-
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 -
International Journal of Pharmaceutical... 2020Allopurinol is an orally administered inhibitor of xanthine oxidase used primarily in the treatment of hyperuricemia associated with gout. Allopurinol reduces serum...
Allopurinol is an orally administered inhibitor of xanthine oxidase used primarily in the treatment of hyperuricemia associated with gout. Allopurinol reduces serum and urinary uric acid concentrations. Its use should be individualized for each patient. The dosage of allopurinol to accomplish full control of gout and to lower serum uric acid to normal or near-normal levels varies with the severity of the disease, and needs to be flexible to permit precise, customized dose titration for individual patients. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of allopurinol currently exists. Allopurinol is commercially available as 100-mg and 300-mg scored tablets. An extemporaneously compounded suspension from pure drug powder or commercial tablets would provide a convenient option to meet unique patient needs. The purpose of this study was to determine the physicochemical stability of extemporaneously compounded allopurinol suspensions in the PCCA Base SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two allopurinol concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability-indicating ultra-performance liquid chromatography assay for the determination of the chemical stability of allopurinol in SuspendIt was developed and validated. Suspensions of allopurinol were prepared in SuspendIt at 10.0-mg/mL and 20.0-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in plastic amber prescription bottles at two temperature conditions (5°C and 25°C). Samples were assayed initially and at the following time points: 7 days, 14 days, 30 days, 45 days, 60 days, 88 days, 120 days, and 182 days. Physical data such as pH, viscosity, and appearance were also noted. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period. The study showed that allopurinol concentrations did not go below 93% of the label claim (initial drug concentration) at both temperatures studied. Viscosity and pH values also did not change significantly. This study demonstrates that allopurinol is physically and chemically stable in SuspendIt for 180 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for allopurinol in a liquid dosage form, with an extended beyond-use-date to meet patient needs.
Topics: Administration, Oral; Allopurinol; Chromatography, High Pressure Liquid; Drug Compounding; Drug Stability; Drug Storage; Humans; Suspensions; Uric Acid
PubMed: 32886640
DOI: No ID Found -
BMC Pharmacology & Toxicology Feb 2023The study was aimed at evaluating the bioequivalence and safety of oseltamivir phosphate for suspension, provided by Shenzhen Beimei Pharmaceutical Co. Ltd. and... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The study was aimed at evaluating the bioequivalence and safety of oseltamivir phosphate for suspension, provided by Shenzhen Beimei Pharmaceutical Co. Ltd. and manufactured by Hetero Labs Limited, and the reference product TAMIFLU® in healthy Chinese subjects.
METHODS
A single-dose, randomized, two-phase, self-crossed model was adopted. Among 80 healthy subjects, 40 subjects in the fasting group and 40 subjects in the fed group. Subjects in the fasting group were randomized into two sequences according to the proportion of 1:1, each given 75 mg/12.5 mL of Oseltamivir Phosphate for Suspension or TAMIFLU®, and cross-administered after 7 days. Postprandial group is the same as fasting group.
RESULTS
The T of TAMIFLU® and Oseltamivir Phosphate for Suspension in the fasting group were 1.50 h and 1.25 h, which in the fed group were both 1.25 h. Geometrically adjusted mean ratios of the PK parameters of Oseltamivir Phosphate for Suspension along with TAMIFLU® under fasting and postprandial conditions were in the range of 80.00-125.00% at the 90% confidence interval (CI). The 90% CI of C, AUC, AUC for fasting group and postprandial group were (92.39,106.50), (94.26,100.67), (94.32,100.89) and (93.61,105.83),(95.64,100.19),(96.06,102.66). Among the subjects on medication, a total of 18 subjects reported 27 adverse events, all of which were treatment-emergent adverse events (TEAEs), six of these TEAEs were rated as grade 2 in severity and the rest were as grade 1. The number of TEAEs in the test product and the reference product were 14,13 respectively.
CONCLUSION
Two Oseltamivir phosphate for suspensions are safe and bioequivalent.
Topics: Humans; Oseltamivir; Therapeutic Equivalency; Suspensions; Cross-Over Studies; Area Under Curve; Fasting; Healthy Volunteers; Phosphates; Tablets
PubMed: 36810140
DOI: 10.1186/s40360-023-00646-1 -
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 -
Drug Delivery and Translational Research Feb 2023There has been a constant evolution in the pharmaceutical market concerning the new technologies imbibed in delivering drug substances for various indications. This is... (Review)
Review
There has been a constant evolution in the pharmaceutical market concerning the new technologies imbibed in delivering drug substances for various indications. This is either market-driven or technology-driven to improve the overall therapeutic efficacy and patients' quality of life. The pharmaceutical industry has experienced rapid growth in the area of complex injectable products because of their effectiveness in the unmet market. These novel parenteral products, viz, the nanoparticles, liposomes, microspheres, suspensions, and emulsions, have proven their worth as "Safe and Effective" products. However, the underlying challenges involved in the development, scalability, and characterization of these injectable products are critical. Moreover, the guidelines available do not provide a clear understanding of these complex products, making it difficult to anticipate the regulatory requirements. Thus, it becomes imperative to comprehend the criticalities and develop an understanding of these products. This review discusses various complexities involved in the parenteral products such as complex drug substances, excipients, dosage forms, drug administration devices like pre-filled syringes and injector pens, and its different characterization tools and techniques. The review also provides a brief discussion on the regulatory aspects and associated hurdles with other parenteral products.
