Slow Dissolution Rate Research Articles

Design and in vivo evaluation of entecavir-3-palmitate microcrystals for subcutaneous sustained delivery

The objectives of this study were to formulate microcrystals of entecavir-3-palmiate (EV-P), a palmitic acid ester of entecavir (EV), and evaluate the influence of particle size on its pharmacokinetic behavior following subcutaneous (SC) injection. Systemic toxicity and local tolerability of the hepatitis B anti-viral suspension were further evaluated in normal rats. EV-P microcrystals possessing median diameters of 2.1, 6.3, and 12.7 µm were fabricated using anti-solvent crystallization technique with polysorbate 20 and polyethylene glycol 4000 as steric stabilizer. Dissolution rate of EV-P microcrystals was controlled by adjusting the particle size, under sink condition. Pharmacokinetic profiles of 2.1 µm-sized and 6.3 µm-sized EV-P microcrystals were quite comparable (1.44 mg/kg as EV), over 46 days in rats. The absorption rate and extent of EV after SC injection of 12.7 µm-sized microcrystals were significantly retarded, due to its slower dissolution rate in aqueous media. No single-dose systemic toxicity was observed after SC injection of high dose of EV-P microcrystal suspension (30–300 mg/kg as EV). The microcrystals were tolerable in the injected site, showing mild inflammatory responses at a dose of 30 mg/kg. Therefore, the novel microcrystal system with median particle size of below 6.3 µm is expected to be a unique long-acting system of the anti-viral agent, improving patient’s compliance with chronic disease.

Nanocrystalization of Pioglitazone by Precipitation Method.

Poor solubility in aqueous medium limits the use of many drugs. Different methods have been adopted to promote the rate of dissolution of slightly water soluble drugs. Crystallization improves solubility, and bioavailability by increasing the surface area of slightly water soluble drugs. Pioglitazone (PGZ), which is a class II Biopharmaceutical Classification System drug has a slight solubility in water and a slow rate of dissolution, which may have a negative effect on its metabolism leading to a therapeutic failure. The aim of this study was to improve the solubility of PGZ-HCl; an antidiabetic drug using precipitation method. Formulations were prepared with polyethylene glycol 6000 and isomalt using different speed of homogenizer and quantity of solvent by precipitation method. Drug-polymer interactions were examined using differential scanning calorimetry (DSC), and Powder X-Ray Diffraction (PXRD). Surface structure were shown by SEM photographs. The particle size was significantly decreased and solubility was enhanced with increase speed, ethanol solvent and increase stabilizer, however very high amount of stabilizer resulted in a decrease in solubility. This result however showed that solid dispersion technique is a potential method for increasing dissolution profile of a poorly aqueous soluble agent.

Nevirapine-polycaprolactone crystalline inclusion complex as a potential long-acting injectable solid form

Nevirapine (NVP) is recommended by WHO as the antiretroviral treatment to prevent HIV passing from mother to child. However, the once-daily oral administration results in poor patient compliance, and a long-acting injectable form of NVP is desirable. Using single-crystal X-ray diffraction and other characterization methods, we demonstrated NVP can form crystalline inclusion complex (IC) with the biodegradable hydrophobic poly(ε-caprolactone) (PCL), and investigated the potential of the NVP-PCL IC microparticles as a long-acting injectable solid form. Compared with pure NVP crystals and NVP/polylactide microparticles, the NVP-PCL IC crystals showed significantly decreased solubility and slower dissolution rate, making it more suitable to be developed to achieve sustained-release profiles. In addition, the NVP-PCL IC microparticles with an average diameter below 10 μm can be conveniently prepared by spray drying and are found to be easily injectable through a 25G needle. These results demonstrated the possibility of using drug-polymer IC microparticles as long-acting injectable forms, providing a new approach to design sustained-release drug products.

