-
Regenerative Biomaterials 2024The incidence of intrauterine adhesions (IUA) has increased with the rising utilization of intrauterine surgery. The postoperative physical barrier methods commonly...
The incidence of intrauterine adhesions (IUA) has increased with the rising utilization of intrauterine surgery. The postoperative physical barrier methods commonly used, such as balloons and other fillers, have limited effectiveness and may even cause further damage to the remaining endometrial tissue. Herein, we developed an injectable thermosensitive hydrogel using Pluronic F127/F68 as pharmaceutical excipients and curcumin as a natural active molecule. The hydrogel effectively addresses solubility and low bioavailability issues associated with curcumin. , drug release assays revealed that the amorphous curcumin hydrogel promotes dissolution and sustained release of curcumin. experiments reveal high biocompatibility of the hydrogel and its ability to enhance vascular formation while inhibiting the expression of fibrotic factor TGF-β1. To assess the effectiveness of preventing IUAs, experiments were conducted using IUA rats and compared with a class III medical device, a new-crosslinked hyaluronic acid (NCHA) gel. According to the study, curcumin hydrogel is more effective than the NCHA group in improving the regeneration of the endometrium, increasing the blood supply to the endometrium and reducing the abnormal deposition of fibrin, thus preventing IUA more effectively. This study provides a promising strategy for treating and preventing IUA.
PubMed: 38779348
DOI: 10.1093/rb/rbae043 -
European Journal of Pharmaceutical... May 2024Poorly water-soluble drugs present a significant challenge in the development of oral solid dosage forms (OSDs). In formulation development the appropriate use of...
The challenge of downstream processing of spray dried amorphous solid dispersions into minitablets designed for the paediatric population - A sustainable product development approach.
Poorly water-soluble drugs present a significant challenge in the development of oral solid dosage forms (OSDs). In formulation development the appropriate use of excipients to adjust solubility, and the choice of manufacturing method and pharmaceutical processes to obtain a dosage form to meet the needs of the patient group, is crucial. Preparing an amorphous solid dispersion (ASD) is a well-established method for solubility enhancement, and spray drying (SD) a common manufacturing method. However, the poor flowability of spray dried materials poses a significant challenge for downstream processing. Promoting sustainability in OSD development involves embracing a versatile formulation design, which enables a broader spectrum of patients to use the product, as opposed to altering existing dosage forms retrospectively. The objective of the current study was to develop a formulation of spray dried indomethacin ASD suited to the production, by direct compression, of instant release paediatric minitablets. Excipients evaluated were PVP or HPMCAS in solid dispersions at the preformulation phase, and MCC and lactose as a filler in direct compression. From the studied formulations, a 3:1 ratio blend of Vivapur 200/Pharmatose 200 M (MCC/lactose) with 0.5% (w/w) magnesium stearate was found to be the most promising in tableting, and minitablets containing a 6.22% content of spray-dried ASD of indomethacin/PVP K 29-32 could be obtained with desired tablet hardness and pharmaceutical quality, complying with tests of weight variation and fast disintegration in an aqueous environment. As a case example, this study provides a good foundation for further studies in harnessing a sustainable approach to the development of pharmaceutical formulations that can appropriately serve different patient sub-populations.
PubMed: 38518998
DOI: 10.1016/j.ejps.2024.106752 -
Gels (Basel, Switzerland) Jan 2024The injectability of cross-linked hyaluronic acid (HA) dermal fillers is influenced by polymer concentration, polymer cross-linking type and degree, the presence of...
Clinical Perspectives on the Injectability of Cross-Linked Hyaluronic Acid Dermal Fillers: A Standardized Methodology for Commercial Product Benchmarking with Inter-Injector Assessments.
