The Stability of Aspirin in a Moisture Containing Direct Compression Tablet Formulation

Studies were conducted on the stability of a direct compression tablet formulation containing aspirin as a model hydrolabile drug. Emdex^R (a mixed-sugar diluent containing approximately 8 percent moisture) and stearic acid (a lubricant) made up the remainder of the formulation. Both tablets and uncompressed powder blend were manufactured, packaged in storage containers and placed on stability at different storage temperatures. Stability samples were assayed for aspirin and salicylic acid using a stability indicating analytical method. Analysis of the stability data showed that the rate of aspirin decomposition accelerated with time. Also, the aspirin decomposition rate increased with temperature. The data were fit to the empirical equation y = 100 - ktⁿ, where y is the percent aspirin remaining, t is time, and k and n are constants. The formulation showed good stability, with less than one percent decomposition occuring after 1.75 years of storage at room temperature. This result indicates that although the aspirin formulation contained approximately 8 percent moisture, at room temperature the majority of the moisture present in the formulation is not available to react with the aspirin. The apparent activation energy of the solid-state aspirin decomposition was 46 kcal/mole, which is higher than expected. This result may be due to a temperature dependent release of moisture from the Emdex^R. Further studies are needed to verify this explanation.     

The Stability of Aspirin in a Moisture Containing Direct Compression Tablet Formulation

Abstract

Studies were conducted on the stability of a direct compression tablet formulation containing aspirin as a model hydrolabile drug. Emdex^R (a mixed-sugar diluent containing approximately 8 percent moisture) and stearic acid (a lubricant) made up the remainder of the formulation. Both tablets and uncompressed powder blend were manufactured, packaged in storage containers and placed on stability at different storage temperatures. Stability samples were assayed for aspirin and salicylic acid using a stability indicating analytical method. Analysis of the stability data showed that the rate of aspirin decomposition accelerated with time. Also, the aspirin decomposition rate increased with temperature. The data were fit to the empirical equation y = 100 – ktⁿ, where y is the percent aspirin remaining, t is time, and k and n are constants. The formulation showed good stability, with less than one percent decomposition occuring after 1.75 years of storage at room temperature. This result indicates that although the aspirin formulation contained approximately 8 percent moisture, at room temperature the majority of the moisture present in the formulation is not available to react with the aspirin. The apparent activation energy of the solid-state aspirin decomposition was 46 kcal/mole, which is higher than expected. This result may be due to a temperature dependent release of moisture from the Emdex^R. Further studies are needed to verify this explanation.     

Preformulation the Role of Moisture in Solid Dosage Forms

Moisture plays an important role in the individual stages of preformulation studies for solid dosage forms. Examples are given to demonstrate this

The first stage involves chemical tests with the pure active substance using a reliable storage scheme. Then compatibility testing between active and inactive substances is performed. Under the general heading of sorption tests, the determination of sorption isotherms using special apparatus and their correlation with the physical and chemical changes which occur in the samples are discussed. With the results of these tests it is often possible to influence the sorption properties of the finished dosage form, for example by selection of the excipients and the salt form of the active substance, or by deferring the point of ansorption

Finally, as an example of special tests used in pre-formulation, the development of compound preparations is described and the galenical pre-stages are discussed     

Preformulation the Role of Moisture in Solid Dosage Forms

Abstract

Moisture plays an important role in the individual stages of preformulation studies for solid dosage forms. Examples are given to demonstrate this

The first stage involves chemical tests with the pure active substance using a reliable storage scheme. Then compatibility testing between active and inactive substances is performed. Under the general heading of sorption tests, the determination of sorption isotherms using special apparatus and their correlation with the physical and chemical changes which occur in the samples are discussed. With the results of these tests it is often possible to influence the sorption properties of the finished dosage form, for example by selection of the excipients and the salt form of the active substance, or by deferring the point of ansorption

Finally, as an example of special tests used in pre-formulation, the development of compound preparations is described and the galenical pre-stages are discussed     

Effect of Moisture on the Stability of Solid Dosage Forms

Abstract

It has long been known that moisture affects the stability of some drug substances. Aspirin is a classical example. Aspirin is not wet granulated. Even though the water is driven off in a wet granulation, there is still sufficient moisture stress in the process to induce excessive decomposition on subsequent storage. Dry methods (slugging, roller compaction) are therefore resorted to. In other instances, the moisture sensitivity of a drug may warrant using a hard shall capsule approach. This presumes that the drug substance is not particularly hygroscopic, since, otherwise, the capsule shell will provide an unwanted source of moisture.     