Sustained-release amorphous solid dispersions

The use of amorphous solid dispersions (ASD) to overcome poor drug solubility has gained interest in the pharmaceutical industry over the past decade. ASDs are challenging to formulate because they are thermodynamically unstable, and the dispersed drugs tend to recrystallize. Until now, most research on ASDs has focused on immediate-release formulations, supersaturation, and stability; only a few studies have recently reported on the manufacturing of sustained-release ASDs. Sustained-release ASDs can minimize the frequency of administration and prevent high concentrations that can lead to toxicity. Sustained-release ASDs can also decrease the reprecipitation rate in the medium, which can lead to increased bioavailability. However, sustained-release ASDs also pose some significant challenges, such as intramatrix recrystallization, inhibition of drug release as a result of drug-polymer gelling, and low supersaturation due to a slow dissolution rate. This review details the challenges and the formulation approaches that have been investigated to manufacture sustained-release ASDs. In particular, the advantages and drawbacks of hydrophilic polymers, hydrophobic polymers, and lipid-based systems are discussed.

Production of Curcumin-Loaded Silk Fibroin Nanoparticles for Cancer Therapy.

Curcumin, extracted from the rhizome of Curcuma longa, has been widely used in medicine for centuries due to its anti-inflammatory, anti-cancer, anti-oxidant and anti-microbial effects. However, its bioavailability during treatments is poor because of its low solubility in water, slow dissolution rate and rapid intestinal metabolism. For these reasons, improving the therapeutic efficiency of curcumin using nanocarriers (e.g., biopolymer nanoparticles) has been a research focus, to foster delivery of the curcumin inside cells due to their small size and large surface area. Silk fibroin from the Bombyx mori silkworm is a biopolymer characterized by its biocompatibility, biodegradability, amphiphilic chemistry, and excellent mechanical properties in various material formats. These features make silk fibroin nanoparticles useful vehicles for delivering therapeutic drugs, such as curcumin. Curcumin-loaded silk fibroin nanoparticles were synthesized using two procedures (physical adsorption and coprecipitation) more scalable than methods previously described using ionic liquids. The results showed that nanoparticle formulations were 155 to 170 nm in diameter with a zeta potential of approximately −45 mV. The curcumin-loaded silk fibroin nanoparticles obtained by both processing methods were cytotoxic to carcinogenic cells, while not decreasing viability of healthy cells. In the case of tumor cells, curcumin-loaded silk fibroin nanoparticles presented higher efficacy in cytotoxicity against neuroblastoma cells than hepatocarcinoma cells. In conclusion, curcumin-loaded silk fibroin nanoparticles constitute a biodegradable and biocompatible delivery system with the potential to treat tumors by local, long-term sustained drug delivery.

Improving Properties of Albendazole Desmotropes by Supramolecular Systems with Maltodextrin and Glutamic Acid.

Albendazole, an effective broad-spectrum anthelmintic agent, showed unpredictable therapeutic response caused by poor water solubility and slow dissolution rate. Then, novel binary and multicomponent supramolecular systems of two different solid forms of albendazole (I and II) with maltodextrin alone or with glutamic acid were studied as an alternative to improve the oral bioavailability of albendazole. The interactions and effects on the properties of albendazole were studied in solution and solid state. The solid systems were characterized using Raman and Fourier transform-infrared spectroscopy, thermal analysis, powder X-ray diffraction, and scanning electron microscopy. The solubility measurements, performed in aqueous and simulated gastric fluid, showed that albendazole (form II) was the most soluble form, while its supramolecular systems showed the highest solubility in simulated gastric fluid. On the other hand, the dissolution profiles of binary and multicomponent systems in simulated gastric fluid displayed pronounced increments of the dissolved drug and a faster dissolution rate compared to those of free albendazole forms. Thus, these supramolecular structures constitute an interesting alternative to improve the physicochemical properties of albendazole, with potential application for the preparation of pharmaceutical oral formulations.

