Dissolution Parameters Research Articles

The Milling Method in Formation of Inclusion Complex p-Methoxycinnamic Acid-Hydroxypropyl-β-Cyclodextrin.

p-methoxycinnamic acid (pMCA) is a substance with several pharmacological activities, derived from the rhizome of Kaempferia galanga Linn. The solubility of pMCA can be increased by the formation of inclusion complexes (IC) using hydroxypropyl-βcyclodextrin (HPβCD) compounds. IC are obtained through the milling method, which is a simple, environmentally friendly, and low-cost manufacturing method. The process involves the pounding of material with a certain speed and impact force. This research aims to characterize the pMCA-HPβCD IC made using the milling method. Milling the mixture of pMCA and HPβCD using a ball mill is a common technique to enhance the formation of the inclusion complex. The IC’s physical characteristics were analyzed in terms of their morphology, particle size, crystallinity, and thermal properties. The dissolution profile was also performed using paddle-typed dissolution apparatus (Type II) with 500 mL distilled water as dissolution medium. The amount of pMCA dissolved was determined using UV spectrophotometry. The dissolution parameter was determined as dissolution efficiency at 60 minutes (DE60). The IC particles were irregular in shapes and porous. The size was reduced as compared to the individual components. The XRD revealed that the ICs were amorphous. The DE60 of IC increased by a factor of 4.3 compared to the pure pMCA. In conclusion, the milling method successfully formed complex of pMCA-HPβCD with different characteristics from the initial compound and was significantly increased the percentage of the dissolved pMCA.

Study on the mass transfer characteristics of hydrogen in heavy oil by a modified dynamic pressure step method

The dissolved hydrogen, rather than gaseous hydrogen, plays a crucial role in the hydrogenation process. A thorough understanding of hydrogen dissolution is essential for optimizing the hydrogenation process. In this paper, the dynamic pressure step method was modified to reduce the temperature difference between the hydrogen and solution, from which the hydrogen solubility and volumetric liquid-side mass transfer coefficient (kLa) of the vacuum residue were obtained. It was discovered that temperature was the most critical factor in hydrogen dissolution, simultaneously enhancing both the hydrogen solubility and kLa. Pressure played a significant role in promoting hydrogen solubility, but had a relatively small impact on kLa. Stirring speed, although it enhanced kLa, did not affect hydrogen solubility. By normalizing the dissolution parameter, the results showed that the gas-liquid mass transfer rate decreased continuously during hydrogen dissolution and that the SD-tD curves after normalization were almost the same in all experimental conditions.

Dissolution behavior and kinetic investigation of in solution in the reaction of colemanite ore with propionic acid

Colemanite ore, which is one of the most significant commercially substantial boron minerals, is used to produce various boron compounds in the industry with its rich B_2 O_3 content. Calcium propionate, used in the food industry, is formed as a by-product in its production. In the production of boric acid from colemanite, the use of different solvent reagents is at the forefront to prevent the formation of Mg^(2+), Ca^(2+) and SO_4^(2-) impurities and borogypsum by-products. For this reason, in our study, the dissolution kinetics of colemanite ore in propionic acid solution in an aqueous medium were carried out in a batch reactor system. As dissolution parameters; reaction temperature, solid/liquid ratio, propionic acid (CH_3 CH_2 COOH) concentration, stirring speed and particle size were selected as. According to the experimental results, the amount of Mg^(2+) passed to the solution; was observed that the solution increased with the increase in reaction temperature with the decrease in solid-liquid ratio, grain size, and acid concentration. In addition, it was determined that the mixing speed was not effective. Obtained experimental data were analyzed according to homogeneous and heterogeneous reaction models using the Statistica 10.0 package program. It was determined that the dissolution kinetic of Mg^(2+) passing to solution conformed to the "Avrami model" and activation energy (E) was calculated as 8.18 kJ⁄mol.

