Electrospun Polymer Blend Nanofibers for Tunable Drug Delivery: The Role of Transformative Phase Separation on Controlling the Release Rate.

Electrospun fibrous materials have a wide range of biomedical applications, many of them involving the use of polymers as matrices for incorporation of therapeutic agents. The use of polymer blends improves the tuneability of the physicochemical and mechanical properties of the drug loaded fibers. This also benefits the development of controlled drug release formulations, for which the release rate can be modified by altering the ratio of the polymers in the blend. However, to realize these benefits, a clear understanding of the phase behavior of the processed polymer blend is essential. This study reports an in depth investigation of the impact of the electrospinning process on the phase separation of a model partially miscible polymer blend, PVP K90 and HPMCAS, in comparison to other conventional solvent evaporation based processes including film casting and spin coating. The nanoscale stretching and ultrafast solvent removal of electrospinning lead to an enhanced apparent miscibility between the polymers, with the same blends showing micronscale phase separation when processed using film casting and spin coating. Nanoscale phase separation in electrospun blend fibers was confirmed in the dry state. Rapid, layered, macroscale phase separation of the two polymers occurred during the wetting of the fibers. This led to a biphasic drug release profile from the fibers, with a burst release from PVP-rich phases and a slower, more continuous release from HPMCAS-rich phases. It was noted that the model drug, paracetamol, had more favorable partitioning into the PVP-rich phase, which is likely to be a result of greater hydrogen bonding between PVP and paracetamol. This led to higher drug contents in the PVP-rich phases than the HPMCAS-rich phases. By alternating the proportions of the PVP and HPMCAS, the drug release rate can be modulated.

Effect of Vitamin D Supplementation on Muscle Function in Patients With I131-Induced Hypothyroidism: A Pilot Randomized Trial.

Background: There is a lack of data regarding the effect of vitamin D supplements in patients with I131-induced hypothyroidism. The primary aim of this study was to investigate the effect of vitamin D supplements on muscle function, and the secondary aim was to observe the effect on body composition, insulin resistance, and quality of life (QOL) in patients with I131-induced hypothyroidism. Methods: In this pilot randomized placebo-controlled trial, patients with I131-induced hypothyroidism on a stable dose of levothyroxine were enrolled and allocated into 2 groups to receive oral vitamin D 20 000 IU weekly or placebo for 24 weeks. Baseline biochemical values, body composition, handgrip strength, the 5 times sit-to-stand test (5TSTS), homeostatic model assessment for insulin resistance (HOMA-IR), and QOL were measured before intervention and after 3 and 6 months in both groups. Mixed model regression analysis was used to compare the outcomes between the 2 groups. Significance was set at P value of < .05. Results: There were 20 participants in each group. The time taken for 5TSTS in the vitamin D group was significantly lower than the placebo group at 3 (P = .032) and 6 months (P = .006). Other outcomes, including handgrip strength, body composition, HOMA-IR, and QOL, showed no significant difference between the 2 groups. Conclusion: A supplement of vitamin D2 at 20 000 IU per week for 24 weeks could help improve performance in 5TSTS in patients with I131-induced hypothyroidism.

Polymer Matrix and Manufacturing Methods in Solid Dispersion System for Enhancing Andrographolide Solubility and Absorption: A Systematic Review.

Background: Andrographolide (ADG) has poor aqueous solubility and low bioavailability. This study systematically reviews the use of solid dispersion (SD) techniques to enhance the solubility and absorption of ADG, with a focus on the methods and polymers utilized. Methodology: We searched electronic databases including PubMed, Web of Science, Scopus®, Embase and ScienceDirect Elsevier® up to November 2023 for studies on the solubility or absorption of ADG in SD formulations. Two reviewers independently reviewed the retrieved articles and extracted data using a standardized form and synthesized the data qualitatively. Results: SD significantly improved ADG solubility with up to a 4.7-fold increase and resulted in a decrease in 50% release time (T1/2) to less than 5 min. SD could also improve ADG absorption, as evidenced by higher Cmax and AUC and reduced Tmax. Notably, Soluplus-based SDs showed marked solubility and absorption enhancements. Among the five SD techniques (rotary evaporation, spray drying, hot-melt extrusion, freeze drying and vacuum drying) examined, spray drying emerged as the most effective, enabling a one-step process without the need for post-milling. Conclusions: SD techniques, particularly using Soluplus and spray drying, effectively enhance the solubility and absorption of ADG. This insight is vital for the future development of ADG-SD matrices.