The injectability of cross-linked hyaluronic acid (HA) dermal fillers is influenced by polymer concentration, polymer cross-linking type and degree, the presence of lidocaine or other functional excipients, types of syringes, and injection techniques. Finished product injectability constitutes a critical quality attribute for clinical injectors, as it strongly influences product applicability and ease of use in aesthetic medicine. While injectable product extrusion force specifications are provided by the respective device manufacturers, the qualitative informative value of such datasets is low for injectors wishing to compare product brands and technologies from an injectability standpoint. Therefore, the present study comparatively assessed 28 cross-linked HA dermal fillers (JUVÉDERM, Restylane, BELOTERO, TEOSYAL RHA, and STYLAGE brands) using various injectability benchmarking setups for enhanced clinical-oriented relevance. Manual product injections were performed by three specialized and experienced clinicians, whereas automatic product extrusion was performed using a Texture Analyzer instrument. The various hydrogel products were injected into ex vivo human skin and into SimSkin cutaneous equivalents to appropriately account for injection-related counterpressure. The injectability results revealed important variability between and within product brands, with a strong influence of the local anesthetic lidocaine, HA contents, and needle gauge size. Critical appraisals of the investigated products were performed, notably from manufacturing process-based and clinical ease of application-based standpoints, centered on respective experimental injectability quality levels. Generally, it was confirmed that each HA-based dermal filler product requires specific expertise for optimal injection, mainly due to differing viscoelastic characteristics and injectability attributes. Overall, the present study set forth evidence-based and clinical-oriented rationale elements confirming the importance for injectors to work with injectable products with which they are experienced and comfortable to optimize clinical results.
PubMed: 38391431
DOI: 10.3390/gels10020101 -
International Journal of Pharmaceutics Mar 2024Pharmaceutical three-dimensional printing (3DP) is now in its golden age. Recent years have seen a dramatic increase in the research in 3D printed pharmaceuticals due to...
Systematic screening of photopolymer resins for stereolithography (SLA) 3D printing of solid oral dosage forms: Investigation of formulation factors on printability outcomes.
Pharmaceutical three-dimensional printing (3DP) is now in its golden age. Recent years have seen a dramatic increase in the research in 3D printed pharmaceuticals due to their potential to deliver highly personalised medicines, thus revolutionising the way medicines are designed, manufactured, and dispensed. A particularly attractive 3DP technology used to manufacture medicines is stereolithography (SLA), which features key advantages in terms of printing resolution and compatibility with thermolabile drugs. Nevertheless, the enthusiasm for pharmaceutical SLA has not been followed by the introduction of novel excipients specifically designed for the fabrication of medicines; hence, the choice of biocompatible polymers and photoinitiators available is limited. This work provides an insight on how to maximise the usefulness of the limited materials available by evaluating how different formulation factors affect printability outcomes of SLA 3D printed medicines. 156 photopolymer formulations were systematically screened to evaluate the influence of factors including photoinitiator amount, photopolymer molecular size, and type and amount of liquid filler on the printability outcomes. Collectively, these factors were found highly influential in modulating the print quality of the final dosage forms. Findings provide enhanced understanding of formulation parameters informing the future of SLA 3D printed medicines and the personalised medicines revolution.
Topics: Stereolithography; Printing, Three-Dimensional; Polymers; Excipients; Technology, Pharmaceutical; Dosage Forms
PubMed: 38307399
DOI: 10.1016/j.ijpharm.2024.123862 -
ACS Omega Jan 2024Keeping in mind the health scenario in Kingdom of Saudi Arabia with respect to vitamin D3 (VD3) deficiency and its significant role in calcium homeostasis and human...
Keeping in mind the health scenario in Kingdom of Saudi Arabia with respect to vitamin D3 (VD3) deficiency and its significant role in calcium homeostasis and human metabolism, this research is exploring the combination of eggshell (as a source of calcium) and VD3 as a very economical solution for this problem. Eggshells from local restaurant were collected, washed, ground, sieved, and characterized by Fourier transforms infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Brunauer-Emmett-Teller (BET) techniques. The results of FTIR, SEM, DSC, XRD, and BET indicate that eggshell powder (ESP) was properly processed. Directly compressed tablets containing 2.5 mg of VD3 (equivalent to 50,000 IU), that are based on the use of ESP as tablet filler, were manufactured based on mixing Avicel PH 101 with ESP in different ratios (9:1, 1:1, and 1:9) in addition to the use of both Avicel PH 101 and ESP alone as tablet filler. Tablets properties were evaluated according to USP30-NF25 pharmacopoeia tests in terms of weight variation test, drug content uniformity, tablet hardness, tablet friability, tablet disintegration, and in vitro dissolution profile. The VD3 contents were found to be 98.77-102.35% in all formulations. After 90 min of study, all formulations showed in vitro drug release content in the range of 99.29-101.05%. All of the tested parameters of ESP tablets were similar to those of commercial Avicel PH 101. All of the tested properties of tablets with ESP as a filler were found to be within the acceptable limits of the pharmacopeia recommendations. Therefore, ESP could be exploited for its use as a filler in direct compression tablets.
