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The International Journal of... Nov 2023Tablets are the most widely available dosage form for the treatment of TB; however, adult tablets fail to meet the needs of young children who cannot swallow these...
Tablets are the most widely available dosage form for the treatment of TB; however, adult tablets fail to meet the needs of young children who cannot swallow these tablets or require dose titration. We tested a new, simple device (XTEMP-R) and the methodology for converting tablets of TB drugs into a homogeneous suspension for home use by children and caregivers. XTEMP-R is a new device used for converting tablets into liquid preparations. Four TB drugs - pretomanid, delamanid, clofazimine and bedaquiline - were dispersed in the device utilizing water and simple syrup. The reproducibility of accurately delivering aliquots from the suspension upon preparation and upon redispersion after storing for 2 days was studied. Suspensions of each of the drugs tested were easily prepared in about 10 min and were visually uniform in consistency. Dosages in 2 and 5 mL were assessed in suspension, and those in 5 mL tested upon redispersion after 2 days. The observed range for these dosages spanned from 94.6% to 101.1% of the theoretical concentration for the suspensions under examination. The cleaned device had no detectable residual drug. XTEMP-R can be used at home by caregivers to prepare doses of suspensions accurately for children and patients who cannot swallow tablets.
Topics: Child; Adult; Humans; Child, Preschool; Reproducibility of Results; Tuberculosis; Tablets; Suspensions; Drug Stability
PubMed: 37880886
DOI: 10.5588/ijtld.23.0165 -
International Journal of Biological... Jul 2023Rod-shaped cellulose nanocrystals (CNCs), also called cellulose nanorods (CNRs), possess anisotropic properties that allow for their self-organization into chiral...
Rod-shaped cellulose nanocrystals (CNCs), also called cellulose nanorods (CNRs), possess anisotropic properties that allow for their self-organization into chiral nematic liquid crystals. Interestingly, spherical cellulose nanocrystals (cellulose nanospheres, CNSs) have also been shown to form a chiral liquid-crystalline phase in recent years. Herein, to understand how the similar assembly takes places as particle dimension changes, the organization features of CNSs were investigated. Results of this study demonstrate that above a critical concentration in suspension, CNSs organize into a liquid-crystal phase consisting of periodically parallel-aligned layer structures. This structure persists after suspension drying. In comparison with CNRs, the alignment of CNSs exhibits a shorter layer distance, lower order degree, and weaker long-range orientation. To explain the early stages of tactoid formation, a "caterpillar-like" model was proposed, which was captured by freezing the CNS suspension in an intermediate aggregation state. This structure serves as the fundamental unit for further liquid-crystal assembly.
Topics: Cellulose; Liquid Crystals; Nanospheres; Nanotubes; Anisotropy; Suspensions
PubMed: 37169056
DOI: 10.1016/j.ijbiomac.2023.124738 -
Molecular Pharmaceutics Mar 2022Developing biological formulations to maintain the chemical and structural integrity of therapeutic antibodies remains a significant challenge. Monoclonal antibody (mAb)...
Developing biological formulations to maintain the chemical and structural integrity of therapeutic antibodies remains a significant challenge. Monoclonal antibody (mAb) crystalline suspension formulation is a promising alternative for high concentration subcutaneous drug delivery. It demonstrates many merits compared to the solution formulation to reach a high concentration at the reduced viscosity and enhanced stability. One main challenge in drug development is the lack of high-resolution characterization of the crystallinity and stability of mAb microcrystals in the native formulations. Conventional analytical techniques often cannot evaluate structural details of mAb microcrystals in the native suspension due to the presence of visible particles, relatively small crystal size, high protein concentration, and multicomponent nature of a liquid formulation. This study demonstrates the first high-resolution characterization of mAb microcrystalline suspension using magic angle spinning (MAS) NMR spectroscopy. Crystalline suspension formulation of pembrolizumab (Keytruda, Merck & Co., Inc., Kenilworth, NJ 07033, U.S.) is utilized as a model system. Remarkably narrow C spectral linewidth of approximately 29 Hz suggests a high order of crystallinity and conformational homogeneity of pembrolizumab crystals. The impact of thermal stress and dehydration on the structure, dynamics, and stability of these mAb crystals in the formulation environment is evaluated. Moreover, isotopic labeling and heteronuclear C and N spectroscopies have been utilized to identify the binding of caffeine in the pembrolizumab crystal lattice, providing molecular insights into the cocrystallization of the protein and ligand. Our study provides valuable structural details for facilitating the design of crystalline suspension formulation of Keytruda and demonstrates the high potential of MAS NMR as an advanced tool for biophysical characterization of biological therapeutics.
