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Drug Development and Industrial Pharmacy 2016
Topics: Drug Delivery Systems; Nanoparticles; Particle Size; Suspensions
PubMed: 27019193
DOI: 10.3109/03639045.2016.1168599 -
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 -
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 -
Veterinary Parasitology Nov 2021Toltrazuril (TOL) is a broad-spectrum anticoccidial drug which is widely used in poultry and livestock. A novel oral suspension based on soybean oil-based TOL...
Pharmacokinetics of toltrazuril and its metabolites after oral and parenteral administration of novel oil-based suspension based on micro-environmental pH-modifying solid dispersion in rabbits.
Toltrazuril (TOL) is a broad-spectrum anticoccidial drug which is widely used in poultry and livestock. A novel oral suspension based on soybean oil-based TOL micro-environmental pH-modifying solid dispersion (micro pHm SD) and a novel injectable suspension based on white oil-based TOL micro pHm SD were developed, showing high physicochemical stability and high drug release in vitro with good histocompatibility. The present study is to evaluate the pharmacokinetic profiles of TOL and its major metabolites, e.g. toltrazuril sulfoxide (TOLSO) and toltrazuril sulfone (TOLSO) in rabbits following oral or subcutaneous administration with these two TOL SD suspensions. The plasma concentrations of TOL, TOLSO and TOLSO were determined by high performance liquid chromatography (HPLC). Plasma concentration-time data were analyzed by a non-compartmental model analysis. The soybean oil-based TOL suspension after single oral administration at 20 mg/kg body weight (bw) significantly increased the plasma concentrations of TOL, TOLSO and TOLSO compared with Baycox® 5 % suspension. Following subcutaneous administration of the white oil-based TOL suspension (20 mg/kg bw), TOL was well absorbed and metabolized more slowly to TOLSO and TOLSO, compared with oral administration, resulting in the significantly prolonged residence time in rabbits. The two suspensions significantly improved the relative bioavailability of TOL and its two metabolites, showing their potential usage in the control of coccidian in poultry and livestock.
Topics: Administration, Oral; Animals; Coccidiostats; Hydrogen-Ion Concentration; Rabbits; Suspensions; Triazines
PubMed: 34597913
DOI: 10.1016/j.vetpar.2021.109580 -
AAPS PharmSciTech May 2020The relationship between the geometric particle size distribution (GPSD) and the aerodynamic particle size distribution (APSD) of commercial solution and suspension...
The relationship between the geometric particle size distribution (GPSD) and the aerodynamic particle size distribution (APSD) of commercial solution and suspension metered-dose inhaler (MDI) formulations was assessed to clarify the use of GPSD to estimate the APSD. The size distribution of particles discharged from four suspension and four solution MDIs was measured using the Inas®100 light-scattering spectrometer and a Next Generation Impactor. The conversion factor was calculated by measuring the GPSD and APSD of MDIs. The morphology and physical properties of MDIs were studied using scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). Six of the eight MDIs showed similar conversion factor profiles, irrespective of their composition and formulation types. Applying the conversion factor obtained from one of the six MDIs resulted in a particle size distribution comparable to each APSD except for some formulations. The two other solution MDIs, which contained citric acid, had much higher and variable conversion factors. SEM images and DSC scans of the solids obtained by nebulization of the solutions containing beclomethasone and/or citric acid showed the formation of a paste-like amorphous solid. These results indicated that APSD of solution and suspension MDIs that form rigid particles may be estimated by using the conversion factor and GPSD. Contrarily, the estimation is more difficult in formulations that tend to lose the particle structure during the measurement.