伴同蛋白GroE的纯化及对蛋白质复性的作用

伴同蛋白是近几年发现的一类促进其它蛋白质“组装”而它本身并不参与终产物形成的蛋白质。为此，我们纯化了伴同蛋白ＧｒｏＥＬ、ＧｒｏＥＳ，并研究了在重组人的γ－干扰素体外复性过程中加入伴同蛋白ＧｒｏＥＬ、ＧｒｏＥＳ，使得γ－干扰素复性的百分比从６．４％增加到大于５０％，比活从６．６×１０４Ｕ／ｍｇ增加到大于１．０×１０７Ｕ／ｍｇ。结果表明，伴同蛋白对蛋白质的复性是有效的。     

The Role of Moisture and Gap Air Pressure in the Formation of Spherical Granules by Rotary Processing

Spheroids are usually produced by a multi-step extrusion-spheronization process. The single-step production of spheroids may be carried out in a rotoprocessor. The use of feed materials in powder form requires an adaptation of the spheronizer machinery. This study investigates the formation and growth of spheroids and the changes in the spheroid moisture content in a single-step agglomeration-spheronization method. There was a rapid increase in size and formfactor values when spheroids started to form and grow from the powder mix. Although there was a continual and considerable loss of moisture with time, this did not have an appreciable effect on spheroid size and shape after the spheroid formation stage as the spheroid structure had already been determined. Spheroid size increased with higher liquid spray rates. The use of higher gap air pressures resulted in a greater rate of moisture loss and the production of smaller spheroids.     

The Role of Moisture and Gap Air Pressure in the Formation of Spherical Granules by Rotary Processing

Spheroids are usually produced by a multi-step extrusion-spheronization process. The single-step production of spheroids may be carried out in a rotoprocessor. The use of feed materials in powder form requires an adaptation of the spheronizer machinery. This study investigates the formation and growth of spheroids and the changes in the spheroid moisture content in a single-step agglomeration-spheronization method. There was a rapid increase in size and formfactor values when spheroids started to form and grow from the powder mix. Although there was a continual and considerable loss of moisture with time, this did not have an appreciable effect on spheroid size and shape after the spheroid formation stage as the spheroid structure had already been determined. Spheroid size increased with higher liquid spray rates. The use of higher gap air pressures resulted in a greater rate of moisture loss and the production of smaller spheroids.     

The Role of Lymphatic Transport in Enhancing Oral Protein and Peptide Drug Delivery

ABSTRACT

The gastrointestinal lymphatic system is a specific transport pathway through which dietary lipids, fat-soluble vitamins, and water-insoluble peptide-type molecules (e.g., cyclosporine A) can gain access to the systemic circulation. Drugs transported by way of the gastrointestinal lymphatic system bypass the liver and avoid potential hepatic first-pass metabolism. Lymphatic delivery of immunomodulatory and low therapeutic index protein and peptide drugs used in the treatment of cancer cell metastases and HIV presents an opportunity to maximize therapeutic benefit while minimizing general systemic drug exposure. Furthermore, lymphatic drug transport may promote drug incorporation into the body's lipid-handling system, thus offering the potential to manipulate drug distribution and residence time within the body. This review article will discuss the potential utilization of lymphatic transport in enhancing the oral absorption of protein- and peptide-like drugs.     

Stability of DNA Origami Nanostructures in Physiological Media: The Role of Molecular Interactions

Programmable, custom-shaped, and nanometer-precise DNA origami nanostructures have rapidly emerged as prospective and versatile tools in bionanotechnology and biomedicine. Despite tremendous progress in their utilization in these fields, essential questions related to their structural stability under physiological conditions remain unanswered. Here, DNA origami stability is explored by strictly focusing on distinct molecular-level interactions. In this regard, the fundamental stabilizing and destabilizing ionic interactions as well as interactions involving various enzymes and other proteins are discussed, and their role in maintaining, modulating, or decreasing the structural integrity and colloidal stability of DNA origami nanostructures is summarized. Additionally, specific issues demanding further investigation are identified. This review – through its specific viewpoint – may serve as a primer for designing new, stable DNA objects and for adapting their use in applications dealing with physiological media.     

The Effect of Environmental Moisture and Temperature on the Physical Stability of Effervescent Tablets in Foil Laminate Packages Containing Minute Imperfections

Abstract

The effect of environmental moisture on the physical stability of effervescent tablets in foil laminate packages containing microscopic imperfections (openings) was examined. Packaged tablets were stored at different relative humidity (RH) and temperature conditions and evaluated for physical stability at predetermined time intervals. Physical stability was assessed by noting if the tablet components reacted prematurely to yield soft tablets during storage. A penetrating dye solution test was used to determine if the foil packages contained imperfections which might allow transmission of moisture. The results of the investigation indicated that absolute moisture integrity of the foil package is required for product stability.     

The Effect of Environmental Moisture and Temperature on the Physical Stability of Effervescent Tablets in Foil Laminate Packages Containing Minute Imperfections

The effect of environmental moisture on the physical stability of effervescent tablets in foil laminate packages containing microscopic imperfections (openings) was examined. Packaged tablets were stored at different relative humidity (RH) and temperature conditions and evaluated for physical stability at predetermined time intervals. Physical stability was assessed by noting if the tablet components reacted prematurely to yield soft tablets during storage. A penetrating dye solution test was used to determine if the foil packages contained imperfections which might allow transmission of moisture. The results of the investigation indicated that absolute moisture integrity of the foil package is required for product stability.     

