A Study of The Moisture-Uptake Kinetics of a Hygroscopic Pharmaceutical Powder

Abstract

The moisture-uptake kinetics of a hygroscopic powder, sodium heparin contained in a cylindrical container, was determined using a novel moisture-uptake measuring device under a constant convective air flow. The amount of moisture uptake increased with the increase in the relative humidity of the air. The effect of powder-bed height on the total amount of moisture uptake was found to be significant only at the highest relative humidity (75%) evaluated in this study. However, the percent of weight increase of the powder as a result of moisture uptake decreases as the height of the powder bed increases. The results of this study are explained by the dynamic nature of the moisture-uptake process associated with the instrument.     

The Use of a Flow Microcalorimeter to Characterise Powder Surfaces

When a material is exposed to air at a definite temperature and humidity, it will gain or lose moisture until on equilibrium moisture content is attained. This value depends on the chemical and physical properties of the material and is generally lower for non-porous solids and higher but more variable for fibrous or colloidal organic substances. In pharmaceutical powders the sorption of moisture poses many problems for the formulator. Moisture uptake can have a profound effect on both the physical and chemical stability of the powder. The presence of a film of moisture can provide a medium where chemical reactions such as hydrolysis can take place. This in turn affects the powder properties such as the potency of the drug or may result in the formation of insoluble products on the surface thus affecting drug availability. It can also lead to changes in coloration of the drug. From a manufacturing point of view, moisture uptake has an added adverse effect in terms of the handling properties of the material. This is because an increase in moisture content generally causes- a free-flowing powder to cohere, thus causing inefficient mixing with other powders, blocking of machinery and resultant non-uniformity of the product. On the other hand a very fine dry powder may become easier to handle when a little moisture is present and may also reduce the dustiness of the powder and increase the powder's capacity to consolidate.

Moisture usually condenses on the surface of the substance exposed to the atmosphere. However in porous powders, it may penetrate the depth of the powder bed. At a given temperature condensation increases with an increase in the partial pressure of water vapour in the atmosphere. Powder surfaces in general are very reactive and the amount of moisture adsorbed increases as the surface area of a powder increases, because moisture uptake is essentially a surface phenomenon (Sprowls²). For the measurement of adsorption at liquid/solid interfaces, Groszek³developed the flow microcalorimeter. This instrument has been used to measure the lubricating action of solid lubricants such as graphite^4,5 and more recently for the study of dental enamel surfaces⁶ In addition the instrument has been used for the measurement of specific surface area^7,8 The flow micro-calorimeter has been modified and adapted for use in the present work in order to evaluate heats of adsorption and desorption of moist air at various powder surfaces.     

The Use of a Flow Microcalorimeter to Characterise Powder Surfaces

Abstract

When a material is exposed to air at a definite temperature and humidity, it will gain or lose moisture until on equilibrium moisture content is attained. This value depends on the chemical and physical properties of the material and is generally lower for non-porous solids and higher but more variable for fibrous or colloidal organic substances. In pharmaceutical powders the sorption of moisture poses many problems for the formulator. Moisture uptake can have a profound effect on both the physical and chemical stability of the powder. The presence of a film of moisture can provide a medium where chemical reactions such as hydrolysis can take place. This in turn affects the powder properties such as the potency of the drug or may result in the formation of insoluble products on the surface thus affecting drug availability. It can also lead to changes in coloration of the drug. From a manufacturing point of view, moisture uptake has an added adverse effect in terms of the handling properties of the material. This is because an increase in moisture content generally causes- a free-flowing powder to cohere, thus causing inefficient mixing with other powders, blocking of machinery and resultant non-uniformity of the product. On the other hand a very fine dry powder may become easier to handle when a little moisture is present and may also reduce the dustiness of the powder and increase the powder's capacity to consolidate.

Moisture usually condenses on the surface of the substance exposed to the atmosphere. However in porous powders, it may penetrate the depth of the powder bed. At a given temperature condensation increases with an increase in the partial pressure of water vapour in the atmosphere. Powder surfaces in general are very reactive and the amount of moisture adsorbed increases as the surface area of a powder increases, because moisture uptake is essentially a surface phenomenon (Sprowls²). For the measurement of adsorption at liquid/solid interfaces, Groszek³developed the flow microcalorimeter. This instrument has been used to measure the lubricating action of solid lubricants such as graphite^4,5 and more recently for the study of dental enamel surfaces⁶ In addition the instrument has been used for the measurement of specific surface area^7,8 The flow micro-calorimeter has been modified and adapted for use in the present work in order to evaluate heats of adsorption and desorption of moist air at various powder surfaces.     