Design and Optimization of 3D-Printed Tablets Containing Mucuna Extracts for Erectile Dysfunction Management: A DoE-Guided Study.

Erectile dysfunction (ED) refers to the inability of the penis to maintain a firm erection during sexual activity. Mucuna, or M. pruriens, contains levodopa, a compound showing promise in ED treatment. However, formulating Mucuna extract into tablet dosage forms is challenging due to its semisolid nature. This study aimed to develop sustained-release tablets containing Mucuna extract via semisolid extrusion 3D printing. Eudragit RS PO (Eudragit) served as a sustained-release polymer, with poly (vinyl alcohol) (PVA) as a co-polymer for forming the tablet matrices. This study had the following two main phases: screening, which identified the factors affecting the printability, and optimization, which focused on the factors influencing the levodopa release and its consistency. The results showed that both the polymeric solid percentage content (PSPC) in the semisolid slurry and the Eudragit-PVA ratio significantly affected the printability. All of the formulations were printable, and the PSPC and Eudragit-PVA ratios were incorporated into the optimized model. The desired formulation, achieving targeted levodopa release and consistency, had a PSPC of 58.8% and a Eudragit-PVA ratio of 2.87:1. In conclusion, semisolid extrusion 3D printing guided by the design of experiments (DoE) proved feasible for producing reliable 3D-printed tablets with consistent active ingredients and desired release rates.

Potential of electro-sprayed purified mangiferin nanoparticles for anti-aging cosmetic applications.

The fabrication of mangiferin nanoparticles using an electrospraying technique is a new and promising method for developing nanoparticles with higher efficiency and safety. This study aimed to fabricate mangiferin nanoparticles (MNPs) using cellulose acetate (CA) as a polymer at various parameters using electrospraying. Commercial mangiferin (CM) was purified from 88.46 to 95.71% by a recrystallization method to improve its purity and biological activities and remove any residue. The properties of recrystallized mangiferin (RM) were characterized using DSC, FTIR, X-ray diffraction (XRD) and HPLC. Then its biological activity and proteomics were determined. Proteomics analysis of RM showed that up-regulated proteins were involved in more biological processes than CM. MNPs were fabricated by varying the electrospraying parameters including voltage, the distance between the needle-tip-collector and flow rate. Skin permeation, release and irritation were also evaluated. The results revealed that the average particle size of the MNPs ranged between 295.47 ± 5.58 and 448.87 ± 3.00 nm, and had a smooth spherical morphology in SEM images. The MNPs also showed good potential in antioxidant and anti-aging properties. The encapsulation efficiency of MNPs was determined to be 85.31%. From skin permeation studies of CM, RM, and MNPs, the mangiferin content was found in the stratum corneum and dermis skin layers. Moreover, the MNPs solution had 23.68 ± 0.27% and 11.98 ± 0.13% of mangiferin in the stratum corneum and viable epidermis and dermis, respectively. Additionally, the irritation test by HET-CAM was mild and safe. Therefore, MNPs produced by electrospraying are a promising delivery system for cosmetic/cosmeceutical applications.

Enhanced mechanical properties and biocompatibility of bacterial cellulose composite films with inclusion of 2D MoS2 and helical carbon nanotubes for use as antimicrobial drug carriers.

Bacterial cellulose (BC) is a biomaterial being investigated for a range of applications. Herein, BC films derived from nata de coco pieces are reinforced by two-dimensional molybdenum disulfide (MoS2) and helical carbon nanotubes (HCNTs) to enhance their tensile mechanical properties, and the biocompatibility of the BC composite films is demonstrated. A simple preparation is presented using a kitchen blender to disperse and blend the BC fibers and additives in a common fabrication medium, followed by vacuum filtration. The mechanical properties of the BC/MoS2/HCNTs composite films are enhanced due to the synergistic effect of MoS2 and HCNTs embedded in the BC films. The MoS2/HCNTs binary additive (1 phr) is capable of increasing the strength and Young's modulus by 148 % and 333 %, respectively, relative to the BC films. The cell cytotoxicity of the BC/MoS2/HCNTs films was assessed using an MTT assay. The composite films are biocompatible with a cell viability of L929 fibroblast cells >70 %, coupled with observations of direct cell attachment on the films. The composite films also exhibited good performance in absorbing and releasing gentamicin antibiotics to inhibit the growth of Escherichia coli and Staphylococcus aureus. The BC/MoS2/HCNTs films are thus potential BC-based candidates as biocompatible robust antibiotic carriers.