Effect of calcium sulfate type and dosage on properties of calcium aluminate cement-based self-leveling mortar

In this paper, the influence of calcium sulfate type (α-hemihydrate, anhydrite and dihydrate) and amount (0%, 2%, 4% and 6%) on the performances of calcium aluminate cement-based self-leveling mortar (SLM) were investigated. The influence of calcium sulfate on fluidity and mechanical properties was investigated. Moreover, the impact of calcium sulfate on the hydration products, morphology and heat evolution of pastes hydrated up to 3 days were determined by using X-ray diffraction (XRD), Scanning electron microscope (SEM) and isothermal heat-conduction calorimeter. Test results revealed that SLM prepared with anhydrite exhibited the highest initial flow value (∼160 mm) and setting time and the lowest fluidity loss due to the slow dissolution rate of anhydrite compared to other calcium sulfate. In comparison to control formulation, the enhancement in flexural and compressive strength for T4 (dihydrate) was the highest and was found to be 485.71% and 437.5% respectively and hence it can be concluded that dihydrate is favorable to the early strength of SLM as compared to other SLM formulations containing α-hemihydrate and anhydrite respectively. The shrinkage compensating effect became more obvious with the increase in the amount of C$ in SLM samples. Due to the fast dissolution rate, mortar containing α-hemihydrate exhibited more expansion as compared to other calcium sulfate. SLM prepared with dihydrate showed the highest early strength due to the lowest influence on C3S hydration while the influence of α-hemihydrate was more obvious. Hence, the hydration of PC in the ternary system can be limited by increasing calcium sulfate due to the formation of ettringite. Finally, the type of calcium sulfate has an important influence on the quantity and morphology of ettringite.

FORMULATION AND EVALUATION OF NANOSUSPENSION OF ROSUVASTATIN CALCIUM

Poor water solubility and slow dissolution rate are issues for majority of upcoming and existing biologically active compounds. The aim of present work was to increase the dissolution rate of Rosuvastatin Calcium, a poorly water soluble drug and hence improve its oral bioavailability by Nanosuspension technology. Nanosuspension is new carrier free colloidal drug delivery system with nano sized particles below 1000 nm, and considered as a great drug delivery technique to enhance the drug dissolution and solubility. In the present work Nanosuspension is made by nanoprecipitation technique in the presence of sodium lauryl sulfate as surfactant and PVPK-30 as stabilizer. Prepared Nanosuspension was evaluated for its particle size study, in vitro dissolution study and characterized by Screening Electron microscopy (SEM).
 Different concentrations of sodium lauryl sulphate (SLS) and PVPK-30 were evaluated. All formulations were in the nano size and showed marked improvement in dissolution and solubility compared to pure drug of micron size. Finally it was concluded that formulating poorly soluble drugs in the form of Nanosuspension would be a promising approach in delivery of poor water soluble drugs by oral route in a simple and effective way.

Controlled-release of antacids from biopolymer microgels under simulated gastric conditions: Impact of bead dimensions, pore size, and alginate/pectin ratio

The highly acidic nature of the gastric fluids inside the human stomach can cause have health problems in certain individuals e.g., acid reflux and ulcers. Antacid-loaded biopolymer microgels can be used to control the acidity of the gastric fluids, which may be useful for developing functional foods to treat these problems. In this study, the impact of biopolymer microgel dimensions and composition on the dissolution rate of encapsulated antacid was determined under simulated gastric conditions. The microgels were formed by injecting antacid (magnesium hydroxide) and biopolymers (alginate or alginate/pectin) into a calcium chloride solution to promote cross-linking. Microgels of varying dimensions were formed using either a hand-held syringe or a vibrating nozzle encapsulation device with different nozzle sizes. The rate of antacid dissolution was measured using an automatic titration device (pH stat) that added HCl solution into the simulated gastric fluids to maintain a constant pH of 2.5. The antacid dissolution rate decreased with increasing microgel diameter (300 to 1660 μm) and decreasing pore size (0.8 to 2.0% alginate). The slowest dissolution rate was observed in microgels containing 80% alginate and 20% pectin, which may have been due to the impact of biopolymer composition on bead dimensions and pore size. The results of this study may be useful for the design of biopolymer microgels that can control the release of antacids in the stomach, thereby leading to better control over the pH of the gastric fluids.

