation of coPVP into OLN ASDs with Syloid 244 FP is considered a highly promising technique for increasing the degree of OLN supersaturation in in vitro dissolution studies and improving the stability of systems.

Multidimensional 3D-Printed Scaffolds and Regeneration of Intrabony Periodontal Defects: A Systematic Review.

BACKGROUND: The utilization of regenerative techniques in periodontology involves tailoring tissue engineering principles to suit the oral cavity's unique environment. Advancements in computer-assisted technology, specifically utilizing cone beam computed tomography (CBCT), enabled the fabrication of 3D-printed scaffolds. The current review aims to explore whether 3D-printed scaffolds are effective in promoting osteogenesis in patients with periodontal defects. METHODS: A thorough exploration was undertaken across seven electronic databases (PubMed, Scopus, ScienceDirect, Google Scholar, Cochrane, Web of Science, Ovid) to detect pertinent research in accordance with specified eligibility criteria, aligning with the PRISMA guidelines. Two independent reviewers undertook the screening and selection of manuscripts, executed data extraction, and evaluated the bias risk using the Newcastle-Ottawa Scale for non-randomized clinical trials and SYRCLE's risk of bias tool for animal studies. RESULTS: Initially, 799 articles were identified, refined by removing duplicates. After evaluating 471 articles based on title and abstract, 18 studies remained for full-text assessment. Eventually, merely two manuscripts fulfilled all the eligibility criteria concerning human trials. Both studies were prospective non-randomized clinical trials. Moreover, 11 animal studies were also included. CONCLUSIONS: The use of multidimensional, 3D-printed, customized scaffolds appears to stimulate periodontal regeneration. While the reported results are encouraging, additional studies are required to identify the ideal characteristics of the 3D scaffold to be used in the regeneration of periodontal tissue.

The Role of Cone Beam Computed Tomography in Periodontology: From 3D Models of Periodontal Defects to 3D-Printed Scaffolds.

The treatment of osseous defects around teeth is a fundamental concern within the field of periodontology. Over the years, the method of grafting has been employed to treat bone defects, underscoring the necessity for custom-designed scaffolds that precisely match the anatomical intricacies of the bone cavity to be filled, preventing the formation of gaps that could allow the regeneration of soft tissues. In order to create such a patient-specific scaffold (bone graft), it is imperative to have a highly detailed 3D representation of the bone defect, so that the resulting scaffold aligns with the ideal anatomical characteristics of the bone defect. In this context, this article implements a workflow for designing 3D models out of patient-specific tissue defects, fabricated as scaffolds with 3D-printing technology and bioabsorbable materials, for the personalized treatment of periodontitis. The workflow is based on 3D modeling of the hard tissues around the periodontal defect (alveolar bone and teeth), scanned from patients with periodontitis. Specifically, cone beam computed tomography (CBCT) data were acquired from patients and were used for the reconstruction of the 3D model of the periodontal defect. The final step encompasses the 3D printing of these scaffolds, employing Fused Deposition Modeling (FDM) technology and 3D-bioprinting, with the aim of verifying the design accuracy of the developed methodοlogy. Unlike most existing 3D-printed scaffolds reported in the literature, which are either pre-designed or have a standard structure, this method leads to the creation of highly detailed patient-specific grafts. Greater accuracy and resolution in the macroarchitecture of the scaffolds were achieved during FDM printing compared to bioprinting, with the standard FDM printing profile identified as more suitable in terms of both time and precision. It is easy to follow and has been successfully employed to create 3D models of periodontal defects and 3D-printed scaffolds for three cases of patients, proving its applicability and efficiency in designing and fabricating personalized 3D-printed bone grafts using CBCT data.

Utilizing Drug Amorphous Solid Dispersions for the Preparation of Dronedarone per os Formulations.

Dronedarone (DRN), an antiarrhythmic drug, exhibits potent pharmacological effects in the management of cardiac arrhythmias. Despite its therapeutic potential, DRN faces formulation challenges due to its low aqueous solubility. Hence, the present study is dedicated to the examination of amorphous solid dispersions (ASDs) as a strategic approach for enhancing the solubility of DRN. Initially, the glass forming ability (GFA) of API was assessed alongside its thermal degradation profile, and it was revealed that DRN is a stable glass former (GFA III compound) that remains thermally stable up to approximately 200 °C. Subsequently, five commonly used ASD matrix/carriers, i.e., hydroxypropyl methylcellulose (HPMC), povidone (PVP), copovidone (PVP/VA), Soluplus® (SOL), and Eudragit® E PO (EPO), were screened for the formation of a DRN-based ASD using film casting and solvent shift methods, along with miscibility evaluation measurements. SOL proved to be the most promising matrix/carrier among the others, and, hence, was used to prepare DRN ASDs via the melt-quench method. The physicochemical characterization of the prepared systems (via pXRD) revealed the complete amorphization of the API within the matrix/carrier, while the system was physically stable for at least three months after its preparation. In vitro release studies for the ASDs, conducted under non-sink conditions, revealed the sustained supersaturation of the drug for at least 8 h. Finally, the use of attenuated total reflectance (ATR) FTIR spectroscopy showed the formation of a strong molecular interaction between the drug molecules and SOL.

Synthesis of novel interpenetrated network for ocular co-administration of timolol maleate and dorzolamide hydrochloride drugs.