An experimental study of the effect of humidity on the distribution of charged particles in a glow-discharge plasma

The charged-particle distribution in a glow-discharge plasma in air with differing moisture concentration was studied using a double electric probe. An important difference is found in the distribution of charged particles in the discharge, depending on the humidity of the air. The amount of water vapor with a relative concentration of 2% does not affect the distribution of charged particles in the plasma, and, with an increase in moisture content up to 15%, a twofold increase in the ion concentration along the discharge axis is observed.     

Solid-State Stability of Theophylline Anhydrous in Theophylline Anhydrous-Polyvinylpyrrolidone Physical Mixtures

There are contradictory evidences in the literature concerning the role of excipients with a high affinity for water in the formulation when the formulation is exposed to moisture. A few reports indicate the stabilization of a drug in the presence of hygroscopic excipients. Other reports indicate the rapid moisture-induced changes of the drug in the presence of an excipient with high affinity for water. The objective of this study was to understand the effect of PVP and the relative humidity of storage on the solid-state stability of anhydrous theophylline. In this study, physical mixtures of theophylline anhydrous and polyvinylpyrrolidone were prepared in varying proportions. These mixtures were then stored in a range of humidities at room temperature. X-ray powder diffraction, moisture uptake, HPLC, and FTIR spectroscopy were used to monitor the physical and chemical changes occurring in the mixtures. A hypothesis is presented on the role of amorphous polymeric excipients in the formulation. The hypothesis agrees with the recent knowledge on the mobility of water associated with amorphous polymeric materials. The mechanism of protection by the PVP against the hydration of theophylline could be described as desiccant action. The efficiency of this desiccant action of PVP will then be dependent on the amount of water molecules in the system and the kinetics of reaching the equilibrium moisture content.     

Solid-State Stability of Theophylline Anhydrous in Theophylline Anhydrous-Polyvinylpyrrolidone Physical Mixtures

Abstract

There are contradictory evidences in the literature concerning the role of excipients with a high affinity for water in the formulation when the formulation is exposed to moisture. A few reports indicate the stabilization of a drug in the presence of hygroscopic excipients. Other reports indicate the rapid moisture-induced changes of the drug in the presence of an excipient with high affinity for water. The objective of this study was to understand the effect of PVP and the relative humidity of storage on the solid-state stability of anhydrous theophylline. In this study, physical mixtures of theophylline anhydrous and polyvinylpyrrolidone were prepared in varying proportions. These mixtures were then stored in a range of humidities at room temperature. X-ray powder diffraction, moisture uptake, HPLC, and FTIR spectroscopy were used to monitor the physical and chemical changes occurring in the mixtures. A hypothesis is presented on the role of amorphous polymeric excipients in the formulation. The hypothesis agrees with the recent knowledge on the mobility of water associated with amorphous polymeric materials. The mechanism of protection by the PVP against the hydration of theophylline could be described as desiccant action. The efficiency of this desiccant action of PVP will then be dependent on the amount of water molecules in the system and the kinetics of reaching the equilibrium moisture content.     

Heat and Mass Transfer Measurements for Tray-Fermented Fungal Products

In this study, heat and mass transfer in static tray fermentation, which is widely used in solid-state fermentation (SSF) to produce fungal products, such as enzymes or koji, is investigated. Specifically, kinetic models of transport phenomena in the whole-tray chamber are emphasized. The effects of temperature, moisture, and humidity on microbial growth in large-scale static tray fermentation are essential to scale-up SSF and achieve uniform fermentation. In addition, heat and mass transfer of static tray fermentation of Trichoderma fungi with two tray setups??traditional linen coverings and stacks in a temperature?Chumidity chamber is examined. In both these setups, the following factors of fermentation were measured: air velocity, air temperature, illumination, pH, carbon dioxide (CO₂) concentration, and substrate temperature, and the effects of bed height, moisture of substrate, and relative humidity of air are studied. A thin (1 cm) bed at 28 °C and 95 % relative humidity is found to be optimum. Furthermore, mixing was essential for achieving uniform fermentation of Trichoderma fungi. This study has important applications in large-scale static tray fermentation of fungi.     