Ethyl cellulose composite membranes containing a 2D material (MoS2) and helical carbon nanotubes for efficient solar steam generation and desalination.

With the increasing water consumption, water evaporators have been investigated for clean water production. Herein, the fabrication of electrospun composite membrane evaporators based on ethyl cellulose (EC), with the incorporation of light-absorption enhancers 2D MoS2 and helical carbon nanotubes, for steam generation and solar desalination is described. Under natural sunlight, the maximum water evaporation rate was 2.02 kg m-2 h-1 with an evaporation efficiency of 93.2 % (1 sun) and reached 2.42 kg m-2 h-1 at 12:00 pm (1.35 sun). The composite membranes demonstrated self-floating on the air-water interface and minimal accumulation of superficial salt during the desalination process due to the hydrophobic character of EC. For concentrated saline water (21 wt% NaCl), the composite membranes maintained a relatively high evaporation rate of up to ~79 % compared to the freshwater evaporation rate. The composite membranes are robust due to the thermomechanical stability of the polymer even while operating under steam-generating conditions. Over repeated use, they exhibited excellent reusability with a relative water mass change of >90 % compared to the first evaporation cycle. Moreover, desalination of artificial seawater produced a lower cation concentration (~3-5 orders of magnitude) and thereby yielded potable water, indicating the potential for solar-driven freshwater generation.

Carboxymethyl cellulose/poly(vinyl alcohol) blended films reinforced by buckypapers of carbon nanotubes and 2D material (MoS2): Enhancing mechanical strength, toughness, and barrier properties.

Plastic waste is one cause of climate change. To solve this problem, packaging films are increasingly produced from biodegradable polymers. Eco-friendly carboxymethyl cellulose and its blends have been developed for such a solution. Herein, a unique strategy is demonstrated to improve the mechanical and barrier properties of carboxymethyl cellulose/poly(vinyl alcohol) (CMC/PVA) blended films for the packaging of nonfood dried products. The blended films were impregnated with buckypapers containing different combinations of multiwalled carbon nanotubes, two-dimensional molybdenum disulfide (2D MoS2) nanoplatelets, and helical carbon nanotubes (HCNTs). Compared to the blend, the polymer composite films exhibit significant increases in tensile strength (~105 %, from 25.53 to 52.41 MPa), Young's modulus (~297 %, from 155.48 to 617.48 MPa), and toughness (~46 %, from 6.69 to 9.75 MJ m-3). Polymer composite films containing HCNTs in buckypapers offer the highest toughness. For barrier properties, the polymer composite films are opaque. The water vapor transmission rate of the blended films decreases (~52 %, from 13.09 to 6.25 g h-1 m-2). Moreover, the maximum thermal-degradation temperature of the blend rises from 296 to 301 °C, especially for the polymer composite films with buckypapers containing MoS2 nanosheets that contribute to the barrier effect for both water vapor and thermal-decomposition gas molecules.

The use of polymer blends to improve stability and performance of electrospun solid dispersions: The role of miscibility and phase separation.

Solid dispersion-based nanofiber formulations of poorly soluble drugs prepared by electrospinning (ES) with a water-soluble polymer, can offer significant improvements in drug dissolution for oral drug administration. However, when hygroscopic polymers, such as polyvinylpyrrolidone (PVP) are used, environmental moisture sorption can lead to poor physical stability on storage. This study investigated the use of polymer blends to modify PVP-based ES formulations of a model poorly soluble drug, fenofibrate (FF), to improve its physical stability without compromising dissolution enhancement. FF-PVP ES dispersions demonstrated clear dissolution enhancement, but poor storage stability against high humidity. Polymer blends of PVP with Eudragit E, Soluplus and hypromellose acetate succinate (HPMCAS), were selected because of the low intrinsic moisture sorption of these polymers. The drug-polymer and polymer-polymer miscibility study revealed that FF was more miscible with Eudragit E and Soluplus than with PVP and HPMCAS, and that PVP was more miscible with HPMCAS than Eudragit E and Soluplus. This led to different configurations of phase separation in the placebo and drug-loaded fibres. The in vitro drug release data confirmed that the use of PVP-Eudragit E retained the dissolution enhancement of the PVP formulation, whereas PVP-Soluplus reduced the drug release rate in comparison to FF-PVP formulations. The moisture sorption results confirmed that moisture uptake by the polymer blends was reduced, but formulation deformation occurred to phase-separated blend formulations. The data revealed the importance of miscibility and phase separation in understanding the physical stability of the ES fibre mats. The findings provide insight into the design of formulations that can provide dissolution enhancement balanced with improved storage stability.