Investigation on itraconazole solubility in aqueous solutions based on models, solvent effect, thermodynamic analysis and quantum chemical calculations

The mole-fraction solubility of itraconazole in four aqueous blends of ethanol/isopropanol/DMSO/methanol within the temperature range of 283.15 to 323.15 K was experimentally obtained using the isothermal shake-flask method. Under the identical temperature and ethanol/isopropanol/DMSO/methanol composition, itraconazole solubility in DMSO+water is much higher than that in ethanol/isopropanol/methanol + water. At the same temperature, the solubility increases monotonically with organic solvent concentration. X-ray power diffraction analysis demonstrated that over the course of the investigations, there was no crystal transition or solvate formation. The modified van’t Hoff-Jouyban-Acree and Jouyban-Acree models adequately related the solubility to solvent composition and temperature, with relative average deviations (RADs) not exceeding 7.65 %. Furthermore, the extended Hildebrand solubility approach was utilized to quantitatively characterize the solubility behavior at 298.15 K for the mixtures of ethanol/isopropanol/DMSO/methanol plus water. In both instances, the RADs were maintained below 4.12 %. The solubility parameter and dipolarity-polarizability of solutions have a major impact on the solubility fluctuation, as indicated by the analysis of the linear solvation energy relationship. The preferential solvation of itraconazole at 298.15 K was examined using the efficient approach of inverse Kirkwood-Buff integrals. The preferred solvation parameters showed positive values in blends within rich and moderate ethanol/isopropanol/DMSO/methanol composition regions. This suggests that the organic solvents preferentially solvated itraconazole. When itraconazole dissolved in the blends, thermodynamic analysis of the entropy-enthalpy compensation and dissolution parameters revealed both an endothermic and an enthalpy-driven mechanism. Furthermore, the microscopic electrostatic characteristics of basicity and acidity were effectively demonstrated by means of the electrostatic potential of molecular surface. The −C=O and −N=groups of the itraconazole molecule, which link the five-membered ring, are the primary targets of the electrophilic attack. An independent gradient model based on Hirshfeld partition analysis was used to demonstrate the weak interactions between itraconazole and solvents.

Impacts of storage conditions on the dissolution performance of commercial metronidazole tablets available in Saudi Arabia

This study aimed to investigate the impact of storage conditions on the dissolution performance of commercial metronidazole (MTZ) tablets available in Saudi Arabia; these were coded as the reference and Test A, Test B, and Test C products. Moreover, the hardness and the disintegration time were measured. The UV spectrophotometrically analytical technique was utilized to quantify MTZ. All the control tablets, which were tested upon receipt, met the USP requirement as not less than 85 % of the labeled amount of MTZ was dissolved in 60 min. The MTZ reference released 91.79 % ± 1.23 after 60 min, while the products A, B, and C released 87.96 % ± 2.60, 93.26 % ± 2.01, and 88.61 % ± 2.04, respectively. The different dissolution parameters calculated for all the control tablets showed that the MTZ products A and B had optimal dissolution performances and were considered similar to the reference product. The product C showed a significantly reduced dissolution performance and was considered different from the reference. The in vitro dissolution of the MTZ tablets stored at 40oC ± 2 oC/75 % RH ± 5 % for 6 months indicated that the tablets maintained compliance with the USP requirement. The MTZ reference released 89.36 % ± 3.64 after 60 min, while the products A, B, and C released 95.79 % ± 3.91, 88.52 % ± 2.52, and 87.79 % ± 5.04, respectively. However, a slight reduction in the percentage released after 30 min (% DE30) and a slight increase in the mean dissolution time (MDT) were observed during the first 3 months of storage under stressed conditions. These changes were more obvious after 6 months of storage under the same conditions. Furthermore, in vitro dissolution of the product C stored at 40oC ± 2 oC/75 % RH ± 5 % for 3 months with further protection against high humidity revealed an improvement in the dissolution parameters due to the similar protective effects exerted by the two packaging forms. Furthermore, the study shows that storage conditions such as humidity and temperature affect in vitro dissolution of MTZ marketed tablets which may have an impact on efficiency and patient safety.