Chemical and textural equilibration of garnet during amphibolite facies metamorphism: The influence of coupled dissolution–reprecipitation

AbstractMetamorphic equilibration requires chemical communication between minerals and may be inhibited through sluggish volume diffusion and or slow rates of dissolution in a fluid phase. Relatively slow diffusion and the perceived robust nature of chemical growth zoning may preclude garnet porphyroblasts from readily participating in low‐temperature amphibolite facies metamorphic reactions. Garnet is widely assumed to be a reactant in staurolite‐isograd reactions, and the evidence for this has been assessed in the Late Proterozoic Dalradian pelitic schists of the Scottish Highlands. The 3D imaging of garnet porphyroblasts in staurolite‐bearing schists reveals a good crystal shape and little evidence of marginal dissolution; however, there is also lack of evidence for the involvement of either chlorite or chloritoid in the reaction. Staurolite forms directly adjacent to the garnet, and its nucleation is strongly associated with deformation of the muscovite‐rich fabrics around the porphyroblasts. “Cloudy” fluid inclusion‐rich garnet forms in both marginal and internal parts of the garnet porphyroblast and is linked both to the production of staurolite and to the introduction of abundant quartz inclusions within the garnet. Such cloudy garnet typically has a Mg‐rich, Mn‐poor composition and is interpreted to have formed during a coupled dissolution–reprecipitation process, triggered by a local influx of fluid. All garnet in the muscovite‐bearing schists present in this area is potentially reactive, irrespective of the garnet composition, but very few of the schists contain staurolite. The staurolite‐producing reaction appears to be substantially overstepped during the relatively high‐pressure Barrovian regional metamorphism reflecting the limited permeability of the schists in peak metamorphic conditions. Fluid influx and hence reaction progress appear to be strongly controlled by subtle differences in deformation history. The remaining garnet fails to achieve chemical equilibrium during the reaction creating distinctive patchy compositional zoning. Such zoning in metamorphic garnet created during coupled dissolution–reprecipitation reactions may be difficult to recognize in higher grade pelites due to subsequent diffusive re‐equilibration. Fundamental assumptions about metamorphic processes are questioned by the lack of chemical equilibrium during this reaction and the restricted permeability of the regional metamorphic pelitic schists. In addition, the partial loss of prograde chemical and textural information from the garnet porphyroblasts cautions against their routine use as a reliable monitor of metamorphic history. However, the partial re‐equilibration of the porphyroblasts during coupled dissolution–reprecipitation opens possibilities of mapping reaction progress in garnet as a means of assessing fluid access during peak metamorphic conditions.

DISSOLUTION ENHANCEMENT OF DIACEREIN USING WATER SOLUBLE CARRIER BY SOLID DISPERSION TECHNOLOGY

Diacerein is generally used in the treatment of Osteoarthritis , this drug comes under the class anthraquinone. The drug is practically insoluble in water and exhibits exceptionally slow and intrinsic dissolution rate with poor bioavailability. In the present study, diacerein and I²-cyclodextrin (I²-CD) solid dispersions were prepared with a view to study the effect and influence of I²-CD on the solubility and dissolution rate of this poorly aqueous soluble drug. Phase solubility profile revealed that the solubility of diacerein was significantly increased in the presence of I²-CD and indicating the possible 1:1 stoichiometric inclusion complex with a stability constant of 339.66 M-1. Effect of variable such as drug: Carrier ratios were studied. Physical characterization of the solid dispersion was characterized by Fourier transform infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC) and X-ray diffraction studies (XRD). These studies revealed that a distinct loss of drug crystallinity in the solid dispersion is ostensibly accounting for enhancement of dissolution rate in distilled water containing 0.1% Tween 80. The scanning electron microscopy (SEM) study revealed that all the binary systems appeared as agglomerates and exhibiting the presence of a homogenous solid phase which could also be responsible for the enhanced dissolution rate in comparison with the pure drug. The drug release from the prepared solid dispersion exhibited a first order kinetics. Solid dispersion of diacerein showed a 7.66 times fold increase in dissolution rate over the pure drug.