Characterization of Hydrophilic Polymers as a Syringe Extrusion 3D Printing Material for Orodispersible Film.

The application of hydrophilic polymers in designing and three-dimensional (3D) printing of pharmaceutical products in various dosage forms has recently been paid much attention. Use of hydrophilic polymers and syringe extrusion 3D printing technology in the fabrication of orodispersible films (ODFs) might hold great potential in rapid drug delivery, personalized medicine, and manufacturing time savings. In this study, the feasibility of 3D-printed ODFs fabrication through a syringe extrusion 3D printing technique and using five different hydrophilic polymers (e.g., hydroxypropyl methylcellulose E15, hydroxypropyl methylcellulose E50, high methoxyl pectin, sodium carboxymethylcellulose, and hydroxyethylcellulose) as film-forming polymers and printing materials has been investigated. Rheology properties and printability of printing gels and physicochemical and mechanical properties of 3D-printed ODFs were evaluated. Amongst the investigated hydrophilic polymers, sodium carboxymethylcellulose at a concentration of 5% w/v (SCMC-5) showed promising results with a good printing resolution and accurate dimensions of the 3D-printed ODFs. In addition, SCMC-5 3D-printed ODFs exhibited the fastest disintegration time within 3 s due to high wettability, roughness and porosity on the surface. However, the results of the mechanical properties study showed that SCMC-5 3D printed ODFs were rigid and brittle, thus requiring special packaging to prevent them from any damage before practical use.

Formulation of Orally Disintegrating Films as an Amorphous Solid Solution of a Poorly Water-Soluble Drug.

The objective of the present study was to develop an orally disintegrating film (ODF) for a poorly water-soluble drug, phenytoin (PHT), using the cosolvent solubilization technique to achieve the amorphization of the drug, followed by the preparation of ODFs. Eleven formulations were prepared with different polymers, such as polyvinyl alcohol (PVA) and high methoxyl pectin (HMP) by the solvent casting method. The prepared films were subjected to characterization for weight variations, thickness, surface pH, disintegration time and mechanical strength properties. Then, differential scanning calorimetry, X-ray diffraction analysis and the drug release patterns of the selected films were evaluated. Among the prepared formulations, the formulation composed of 1% w/w of PVA, 0.04% w/w of sodium starch glycolate with polyethylene glycol 400, glycerin and water as cosolvents (PVA-S4) showed promising results. The physical appearance and mechanical strength properties were found to be good. The PVA-S4 film was clear and colorless with a smooth surface. The surface pH was found to be around 7.47 and the in vitro disintegration time was around 1.44 min. The drug content of the PVA-S4 film was 100.27%. X-ray diffractometry and thermal analysis confirmed the transition of phenytoin in the PVA-S4 film into a partially amorphous state during film preparation using the cosolvent solubilization approach. The resulting PVA-S4 film showed a higher dissolution rate in comparison to the film without a cosolvent. Overall, this study indicated the influence of cosolvents on enhancing the solubility of a poorly water-soluble drug and its film dissolution.

Towards controlling the crystallisation behaviour of fenofibrate melt: triggers of crystallisation and polymorphic transformation.

Fenofibrate (FEN) is a dyslipidemia treatment agent which is poorly soluble in water. FEN has tendency to form polymorphs and its crystallisation behaviour is difficult to predict. The nucleation process can be initiated by mechanical disruption such as ball milling or surface scratching which may result in different crystallisation behaviour to that observed in the unperturbed system. This study has obtained insights into the controllability of FEN crystallisation by means of regulating the exposed surface and growth temperatures during its crystallisation. The availability of an open top surface (OTS) during the crystallisation of the FEN melt resulted in a mixture containing FEN form I and IIa (I ≫ IIa) at room temperature, and in the range 40 to 70 °C. Covering the surface led to significant increases in the yield of form IIa at room temperature and at 40 and 50 °C. These temperatures also yielded the highest amount of form IIa in the OTS samples whilst crystallisation at 70 °C led to only FEN form I crystals regardless of the availability of the free surface. The metastable FEN form IIa transforms to the stable form I under the influence of a mechanical stress. Additionally, the introduction of OTS before the completion of crystallisation of form IIa led to a 'switch' of from IIa growth to form I. This study demonstrates that the polymorph selection of FEN can be obtained by the manipulation of the crystallisation conditions.