Topics: Antibodies, Monoclonal, Humanized; Magnetic Resonance Spectroscopy; Molecular Conformation; Proteins; Suspensions
PubMed: 35107019
DOI: 10.1021/acs.molpharmaceut.1c00915 -
Journal of Pharmaceutical Sciences Apr 2019Oral pediatric formulations are either ready-to-use or require manipulation and multiuse or single-use. Strong encouragement for preservative-free pediatric formulations... (Review)
Review
Oral pediatric formulations are either ready-to-use or require manipulation and multiuse or single-use. Strong encouragement for preservative-free pediatric formulations has resulted in fewer multiuse solutions or suspensions in favor of single-use solid oral dosage forms. This updated review covering new pediatric formulations marketed in the United States of America, Europe, and Japan spanning the years 2007 to mid-2018 identified 16 types of pediatric oral formulations of which 7 are ready-to-use and 9 require manipulation, and 51 total new pediatric oral formulations of which 21 are ready-to-use and 30 require manipulation. Ready-to-use formulations include oral solution, oral suspension, oral soluble film, tablet, scored tablets, orally disintegrating tablet, chewable tablet, and mini-tablets. Formulations requiring manipulation include sprinkle capsule, powder for oral solution, powder for oral suspension, granules for oral suspension, oral powder, oral granules, tablet, dispersible tablet, dispersible scored tablet, tablet for oral suspension, and mini-tablets (oral granules). Significant advances in packaging technology include filling mini-tablets, granules, or powders into sachets, stick packets, blisters, and 2-piece capsules. The future of pediatric oral formulations will increasingly be with user-friendly, preservative-free, taste-masked formulations including multiparticulate single-use solid dosage forms including mini-tablets, orally disintegrating tablets, and sprinkle capsules with or without a specialized package configuration.
Topics: Administration, Oral; Adolescent; Age Factors; Child; Child, Preschool; Drug Compounding; Drug Packaging; Humans; Infant; Infant, Newborn; Powders; Preservatives, Pharmaceutical; Suspensions; Tablets
PubMed: 30447227
DOI: 10.1016/j.xphs.2018.11.013 -
Sensors (Basel, Switzerland) Oct 2021Active suspension control strategies are a top priority in active suspension system. The current research on active suspension control strategies is mostly focused on...
Active suspension control strategies are a top priority in active suspension system. The current research on active suspension control strategies is mostly focused on two-axle vehicles, and there is less research investigating multi-axle vehicles. Additionally, their effective implementation is dependent on accurate mathematical models, and most of them adopt force feedback control, which is vulnerable to external interference. To solve these problems, this paper proposes an active suspension control strategy based on Inertial Measurement Unit. The multi-axle emergency rescue vehicle is made to be equivalent to a 3-degrees-of-freedom parallel mechanism by using the method of grouping and interconnecting the suspension units of the whole vehicle. The attitude change of the vehicle body was transformed into the servo actuator's displacement by solving the inverse solution of the parallel mechanism position and the action of the servo actuator was driven in reverse according to the displacement obtained. In this way, the vehicle body attitude can be compensated, and the ride comfort and the handling stability of the vehicle can be improved. To verify the effectiveness of the control strategy proposed, the three-axle six vehicle was taken as the research object, the position inverse solution of its equivalent 3-degrees-of-freedom parallel mechanism was deduced, and a high-pass filter was designed. The three-axle vehicle experiment platform integrating active suspension and hydro-pneumatic suspension was built, and the gravel road and slope road experiments were carried out and the results compared with those obtained with hydro-pneumatic suspension. The experiment results showed that, compared with hydro-pneumatic suspension, the active suspension control strategy based on Inertial Measurement Unit proposed in this paper can not only stabilize the body attitude, but also effectively suppress body vibration, improving the ride comfort and handling stability of the vehicle significantly.
Topics: Equipment Design; Suspensions; Vibration
PubMed: 34696090
DOI: 10.3390/s21206877 -
Scientific Reports May 2023The accuracy of blood group identification is the basis of blood transfusion safety. In order to increase the detection rate of weak agglutination, unexpected antibodies...