REE partition among zircon, orthopyroxene, amphibole and garnet in a high-grade metabasic system

AbstractA mafic amphibole-bearing granulite with porphyroblastic garnet was investigated to evaluate: (1) the rare earth element (REE) partition among garnet, zircon, orthopyroxene and amphibole during the metamorphic evolution; (2) the significance of the REE distribution along lobes and bights of reabsorbed garnet rim; and (3) REE distribution coefficient values (DREE) suggestive of chemical equilibrium, assuming garnet as a reference. The results have been compared with those deriving from an intermediate granulite containing porphyroblastic garnet, without amphibole. Porphyroblastic garnet from both samples is rimmed by a continuous corona formed during post-peak decompression characterized by REE-enriched lobes and REE-poor bights. The amphiboles from corona have various REE abundances, reflecting a different dissolution rate of original garnet rim. The initial slow rate of garnet dissolution caused high REE concentration in the new garnet rim due to intra-crystalline diffusion, leading to the formation of REE-poorer amphiboles in corona. Subsequently, under an increasing geothermal gradient and fluid-present conditions, the faster dissolution of garnet determined the formation of bights and the transfer of REEs towards the corona. The timing of garnet growth and its dissolution were checked by U–Pb zircon ages. The zircons dated from 339 Ma to 303 Ma in two rock types combined with the garnet domains (core, outer core, rim) show similar distribution of patterns relative to heavy rare earth elements for zircon and garnet (DHREEzrn/grt), suggesting chemical equilibrium. Zircons dated at c. 300 Ma do not appear in equilibrium with REE-rich garnet lobes, and younger zircons (278 Ma) show a new equilibrium with REE-poor garnet bights. On this basis, the DHREEamph/grt values obtained in specific textural sites might be interpreted as suggestive of equilibrium under granulite conditions.

Integrating In Vitro, Modeling, and In Vivo Approaches to Investigate Warfarin Bioequivalence.

We demonstrate the use of modeling and simulation to investigate bioequivalence (BE) concerns raised about generic warfarin products. To test the hypothesis that the loss of isopropyl alcohol and slow dissolution in acidic pH has significant impact on the pharmacokinetics of warfarin sodium tablets, we conducted physiologically based pharmacokinetic absorption modeling and simulation using formulation factors or in vitro dissolution profiles as input parameters. Sensitivity analyses indicated that warfarin pharmacokinetics was not sensitive to solubility, particle size, density, or dissolution rate in pH 4.5, but was affected by dissolution rate in pH 6.8 and potency. Virtual BE studies suggested that stressed warfarin sodium tablets with slow dissolution rate in pH 4.5 but having similar dissolution rate in pH 6.8 would be bioequivalent to the unstressed warfarin sodium tablets. A four‐way, crossover, single‐dose BE study in healthy subjects was conducted to test the same hypothesis and confirmed the simulation conclusion.