Topics: Humans; Quality of Life; Liposomes; Suspensions; Excipients; Nanoparticles
PubMed: 35963928
DOI: 10.1007/s13346-022-01223-5 -
Clinical Pharmacokinetics Jul 2023Posaconazole (PSZ) is a triazole antifungal for the management of invasive fungal disease (IFD) in adults and children. Although PSZ is available as an intravenous (IV)...
BACKGROUND AND OBJECTIVE
Posaconazole (PSZ) is a triazole antifungal for the management of invasive fungal disease (IFD) in adults and children. Although PSZ is available as an intravenous (IV) solution, oral suspension (OS) and delayed-release tablets (DRTs), OS is the preferred formulation for pediatric use because of potential safety concerns associated with an excipient in the IV formulation and difficulty in swallowing intact tablets by children. However, poor biopharmaceutical characteristics of the OS formulation leads to an unpredictable dose-exposure profile of PSZ in children, potentially risking therapeutic failure. The goal of this study was to characterize the population pharmacokinetics (PK) of PSZ in immunocompromised children and assess therapeutic target attainment.
METHODS
Serum concentrations of PSZ were collected retrospectively from records of hospitalized patients. A population PK analysis was performed in a nonlinear mixed-effects modeling framework with NONMEM (v7.4). The PK parameters were scaled to body weight, then potential covariate effects were assessed. The final PK model was used to evaluate recommended dosing schemes through simulation of target attainment (as a percentage of the population having steady-state trough concentrations above the recommended target) using Simulx (v2021R1).
RESULTS
Repeated measurement data of 202 serum concentrations of total PSZ were acquired from 47 immunocompromised patients between 1 and 21 years of age receiving PSZ either intravenously or orally, or both. A one-compartment PK model with first-order absorption and linear elimination best fit the data. The estimated absolute bioavailability (95% confidence interval) for suspension (F) was 16% (8-27%), which was significantly lower than the reported tablet bioavailability (F) [67%]. F was reduced by 62% and 75% upon concomitant administration with pantoprazole (PAN) and omeprazole (OME), respectively. Famotidine resulted in a reduction of F by only 22%. Both fixed dosing and weight-based adaptive dosing provided adequate target attainment when PAN or OME were not coadministered with the suspension.
CONCLUSIONS
The results of this study revealed that both fixed and weight-based adaptive dosing schemes can be appropriate for target attainment across all PSZ formulations, including suspension. Additionally, covariate analysis suggests that concomitant proton pump inhibitors should be contraindicated during PSZ suspension dosing.
Topics: Adult; Humans; Child; Retrospective Studies; Administration, Oral; Invasive Fungal Infections; Antifungal Agents; Triazoles; Tablets; Suspensions
PubMed: 37179512
DOI: 10.1007/s40262-023-01254-2 -
Scientific Reports May 2017An increase in number of newly developed synthetic drugs displays bioavailability constraints because of poor water solubility. Nanosuspensions formulation may help to...
An increase in number of newly developed synthetic drugs displays bioavailability constraints because of poor water solubility. Nanosuspensions formulation may help to overwhelm these problems by increasing dissolution velocity and saturation solubility. In the present study, cyadox (Cyx) nanosuspension was successfully prepared by recrystallization based on acid-base neutralization combined with high pressure homogenization method using Polyvinylpyrrolidone K30 (PVP) as stabilizer. The nanosuspension had uniform particle distribution, excellent sedimentation rate and redispersibility. The nanosuspension significantly improved the solubility, dissolution and bioavailability. The saturation solubility of Cyx nanocrystal was higher than that of bulk Cyx and released the total drug in very short time. Further, pharmacokinetics of Cyx nanosuspension and normal suspension following oral administration was investigated in beagle dogs. Nanosuspension improved the bioavailability of Cyx which could be beneficial for intestinal bacterial infection in animals. Maximum concentration and area under concentration time curve were increased with particles size reduction which might give rise to pronounce fluctuations in plasma concentration and more intensified antibacterial effects. The terminal half-life and mean resident time of Cyx nanosuspension had also increased compared to normal Cyx suspension. In conclusion, nanosuspensions may be a suitable delivery approach to increase the bioavailability of poorly soluble drugs.
Topics: Animals; Biological Availability; Dogs; Drug Compounding; Drug Stability; Female; Male; Microscopy, Electron, Scanning; Nanoparticles; Particle Size; Povidone; Quinoxalines; Solubility; Suspensions
PubMed: 28536446
DOI: 10.1038/s41598-017-02523-4 -
Daru : Journal of Faculty of Pharmacy,... Jun 2019Nanosuspensions, liquid dispersions with nanometer size distribution, are becoming trendy in pharmaceutical practice to formulate poorly water-soluble drugs and to... (Review)
Review
BACKGROUND
Nanosuspensions, liquid dispersions with nanometer size distribution, are becoming trendy in pharmaceutical practice to formulate poorly water-soluble drugs and to enhance their bioavailability. Generally, nanosuspensions are produced in two main approaches; top-down or bottom-up. The former is based on size-reduction of large particles via milling or high pressure homogenization. The latter is focused on the mechanisms of nucleation and particle growth.