Formulation, Evaluation, and Characterization of Indapamide Niosomes

Niosomes, also known as nonionic surfactant vesicles, are one of the many carriers used to carry drug molecules to their target sites. They can hold both hydrophilic and hydrophobic medicines. Indapamide is an angiotensin II type 1 receptor (AT1) antagonist medication primarily used to treat high blood pressure. Niosomes containing Indapamide were created utilizing the thin film hydration process with various cholesterol concentrations and nonionic surfactants (span 60). All noisome formulations were assessed for entrapment efficiency, drug content, reproducibility, vesicular diameter, shape and size distribution microphotography, FTIR analysis, and in vitro release experiments. The results indicate that in all of the created niosomal formulations, as the surfactant content increases, the entrapment efficiency also increases. The drug content ranged between 90.06±0.57 and 96.15±0.42, with a low standard deviation. Niosomes range in size from 0.280±0.098µm to 0.299±0.044µm and have a spherical shape. The IR spectrum analysis indicated no interaction between the medication and the formulation ingredients. Membrane diffusion cells were used to study the in vitro dissolution parameters. The results demonstrate that formulation F6 had a better-controlled release action than other formulations, with an 'n' value of 0.917, indicating that the medication was released using zero-order kinetics.

Preparation and characterization of citreorosein nanoparticles with improved bioavailability and cytotoxic potential

The present study was designed to improve the aqueous solubility and dissolution rate of citreorosein, a poorly water soluble drug, by producing its nanoparticles (NPs) using an “antisolvent precipitation with a syringe pump” (APSP) method. Various process parameters including flow rate, stirring speed, temperature, drug concentration and solvent-antisolvent ratio were investigated and optimized to obtain the smallest particle size of citreorosein. The prepared NPs were subjected to different analytical techniques such as SEM, FTIR, XRD and DLS. The NPs were tested for different dissolution parameters including difference (f1) and similarity factors (f2), dissolution efficiency (DE) and mean dissolution time (MDT). The antioxidant potential of citreorosein and its NPs were evaluated using DPPH, ABTS, and FRAP models, while their cytotoxicity was tested on various cancer cell lines such as breast (MDA-MB-231), lung (A549) and liver (HepG2), using the MTT assay. The specificity of the test compound was investigated against two normal human primary epithelial cells including renal (HRPTEpiC) and alveolar (HPAEpiC) cells. DLS analysis revealed that the prepared NPs were less than 200 nm in size while SEM and XRD confirmed their rod shape and amorphous nature, respectively. Citreorosein-NPs exhibited enhanced solubility and dissolution rate in all medias as compared to pure citreorosein. The NPs displayed significant antioxidant effects against ABTS, DPPH and FRAP models, with IC50 values of22.6, 21.45 and 27.30 µg/ml, respectively. Moreover, it showed significant cytotoxic activity against MDA-MB-231, A549 and HepG2 cells, with IC50 values of 3.45, 4.5 and 6.23 µg/ml, respectively. Furthermore, the NPs demonstrated high selectivity index values for the aforementioned cell lines as compared to reference drugs. This study demonstrated that APSP method successfully produced citreorosein-NPs and hence, showed better aqueous solubility, dissolution rate, antioxidant and cytotoxic activities than the pure compound.

Fabrication and In-Vivo Evaluation of Polyvinyl pyrrolidone/Poloxamer 188 Hybrid Nanofibers of Deflazacort

