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International Journal of Molecular... Sep 2022Hyaluronic acid (HA) fillers have become the most popular material for facial volume augmentation and wrinkle correction. Several filler brands are currently on the... (Review)
Review
Hyaluronic acid (HA) fillers have become the most popular material for facial volume augmentation and wrinkle correction. Several filler brands are currently on the market all around the world and their features are extremely variable; for this reason, most users are unaware of their differences. The study of filler rheology has become a wellspring of knowledge, differentiating HA fillers, although these properties are not described thoroughly by the manufacturers. The authors of this review describe the more useful rheological properties that can help clinicians understand filler characteristics and the likely correlation of these features with clinical outcomes.
Topics: Cosmetic Techniques; Dermal Fillers; Excipients; Hyaluronic Acid; Rheology; Skin Aging
PubMed: 36142430
DOI: 10.3390/ijms231810518 -
Journal of Pharmaceutical Sciences Jun 2023N-Nitrosamine risk assessment and control have become an integral part of pharmaceutical drug product development and quality evaluation. Initial reports of nitrosamine...
N-Nitrosamine risk assessment and control have become an integral part of pharmaceutical drug product development and quality evaluation. Initial reports of nitrosamine contamination were linked with the drug substance and its manufacturing process. Subsequently, the drug product and aspects of the formulation process have shown to be relevant. Regarding specific formulation contributions to nitrosamine content in a product, one risk lies in possible interactions between nitrosating agents, derived from nitrite in excipients, and vulnerable amines, either present as moieties of the active molecule or as impurities / degradants. However, the limited validated information on nitrite levels in excipients available until now, has been an obstacle for scientists to assess the risk of nitrosamine formation in pharmaceutical products. This has driven the creation of a database to store and share such validated information. The database, maintained by Lhasa Limited, constitutes a central platform to hold the data donated by the pharmaceutical company members on the nitrite concentrations in common excipients measured with validated analytical procedures. The goal of this data sharing initiative is to provide a common framework to contextualize and estimate the risk posed by presence of nitrites to contribute to the formation of nitrosamines in drug products. The major findings from the database analyses are: (1) average nitrite content and batch to batch variance differ among excipients, (2) for solid dosage forms, the nitrite contribution is dominated by the highest formula % excipients, e.g., the fillers (diluents), which are typically used in larger proportion, and are characterized by low nitrite levels and low variability, leading to an average value of 1 µg/g nitrite in a typical formulation, (3) substantial differences in average nitrite content in batches from different excipient vendors potentially reflecting differences in source materials or processing methods for excipient manufacturing. That final point suggests that future selection of raw materials or processing by excipient manufacturers may help reduce nitrite levels in finished drug product formulations, and thus the overall risk of nitrosamine formation in cases where the product contains vulnerable amines.
Topics: Nitrites; Nitrosamines; Excipients; Chemistry, Pharmaceutical; Amines; Risk Assessment
PubMed: 35500671
DOI: 10.1016/j.xphs.2022.04.016 -
Journal of Cosmetic Dermatology Dec 2022Any implant or external material used in the body tissues can potentially be followed by autoimmune or inflammatory reactions. With the global vaccination program... (Review)
Review
BACKGROUND
Any implant or external material used in the body tissues can potentially be followed by autoimmune or inflammatory reactions. With the global vaccination program against COVID-19, the reports of tissue filler reactions would be increasingly demonstrated.
AIM
To summarize the data regarding COVID vaccination and filler reactions.
METHOD
We reviewed the existing data in this regard through searching on PubMed, Google Scholar and Scopus. All of the relevant papers published until March 2022, which we could access to their fulltexts were included.
RESULTS
Here, we summarized the data regarding COVID-19 vaccination and filler reactions and discussed its etiopathogenesis, management, and importance.
CONCLUSION
Although the end of pandemic was announced, the necessity of continuing COVI-D19 vaccination in future mandates gathering data regarding safety of vaccines.