The accuracy of blood group identification is the basis of blood transfusion safety. In order to increase the detection rate of weak agglutination, unexpected antibodies (UAb) and blood subtypes for pre-transfusion testing, the blood group screening process of automated blood group analyzer (ABGA) is ameliorated by introducing one static step and establishing a suspension static method (SSM). One static step was introduced in the blood group screening process of ABGA and three static time conditions were designed: 300 s, 400 s and 500 s, from which the optimal static time was selected and SSM was established; By comparing the detection of weak agglutination and UAb before and after the application of SSM, the feasibility and effect of suspension static method were verified and evaluated. The last two steps of the automatic blood group screening process were replaced with static, light centrifugation and imaging. The optimal static time parameter was selected as 400 s and SSM was established; After the application of SSM, it was verified that: (1) The detection level of weak antibodies (anti-A and anti-B) and weak antigens (weak D phenotype) could be improved by SSM, including antibodies in plasma of known type O samples with 0, 2, 4, 8, 16 and 32 times serial dilutions(simulating weak anti-A and weak anti-B), weak antibodies (anti-B) in plasma of one normal A-type sample and weak antigens on red blood cells (RBC) of 5 weak D phenotype samples (weak D antigen); (2) Three blood donor samples (type A, O and B) with known UAb were detected by SSM. The results showed that SSM could detect both weak antibodies (anti-A and anti-B) and UAb; (3) SSM was applied to detect the samples of 3 AB and 3 subtype B blood donors and the blood subtypes could be clearly detected; (4) The number of screening samples was 95,314 and 106,814 before SSM (2018) and after (2020) the application of SSM and the positive rate of UAb (63/95,314 and 187/106,814) increased after SSM, discrepancy of which was statistically significant (χ = 48.42, P < 0.01). The above results demonstrate that SSM of ABGA is conducive to the detection of weak agglutination, UAb and blood subtypes in blood samples, which can improve the sensitivity of blood group detection and ensure the safety of clinical blood transfusion to a certain extent.
Topics: Humans; Blood Group Antigens; Suspensions; Antibodies; Erythrocytes; Blood Donors
PubMed: 37160939
DOI: 10.1038/s41598-023-34495-z -
Journal of Environmental Sciences... May 2023Altrenogest (ALT), drospirenone (DRO), and melengestrol acetate (MLA) are three highly potent synthetic progestins that can be released into agricultural soils, while...
Altrenogest (ALT), drospirenone (DRO), and melengestrol acetate (MLA) are three highly potent synthetic progestins that can be released into agricultural soils, while their fate in soil minerals remains unclear. This study explored the transformation of these progestins in MnO, SiO, and ferrihydrite suspensions and identified their transformation products (TPs) via high resolution mass spectrometry and density functional theory calculations. Transformations were only observed for DRO and MLA in SiO suspension and ALT in MnO suspension (half-lives = 0.86 min - 9.90 day). ALT transformation was facilitated at higher MnO loadings, while DRO and MLA transformations were inhibited at higher SiO loadings. These data indicated that hydrophobic partitioning interaction was dominant at higher SiO loadings rather than specific interaction, which limited subsequent surface-catalyzed transformation. ALT transformation rate decreased with increasing pH because MnO reduction requires proton participation. In contrast, relatively high pH facilitated MLA and DRO transformation, indicating that base-catalyzed hydrolysis occurred in SiO suspension. The clustermap demonstrated the formation of abundant TPs. Lactone ring and acetoxy group hydrolysis was the major transformation pathway for DRO and MLA, with estimated yields of 57.7% and 173.2% at 6 day, respectively. ALT experienced C12 hydroxylation and formed the major TP 326g (yield of 15.4% at 8 hr). ALT also experienced allyl group oxidation and subsequent C5 hydroxylation, forming the major TP 344a (yield of 14.1% at 8 hr). This study demonstrates that TPs of metastable progestins are likely the main species in soils and that TP identification is a particular priority for risk assessment.
Topics: Soil; Manganese Compounds; Progestins; Suspensions; Silicon Dioxide; Oxides; Minerals; Progesterone Congeners; Oxidation-Reduction
PubMed: 36522069
DOI: 10.1016/j.jes.2022.06.007 -
Scientific Reports Aug 2023Colloidal silica grouting is a ground improvement technique capable of stabilizing weak problematic soils and achieving large reductions in soil hydraulic conductivities...
Colloidal silica grouting is a ground improvement technique capable of stabilizing weak problematic soils and achieving large reductions in soil hydraulic conductivities for applications including earthquake-induced liquefaction mitigation and groundwater flow control. In the conventional approach, chemical accelerants are added to colloidal silica suspensions that are introduced into soils targeted for improvement and the formation of a semi-solid silica gel occurs over time at a rate controlled by suspension chemistry and in situ geochemical conditions. Although the process has been extensively investigated, controlling the rate of gel formation in the presence of varying subsurface conditions and the limited ability of conventional methods to effectively monitor the gel formation process has posed practical challenges. In this study, a biomediated soil improvement process is proposed which utilizes enriched fermentative microorganisms to control the gelation of colloidal silica grouts through solution pH reductions and ionic strength increases. Four series of batch experiments were performed to investigate the ability of glucose fermenting microorganisms to be enriched in natural sands to induce geochemical changes capable of mediating silica gel formation and assess the effect of treatment solution composition on pH reduction behaviors. Complementary batch and soil column experiments were subsequently performed to upscale the process and explore the effectiveness of chemical, hydraulic, and geophysical methods to monitor microbial activity, gel formation, and engineering improvements. Results demonstrate that fermentative microorganisms can be successfully enriched and mediate gel formation in suspensions that would otherwise remain highly stable, thereby forgoing the need for chemical accelerants, increasing the reliability and control of colloidal silica grouting, enabling new monitoring approaches, and affording engineering enhancements comparable to conventional colloidal silica grouts.