The superior flexibility, efficient drug loading, high surface-to-volume ratio, ease of formulation, and cost-controlled production are considered exceptional advantages of nanofibers (NFs) as a smart delivery system. Deflazacort (DEF) is an anti-inflammatory and immunosuppressant agent. It is categorized as a poorly soluble class II drug. In this study, DEF-loaded polymeric nanofibrous using the electrospinning technique mats, Polyvinyl pyrrolidone (PVP) with or without Poloxamer 188 (PX) were used as mat-forming polymers. Microscopical imaging, drug content (%), and in vitro dissolution studies were conducted for all NFs formulae (F1-F7). All NFs improved the DEF dissolution compared to the unprocessed form, with the superiority of the PVP/PX hybrid. The optimized formula (F7) exhibited an average diameter of 655.46 ± 90.4 nm and % drug content of 84.33 ± 5.58. The dissolution parameters of DEF loaded in PVP/PX NFs (F7) reflected a release of 95.3 % ± 3.1 and 102.6 % ± 1.7 after 5 and 60 min, respectively. NFs (F7) was investigated for drug-polymer compatibility using Fourier-Transform Infrared Spectroscopy (FTIR), Powder X-ray diffraction analysis (PXRD), and Differential Scanning Calorimetry (DSC). In vivo anti-inflammatory study employing male Sprague-Dawley rats showed a significant reduction of rat paw edema for F7 (p < 0.05) compared with unprocessed DEF with a normal epidermal and dermal skin structure comparable to the healthy negative control. Immunohistochemical and morphometric data displayed similarities between the immune reaction of F7 and the negative healthy control. The finding of this work emphasized that DEF loaded in PVP/PX NFs could be considered a useful strategy for enhancing the therapeutic performance of DEF.

Formulation, Evaluation and Characterization of Hydrochlorothiazide Niosomes

One of the many different carriers for getting a drug molecule to its site of action is a niosome, also known as a nonionic surfactant vesicle. Hydrophilic and hydrophobic medicines can both be trapped by them. The primary purpose of the medication hydrochlorothiazide, an angiotensin II type 1 receptor (AT1) antagonist, is to treat high blood pressure. Using cholesterol and nonionic surfactants (span 60) at varying concentrations, niosomes containing hydrochlorothiazide were created by the thin film hydration method. FTIR investigations, in vitro release studies, vesicular diameter, drug content, repeatability, shape and size distribution microphotography, and entrapment efficiency were all assessed for each niosome formulation.According to the findings, entrapment efficiency rises with surfactant concentration in all developed niosomal formulations. Low SD was found for the drug content, which ranged from 90.060.57 to 96.150.42. It was discovered that niosomes ranged in size from 0.280±0.098µm to 0.299±0.044µm and had a spherical shape. The medicine and formulation additives did not interact, according to the IR spectral analysis. Membrane diffusion cells were used to study the in vitro dissolution parameters. The findings indicate that formulation F6 exhibits a more controlled release action compared to the other formulation, with a 'n' value of 0.917, indicating that zero order kinetics were used to release the medication.

Comprehensive solubility study and inter-molecular interactions on fenbendazole dissolved in some aqueous aprotic and protic co-solvent solutions

The isothermal shake-flask saturation method was used to experimentally determine the mole-fraction solubility of fenbendazole in three aqueous co-solvent blends of 1,4-dioxane/acetone/NMP encompassing the range of 283.15 to 328.15 K. The solubility of fenbendazole in various blended solvents ranks NMP + water (4.852 × 10−2) > 1,4-dioxane + water (14.81 × 10−4) > acetone + water (2.285 × 10−4) with composition of 1,4-dioxane (acetone or NMP) of 1 at 298.15 K. The solubility data rises monotonically with 1,4-dioxane/acetone/NMP concentration at the same temperature. X-ray power diffraction images show that no solvate production or crystal transition appeared throughout the studies. The solubility to solvent composition and temperature was satisfactorily associated by the modified van't Hoff-Jouyban-Acree, quantitative structure–property relationship, and Jouyban-Acree models with relative average deviations of no higher than 7.05 % and root-mean-square deviation of no higher than 1.225 × 10−3. In addition, the 1,4-dioxane/acetone/NMP + water blends studied in this paper and the methanol/ethanol/EG/DMF + water blends previously reported both used the extended Hildebrand solubility approach to quantitatively describe the solubility behavior at 298.15 K. The average relative deviations were kept under 4.06 % on both cases. As stated by the examination of the linear solvation energy relationship, the solubility parameter and dipolarity-polarizability of solutions have a significant influence on the solubility variation. The effective method of inverse Kirkwood-Buff integrals was used to investigate the preferred solvation of fenbendazole at 298.15 K. In blends with intermediate and rich ethanol/DMF/1,4-dioxane/acetone/NMP composition areas, the preferred solvation parameters of ethanol/DMF/1,4-dioxane/acetone/NMP displayed positive values, indicating the preferential solvation of fenbendazole by the co-solvents. Thermodynamic examination of the entropy-enthalpy compensation and dissolution parameters for fenbendazole dissolving in blends led to the identification of an enthalpy and/or entropy-driven mechanism as well as an endothermic process. Moreover, the average local ionization energy and electrostatic potential of molecular surface were utilized as effective instruments to demonstrate the microscopic electrostatic properties of acidity and basicity, respectively. The fenbendazole molecule's groups of –N in the five-membered ring and –NH in the straight chain serve as the main targets for electrophilic and nucleophilic assault. The weak interactions between fenbendazole and several solvents were shown using an independent gradient model based on Hirshfeld partition analysis.