Topics: Humans; COVID-19 Vaccines; COVID-19; Excipients; Inflammation; Pandemics
PubMed: 36181343
DOI: 10.1111/jocd.15428 -
Dental Materials : Official Publication... Nov 2022The aim of this study was to investigate the degradation of inert glass fillers which are commonly used in conventional resin-based composites to provide radiopacity,...
OBJECTIVES
The aim of this study was to investigate the degradation of inert glass fillers which are commonly used in conventional resin-based composites to provide radiopacity, reduce the polymerization shrinkage and improve the mechanical properties.
METHODS
75 mg of five different glass powders (1 µm) was immersed separately into 50 mL of acetic acid (pH 4) and tris buffer (pH 7.4) for up to 4 weeks. At each time point the glass powder was filtered and dried for characterization using ATR-FTIR and XRD to assess the degradation behavior and crystallization. ICP-OES, ISE and pH measurements were performed on the supernatant solutions to monitor the pH and ion release.
RESULTS
Although FTIR and XRD analysis showed no significant glass degradation or crystallization upon immersion, there was a substantial release of ions from the inert fillers, especially from BABFG and CDL. Barium release for these fillers were 270 and 165 ppm respectively. G018-373 glass presented the lowest ion release followed by GM27884 and BABG. The ion release was more pronounced in acidic conditions compared to neutral conditions apart from the fluoride release.
SIGNIFICANCE
Inert glasses are not as inert as previously thought. This may result in leaching of ions, potentially causing toxicity, reduction in mechanical properties, increased wear and subsequent failure of the composite material. The ions released from the inert glass may interfere with other glass fillers such as bioactive glass fillers, inhibiting degradation of the bioactive glass, beneficial ion release from the bioactive glass, pH neutralization and apatite formation.
Topics: Apatites; Barium; Fluorides; Glass; Materials Testing; Powders; Tromethamine
PubMed: 36154969
DOI: 10.1016/j.dental.2022.09.004 -
Polymers Jun 2022Glucomannan (GM)-a polysaccharide generally extracted from the tuber of -has great potential as a filler-binder in direct compression, disintegrant in tablets, or... (Review)
Review
Glucomannan (GM)-a polysaccharide generally extracted from the tuber of -has great potential as a filler-binder in direct compression, disintegrant in tablets, or gelling agent due to its strong hydrophilicity and extremely high viscosity. However, it has poor water resistance and low mechanical strength when used as an excipient in solid form. Several physical and chemical modifications have been carried out to improve these drawbacks. Chemical modification affects the characteristics of GM based on the DS. Carboxymethylation improves GM functionality by modifying its solubility and viscosity, which in turn allows it to bind water more efficiently and thus improve its elongation and gel homogeneity. Meanwhile, physical modification enhances functionality through combination with other excipients to improve mechanical properties and modify swelling ability and drug release from the matrix. This review discusses extraction of GM and its modification to enhance its applicability as an excipient in solid form. Modified GM is a novel excipient applicable in the pharmaceutical industry for direct compression, as a tablet disintegrant, a film-forming agent, and for encapsulation of macromolecular compounds or drug carriers for controlled release.
