Sublimation of Drugs from the Site of Application of Topical Products.

The objective of the project was to investigate the plausibility of active pharmaceutical ingredients (APIs) to undergo sublimation from topical application following evaporation of solvent. Topical formulations with different APIs were subjected to a sublimation screening test. The APIs in the selected topical products were found to undergo sublimation to a different extent. The salicylic acid topical product was found to undergo a significant loss due to sublimation. The extent of sublimation of salicylic acid was significantly greater at skin temperature compared to room temperature. When the APIs were subjected to the sublimation screening test in their neat form at 32 ± 1 °C, the natural log of the rate of sublimation decreased linearly with the standard enthalpy of sublimation of compound (R2 = 0.89). The formulation composition was found to have a significant impact on the extent of sublimation of the representative API, salicylic acid. The sublimation of APIs from the topical product was found to affect the mass balance studies in the case of the salicylic acid ointment. Furthermore, the results of the human studies agreed with the in vitro experimental results demonstrating the plausibility of loss of API due to sublimation from the site of application.

ESEM Methodology for the Study of Ice Samples at Environmentally Relevant Subzero Temperatures: "Subzero ESEM".

Frozen aqueous solutions are an important subject of study in numerous scientific branches including the pharmaceutical and food industry, atmospheric chemistry, biology, and medicine. Here, we present an advanced environmental scanning electron microscope methodology for research of ice samples at environmentally relevant subzero temperatures, thus under conditions in which it is extremely challenging to maintain the thermodynamic equilibrium of the specimen. The methodology opens possibilities to observe intact ice samples at close to natural conditions. Based on the results of ANSYS software simulations of the surface temperature of a frozen sample, and knowledge of the partial pressure of water vapor in the gas mixture near the sample, we monitored static ice samples over several minutes. We also discuss possible artifacts that can arise from unwanted surface ice formation on, or ice sublimation from, the sample, as a consequence of shifting conditions away from thermodynamic equilibrium in the specimen chamber. To demonstrate the applicability of the methodology, we characterized how the true morphology of ice spheres containing salt changed upon aging and the morphology of ice spheres containing bovine serum albumin. After combining static observations with the dynamic process of ice sublimation from the sample, we can attain images with nanometer resolution.

Cryopreservation without dry ice-induced acidification during sample transport.

Dry ice (solid CO2) remains highly useful when temperature-sensitive biological samples need to be cryogenically transported. CO2 released during the sublimation of dry ice can diffuse through gas permeable receptacle material or any defective seals resulting in potential sample acidification and compromised integrity. In addition, the quality of cryopreservation can be undermined once the dry ice is exhausted. The dry ice carrier design described here has been demonstrated to prevent sublimated CO2 from reaching the samples while maintaining storage temperature below -60 °C for 19 h. It is also equipped with microcontroller-based temperature monitoring for traceability and CO2 gas monitoring for safety.

Close-Space Sublimation-Deposited Ultra-Thin CdSeTe/CdTe Solar Cells for Enhanced Short-Circuit Current Density and Photoluminescence.

Developments in photovoltaic device architectures are necessary to make solar energy a cost-effective and reliable source of renewable energy amidst growing global energy demands and climate change. Thin film CdTe technology has demonstrated cost-competitiveness and increasing efficiencies due partially to rapid fabrication times, minimal material usage, and introduction of a CdSeTe alloy into a ~3 µm absorber layer. This work presents the close-space sublimation fabrication of thin, 1.5 µm CdSeTe/CdTe bilayer devices using an automated in-line vacuum deposition system. The thin bilayer structure and fabrication technique minimize deposition time, increase device efficiency, and facilitate future thin absorber-based device architecture development. Three fabrication parameters appear to be the most impactful for optimizing thin CdSeTe/CdTe absorber devices: substrate preheat temperature, CdSeTe:CdTe thickness ratio, and CdCl2 passivation. For proper sublimation of the CdSeTe, the substrate temperature prior to deposition must be ~540 °C (higher than that for CdTe) as controlled by dwell time in a preheat source. Variation in the CdSeTe:CdTe thickness ratio reveals a strong dependence of device performance on this ratio. The optimal absorber thicknesses are 0.5 µm CdSeTe/1.0 µm CdTe, and non-optimized thickness ratios reduce efficiency through back-barrier effects. Thin absorbers are sensitive to CdCl2 passivation variation; a much less aggressive CdCl2 treatment (compared to thicker absorbers) regarding both temperature and time yields optimal device performance. With optimized fabrication conditions, CdSeTe/CdTe increases device short-circuit current density and photoluminescence intensity compared to single-absorber CdTe. Additionally, an in-line close-space sublimation vacuum deposition system offers material and time reduction, scalability, and attainability of future ultra-thin absorber architectures.