PubMed: 38284045
DOI: 10.1021/acsomega.3c08416 -
International Journal of Molecular... Jan 2024Cell membrane chromatography (CMC) has been widely recognized as a highly efficient technique for in vitro screening of active compounds. Nevertheless, conventional CMC...
Cell membrane chromatography (CMC) has been widely recognized as a highly efficient technique for in vitro screening of active compounds. Nevertheless, conventional CMC approaches suffer from a restricted repertoire of cell membrane proteins, making them susceptible to oversaturation. Moreover, the binding mechanism between silica gel and proteins primarily relies on intermolecular hydrogen bonding, which is inherently unstable and somewhat hampers the advancement of CMC. Consequently, this investigation aimed to establish a novel CMC column that could augment protein loading, enhance detection throughput, and bolster binding affinity through the introduction of covalent bonding with proteins. This study utilizes polydopamine (PDA)-coated silica gel, which is formed through the self-polymerization of dopamine (DA), as the carrier for the CMC column filler. The objective is to construct the HK-2/SiO-PDA/CMC model to screen potential therapeutic drugs for gout. To compare the quantity and characteristics of Human Kidney-2 (HK-2) cell membrane proteins immobilized on SiO-PDA and silica gel, the proteins were immobilized on both surfaces. The results indicate that SiO-PDA has a notably greater affinity for membrane proteins compared to silica gel, resulting in a significant improvement in detection efficiency. Furthermore, a screening method utilizing HK-2/SiO-PDA/CMC was utilized to identify seven potential anti-gout compounds derived from L. (PAL). The effectiveness of these compounds was further validated using an in vitro cell model of uric acid (UA) reabsorption. In conclusion, this study successfully developed and implemented a novel CMC filler, which has practical implications in the field.
Topics: Humans; Plantago; Silica Gel; Silicon Dioxide; Cell Membrane; Membrane Proteins; Kidney; Chromatography; Excipients; Gout; Indoles; Polymers
PubMed: 38256226
DOI: 10.3390/ijms25021153 -
International Journal of Molecular... Jan 2024In this work, we present the effect of graphene nanoplatelets (GnPs) modification with ionic liquids (ILs). The textural properties of graphene nanoplatelets (GnPs) used...
In this work, we present the effect of graphene nanoplatelets (GnPs) modification with ionic liquids (ILs). The textural properties of graphene nanoplatelets (GnPs) used as styrene-butadiene rubber's filler and the thermal properties of the composites obtained with the use of the mentioned fillers were investigated. GnPs were modified with 1-butylpyridinium bromide (BPyBr) and 4-methyl-1-butylpyridinium bromide (BmPyBr) through two different ways. One strategy has been to deposit the filler modifier from the solution. The second one involved the modification of the filler with ionic liquids in bulk during the preparation of elastomer blends. Settlement of the proposed ionic liquids onto the GnPs' surface led to significant changes in the textural characteristics. BPyBr has restricted the filler's microporosity, whereas BmPyBr has caused the formation of a more opened filler structure without the increase in its average pore size. GnPs modified with ILs led to reducing the temperature of vulcanization of SBR compounds and affected the thermal stability of the composites.
Topics: Bromides; Graphite; Ionic Liquids; Elastomers; Excipients; Hydrocarbons, Brominated
PubMed: 38255957
DOI: 10.3390/ijms25020885 -
International Journal of Pharmaceutics:... Jun 2024In this study, an in-depth comparison was made between batch and continuous direct compression using similar compression set-ups. The overall material processability and...