PubMed: 35808596
DOI: 10.3390/polym14132550 -
European Journal of Dermatology : EJD Sep 2022In 2014, the hyaluronic acid-based fillers, Hyacorp-1000 and Hyacorp H-S (H-800), were withdrawn from the Dutch market after concerns about their safety
BACKGROUND
In 2014, the hyaluronic acid-based fillers, Hyacorp-1000 and Hyacorp H-S (H-800), were withdrawn from the Dutch market after concerns about their safety
OBJECTIVES
To determine the most plausible factors for the increased number of adverse events, either patient-related factors or those inherent to the filler itself. We also assessed how new European legislation will affect the approval process for new fillers and improve related safety issues
MATERIALS & METHODS
A total of 42 patients–37 women (88%) and five men (11%)–were included. Patients were separated into three groups: 13 patients injected with Hyacorp-1000 and Hyacorp H-S (H-800) who had reported inflammatory adverse events; 12 injected with Hyacorp-1000 and Hyacorp H-S (H-800) who had not reported inflammatory adverse events; and 17 injected with other HA fillers who had reported inflammatory adverse events
RESULTS
Patients treated with Hyacorp-1000 and Hyacorp-S (H-800) who reported adverse events were significantly older than those in the Hyacorp-1000 and Hyacorp-S (H-800) group without adverse events, and the filler remained in situ for significantly longer than in patients who had adverse events related to another HA filler
CONCLUSION
Hyacorp-1000 and Hyacorp-S (H-800) filler is associated with an increased chance of developing adverse events compared to other HA fillers, probably because it remains in the body for a longer period of time. The upcoming legislative EU update of the Medical Device Regulation (MDR) will prevent unsafe filler from entering the EU market and will enable issues related to safety to be identified much earlier
Topics: Male; Humans; Female; Ethnicity; Excipients; Hyaluronic Acid
PubMed: 36468727
DOI: 10.1684/ejd.2022.4328 -
European Journal of Pharmaceutics and... Nov 2022In the current study, the concept of multiparticulate drug delivery systems (MDDS) was applied to tablets intended for the amorphisation of supersaturated granular ASDs...
In the current study, the concept of multiparticulate drug delivery systems (MDDS) was applied to tablets intended for the amorphisation of supersaturated granular ASDs in situ, i.e. amorphisation within the final dosage form by microwave irradiation. The MDDS concept was hypothesised to ensure geometric and structural stability of the dosage form and to improve the in vitro disintegration and dissolution characteristics. Granules were prepared in two sizes (small and large) containing the crystalline drug celecoxib (CCX) and polyvinylpyrrolidone/vinyl acetate copolymer (PVP/VA) at a 50 % w/w drug load as well as sodium dihydrogen phosphate monohydrate as the microwave absorbing excipient. The granules were subsequently embedded in an extra-granular tablet phase composed of either the filler microcrystalline cellulose (MCC) or mannitol (MAN), as well as the disintegrant crospovidone and the lubricant magnesium stearate. The tensile strength and disintegration time were investigated prior to and after 10 min of microwave irradiation (800 and 1000 W) and the formed ASDs were characterised by X-ray powder diffraction and modulated differential scanning calorimetry. Additionally, the internal structure was elucidated by X-ray micro-Computed Tomography (XµCT) and, finally, the dissolution performance of selected tablets was investigated. The MDDS tablets displayed no geometrical changes after microwave irradiation, however, the tensile strength and disintegration time generally increased. Complete amorphisation of CCX was achieved only for the MCC-based tablets at a power input of 1000 W, while MAN-based tablets displayed partial amorphisation independent of power input. The complete amorphisation of CCX was associated with the fusion of individual ASD granules within the tablets, which negatively impacted the subsequent disintegration and dissolution performance. For these tablets, supersaturation was only observed after 60 min. On the other hand, the partially amorphised MDDS tablets displayed complete disintegration during the dissolution experiments, resulting in a fast onset of supersaturation within 5 min and an approx. 3.5-fold degree of supersaturation within the experimental timeframe (3 h). Overall, the MDDS concept was shown to potentially be a feasible dosage form for in situ amorphisation, however, there is still room for improvement to obtain a both fully amorphous and disintegrating system.
Topics: Humans; Chemistry, Pharmaceutical; X-Ray Microtomography; Tablets; Povidone; Excipients; Celecoxib; Mannitol; Drug Delivery Systems; Solubility
PubMed: 36191869
DOI: 10.1016/j.ejpb.2022.09.021 -
The AAPS Journal Jan 2022The work aimed to develop the Absorption Driven Drug Formulation (ADDF) concept, which is a new approach in formulation development to ensure that the drug product meets...