Waste-activated sludge disruption by dry ice: bench scale study and evaluation of heat phase transformations.

The freezing process consists of dissipating heat from the product until the final temperature is lower than the temperature of crystallisation of that product. Freezing can be used for numerous applications, including for disruption of waste-activated sludge (WAS). The aim of this study was to calculate the estimated amount of heat conveyed between the solidified carbon dioxide and the WAS, in the following ratios: 0.25:1; 0.5:1; 0.75:1 and 1:1. In heat of phase transformations, dry ice sublimation, water solidification, the amount of heat transferred by other substances and heat transferred from the sludge (dry sludge) were taken into account during the process of WAS freezing. Heat changes on the surface of WAS were registered using a thermovision camera. The effectiveness of WAS disintegration was confirmed by several biochemical parameters such as soluble chemical oxygen demand (increase over 14 times), degree of disintegration (48%), proteins (increase over 5 times), carbohydrates (increase almost 7 times), RNA (increase by 2.23 mg L-1), ammonia nitrogen (increase over 23 times), phosphates (increase almost 27 times) and turbidity (increased over 7 times). It was found that dry ice pretreatment of WAS can be an intriguing alternative for the conventional methods used.

The self-disproportionation of enantiomers (SDE) of amino acids and their derivatives.

This review covers the phenomenon of the self-disproportionation of enantiomers (SDE) of amino acids and their derivatives in all its guises from phase transformations (recrystallization, sublimation, and distillation), to the application of force fields, through to chromatography including HPLC, MPLC, gravity-driven column chromatography, and SEC. The relevance of the SDE phenomenon to amino acid research and to marketed pharmaceuticals is clear given the potential for alteration of the enantiomeric excess of a portion of a scalemic sample. In addition, the possible contribution of the SDE phenomenon to the genesis of prebiotic homochirality is considered.

Matrix Sublimation Device for MALDI Mass Spectrometry Imaging.

Sublimation is a widely used method for matrix deposition in imaging mass spectrometry experiments. Still, most of the time, standard glass sublimators are used for this purpose, which do not enable optimal matrix deposition reproducibility, compromising inter-experiment comparison of the results. Here, we present an in-house designed stainless steel sublimator in which the parameters that have the strongest influence over matrix deposition reproducibility can be easily monitored. Using sections of human colon biopsies, we demonstrate the capabilities of this new prototype.

Development and evaluation of novel antihypertensive orodispersible tablets.

Objective of present study was to enhance patient compliance in pediatrics and geriatrics patients of Hypertension. To achieve this target, innovative orodispersible tablets of atenolol and atorvastatin was developed to produce instant action by rapidly disintegrating into oral cavity. Three different techniques like direct compression, effervescent and sublimation methods were used to prepare these tablets (Five batches of tablets by each method) by using two superdisintegrants like Sodium starch glycolate and pregelatinized starch alone and in combination. Pre-formulation studies including rheological analysis (Bulk density, tapped density, Angle of repose, Carr's compressibility index, Hausner's ratio), compatibility studies such as Fourier transform infrared spectrophotometry (FTIR) and Differential scanning colorimetry (DSC), Post-compression and stability studies were also performed. Finally, results were statistically evaluated by the applying one way ANOVA test and mean. It was concluded that the formulation F8 containing Sodium starch glycolate 2% and pregelatinized starch 6% found best regarding disintegration time, wetting volume, wetting time, release studies etc. The order in which drug release was quicker is Pregelatinized starch plus Sodium starch glycolate > Pregelatinized starch > Sodium starch glycolate (primojel). It was concluded that sublimation method was the best among three methods used for orodispersible tablets formulations.