METHODS
In this review, the critical factors influencing the kinetics or dynamics of nucleation and growth are discussed. Subsequently, the mechanisms of nanosuspension instability as well as strategies for stabilization are elaborated. Furthermore, the effects of stabilizers on key parameters of instability as well as the process of choosing an appropriate stabilizer is discussed.
RESULTS
Steric and electrostatic stabilizations or combination of them is essential for nanosuspensions formulation to prevent coagulation. Accordingly, some characteristics of stabilizers play critical role on stability and optimization of nanosuspensions; i.e., HLB and concentration. Nevertheless, after reviewing various articles, it is ascertained that each formulation requires individual selection of surfactants according to the parameters of the particle surface and the medium.
CONCLUSIONS
Based on the results, application of excipients such as stabilizers requires proper optimization of type and concentration. This implies that each formulation requires its own optimization process. Graphical Abstract ᅟ.
Topics: Biological Availability; Drug Compounding; Nanoparticles; Particle Size; Static Electricity; Surface-Active Agents; Suspensions
PubMed: 30661188
DOI: 10.1007/s40199-018-00235-2 -
Journal of Pediatric Gastroenterology... Aug 2022The pharmacokinetic (PK) profile of budesonide oral suspension (BOS) was evaluated during a phase 2, randomized, double-blind, placebo-controlled, dose-ranging study in... (Randomized Controlled Trial)
Randomized Controlled Trial
The pharmacokinetic (PK) profile of budesonide oral suspension (BOS) was evaluated during a phase 2, randomized, double-blind, placebo-controlled, dose-ranging study in pediatric patients with eosinophilic esophagitis (EoE) (MPI 101-01/NCT00762073). Non-compartmental methods were used to calculate PK parameters in 37 patients after receiving morning doses of BOS, with volume and dose adjusted for age (low dose: 0.35 or 0.5 mg; high dose: 1.4 or 2.0 mg [2-9 or 10-18 years old, respectively]). Relationships between apparent oral clearance and volume of distribution, and bodyweight and body mass index were also evaluated. Budesonide systemic exposure increased with BOS dose. After oral administration, time to maximum plasma budesonide concentration occurred ~1 hour post dose and the half-life of budesonide was 3.3-3.5 hours. PK parameters were similar between age groups for low- and high-dose BOS, indicating that volume and dose adjustments for age were appropriate for pediatric patients with EoE. BOS was well tolerated.
Topics: Administration, Oral; Adolescent; Budesonide; Child; Double-Blind Method; Eosinophilic Esophagitis; Glucocorticoids; Humans; Suspensions; Treatment Outcome
PubMed: 35666852
DOI: 10.1097/MPG.0000000000003482 -
PloS One 2023The purpose of this study was to assess the differences in muscle activation (EMG) and body weight distribution (%BW) between suspension (TRX™ push-up and TRX™...
The purpose of this study was to assess the differences in muscle activation (EMG) and body weight distribution (%BW) between suspension (TRX™ push-up and TRX™ inverted row) and conventional exercises (bench press and lying barbell row) using different contraction types (isometric and isotonic) and position variations (feet on the ground [FG] and feet on suspension device [FD]). It was also used to determine the intensity of the force applied to the straps of the suspension device corresponding to one repetition maximum (1-RM). Twelve male athletes (ages-24.5±4.2 years (mean±standard deviation [SD]); Height-181.0±6.8 cm; body mass-83.08±6.81 kg) participated in this study. Two suspension devices were used, one for the FD variation and one for the FG variation pectoralis major (PM) and triceps brachii (TRI) activations were assessed during the TRX™ push-up and bench press exercises. Transversus trapezius (TRA) and biceps brachii (BB) activations were assessed during the TRX™ inverted row and lying barbell row exercises. The results showed significant differences between exercises (FG and FD variations of TRX™ push-up and bench press) in PM activities (isometric and isotonic) (p≤0.05). However, these differences were only observed during isometric TRI activation (p≤0.05). In the FG and FD variations of the TRX™ inverted row and lying barbell row exercises, there were only differences in the isometric contractions of the TRA and BB (p≤0.05). In the suspension device of push-ups and inverted row for the FD variations, 70.5% and 72.64% of 1-RM intensity were obtained, respectively. Similar responses to training intensities and muscle activations can be obtained in suspension exercises and conventional exercises. FD variations of suspension exercises can be more effective in terms of muscle activations than FG variations, and isotonic suspension exercises increase exercise intensity more than isometric suspension exercises.
Topics: Male; Humans; Exercise; Exercise Therapy; Foot; Pectoralis Muscles; Isometric Contraction; Suspensions
PubMed: 37738266
DOI: 10.1371/journal.pone.0291608