The work aimed to develop the Absorption Driven Drug Formulation (ADDF) concept, which is a new approach in formulation development to ensure that the drug product meets the expected absorption rate. The concept is built on the solubility-permeability interplay and the rate of supersaturation as the driving force of absorption. This paper presents the first case study using the ADDF concept where not only dissolution and solubility but also permeation of the drug is considered in every step of the formulation development. For that reason, parallel artificial membrane permeability assay (PAMPA) was used for excipient selection, small volume dissolution-permeation apparatus was used for testing amorphous solid dispersions (ASDs), and large volume dissolution-permeation tests were carried out to characterize the final dosage forms. The API-excipient interaction studies on PAMPA indicated differences when different fillers or surfactants were studied. These differences were then confirmed with small volume dissolution-permeation assays where the addition of Tween 80 to the ASDs decreased the flux dramatically. Also, the early indication of sorbitol's advantage over mannitol by PAMPA has been confirmed in the investigation of the final dosage forms by large-scale dissolution-permeation tests. This difference between the fillers was observed in vivo as well. The presented case study demonstrated that the ADDF concept opens a new perspective in generic formulation development using fast and cost-effective flux-based screening methods in order to meet the bioequivalence criteria. Graphical Abstract.
Topics: Drug Compounding; Drug Development; Drug Liberation; Drugs, Generic; Excipients; Humans; Membranes, Artificial; Permeability; Pharmaceutical Preparations; Proof of Concept Study; Solubility; Surface-Active Agents; Therapeutic Equivalency
PubMed: 34988721
DOI: 10.1208/s12248-021-00668-9 -
Pharmaceuticals (Basel, Switzerland) Dec 2021Hydrogen, as a medical gas, is a promising emerging treatment for many diseases related to inflammation and oxidative stress. Molecular hydrogen can be generated through...
Hydrogen, as a medical gas, is a promising emerging treatment for many diseases related to inflammation and oxidative stress. Molecular hydrogen can be generated through hydrogen ion reduction by a metal, and magnesium-containing effervescent tablets constitute an attractive formulation strategy for oral delivery. In this regard, saccharide-based excipients represent an important class of potential fillers with high water solubility and sweet taste. In this study, we investigated the effect of different saccharides on the morphological and mechanical properties and the disintegration of hydrogen-generating effervescent tablets prepared by dry granulation. Mannitol was found to be superior to other investigated saccharides and promoted far more rapid hydrogen generation combined with acceptable mechanical properties. In further product optimization involving investigation of lubricant effects, adipic acid was selected for the optimized tablet, due to regulatory considerations.
PubMed: 34959728
DOI: 10.3390/ph14121327 -
International Journal of Pharmaceutics Apr 2022Porosity is an important property of pharmaceutical tablets since it may affect tablet disintegration, dissolution, and bio-availability. It is, therefore, essential to...
Porosity is an important property of pharmaceutical tablets since it may affect tablet disintegration, dissolution, and bio-availability. It is, therefore, essential to establish non-destructive, fast, and compact techniques to assess porosity, in situ, during the manufacturing process. In this paper, the terahertz frequency-domain (THz-FD) technique was explored as a fast, non-destructive, and sensitive technique for porosity measurement of pharmaceutical tablets. We studied a sample set of 69 tablets with different design factors, such as particle size of the active pharmaceutical ingredient (API), Ibuprofen, particle size of the filler, Mannitol, API concentration, and compaction force. The signal transmitted through each tablet was measured across the frequency range 500-750 GHz using a vector network analyzer combined with a quasi-optical set-up consisting of four off-axis parabolic mirrors to guide and focus the beam. We first extracted the effective refractive index of each tablet from the measured complex transmission coefficients and then translated it to porosity, using an empirical linear relation between effective refractive index and tablet density. The results show that the THz-FD technique was highly sensitive to the variations of the design factors, showing that filler particle size and compaction force had a significant impact on the effective refractive index of the tablets and, consequently, porosity. Moreover, the fragmentation behaviour of particles was observed by THz porosity measurements and was verified with scanning electron microscopy of the cross-section of tablets. In conclusion, the THz-FD technique, based on electronic solutions, allows for fast, sensitive, and non-destructive porosity measurement that opens for compact instrument systems capable of in situ sensing in tablet manufacturing.
Topics: Excipients; Particle Size; Porosity; Tablets; Technology, Pharmaceutical; Terahertz Spectroscopy
PubMed: 35181461
DOI: 10.1016/j.ijpharm.2022.121579