Topics: Administration, Inhalation; Aerosols; Beclomethasone; Metered Dose Inhalers; Nebulizers and Vaporizers; Particle Size; Solutions; Suspensions
PubMed: 32458106
DOI: 10.1208/s12249-020-01675-3 -
International Journal of Pharmaceutical... 2022Amitriptyline hydrochloride is indicated for the relief of symptoms of depression. A review of the therapeutic uses of amitriptyline hydrochloride reveals the need for... (Review)
Review
Amitriptyline hydrochloride is indicated for the relief of symptoms of depression. A review of the therapeutic uses of amitriptyline hydrochloride reveals the need for flexibility in dosing. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of amitriptyline currently exists. Amitriptyline hydrochloride is commercially available only as 10-mg, 25-mg, 50-mg, 75-mg, 100-mg, and 150-mg tablets. An extemporaneously compounded suspension from pure drug powder would provide a flexible, customizable option to meet unique patient needs with convenient and accurate dosing options. The purpose of this study was to determine the physicochemical and microbiological stability of extemporaneously compounded amitriptyline hydrochloride suspensions in 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 amitriptyline hydrochloride concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability- indicating high-performance liquid chromatographic assay for the determination of the chemical stability of amitriptyline hydrochloride in PCCA SuspendIt was developed and validated. Suspensions of amitriptyline hydro- chloride were prepared in PCCA SuspendIt at 1-mg/mL and 5-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in amber plastic prescription bottles at two temperature conditions (5°C and 25°C). Samples were assayed initially, and on the following time points (days): 7, 14, 28, 49, 63, 91, 119, and 185. Physical data such as pH, viscosity, and appearance were also noted. Microbiological stability was tested. 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 and is protected against microbial growth. The study showed that amitriptyline hydrochloride concentrations did not go below 99.8% of the label claim (initial drug concentration) at both temperatures studied. No microbial growth was observed. The pH values remained constant. The viscosity of the suspensions allowed easy re-dispersal of the drug particles upon shaking. This study demonstrates that amitriptyline hydrochloride is physically, chemically, and microbiologically stable in PCCA SuspendIt for 185 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for amitriptyline hydrochloride in a liquid dosage form, with an extended beyond-use date to meet patient needs.
Topics: Amitriptyline; Chromones; Drug Compounding; Drug Stability; Excipients; Humans; Suspensions
PubMed: 35820140
DOI: No ID Found -
Sensors (Basel, Switzerland) Jun 2023This paper presents a method for the identification of control-related signal paths dedicated to a semi-active suspension with MR (magnetorheological) dampers, which are...
This paper presents a method for the identification of control-related signal paths dedicated to a semi-active suspension with MR (magnetorheological) dampers, which are installed in place of standard shock absorbers. The main challenge comes from the fact that the semi-active suspension needs to be simultaneously subjected to road-induced excitation and electric currents supplied to the suspension MR dampers, while a response signal needs to be decomposed into road-related and control-related components. During experiments, the front wheels of an all-terrain vehicle were subjected to sinusoidal vibration excitation at a frequency equal to 12 Hz using a dedicated diagnostic station and specialised mechanical exciters. The harmonic type of road-related excitation allowed for its straightforward filtering from identification signals. Additionally, front suspension MR dampers were controlled using a wideband random signal with a 25 Hz bandwidth, different realisations, and several configurations, which differed in the average values and deviations of control currents. The simultaneous control of the right and left suspension MR dampers made it necessary to decompose the vehicle vibration response, i.e., the front vehicle body acceleration signal, into components related to the forces generated by different MR dampers. Measurement signals used for identification were taken from numerous sensors available in the vehicle, e.g., accelerometers, suspension force and deflection sensors, and sensors of electric currents, which control the instantaneous damping parameters of MR dampers. The final identification was carried out for control-related models evaluated in the frequency domain and revealed several resonances of the vehicle response and their dependence on the configurations of control currents. In addition, the parameters of the vehicle model with MR dampers and the diagnostic station were estimated based on the identification results. The analysis of the simulation results of the implemented vehicle model carried out in the frequency domain showed the influence of the vehicle load on the absolute values and phase shifts of control-related signal paths. The potential future application of the identified models lies in the synthesis and implementation of adaptive suspension control algorithms such as FxLMS (filtered-x least mean square). Adaptive vehicle suspensions are especially preferred for their ability to quickly adapt to varying road conditions and vehicle parameters.
Topics: Suspensions; Algorithms; Computer Simulation; Vibration
PubMed: 37420933
DOI: 10.3390/s23125770 -
Drug Development and Industrial Pharmacy May 2022Patient acceptance of pediatric formulations is critical to compliance and consequently therapeutic outcomes; thus, having an method to evaluate sensory perception of...
OBJECTIVE
Patient acceptance of pediatric formulations is critical to compliance and consequently therapeutic outcomes; thus, having an method to evaluate sensory perception of pharmaceutical products would be beneficial. The objective of this research is to develop a sensitive and reproducible tribological method to characterize pharmaceutical suspensions at low force and sliding speeds.
METHODS
The discriminating potential of the method was examined using tribology profiles (coefficient of friction (COF) vs. sliding speed) for commercially available products and products made for this study with widely varying sweetness, thickness, and grittiness; these formulations were used to judge the sensitivity of the method. Samples were measured using 3M Transpore™ surgical tape to simulate the tongue surface, steel half ring geometry, constant gap setting, target axial force of 2 N in a 600 s exponential ramp for rotation speed.