Solution or suspension – Does it matter for lipid based systems? In vivo studies of chase dosing lipid vehicles with aqueous suspensions of a poorly soluble drug

In this study, the potential of co-administering an aqueous suspension with a placebo lipid vehicle, i.e. chase dosing, was investigated in rats relative to the aqueous suspension alone or a solution of the drug in the lipid vehicle. The lipid investigated in the present study was Labrafil M2125CS and three evaluated poorly soluble model compounds, danazol, cinnarizine and halofantrine. For cinnarizine and danazol the oral bioavailability in rats after chase dosing or dosing the compound dissolved in Labrafil M21515CS was similar and significantly higher than for the aqueous suspension. For halofantrine the chase dosed group had a tendency towards a low bioavailability relative to the Labrafil M2125CS solution, but still a significant higher bioavailability relative to the aqueous suspension. This could be due to factors such as a slower dissolution rate in the intestinal phase of halofantrine or a lower solubility in the colloidal structures formed during digestion, but other mechanisms may also be involved. The study thereby supported the potential of chase dosing as a potential dosing regimen in situations where it is beneficial to have a drug in the solid state, e.g. due to chemical stability issues in the lipid vehicle.

The Effect of some Variables on the Formulation of Captopril as Tablets Shaymaa Nazar Al – Sammarrai

Captopril is an angiotensin converting enzyme inhibitor (ACEI) used to treat hypertension,congestive heart failure, and myocardial infraction.The only dosage form available for captopril is the plain tablet in strength of 12.5,25,50 and 100mgtablet.This investigation is concerned with factors affecting the formulation of captopril as a plaintablet dosage form of 50mg. Many trials were made to prepare satisfactory tablets for the drug byusing wet – granulation methods with various additives. It was found that poly vinyl pyrrolidone(P.V.P.) as binder gave the most satisfactory tablets. At the same time a shorter disintegrantion timeand slower dissolution rate were obtained with the addition of starch intragranular.While the distintegration time and dissolution rate were faster for explotab when it was usedintragranular in comparison with starch.A comparative study on the physical properties of the prepared tablets with Capoten®(Squibb), Miniten® (APM), and Capocard® (DAD) tablets, showed that the release of drug from theselected formula was similar to that obtained from Miniten® at 0.1N HCl and 37C.The stability of the prepared tablet was also studied at 50C, 60C, and 70C for 4 months andthe calculated shelf – life was about 3.5years at 25C.

Poly(hydroxybutyrate‐co‐hydroxyvalerate) and bovine serum albumin blend prepared by electrospinning

ABSTRACTElectrospinning is a method for the preparation of nanosized polymer fibers. Here, electrospinning is used to prepare a blend of a polyester, poly(hydroxybutyrate‐co‐hydroxyvalerate) (PHBV), and a globular protein, bovine serum albumin (BSA). The electrospun blend film is compared with a solution‐cast blend film and with single‐component electrospun films made of PHBV and BSA. In the electrospun blend films, BSA manifests itself as flat ribbons and a fine network formed from fibers less than 50 nm in diameter. The dissolution rate of BSA from the electrospun blended film is lower than from the solution‐cast one. The films are characterized using scanning electron microscopy, differential scanning calorimetry, and contact‐angle measurements. The obtained PHBV+BSA blend films have several emergent properties: a slow BSA dissolution rate, a fine BSA network, and unusual thermal behavior. Thus, the PHBV+BSA blend films introduce a new class of polymer–protein blends. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45090.

Preparation and optimization of tablets containing a self-nano-emulsifying drug delivery system loaded with rosuvastatin