Metolazone co-crystals-loaded oral fast dissolving films: Design, optimization, and in vivo evaluation

This study aimed to formulate and optimize metolazone (MLZ) co-crystals incorporating fast-dissolving films (OFDFs) as an agreeable oral formulation for improving the bioavailability of the drug. The co-crystal formation between MLZ and different co-formers was performed using the solvent evaporation method. The MLZ co-crystal formula (MLZ-nicotinamide) with the highest dissolution parameters was loaded into OFDFs by the solvent casting method after being characterized by FT-IR, DSC, and PXRD. The formulated OFDFs were evaluated for their physicochemical properties. Using Statgraphics Centurion software, a full factorial design was used to examine the impact of formulation variables on the swelling index, the disintegration time, and the cumulative MLZ percent release after 10 min. The optimized OFDF was subjected to palatability, stability, and in vivo studies. Various co-formers lowered the melting point of MLZ, suggesting the development of different crystalline packing arrangements and the formation of co-crystals. All developed co-crystal formulations had higher values for relative dissolving rate (RD) and dissolution efficiency (DE%) when compared to pure MLZ. The obtained FTIR data could reflect the co-crystallization process between MLZ and nicotinamide, which was confirmed by the change of the PXRD pattern and the shift of the endothermic peak obtained by DSC. The optimized OFDF loaded with MLZ had a 4.57 swelling index, a 23.7 s disintegration time, and 99.8% MLZ released after 10 min. The optimized formula was stable for six months under the specified storage conditions. When evaluated in rabbits, the relative bioavailability of the optimized MLZ-OFDF was calculated to be approximately two-fold higher than that of the commercially available Efectinix® tablets.

Sucrose acetate isobutyrate (SAIB) and glyceryl monooleate (GMO) hybrid nanoparticles for bioavailability enhancement of rivaroxaban: an optimization study

This study aims to improve the RXB bioavailability using hybrid nanoparticles. A modified melt dispersion technique created different formulas with varying GMO-SAIB: RXB and GMO: SAIB ratios, with fixed GMO-SAIB: poloxamer 407 ratios. The PS, PDI, ZP, and EE were measured to determine the optimal formula, which was selected using Design-Expert™ software. The optimized formula was lyophilized and tested for PS, PDI, ZP, and EE. The chosen lyophilized formula (L4) was characterized using FTIR, DSC, PXRD, dissolution studies, and pharmacokinetics studies. The study found correlations between variables and identified how GMO-SAIB concentration affects drug encapsulation. The dissolution parameters were calculated, including % Q5 and % DE). The % Q5 values were 68.4 ± 1.7% and 89.7 ± 3.6% for Xarelto and L4 tablets, respectively. The % DE values were 89.7 ± 0.4% and 97.5 ± 2.1% for Xarelto and L4 tablets, respectively. The AUC values were 2117.0 ng.h/mL (±77.3) and 3919.4 ng.h/mL (±134.8) for Xarelto and L4 tablets, respectively. The Cmax values were 241.3 ng/mL (±21.0) and 521.5 ng/mL (±91.5) for Xarelto and L4 tablets, respectively. In conclusion, the study found that using GMO-SAIB as co-formers effectively enhanced the bioavailability of RXB. The authors recommend using the hybrid nanoparticles technique and suggest further research to enhance its effectiveness for drug delivery.