Topics: Fermentation; Reproducibility of Results; Silica Gel; Suspensions; Soil
PubMed: 37648736
DOI: 10.1038/s41598-023-41402-z -
International Journal of Pharmaceutical... 2023Tablet formulations fail to meet the needs of patients unable to swallow tablets such as pediatric, elderly, and patients that must receive medications via feeding...
Tablet formulations fail to meet the needs of patients unable to swallow tablets such as pediatric, elderly, and patients that must receive medications via feeding tubes. Our objective was to develop and test a new, simple device (XTEMP-R) and the methodology for converting tablets into a homogeneous suspension for medication administration. We developed a new device comprised of a flexible receptacle, a tight-fitting cap, and a suction cup bottom to convert tablets into liquid preparations. Tuberculosis treatment drugs, TBAJ-876 and TBI-223, were dispersed within the device utilizing water and commonly available suspending vehicles. We investigated the effectiveness of the XTEMP-R device in dispersing tablets. This was accomplished by visual observations, determining the fineness of dispersion, and measuring the total drug recovery from the dispersions in XTEMP-R. We investigated the accuracy and reproducibility of delivering aliquots from these suspensions by determining the dose reproducibility upon suspension and upon redispersion after 24 hours. The effectiveness of the device was also evaluated using commercially available tablets of acetaminophen, amlodipine, glimepiride, metformin, and valsartan. The suspensions were visually uniform without any large particles. The suspensions passed through a #18 sieve confirming that the particles were less than 1000 µm. The average total dose recovery of three suspensions each was determined to be 101.3% and 99.2% for TBI-223 and TBAJ-876, respectively. Reproducibility from aliquots of 2 mL each was 98.9% to 99.7% for three replicates of TBI-223 suspensions, and 102.6% to 103.2% for TBAJ-876 suspensions. Aliquots tested after 24 hours confirmed uniform redispersibility. We have demonstrated that XTEMP-R can be utilized to prepare homogeneous suspensions conveniently and efficiently in less than 10 minutes without any drug loss. Aliquots for partial dose delivery can be withdrawn accurately. These findings demonstrate that XTEMP-R can be used to accurately deliver doses of suspensions for patients who cannot swallow tablets.
Topics: Humans; Child; Aged; Reproducibility of Results; Suspensions; Drug Compounding; Acetaminophen; Tablets; Administration, Oral
PubMed: 37267527
DOI: No ID Found -
Recent Advances in Drug Delivery and... 2023A wide variety of dosage forms are used for the oral administration of drugs to humans and animals. Apart from solid dosage forms, it also includes liquid dosage forms,... (Review)
Review
A wide variety of dosage forms are used for the oral administration of drugs to humans and animals. Apart from solid dosage forms, it also includes liquid dosage forms, such as solutions, suspensions, and emulsions. The selection is based on the physiochemical attributes of the therapeutically active ingredient. Suspensions are classified as dispersed systems that are heterogeneous in nature and consist of two phases. One phase is the continuous phase, the dispersion medium, or the external phase, which is either liquid or semisolid; the other is a solid particle dispersed in the external phase and called an internal or dispersed phase. They have several advantages over other dosage forms, such as effectively delivering hydrophobic drugs, avoiding the need for cosolvents, masking unpleasant tastes, and providing resistance to degradation and easy swallowing for young or elderly patients. They also attain higher drug concentrations compared to solution forms. This review article aims to study and explore the advantages, novel suspending agents, patent preference, and innovations of pharmaceutical suspension. It was targeted to scrutinize the literature floating in the internet domain regarding pharmaceutical suspension for delivery of drugs by oral route. The literature survey is targeted at the novel herbal suspending agents used, their patents involved, and innovations in the dosage form. Further, the study gives an insight into various aspects of suspension, such as classification of suspension, theories of suspension, various components used in suspension formulation, formulation aspect of suspension, evaluation parameters of suspension, patents, innovations, and regulatory status.
Topics: Humans; Animals; Aged; Excipients; Suspensions; Administration, Oral
PubMed: 38050417
DOI: 10.2174/0126673878246149231010085610