Tissue sublimation follow transarterial embolization of a follicular nodular hyperplasia of the liver-report of a case.

BACKGROUND: Follicular nodular hyperplasia (FNH) is a common benign liver tumor for which conservative management is indicated. Surgical or interventional management is indicated in symptomatic cases. Transarterial embolization (TAE) has been extensively used to manage unresectable liver tumors. Sublimation describes a change of physical state from solid to gas. Hepatic tissue sublimation following TAE has so far not been reported in medical literature. CASE PRESENTATION: A 30 year - old male patient presenting with pain to the upper abdomen due to a large FNH was managed with TAE. Routine radiographic control on post-intervention day one was within normal limits. Imaging due to right upper quadrant pain with fever and elevated inflammatory markers and liver enzymes on day two after TAE revealed a marked reduction of the FNH accompanied by the presence of a large volume of gas collection without signs of abscess formation. This change of state from solid to gas without sign of abscess formation within 2 days after TAE was described as hepatic tissue sublimation. The patient was managed conservatively and discharge 12 days after TAE. CONCLUSION: Tissue sublimation has hardly been reported in medical literature. This to the best of our knowledge is the first documented case of hepatic tissue sublimation following TAE.

Laser Desorption Ionization Mass Spectrometry Imaging of Drosophila Brain Using Matrix Sublimation versus Modification with Nanoparticles.

Laser desorption ionization mass spectrometry (LDI-MS) is used to image brain lipids in the fruit fly, Drosophila, a common invertebrate model organism in biological and neurological studies. Three different sample preparation methods, including sublimation with two common organic matrixes for matrix-assisted laser desorption ionization (MALDI) and surface-assisted laser desorption ionization (SALDI) using gold nanoparticles, are examined for sample profiling and imaging the fly brain. Recrystallization with trifluoroacetic acid following matrix deposition in MALDI is shown to increase the incorporation of biomolecules with one matrix, resulting in more efficient ionization, but not for the other matrix. The key finding here is that the mass fragments observed for the fly brain slices with different surface modifications are significantly different. Thus, these approaches can be combined to provide complementary analysis of chemical composition, particularly for the small metabolites, diacylglycerides, phosphatidylcholines, and triacylglycerides, in the fly brain. Furthermore, imaging appears to be beneficial using modification with gold nanoparticles in place of matrix in this application showing its potential for cellular and subcellular imaging. The imaging protocol developed here with both MALDI and SALDI provides the best and most diverse lipid chemical images of the fly brain to date with LDI.

A source for microhydrated biomolecules.

We describe the construction of an apparatus for the production of a molecular jet of microhydrated biomolecules. Our design uses a water reservoir producing water vapour, which then passes through a separate reservoir containing a vapour of a sublimated biomolecule. The mixture coexpands into a molecular beam apparatus through a conical nozzle. Mass spectra showing water-adenin and water-uracil complexes are shown as typical examples. Suitable expansion conditions are reached without the use of an inert carrier gas.

Sublimation kinetics and diffusion coefficients of TNT, PETN, and RDX in air by thermogravimetry.

The diffusion coefficients of explosives are crucial in their trace detection and lifetime estimation. We report on the experimental values of diffusion coefficients of three of the most important explosives in both military and industry: TNT, PETN, and RDX. Thermogravimetric analysis (TGA) was used to determine the sublimation rates of TNT, PETN, and RDX powders in the form of cylindrical billets. The TGA was calibrated using ferrocene as a standard material of well-characterized sublimation rates and vapor pressures to determine the vapor pressures of TNT, PETN, and RDX. The determined sublimation rates and vapor pressures were used to indirectly determine the diffusion coefficients of TNT, PETN, and RDX for the first time. A linear log-log dependence of the diffusion coefficients on temperature is observed for the three materials. The diffusion coefficients of TNT, PETN, and RDX at 273 K were determined to be 5.76×10(-6)m(2)/sec, 4.94×10(-6)m(2)/s, and 5.89×10(-6)m(2)/s, respectively. Values are in excellent agreement with the theoretical values in literature.

Crystal structure analysis and sublimation thermodynamics of bicyclo derivatives of a neuroprotector family.