Preparation of glutinous rice starch/polyvinyl alcohol copolymer electrospun fibers for using as a drug delivery carrier.

Glutinous rice starch (GRS) is commonly produced in the Northeast of Thailand. GRS is a biopolymer which is widely used in the food industry but not yet commonly applied within the pharmaceutical industry as an alternative resource. GRS exhibits a branch chain structure which is not feasible to fabricate as nanofiber. Therefore, combining GRS with polyvinyl alcohol (PVA) in hybrid form can be a potential platform to produce GRS-PVA nanofibers. Smooth nanofibers of 2% (w/v) GRS combined with 8% (w/v) PVA were fabricated by an electrospinning process. A scanning electron microscope (SEM) revealed an average diameter size of the GRS-PVA nanofibers equal to 191 ± 25 nm. A highly water soluble model drug, Chlorpheniramine maleate (CPM), was incorporated into the GRS-PVA electrospun fibers to prove a drug delivery carrier concept and drug release control of the nanofibers. The GRS-PVA nanofibers exhibited a biphasic CPM release in which approximately 60% of the drug immediately released in 10 min, and it reached 90% drug release in 120 min. This study demonstrated a potential application of GRS combining with PVA as an oral drug delivery carrier. Therefore, it can be a promised step that expands the application GRS in pharmaceuticals and related areas.

Development of Colorectal-Targeted Dietary Supplement Tablets Containing Natural Purple Rice Bran Oil as a Colorectal Chemopreventive.

Colorectal cancer occurs due to various factors. The important risks are dietary lifestyle and inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis. It has been found that the inhibitory enzyme cyclooxygenase-2 (COX-2) in the colorectal region can potentially reduce the risk of colorectal cancer. The present study investigated rice bran oil from natural purple rice bran, which exhibits antioxidant and anti-inflammatory activity. This study aimed to evaluate the bioactive compound content of natural purple rice bran oil (NPRBO) derived from native Thai purple rice and the anti-inflammatory activity of NPRBO in colorectal cancer cells, and to develop a colorectal delivery platform in the form of film-coated tablets. NPRBO from the rice bran of five different Thai purple rice cultivars, namely Khao’ Gam Leum-Phua (KGLP), Khao’ Gam Boung (KGB), Khao’ Gam Thor (KGT), Khao’ Gam Pah E-Kaw (KGPEK), and Khao’ Niaw Dam (KND), were extracted using the supercritical carbon dioxide extraction technique. The amount of γ-oryzanol (ORY), tocotrienols, and tocopherols present in NPRBOs and the in vitro anti-inflammatory activity of NPRBO were investigated. The highest anti-inflammatory NPRBO was transformed into a dry and free-flowing powder by liquisolid techniques. Then, it was compressed into core tablets and coated with Eudragit®L100 and Eudragit® NE30D. The in vitro release study of the film-coated NPRBO tablets was performed in three-phase simulated gastrointestinal media. The cultivar KGLP was superior to the other samples in terms of the ORY, tocotrienol and tocopherol contents and anti-inflammatory activity. Aerosil® was the most suitable absorbent for transforming NPRBO into a free-flowing powder and was used to prepare the NPRBO core tablets. The in vitro KGLP-NPRBO film-coated tablet release profile showed that no ORY was released at gastric pH while 85% of ORY was released at pH 7.4 after 6 h; this would be expected to occur in the colorectal area. Therefore, this study demonstrates the potential of KGLP-NPRBO to prevent colorectal cancer via a specific colorectal dietary supplement delivery system.

Physical stabilization of low-molecular-weight amorphous drugs in the solid state: a material science approach.

Use of the amorphous state is considered to be one of the most effective approaches for improving the dissolution and subsequent oral bioavailability of poorly water-soluble drugs. However as the amorphous state has much higher physical instability in comparison with its crystalline counterpart, stabilization of amorphous drugs in a solid-dosage form presents a major challenge to formulators. The currently used approaches for stabilizing amorphous drug are discussed in this article with respect to their preparation, mechanism of stabilization and limitations. In order to realize the potential of amorphous formulations, significant efforts are required to enable the prediction of formulation performance. This will facilitate the development of computational tools that can inform a rapid and rational formulation development process for amorphous drugs.