The influence of storage relative humidity on aerosolization of co-spray dried powders of hygroscopic kanamycin with the hydrophobic drug rifampicin

The purpose of this study was to investigate the influence of storage humidity on in vitro aerosolization and physicochemical properties of co-spray dried powders of kanamycin with rifampicin. The powders were stored for one-month in an open Petri dish at different relative humidities (RHs) (15%, 43%, and 75%) and 25?±?2?°C. The in vitro aerosolization (fine particle fraction, FPF) of the powders was determined by a next generation impactor (NGI). The moisture content, particle morphology and crystallinity of the powders were determined by Karl Fischer titration, scanning electron microscopy, and X-ray powder diffractometry, respectively. At all RH, the FPF of hydrophobic rifampicin-only powder was unaffected but the FPF of hygroscopic kanamycin-only powder significantly decreased even at 43% RH. The kanamycin-only particles fused together, crystallized and formed hard cakes at 75% RH. The aerosolization of kanamycin and rifampicin in the combination powders remained unaffected at 15% and 43% RH, but aerosolization significantly decreased at 75% RH. Enrichment of the surface of the particles with hydrophobic rifampicin did not protect the combination powders from moisture uptake but it prevented particle agglomeration up to 43% RH. At 75% RH, the moisture uptake led to agglomeration of the particles of the combination powder particles and consequently an increase in aerodynamic diameter. Further studies are required to investigate how rifampicin enrichment prevents particle agglomeration, the possible mechanisms (e.g. particle interactions due to capillary forces or electrostatic forces) for the changes in the aerosolization and changes in surface composition during storage.     

Effect of moisture on crystallization of theophylline in tablets

Needle-like crystals appeared on the surface of theophylline tablets containing anhydrous theophylline, hygroscopic materials such as potassium, and other formulation ingredients, when stored under conditions of high relative humidity. X-ray powder diffraction studies on these crystals showed that anhydrous theophylline was converted to the hydrate.

Crystal growth was accelerated by increased moisture uptake in tablets containing the hygroscopic materials polyethylene glycol 6000 or sodium chloride. The appearance of needle-like crystals on the surface of tablets resulted in a decrease in the rate of release of theophylline.     

Highly Efficient Clean Water Production from Contaminated Air with a Wide Humidity Range

The huge amount of moisture in the air is an unexplored and overlooked water resource in nature, which can be useful to solve the worldwide water shortage. However, direct water condensation from natural or even hazy air is always inefficient and inevitably contaminated by numerous impurities of dust, toxic gas, and microorganisms. In this regard, a drinkable and clean water harvester from complex contaminated air with a wide humidity range based on porous sodium polyacrylate/graphene framework (PGF), which can actively sorb moisture from common or even smoggy environments, efficiently grabs impurities, and then releases clean water with a high rejection rate of impurities under solar irradiation, is proposed. This PGF shows a superhigh equilibrium uptake of 5.20 g of water per gram of PGF at a relative humidity (RH) of 100% and 0.14 g g⁻¹ at a low RH of 15%. The rejection rate of impurities is up to 97% for the collected clean water. Moreover, a water harvesting system is established to produce over 25 L clean water per kilogram of PGF one day, enough to meet several people's drinking water demand. This work provides a new strategy for effective production of clean water from the atmosphere of practical significance.     

温湿度对瓦楞原纸弹性模量影响的研究

试验研究了温湿度条件对瓦楞原纸含水率的影响,以及瓦楞原纸含水率对其弹性模量的影响,构建了含水率与温湿度的三维关系图。试验结果表明:瓦楞原纸的含水率既受相对湿度的影响,又受温度的影响,温度对瓦楞原纸弹性模量的影响比相对湿度的影响小;瓦楞原纸含水率随温度的上升而下降,随相对湿度的上升而上升;瓦楞原纸弹性模量随含水率的上升而下降。     

Distribution of Water in Solid Pharmaceutical Systems

Abstract

Knowledge of the amount of moisture associated with particular components of a solid dosage form, as well as its state, are essential for the pharmaceutical formulator in attaining a system with optimal physical/chemical properties. Moisture is introduced into ultimately closed pharmaceutical systems either associated with the materials or in the headspace as relative humidity. This moisture will distribute (i. e., reequilibrate) between the various components and the headspace to attain a final water activity, aw (-relative humidity/100) in the vapor phase. The Sorption-Desorption Moisture Transfer (SDMT) model allows a priori prediction of this thermodynamic variable for systems in which uptake isotherms and dry masses for individual components, temperature, headspace volume and initial total system moisture content are known. Final component moisture contents are then obtained from the individual materials' respective isotherms. Practical applications of the SDMT model include the rational determination of: initial LOD values of the formulation and capsule to avoid capsule brittleness problems, an adequate headspace volume above nonhydrating crystalline substances to protect against deliquescence, and the appropriate amount of desiccant for a solid product.     