The crystal structures of three new structurally related drug-like bicyclo derivatives are correlated with measured thermodynamic quantities for their sublimation and melting processes. The sublimation thermodynamics are determined using the temperature dependencies of the vapour pressure, and the melting processes are examined using differential scanning calorimetry. The three compounds contain a common N-(3-thia-1-azabicyclo[3.3.1]non-2-ylidene)aniline core, with either a CH3, F or CF3 substituent at the 4-position of the aniline ring. Lattice energy calculations are made using both the PIXEL and Coulomb-London-Pauli (CLP) models, and the conformational flexibility of the molecules is examined using gas-phase density functional theory (DFT) calculations. The experimentally measured crystal lattice energies (ΔH(0)sub) decrease in the order: CH3 > F > CF3. The calculated lattice energies using the PIXEL approach are in good agreement with the experimental values, and the partitioned intermolecular interaction energies suggest that dispersion contributions dominate the crystal structures of all three compounds. The sublimation energies and melting points are inversely correlated for the three molecules, with the melting points increasing in the order CF3 < F < CH3.

Sustained local delivery of structurally diverse HIV-1 microbicides released from sublimation enthalpy controlled matrices.

PURPOSE: Use of coital-dependent products to prevent HIV-1 transmission has resulted in mixed success. We hypothesize that incorporation of antiviral drug candidates into a novel controlled delivery system will prolong their activity, making their use coital independent, thus increasing their chance of prophylactic success. METHODS: Tenofovir, emtricitabine, and C5A peptide HIV microbicides were mechanically incorporated into matrices comprising a series of subliming solids. Matrix sublimation rates and drug release rates were measured in three in vitro and one in vivo environments intended to model human vaginal interior. Antiviral activity studies evaluating matrix incorporated microbicides were performed using in vitro cell cultures and human ectocervical explants. RESULTS: Drug release rates were identical to matrix sublimation rates, and were zero order. Differences in matrix material sublimation enthalpies determined drug release and matrix erosion rates in a thermodynamically definable manner, in vitro and in vivo. Durations of release ranging from several days to several months were readily achieved. Prolonged duration of anti HIV-1 activity was shown for matrix incorporated microbicides, using ectocervical explant and cell culture models of HIV-1 infection. CONCLUSION: Subliming solid matrices show promise as a delivery system providing multi month intravaginal release of a wide range of HIV-1 microbicides.

Formation of ß-cyclodextrin inclusion enhances the stability and aqueous solubility of natural borneol.

UNLABELLED: The aims of this study were to optimize the preparation conditions of natural borneol/ß-cyclodextrin (NB/ß-CD) inclusion complex by ultrasound method, and to investigate its improvement of stability and solubility. The complex was characterized by different various spectroscopic techniques including Fourier transform infrared spectroscopy, X-ray diffractometry, and differential scanning calorimetry. The results demonstrate that NB could be efficiently loaded into ß-CD to form an inclusion complex by ultrasound method at a molar ratio of 1: 1and mass ratio of 1: 6. The complex exhibited different physicochemical characteristics from that of free NB. Typically, formation of ß-CD inclusion significantly enhanced the stability and aqueous solubility of NB. PRACTICAL APPLICATION: Natural borneol (NB) has the potential to be widely used in the fields of medical and functional food, due to its specificity. However, the disadvantages of unstability in the preparation and storage process due to its easy sublimation and the low water solubility limit its application. This research provides an effective way to improve the solubility and stability of NB by preparing NB/ß-CD inclusion complex. Furthermore, theoretical basis is also provided for the application development of NB.

Properties of gastroretentive sustained release tablets prepared by combination of melt/sublimation actions of L-menthol and penetration of molten polymers into tablets.