Modified human respiratory tract model to describe the retention of plutonium in scar tissues.

The Human Respiratory Tract Model described in Publication 130 of the International Commission on Radiological Protection provides some mechanisms to account for retention of material that can be subject to little to no mechanical transport or absorption into the blood. One of these mechanisms is 'binding', which refers to a process by which a fraction ('bound fraction') of the dissolved material chemically binds to the tissue of the airway wall. The value of the bound fraction can have a significant impact on the radiation doses imparted to different parts of the respiratory tract. To properly evaluate-and quantify-bound fraction for an element, one would need information on long-term retention of the element in individual compartments of the respiratory tract. Such data on regional retention of plutonium in the respiratory tract of four workers-who had inhaled materials with solubility ranging from soluble nitrate to very insoluble high-fired oxides-were obtained at the United States Transuranium and Uranium Registries. An assumption of bound fraction alone was found to be inconsistent with this dataset and also with a review of the literature. Several studies show evidence of retention of a large amount of Pu activity in the scar tissues of humans and experimental animals, and accordingly, a model structure with scar-tissue compartments was proposed. The transfer rates to these compartments were determined using Markov Chain Monte Carlo analysis of the bioassay and post-mortem data, considering the uncertainties associated with deposition, dissolution and particle clearance parameters. The models predicted that a significant amount-between 20 and 100% for the cases analyzed-of plutonium retained in the respiratory tract was sequestered in the scar tissues. Unlike chemically-bound Pu that irradiates sensitive epithelial cells, Pu in scar tissues may not be dosimetrically significant because the scar tissues absorb most, if not all, of the energy from alpha emissions.

Silk wastes and autoclaved degumming as an alternative for a sustainable silk process

Silk degumming is considered the first point in the preparation of silk-based materials since this process could modify the silk fiber and the properties of its related products. This study evaluated the differences in morphology, secondary structure, amino acid content, thermal stability, and mechanical properties of two types of raw materials, defective cocoons (DC) and silk fibrous waste (SW), degummed by chemical (C) and autoclaving (A) methods. Subsequently, silk fibroin films were prepared by dissolving each type of degummed fibers, and thermal and structural films properties were determined. The findings demonstrated that autoclaving is an efficient alternative to remove silk sericin, as the resulting fibers presented improved structural, thermal, and mechanical properties compared to those obtained by the chemical method. For films preparation, autoclave resulted in a good option, but dissolution parameters need to be adjusted for defective cocoons. Furthermore, similarities between the physicochemical properties of fibers and films from both fibrous wastes suggest that SW is a promising raw material for producing fibrous resources and regenerated silk fibroin materials. Overall, these findings suggest new recycling methods for fibrous waste and by-products generated in the silk textile production process.

Phase Transformation of Anhydrous to Dihydrate Carbamazepine: Preparation and Comparative Characterization

Carbamazepine, an anticonvulsant drug is one of the suitable activecompounds for the study of crystal and polymorphism study. Hydrate formation or dehydration of a given hydrate may affect the overall performance of the ultimate formulations and it has been estimated that more than 30 % available active drug compound can form a hydrate. The anhydrous form of the compound always shows higher aqueous solubility and dissolution parameter as compared to hydrates. This ultimately led to improved bioavailability when the rate limiting step for the absorption is dissolution rate. The purpose of the present investigation was to compare various techniques for the formation of Carbamazepine dihydrate from anhydrates and also to discriminate crystal forms of Carbamazepine by Melting point, FTIR, DSC, Powder X-ray diffractometry analysis, NMR, scanning electron microscopy, solubility and intrinsic dissolution testing. Carbamazepine phase transformation of solid state occurs when exposed to the environmental condition, which can affect the performance of the drug and the formulations.