RESULTS
The COF ranged from 0.1 to 0.6. For the speeds studied, the high viscosity commercial suspension ibuprofen drops and acetaminophen suspension show a classic Stribeck curve with an increasing COF at the higher rotation speeds, which indicates these formulations entered the hydrodynamic lubrication phase, while the lower viscosity suspensions only reached the mixed lubrication phase.
CONCLUSION
The contribution of particles affects the COF in a dynamic tribologic pattern compared to products that are categorized as either low gritty or high viscosity. These results are important as they provide a potentially rapid method for screening pediatric medications and help to identify the factors that affect the palatability of pediatric formulations.
Topics: Child; Drug Compounding; Friction; Humans; Lubrication; Suspensions; Viscosity
PubMed: 35726510
DOI: 10.1080/03639045.2022.2092125 -
Soft Matter Feb 2024Autonomous out-of-equilibrium agents or cells in suspension are ubiquitous in biology and engineering. Turning chemical energy into mechanical stress, they generate...
Autonomous out-of-equilibrium agents or cells in suspension are ubiquitous in biology and engineering. Turning chemical energy into mechanical stress, they generate activity in their environment, which may trigger spontaneous large-scale dynamics. Often, these systems are composed of multiple populations that may reflect the coexistence of multiple species, differing phenotypes, or chemically varying agents in engineered settings. Here, we present a new method for modeling such multi-population active fluids subject to confinement. We use a continuum multi-scale mean-field approach to represent each phase by its first three orientational moments and couple their evolution with those of the suspending fluid. The resulting coupled system is solved using a parallel adaptive level-set-based solver for high computational efficiency and maximal flexibility in the confinement geometry. Motivated by recent experimental work, we employ our method to study the spatiotemporal dynamics of confined bacterial suspensions and swarms dominated by fluid hydrodynamic effects. Our explorations reproduce observed emergent collective patterns, including features of active dissolution in two-population active-passive swarms, with results clearly suggesting that hydrodynamic effects dominate dissolution dynamics. Our work lays the foundation for a systematic characterization and study of collective phenomena in natural or synthetic multi-population systems such as bacteria colonies, bird flocks, fish schools, colloid swimmers, or programmable active matter.
Topics: Animals; Models, Biological; Hydrodynamics; Suspensions; Bacteria
PubMed: 38305767
DOI: 10.1039/d3sm01196h -
International Journal of Pharmaceutical... 2021Hydrocortisone is indicated in the treatment of primary or secondary adrenal insufficiency. The oral dosage regimen of hydrocortisone needs to be individualized in... (Review)
Review
Hydrocortisone is indicated in the treatment of primary or secondary adrenal insufficiency. The oral dosage regimen of hydrocortisone needs to be individualized in the treatment of congenital adrenal hyperplasia, especially in pediatric patients. A review of the therapeutic uses of hydrocortisone reveals the need for flexibility in dosing. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of hydrocortisone currently exists. Hydrocortisone is commercially available as 5-mg, 10-mg, and 20-mg tablets. An extemporaneously compounded suspension from pure drug powder would provide a convenient option to meet unique patient needs. The purpose of this study was to determine the physicochemical and microbiological stability of extemporaneously compounded hydrocortisone suspensions in 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 hydrocortisone concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability-indicating high-performance liquid chromatographic assay for the determination of the chemical stability of hydrocortisone in SuspendIt was developed and validated. Suspensions of hydrocortisone were prepared in SuspendIt at 1-mg/mL and 20-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 on the following days: 7, 15, 28, 45, 60, 91, 120, and 185. Physical data such as pH, viscosity, and appearance were also noted. Microbiological stability was tested. 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 and is protected against microbial growth. The study showed that hydrocortisone concentrations did not go below 94% of the label claim (initial drug concentration) at both temperatures studied. No microbial growth was observed. Viscosity and pH values did not change significantly. This study demonstrates that hydrocortisone is physically, chemically, and microbiologically stable in SuspendIt for 185 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for hydrocortisone in a liquid dosage form, with an extended beyond-use date to meet patient needs.
Topics: Child; Chromones; Drug Compounding; Drug Stability; Humans; Hydrocortisone; Suspensions
PubMed: 34623970
DOI: No ID Found