A novel floating sustained release tablet having a cavity in the center was developed by utilizing the physicochemical properties of L-menthol and the penetration of molten hydrophobic polymer into tablets. A dry-coated tablet containing famotidine as a model drug in outer layer was prepared with a L-menthol core by direct compression. The tablet was placed in an oven at 80°C to remove the L-menthol core from tablet. The resulting tablet was then immersed in the molten hydrophobic polymers at 90°C. The buoyancy and drug release properties of tablets were investigated using United States Pharmacopeia (USP) 32 Apparatus 2 (paddle 100 rpm) and 900 ml of 0.01 N HCl. The L-menthol core in tablets disappeared completely through pathways in the outer layer with no drug outflows when placed in an oven for 90 min, resulting in a formation of a hollow tablet. The hollow tablets floated on the dissolution media for a short time and the drug release was rapid due to the disintegration of tablet. When the hollow tablets were immersed in molten hydrophobic polymers for 1 min, the rapid drug release was drastically retarded due to a formation of wax matrices within the shell of tablets and the tablets floated on the media for at least 6 h. When Lubri wax® was used as a polymer, the tablets showed the slowest sustained release. On the other hand, faster sustained release properties were obtained by using glyceryl monostearate (GMS) due to its low hydrophobic nature. The results obtained in this study suggested that the drug release rate from floating tablets could be controlled by both the choice of hydrophobic polymer and the combined use of hydrophobic polymers.

Product mass transfer resistance directly determined during freeze-drying cycle runs using tunable diode laser absorption spectroscopy (TDLAS) and pore diffusion model.

The pore diffusion model is used to express the dry layer mass transfer resistance, [Formula: see text], as a function of the ratio r(e)/?, where r(e) is the effective pore radius and ? is the tortuosity factor of the dry layer. Using this model, the effective pore radius of the dry layer can be estimated from the sublimation rate and product temperature profiles measured during primary drying. Freeze-drying cycle runs were performed using the LyoStar II dryer (FTS Systems), with real-time sublimation rate profiles during freeze drying continuously measured by tunable diode laser absorption spectroscopy (TDLAS). The formulations chosen for demonstration of the proposed approach include 5% mannitol, 5% sucrose, 5% lactose, 3% mannitol plus 2% sucrose, and a parenteral nutrition formulation denoted VitaM12. The three different methods used for determination of the product resistance are: (1) Using both the sublimation rate and product temperature profiles, (2) using the sublimation rate profile alone, and (3) using the product temperate profile alone. Unlike the second and third methods, the computation procedure of first method does not need solution of the complex heat and mass transfer equations.

A simple explanation of the enhancement or depletion of the enantiomeric excess in the partial sublimation of enantiomerically enriched amino acids.

In the partial sublimation of three enantiomerically enriched amino acids, the ee of the sublimates can be explained by the ratio between the saturated vapor pressures of the racemate and the pure enantiomers.

Interaction of nitrogen bases with iron-porphyrin nitrito complexes Fe(Por)(ONO) in sublimed solids.

The reactions of the nitrogen Lewis bases (B) 1-methylimidazole (1-MeIm), pyridine (Py), and NH3 as gases with sublimed layers containing the 5-coordinate nitrito iron(III)-porphyrinato complexes Fe(Por)(eta1-ONO) (1) are described (Por = meso-tetraphenyl-porphyrinato or meso-tetra-p-tolyl-porphyrinato dianions). In situ FTIR and optical spectra are used to characterize the formation of the 6-coordinate nitro complexes formed by the reaction of 1 with B = 1-MeIm, Py, or NH3. These represent the first examples of 6-coordinate amino-nitro complexes with sterically unprotected iron-porphyrins. The interaction of ammonia with Fe(Por)(ONO) at 140 K initially led to the nitrito species Fe(Por)(NH3)(eta1-ONO), and this species isomerized to the nitro complexes Fe(Por)(NH3)(eta1-NO2) upon warming to 180 K. When the latter were warmed to room temperature under intense pumping, the initial nitrito complexes Fe(Por)(eta1-ONO) were restored. Assignments of vibrational frequencies for the coordinated nitro group in 6-coordinate iron-porphyrin complexes are given and confirmed using 15N-labeled nitrogen dioxide to identify characteristic infrared bands. For M(Por)(B)(NO2) complexes (M = Fe or Co), an inverse correlation between the net charge transfer from the axial ligand B to the nitro group and the value of Deltanu = nua(NO2) - nus(NO2) is proposed. These observations are discussed in the context of growing interest in potential physiological roles of nitrite ion reactions with ferro- and ferri-heme proteins.