In vivo Evaluation for the Anticoagulant Activity of Dipyridamole Matrix Tablets

Dipyridamole (DYP) is potent drug that prevents the thromboembolic risk. It has been clinically used for chronic treatment of angina pectoris treatment and during the valve replacement. heart valve replacement and long-term angina pectoris treatment and is well absorbed in the stomach with BCS class II drug and low oral bioavailability. The present research investigation was focused on the formulation of matrix tablets of Dipyridamole cocrystals and the evaluation of In vivo anticoagulant activity. The results of the study showed that the formulated matrix tablets of dipyridamole cocrystals showed improved efficacy in comparison with the plain drug by enhancing the pre-compression parameters such as bulk density, tap density, Carr's index, angle of repose and Hausner's ratio and post-compression parameters like thickness and weight variation, hardness and friability, In vitro dissolution parameters. The improved efficacy was confirmed by improvement in the pharmacodynamic parameters such as cutaneous bleeding time and clotting time indicative of enhanced bioavailability of dipyridamole. Thus, it can be concluded that the dipyridamole matrix tablets prove to be more effective in producing the anticoagulant effect in clinical practice as compared to the plain drug resulting in more patient compliance.

Effect of cascade size and damage rate on α’ precipitate stability in Fe-15Cr

Samples of a Fe-15Cr model alloy with an established α' precipitate population were irradiated with 1.25 MeV electrons, 1.5 MeV protons, or 4.4 MeV Fe2+/3+ ions over a range of damage rates to doses of 1 or 10 dpa at 400°C to determine the roles of cascade size and damage rate on the stability of α'. Results showed that α' precipitate size and chromium content increased with dpa for electron irradiations. Proton irradiation also resulted in increases in α' precipitate size and Cr content, but at a slower rate than with electrons due to the influence of ballistic dissolution. Self-ion irradiations caused a reduction in the size and Cr content of α' with dose, and above a threshold damage rate of 1–3 × 10−4 dpa/s, the precipitates were completely dissolved. The ballistic dissolution parameter for self-ion irradiations calculated from both the Nelson-Hudson-Mazey model and a mixing model was in the range 2–5 × 1020 atoms/m2‧dpa compared to a value of ∼9 × 1019 atoms/m2‧dpa for proton irradiation, and explains the different behaviors of the precipitates for these two irradiating particles. Overall, it was found that cascade size strongly determines the stability of α' precipitates and damage rate has its major impact on the rate at which α' precipitates grow or dissolve.

Application of a novel PhysioCell apparatus for biopredictive dissolution tests of oral immediate release formulations – A case study workflow for in vitro-in vivo predictions

Biorelevant dissolution tests of oral solid dosage forms open the gate to valid in vitro-in vivo predictions (IVIVP). A recently developed apparatus, PhysioCell, allows mimicking the fluid flow and pressure waves occurring in the human fasted stomach. In this work, we used the PhysioCell to perform IVIVP for vortioxetine immediate-release (IR) tablets: the originator (Brintellix) and generic product candidates (VORTIO). The dissolved drug was monitored in the gastric (StressCell) and intestinal (Collection Vessel) compartments that contained biorelevant media. Simulated intermittent gastric stress at 15 min and “housekeeping wave” at 30 min increased the dissolution of Brintellix formulations only. A mechanistic model that best described the observations involved the first-order tablet disintegration with a stress-induced enhancement for Brintellix, dissolution of solid particles in the StressCell, and drug transfer to the Collection Vessel. Then, a semi-mechanistic pharmacokinetic model with dissolution parameters as inputs simulated vortioxetine plasma concentrations in healthy volunteers after single and multiple dosing of Brintellix. Despite different dissolution characteristics, VORTIO provided similar concentration profiles to the originator. In conclusion, PhysioCell dissolution tests, combined with semi-mechanistic IVIVP, can be successfully used to develop IR dosage forms exhibiting gastric stress-related effects.