In this study, an in-depth comparison was made between batch and continuous direct compression using similar compression set-ups. The overall material processability and final tablet quality were compared and evaluated. Correlations between material properties, process parameters and final tablet properties were made via multivariate data analyses. In total, 10 low-dosed (1% /w) and 10 high-dosed (40% w/w) formulations were processed, using a total of 10 different fillers/filler combinations. The trials indicated that the impact of filler type, drug load or process settings was similar for batch and continuous direct compression. The main differentiator between batch and continuous was the flow dynamics in the operating system, where properties related to flow, compressibility and permeability played a crucial role. The less consistent flow throughout a batch process resulted in a significantly higher variability within the tablet press (σ) and for the tablet quality responses (σ, σ). However, the better controlled blending procedure prior to batch processing was reflected in a more consistent API concentration variability. Overall, the comparison showed the benefits of selecting appropriate excipients and process settings to achieve a specific outcome, keeping in mind some key differentiators between both processes.
PubMed: 38235316
DOI: 10.1016/j.ijpx.2023.100226 -
Cognitive Research: Principles and... Nov 2023When selecting fillers to include in a police lineup, one must consider the level of similarity between the suspect and potential fillers. In order to reduce...
When selecting fillers to include in a police lineup, one must consider the level of similarity between the suspect and potential fillers. In order to reduce misidentifications, an innocent suspect should not stand out. Therefore, it is important that the fillers share some degree of similarity. Importantly, increasing suspect-filler similarity too much will render the task too difficult reducing correct identifications of a guilty suspect. Determining how much similarity yields optimal identification performance is the focus of the proposed study. Extant research on lineup construction has provided somewhat mixed results. In part, this is likely due to the subjective nature of similarity, which forces researchers to define similarity in relative terms. In the current study, we manipulate suspect-filler similarity via a multidimensional scaling model constructed using objective facial measurements. In doing so, we test the "propitious heterogeneity" and the diagnostic-feature-detection hypotheses which predict an advantage of lineups with low-similarity fillers in terms of discriminability. We found that filler similarity did not affect discriminability. We discuss limitations and future directions.
Topics: Humans; Excipients; Face; Guilt; Multidimensional Scaling Analysis; Police
PubMed: 37930437
DOI: 10.1186/s41235-023-00522-w -
Heliyon Sep 2023Two key properties of excipients for inclusion in direct compression tablets are flowability and compactibility. Glutinous rice starch (GRS) has poor flowability, which...
Two key properties of excipients for inclusion in direct compression tablets are flowability and compactibility. Glutinous rice starch (GRS) has poor flowability, which limits its use in direct compression tablets. This study aimed to create a multifunctional direct compression excipient (filler binder disintegrant) with improved flowability from GRS by the co-precipitation method. The physicochemical and pharmaceutical properties of the co-precipitated GRS (cpGRS) were investigated. The optimum conditions for producing cpGRS (0.43 M sodium hydroxide solution, 7.09% PVP K30, 14.02% calcium carbonate, 95 min of mixing time and pH of 6.97) resulted in 68.80% yield, fair to good flowability, acceptable tablet strength, and fast disintegration. The FT-IR spectra of cpGRS showed no significant shifts in the key peaks, which indicates that there was an absence of chemical interactions within cpGRS. X-ray diffractograms also showed no significant changes, indicating that the GRS granules, calcium carbonate, and PVP K30 components remained unaltered during co-precipitation. cpGRS also demonstrated a dilution capacity of 50% when paracetamol was used as model drug. When cpGRS was combined with domperidone or propranolol hydrochloride it showed a better deformation capability than the physical mixtures. Although cpGRS was sensitive to lubricant, the hardness and tensile strength were higher than common strength for general purpose use in tablets. When compared to the physical mixture, pregelatinized starch and directly compressible calcium carbonate, the results showed that cpGRS tablets of both model drugs passed the friability test, demonstrated the best disintegration property, provided the fastest and highest drug release profile for propranolol, and improved the drug release profile for domperidone. For propranolol-cpGRS tablets, dissolution medium at different pH did not affect the dissolution profile. For domperidone-cpGRS tablets, the pH of dissolution medium did affect the dissolution profile of the tablets. This was according to the API solubility. These results reveal that cpGRS is an excellent multifunctional i.e., filler, binder, and disintegrant excipient suitable for direct compression tablets. The main component is natural. The preparation method is simple, quick, and efficient. This method does not produce harmful waste and requires only basic equipment, and affordable reactants and devices.
PubMed: 37809676
DOI: 10.1016/j.heliyon.2023.e19904