Background: Rosuvastatin (ROS) calcium is the latest synthetic drug in the statin group that has an anti-hyperlipidemic activity. It is available as tablets, and its poor aqueous solubility, slow dissolution rate and low-absorption extent result in less than 20% bioavailability and about 80% being excreted unchanged in the feces without absorption.Objective: To utilize nanotechnology to reformulate ROS as a self-nano-emulsifying drug delivery system (SNEDDS), and utilizing design optimization to fabricate the SNEDDS as a tablet.Methods: The solubility of ROS in different oils, surfactants and co-surfactants was tested. Pseudo-ternary phase diagrams were developed and various SNEDDS formulations were prepared and evaluated regarding globule size, self-emulsification, viscosity and transmittance. The optimized system was examined using transmission electron microscopy. The self-nano-emulsifying tablets were prepared using two types of nano-silica and different percentages of Avicel as a binder and Ac-Di-Sol as a disintegrant. The prepared tablets were evaluated for their physicochemical properties. Bioavailability in human volunteers was assessed.Results: A SNEDDS system was successfully developed with a droplet size range of 15 nm and a composition of 10% Labrafac, 80% Cremophore RH40 and 10% Propylene glycol. The optimized tablet formula contained: hydrophilic nano-silica, 3% Ac-Di-Sol and 30% Avicel. The pharmacokinetic study revealed that the bioavailability was enhanced by more than 2.4-fold compared with the commercially available tablet.Conclusions: Tablets containing SNEDDS loaded with ROS represent a promising novel formula that has higher gastrointestinal absorption and enhanced systemic bioavailability.

Preparation and characterization of quercetin/dietary fiber nanoformulations

Quercetin is well known for its beneficial health effects on the human body. However, the slow dissolution rate leading to poor bioavailability constitutes a barrier to being further developed for nutritional products. In this work, quercetin was co-precipitated with dietary fibers into a fast-dissolving nanoformulation via antisolvent precipitation, followed by spray drying. With the help of cellulose fiber, resistant starch or resistant maltodextrin, a high dissolution rate and good storage stability was achieved for quercetin nanoformulations. In addition, nanoformulations exhibited higher level of antioxidant activities in contrast to raw quercetin. The developed quercetin/dietary fiber nanoformulations could be used as supplements or functional ingredients for food development.

Physicochemical Properties and In Vitro Dissolution of Spiramycin Microparticles Using the Homogenate-Antisolvent Precipitation Process

Due to its low bioavailability and slow dissolution rate, the micronized spiramycin powder was thus prepared by the homogenate-antisolvent precipitation (HAP) process. The optimum micronization conditions of the HAP process were found to be as follows: precipitation temperature of 4.6 °C, precipitation time of 10 min, spiramycin concentration of 20 mg/mL, dripping speed of the added solvent into the antisolvent of 44 mL/h, antisolvent (water) to solvent (dimethyl sulfide (DMSO)) volume ratio of 7:1, and shear rate of 5000 rpm. With this HAP process, the mean particle size was 228.36 ± 3.99 nm. The micronized spiramycin was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, high-performance liquid chromatography, and gas chromatograph analyses. In comparison with the raw drug, the chemical structure of micronized spiramycin was not changed. The dissolution rate experiments showed that the dissolution rate of the spiramycin was significantly increased after micronization.

The Mayak Worker Dosimetry System (Mwds-2013): Plutonium Dissolution in The Lungs-An Analysis of Mayak Workers.

Lung doses resulting from inhalation of plutonium aerosols are highly dependent on the assumed rate of particle clearance, which occurs by two competing processes: (1) particle transport clearance to the alimentary tract and to the thoracic lymph nodes and (2) clearance to systemic tissues, which occurs by dissolution of particles in lung fluid followed by uptake to blood, which is a process collectively known as absorption. Unbiased and accurate estimates of the values of lung absorption parameters are required to obtain reliable estimates of lung dose, particularly those inferred from urine bioassay. Parameter values governing the rate of absorption are best estimated from data, such as autopsy measurements of plutonium in the lungs and systemic tissues, which directly relate to the exposed workers of interest. However, because the mathematical models that determine clearance from the lungs and systemic tissues are complex and consist of many parameters, estimates of model parameter values are subject to significant uncertainties. With this in mind, this paper uses a Bayesian approach to estimate one of the most important dissolution parameters: the slow rate of dissolution. This is estimated for both plutonium nitrate and plutonium oxide bearing aerosols in the lungs of former workers of the Mayak Production Association. A value of 2.6 × 10-4 d-1 is estimated for plutonium nitrates, and 4.7× 10-5 d-1 for plutonium oxides.