Dissolution behavior of ZnO nanoparticles at environmentally relevant low concentrations in surface waters: Equilibrium and kinetics

Environmentally relevant fate parameters are essential in accurate prediction of nanomaterial's exposure. This study investigates the dissolution kinetics and equilibrium of ZnO nanoparticles (ZnONPs) using environmentally relevant low concentrations (50–200 μg/L) of ZnONPs in river water and lake water samples, and a seawater-influenced river water. We found that ZnONPs at an initial concentration of 50 μg/L completely dissolved independent of water matrices, while at 100 and 200 μg/L the dissolution level of ZnONPs was strongly dependent on the water chemistry. Carbonate alkalinity was found to control the dissolution levels, and can react with dissolved Zn ion to form secondary solid product hydrozincite. An analysis of our kinetic data and comprehensive literature results reveals that the dissolution kinetic coefficients largely increased with decreased initial ZnONP concentrations especially in environmental water matrices. The result highlights the importance to measure and derive representative dissolution parameters of nanomaterials using environmentally relevant concentrations.

Application of ISO 17025 Standards in the Validation of a Spectrophotometric Method for Quality Assessment of Generic Brands of Cetirizine Tablets marketed in Nigeria.

Background: The concern for the quality of medicines is to ensure effiffifficacious clinical outcomes and quality health care. The World Health Organization (WHO) estimates that 10–20 % of medicines in&nbsp;developing country markets are sub-standard. Continuous&nbsp; monitoring of the quality of medicines&nbsp;requires both competent analysts and well-equipped drug quality control laboratories with&nbsp;&nbsp;international accreditation. The objective of the study was to evaluate the quality control parameters of&nbsp;the generic cetirizine&nbsp; dihydrochloride 10 mg tablets marketed in Abuja metropolis of Nigeria and to&nbsp;validate and apply a UV spectrophotometric method to&nbsp; the assay of the commercial tablet&nbsp;formulations.&nbsp; Method: Nine brands of cetirizine dihydrochloride tablets were randomly selected from retail&nbsp;pharmacy stores and quality control&nbsp; tests of weight variation, friability, hardness, disintegration, and&nbsp;dissolution parameters were conducted per United States&nbsp; Pharmacopoeia (USP) standards. Thickness&nbsp;and diameter were also evaluated by standard methods. AUVspectrophotometric method&nbsp; was adopted&nbsp;and validated according to ICH guidelines and applied for the drug assay of the tablet dosage units.&nbsp; Results: The&nbsp; thickness, diameter, hardness and disintegration tests for the drug samples ranged from&nbsp;2.81–3.76 mm, 3.88–8.11 mm&nbsp; 1.65–7.50 KgF and 0.44–4.90 min, respectively. All the samples met the&nbsp;compendial specififications for the weight variation test and also&nbsp; for the friability and dissolution tests&nbsp;which ranged 0.18–0.56 % and 90.15–109.18 % at 30 min, respectively. The studies for&nbsp; validation of&nbsp;the UV method demonstrated good linearity with a correlation coeffiffifficient of r2 = 0.9989 in the&nbsp;concentration range of&nbsp; 2.5–25 µg/mL of cetirizine dihydrochloride (CTZ) reference standard and the&nbsp;limit of detection (LOD) and limit of quantitation (LOQ)&nbsp; were 0.42 µg/mL and 1.29 µg/mL,&nbsp;respectively. The % RSD of the precision studies was less than the 2 % standard limit and the&nbsp; accuracy&nbsp;(recovery) ranged from 100.9‒103.4 %. The percentage contents of the generic brands were&nbsp;determined and ranged from&nbsp; 99.12–103.21 % and were within the offiffifficial specififications.&nbsp; Conclusion: The UV method was simple, sensitive and rapid and&nbsp; successfully applied to the assay of&nbsp;nine commercial brands of CTZ&nbsp; tablets. All the drugs met the compendial specififications on the quality&nbsp;parameters.&nbsp;&nbsp