Moisture Absorption and Desorption in an Ionomer-Based Encapsulant: A Type of Self-Breathing Encapsulant for CIGS Thin-Film PV Modules

As an alternative to conventional encapsulation concepts for a double glass photovoltaic (PV) module, we introduce an innovative ionomer-based multi-layer encapsulant, by which the application of additional edge sealing to prevent moisture penetration is not required. The spontaneous moisture absorption and desorption of this encapsulant and its raw materials, poly (ethylene-co-acrylic acid) and an ionomer, are analyzed under different climatic conditions in this work. The relative air humidity is thermodynamically the driving force for these inverse processes and determines the corresponding equilibrium moisture content (EMC). Higher air humidity results in a larger EMC. The homogenization of the absorbed water molecules is a diffusion-controlled process, in which temperature plays a dominant role. Nevertheless, the diffusion coefficient at a higher temperature is still relatively low. Hence, under normal climatic conditions for the application of PV modules, we believe that the investigated ionomer-based encapsulant can “breathe” the humidity: During the day, when there is higher relative humidity, it “inhales” (absorbs) moisture and restrains it within the outer edge of the module; then at night, when there is a lower relative humidity, it “exhales” (desorbs) the moisture. In this way, the encapsulant protects the cell from moisture ingress.     

Physicochemical Stability of Crystalline Sugars and Their Spray-Dried Forms: Dependence upon Relative Humidity and Suitability for Use in Powder Inhalers

Abstract

Lactose, trehalose, sucrose, and mannitol were purchased in crystalline form and fractionated by sieving. Coarse (125-212 µm) and fine (44-74 µm) free-flowing fractions were selected as typical of drug carriers in dry-powder inhalers. In addition, one batch of each sugar was spray-dried to form a respirable powder (> 50% [w/w], < 5 µm). Both fractions and the spray-dried powders were characterized before and after storage for 30 days at < 23%, 23%, 52%, 75% and 93% relative humidity (RH) at 25°C. Moisture uptake was determined by thermogravimetric analysis (TGA) validated by Karl Fischer titration. Sieve fractions (before storage at different RHs) and spray-dried materials (before and after storage) were further characterized by differential scanning calorimetry (DSC) and x-ray powder diffraction (XRPD). All crystalline sieve fractions (except sucrose at 93% RH) were stable at 25°C and showed insignificant moisture uptake when exposed to each relative humidity for 30 days. Sucrose dissolved in sorbed moisture at 93% RH. Spray-dried lactose, sucrose, and trehalose, which were collected in the amorphous form, showed moisture uptake, without recrystallization, when held for 30 days at 23% RH. These sugars recrystallized as sintered masses and became undispersible at ≥ 52% RH. Spray-dried mannitol was apparently 100% crystalline when collected directly from the spray-dryer; it did not show humidity-induced changes.

The physicochemical behavior of each sugar form is discussed as it relates to the sugar's suitability as a powder-inhaler excipient, with both conventional and protein drugs.     

Effect of Moisture on the Physical and Chemical Stability of Granulations and Tablets of the Angiotensin Converting Enzyme Inhibitor, Enalapril Maleate

Granulations and tablets of enalapril maleate in a lactose matrix were stored in open petri dishes at a range of relative humidities and respective moisture uptakes measured, Extrapolation of the moisture uptake rates measured at the exaggerated humidities yielded a critical humidity, i.e. humidity where the moisture uptake rate is zero and, therefore, least detrimental to the product.

Enalapril maleate was reasonably stable at the storage conditions. The hardness of the tablets decreased at all humidities except when stored with silica-gel. The disintegration times were unaffected except at very high humidities. The dissolution profiles of the tablets remained unchanged.     