In the present work, novel interpenetrated networks (IPNs) of [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide) (SBMA) and poly(vinyl alcohol) (PVA) were prepared for the ocular co-administration of timolol maleate (TIM) and dorzolamide hydrochloride (DORZ), two drugs widely used for the treatment of glaucoma. The successful polymerization of SBMA, in the presence of PVA, led to the formation of semi-interpenetrated pSBMA-PVA networks (IPNs), in the form of sponges, exhibiting intrinsic antimicrobial properties attributed to SBMA. Fourier-transform infrared spectroscopy (FTIR) was utilized to confirm the successful synthesis of the IPNs. Further assessments, including contact angle and water sorption measurements, highlighted their significant hydrophilicity, a feature that makes them suitable for ocular applications. Differential scanning calorimetry (DSC) measurements indicated that PVA serves as a plasticizer, while an assessment of the water sorption capacity of these materials suggested that although the incorporation of PVA results in slightly less hydrophilic materials, the prepared sponges still remain sufficiently hydrophilic for ocular use. Following their characterization, the optimal pSBMA-PVA IPN was used to encapsulate TIM and DORZ. Irritation tests, performed using the HET-CAM method, confirmed that the drug-loaded sponges were safe and potentially well-tolerated for ophthalmic use. Finally, the co-release study for the two drugs revealed a sustained release pattern in both cases, while drug release from the sponges was primarily controlled by diffusion.

Assessing the performance of thermally crosslinked amorphous solid dispersions with high drug loadings.

Continuing what previous studies had also intended, the present study aims to shed light on some unanswered questions concerning a recently introduced class of high drug loading (HD) amorphous solid dispersions (ASDs), based on the in-situ thermal crosslinking of poly (acrylic acid) (PAA) and poly (vinyl alcohols) (PVA). Initially, the effect of supersaturated dissolution conditions on the kinetic solubility profiles of the crosslinked HD ASDSs having indomethacin (IND) as a model drug, was determined. Subsequently, the safety profile of these new crosslinked formulations was determined for the first time by evaluating their cytotoxic effect on human intestinal epithelia cell line (Caco-2), while their ex-vivo intestinal permeability was also studied via the non-everted gut sac method. According to the obtained findings, the in-situ thermal crosslinked IND HD ASDs present similar kinetic solubility profiles when the dissolution studies are conducted with a steady sink index value, regardless of the different dissolution medium's volume and the total dose of the API. Additionally, the results showed a concentration- and time- dependent cytotoxicity profile for all formulations, while the neat crosslinked PAA/PVA matrices did not elicit cytotoxicity during the first 24 h, even at the highest examined concentration. Finally, the newly proposed HD ASD system, resulted in a remarkably increased ex-vivo intestinal permeability of IND.

A Review of the Role of Natural Products as Treatment Approaches for Xerostomia.

Xerostomia, commonly known as dry mouth, is a widespread oral health malfunction characterized by decreased salivary flow. This condition results in discomfort, impaired speech and mastication, dysphagia, heightened susceptibility to oral infections, and ultimately, a diminished oral health-related quality of life. The etiology of xerostomia is multifaceted, with primary causes encompassing the use of xerostomic medications, radiation therapy to the head and neck, and systemic diseases such as Sjögren's syndrome. Consequently, there is a growing interest in devising management strategies to address this oral health issue, which presents significant challenges due to the intricate nature of saliva. Historically, natural products have served medicinal purposes, and in contemporary pharmaceutical research and development, they continue to play a crucial role, including the treatment of xerostomia. In this context, the present review aims to provide an overview of the current state of knowledge regarding natural compounds and extracts for xerostomia treatment, paving the way for developing novel therapeutic strategies for this common oral health issue.

The influence of surfactant HLB and oil/surfactant ratio on the formation and properties of self-emulsifying pellets and microemulsion reconstitution.

Self-emulsifying oil/surfactant mixtures can be incorporated into pellets that have the advantages of the oral administration of both microemulsions and a multiple-unit dosage form. The purpose of this work was to study the effects of surfactant hydrophilic-lipophilic balance (HLB) and oil/surfactant ratio on the formation and properties of self-emulsifying microcrystalline cellulose (MCC) pellets and microemulsion reconstitution. Triglycerides (C(8)-C(10)) was the oil and Cremophor ELP and RH grades and Solutol the surfactants. Pellets were prepared by extrusion/spheronization using microemulsions with fixed oil/surfactant content but with different water proportions to optimize size and shape parameters. Microemulsion reconstitution from pellets suspended in water was evaluated by turbidimetry and light scattering size analysis, and H-bonding interactions of surfactant with MCC from FT-IR spectra. It was found that water requirements for pelletization increased linearly with increasing HLB. Crushing load decreased and deformability increased with increasing oil/surfactant ratio. Incorporation of higher HLB surfactants enhanced H-bonding and resulted in faster and more extensive disintegration of MCC as fibrils. Reconstitution was greater at high oil/surfactant ratios and the droplet size of the reconstituted microemulsions was similar to that in the wetting microemulsions. The less hydrophilic ELP with a double bond in the fatty acid showed weaker H-bonding and greater microemulsion reconstitution. Purified ELP gave greater reconstitution than the unpurified grade. Thus, the work demonstrates that the choice of type and quantity of the surfactant used in the formulation of microemulsions containing pellets has an important influence on their production and performance.