Stability of the Mokohydrate Crystal form of Cefazolin Sodium as a Function of Moisture

Abstract

Moisture effects on the stability of the monohydrate crystal form of cefazolin sodium were investigated. Results show that increased moisture content of this compound adversely affects the microbiological and polarographic stability at elevated temperatures. In addition, butyl rubber stoppers provided more protection against moisture than natural rubber stoppers at higher humidity conditions.     

Stability of the Mokohydrate Crystal form of Cefazolin Sodium as a Function of Moisture

Moisture effects on the stability of the monohydrate crystal form of cefazolin sodium were investigated. Results show that increased moisture content of this compound adversely affects the microbiological and polarographic stability at elevated temperatures. In addition, butyl rubber stoppers provided more protection against moisture than natural rubber stoppers at higher humidity conditions.     

Perovskite Photovoltaics: The Significant Role of Ligands in Film Formation,Passivation, and Stability

Due to their outstanding optoelectronic properties, metal halide perovskites have been intensively studied in recent years. The latest certificated efficiency of 23.3% recently achieved in perovskite solar cells (PVSCs) enables them to be used as a very promising candidate for next‐generation photovoltaics. The morphology, defect density, and water resistance of perovskite films have an enormous impact on the performance and stability of PVSCs. Ligands, with coordinating capability, have been widely developed to improve the quality and stability of perovskite materials significantly. In the first section of this review, the role of ligands in fabricating perovskite films by different methods (one‐step, two‐step, and postdeposition treatment) is discussed. In the second section, the progress on ligand‐passivated perovskites via post‐treatment, in situ passivation during perovskite formation, and modifying the substrates before perovskite formation is reviewed. In the third section, a discussion of ligand‐stabilized perovskite films from the perspectives of crystal crosslinking, dimensionality engineering, and interfacial modification is presented. Finally, a summary and an outlook are given.     

The Role of Demixing and Crystallization Kinetics on the Stability of Non-Fullerene Organic Solar Cells

With power conversion efficiency now over 17%, a long operational lifetime is essential for the successful application of organic solar cells. However, most non-fullerene acceptors can crystallize and destroy devices, yet the fundamental underlying thermodynamic and kinetic aspects of acceptor crystallization have received limited attention. Here, room-temperature (RT) diffusion coefficients of 3.4 × 10⁻²³ and 2.0 × 10⁻²² are measured for ITIC-2Cl and ITIC-2F, two state-of-the-art non-fullerene acceptors. The low coefficients are enough to provide for kinetic stabilization of the morphology against demixing at RT. Additionally profound differences in crystallization characteristics are discovered between ITIC-2F and ITIC-2Cl. The differences as observed by secondary-ion mass spectrometry, differential scanning calorimetry (DSC), grazing-incidence wide-angle X-ray scattering, and microscopy can be related directly to device degradation and are attributed to the significantly different nucleation and growth rates, with a difference in the growth rate of a factor of 12 at RT. ITIC-4F and ITIC-4Cl exhibit similar characteristics. The results reveal the importance of diffusion coefficients and melting enthalpies in controlling the growth rates, and that differences in halogenation can drastically change crystallization kinetics and device stability. It is furthermore delineated how low nucleation density and large growth rates can be inferred from DSC and microscopy experiments which could be used to guide molecular design for stability.     

The Hygroscopicity of Moisture Barrier Film Coatings

ABSTRACT

The hygroscopicity of three commercial moisture-barrier film coatings, namely, Eudragit L30 D-55 (methacrylic acid–ethyl acrylate copolymer), Opadry AMB (polyvinyl alcohol based system), and Sepifilm LP 014 (hypromellose, microcrystalline cellulose, and stearic acid based formulation), was investigated using a dynamic vapor sorption apparatus. Moisture uptake by cast films and uncoated and coated tablet cores, which were designed to be hygroscopic, low hygroscopic, and waxy, was measured following exposure to repeat relative humidity (RH) cycles of 0-50-0-50-0%, 0-75-0-75-0%, and 0-90-0-90-0% RH at 25°C. Eudragit cast film exhibited the fastest equilibration but was also the least hygroscopic. Sepifilm had the fastest sorption and took up the greatest mass of water. The rate of uptake for Opadry film was similar to Sepifilm. However, this film continued to sorb moisture for a longer period. When returned to 0% RH it retained moisture in the film showing that it had a high affinity for moisture within the film. The data for the different cores indicated that there was very little benefit in using a moisture barrier film on cores with low hygroscopicity, the mass gain being a sum of that which would be expected to sorb to the film and that which sorbs to the uncoated core. There was, however, some advantage for hygroscopic cores where, even though the barrier coatings allowed substantial water sorption into the core, the extent of this was less and the rate of uptake lower than for the uncoated sample.