Effect of Moisture Content on Compression Properties of Directly Compressible High Beta-Content Anhydrous Lactose

Moisture sorption characteristics and the role of moisture on the compression properties of direct compression anhydrous lactose was investigated. Anhydrous lactose sorbed little moisture even when exposed to very high relative humidities. The equilibrium moisture content of the diluent was less than 1% at 55% relative humidity, 1.66% at 80% relative humidity and 2.03% at 92% relative humidity. An increase in moisture content of lactose resulted in a reduction in hardness of the tablets and increased pressure requirements to achieve specified hardness values. Heckel plots obtained from the compression data of the diluent were linear for all moisture contents. Yield pressures calculated from the Heckel plots increased at moisture contents greater than that of the original diluent. Differential scanning calorimetry performed on the diluent with 5.13% moisture showed that the added water was bound as the crystalline hydrate.     

Effect of Moisture Content on Compression Properties of Directly Compressible High Beta-Content Anhydrous Lactose

Abstract

Moisture sorption characteristics and the role of moisture on the compression properties of direct compression anhydrous lactose was investigated. Anhydrous lactose sorbed little moisture even when exposed to very high relative humidities. The equilibrium moisture content of the diluent was less than 1% at 55% relative humidity, 1.66% at 80% relative humidity and 2.03% at 92% relative humidity. An increase in moisture content of lactose resulted in a reduction in hardness of the tablets and increased pressure requirements to achieve specified hardness values. Heckel plots obtained from the compression data of the diluent were linear for all moisture contents. Yield pressures calculated from the Heckel plots increased at moisture contents greater than that of the original diluent. Differential scanning calorimetry performed on the diluent with 5.13% moisture showed that the added water was bound as the crystalline hydrate.     

Effect of Moisture on the Physical and Chemical Stability of Granulations and Tablets of the Angiotensin Converting Enzyme Inhibitor,Enalapril Maleate

Abstract

Granulations and tablets of enalapril maleate in a lactose matrix were stored in open petri dishes at a range of relative humidities and respective moisture uptakes measured, Extrapolation of the moisture uptake rates measured at the exaggerated humidities yielded a critical humidity, i.e. humidity where the moisture uptake rate is zero and, therefore, least detrimental to the product.

Enalapril maleate was reasonably stable at the storage conditions. The hardness of the tablets decreased at all humidities except when stored with silica-gel. The disintegration times were unaffected except at very high humidities. The dissolution profiles of the tablets remained unchanged.     

Moisture conditioning and transport properties of concrete test specimens

An experimental investigation is reported of drying and conditioning concrete at 50°C to obtain a uniform moisture distribution, prior to testing for air permeability and water absorption rate. The use of 100 mm cubes of concrete with a cast-in cylindrical cavity facilitated assessment of moisture distribution and measurement of air permeation through the surface layers of concrete: the moisture distribution was assessed by comparing the relative humidities measured within the cavity and at the surface of the test specimen. Partial drying followed by sealed storage at 50°C for a few days provided a rapid and convenient method of obtaining a uniform moisture distribution. The test results for a range of concretes indicated that air permeability and water absorption rate were very sensitive to the moisture content of the concrete, particularly at relative humidities above 60% and which were common for field exposure. The transport properties of the empty capillary pore system could be assessed using test specimens preconditioned at 60% relative humidity, but preconditioning at 85% relative humidity might be more appropriate for assessing field performance if there is a risk of carbonation induced corrosion.     

金属基复合吸附剂的吸湿性能测试

金属基复合吸附剂是将复合吸附剂涂覆于铝箔表面制成。选用不同粒径的硅胶作为基质制作样片,发现在实验条件下,大粒径的硅胶有利于提高铝箔表面的吸附剂涂覆量。采用优选粒径的硅胶制作样片,并对比复合吸附剂样片和单一硅胶样片的吸湿性能。在材料初始完全干燥,且吸湿条件恒定的情况下,卤素盐复合吸附剂吸湿速率更快,且最大吸湿量比硅胶高30%~45%,其中氯化锂复合吸附剂吸湿速率和最大吸湿量高于氯化钙复合吸附剂;在材料初始未进行干燥处理,且在吸湿,放湿工况周期性切换的情况下,复合吸附剂循环吸湿量比硅胶高出70%~120%,且高相对湿度的吸湿条件下,氯化钙循环吸湿量比氯化锂复合吸附剂高。