The influence of swelling capacity of superdisintegrants in different pH media on the dissolution of hydrochlorothiazide from directly compressed tablets

The purpose of this study was to investigate the efficiency of superdisintegrants in promoting tablet disintegration and drug dissolution under varied media pH. Significant reductions in the rate and extent of water uptake and swelling were observed for both sodium starch glycolate (Primojel) and croscarmellose sodium (Ac-Di-Sol) in an acidic medium (0.1 N HCl) but not for crospovidone NF (Polyplasdone XL10), a nonionic polymer. When Primojel and Ac-Di-Sol were incorporated in model formulations, a significant increase in tablet disintegration time was observed for slowly disintegrating tablets (lactose-based tablets) but not for the rapidly disintegrating tablets (dicalcium phosphate-based tablets). The dissolution rate of the model drug, hydrochlorothiazide, was found highly dependent on both tablet disintegration efficiency and the solubility of base material(s) in the testing medium. A laser diffraction particle size analyzer proved to be an effective tool for determining the intrinsic swelling of disintegrant particles in different media. Water uptake and swelling were confirmed as 2 important functions of superdisintegrants. The reduced water uptake and swelling capacity of disintegrants containing ionizable substituents in an acidic medium can potentially jeopardize their efficiency in promoting tablet disintegration and the drug dissolution rate. Published: September 20, 2005     

Effect of humidity on the disintegrant property of α-cellulose,Part II: A technical note

Conclusion  The summary is that the high humidity impaired the disintegrant property of α-cellulose in all 3 tablets tested. Tablets of aspirin, which is the more hygroscopic drug, were also more sensitive to the humidity effect, while tablets of chloroquine phosphate, which is a water-soluble drug, were the least sensitive to the humidity effect. The results permit the conclusion that moisture uptake with subsequent gelling of the α-cellulose is the mechanism of impairment of its disintegrant property. The tablets would not normally be stored under an RH as high as 100%, nevertheless, the results of the accelerated stability study have underscored the need to protect tablets containing α-cellulose as disintegrant from moisture. Published: August 10, 2005     

Functional Assessment of Four Types of Disintegrants and their Effect on the Spironolactone Release Properties

Spironolactone is a drug derived from sterols that exhibits an incomplete oral absorption due to its low water solubility and slow dissolution rate. In this study, formulations of spironolactone with four disintegrants named as croscarmellose sodium, crospovidone, sodium starch glycolate and microcrystalline cellulose II (MCCII) were conducted. The effect of those disintegrants on the tensile strength, disintegration time and dissolution rate of spironolactone-based compacts was evaluated using a factorial design with three categorical factors (filler, lubricant, and disintegrant). The swelling values, water uptake and water sorption studies of these disintegrants all suggested that MCCII compacts disintegrate by a wicking mechanism similar to that of crospovidone, whereas a swelling mechanism was dominant for sodium starch glycolate and croscarmellose sodium. The disintegration time of MCCII and sodium starch glycolate remained unchanged with magnesium stearate. However, this lubricant delayed the disintegration time of crospovidone and croscarmellose sodium. MCCII presented the fastest disintegration time independent of the medium and lubricant employed. The water sorption ratio and swelling values determined sodium starch glycolate followed by croscarmellose sodium as the largest swelling materials, whereas crospovidone and MCCII where the least swelling disintegrants. The swelling property of sodium starch glycolate and croscarmellose sodium was strongly affected by the medium pH. The disintegration time of spironolactone compacts was faster when starch was used as a filler due to the formation of soft compacts. In this case, the type of filler employed rather than the disintegrant had a major effect on the disintegration and dissolution times of spironolactone.     

Functionality comparison of 3 classes of superdisintegrants in promoting aspirin tablet disintegration and dissolution

The aims of this study are (1) to compare the disintegration efficiency, and (2) to develop a discriminating test model for the 3 classes of superdisintegrants represented by Ac-Di-Sol, Primojel, and Polyplasdone XL10. Using a digital video camera to examine the disintegration process of tablets containing the same wt/wt percentage concentration of the disintegrants, Ac-Di-Sol was found to disintegrate tablets rapidly into apparently primary particles; Primojel also apparently disintegrated tablets into primary particles but more slowly; Polyplasdone XL10 disintegrated tablets rapidly but into larger masses of aggregated particles. The differences in the size distribution generated in the disintegrated tablets likely contribute to the drug dissolution rate differences found for aspirin tablets with similar disintegration rates. The aspirin tablet matrix is proposed as a model formulation for disintegrant efficiency comparison and performance consistency testing for quality control purposes. Published: December 12, 2005     

Development of Tablet Formulation of Amorphous Solid Dispersions Prepared by Hot Melt Extrusion Using Quality by Design Approach

The objective of the study was to identify the extragranular component requirements (level and type of excipients) to develop an immediate release tablet of solid dispersions prepared by hot melt extrusion (HME) process using commonly used HME polymers. Solid dispersions of compound X were prepared using polyvinyl pyrrolidone co-vinyl acetate 64 (PVP VA64), Soluplus, and hypromellose acetate succinate (HPMCAS-LF) polymers in 1:2 ratio by HME through 18 mm extruder. A mixture design was employed to study effect of type of polymer, filler (microcrystalline cellulose (MCC), lactose, and dicalcium phosphate anhydrous (DCPA)), and disintegrant (Crospovidone, croscarmellose sodium, and sodium starch glycolate (SSG)) as well as level of extrudates, filler, and disintegrant on tablet properties such as disintegration time (DT), tensile strength (TS), compactibility, and dissolution. Higher extrudate level resulted in longer DT and lower TS so 60–70% was the maximum amount of acceptable extrudate level in tablets. Fast disintegration was achieved with HPMCAS-containing tablets, whereas Soluplus- and PVP VA64-containing tablets had higher TS. Crospovidone and croscarmellose sodium were more suitable disintegrant than SSG to achieve short DT, and MCC was a suitable filler to prepare tablets with acceptable TS for each studied HME polymer. The influence of extragranular components on dissolution from tablets should be carefully evaluated while finalizing tablet composition, as it varies for each HME polymer. The developed statistical models identified suitable level of fillers and disintegrants for each studied HME polymer to achieve tablets with rapid DT (<15 min) and acceptable TS (≥1 MPa at 10–15% tablet porosity), and their predictivity was confirmed by conducting internal and external validation studies.     

Acid-treated yeast cell wall as a binder displaying function of disintegrant

This investigation examined the application of acid-treated yeast cell wall (AYC) as a binder functioning as a disintegrant. Acetylsalicylic acid (ASA) was granulated with AYC, hydroxypropylcellulose (HPC), polyvinylpyrrolidone (PVP), or pullulan (PUL) and compressed into a tablet in the absence of disintegrant. Particle size and angle of repose of the granules, tensile strength, disintegration time, and water absorption behavior of the tablets and ASA release profiles from the tablets were measured. The surface of AYC-granules was observed with a scanning electron microscope. As was the case with the granules of HPC, PVP, or PUL, D50 of the granules of AYC increased with increasing AYC addition percentage, indicating that it is possible to granulate ASA with AYC. Tablets incorporating HPC, PVP, and PUL failed to disintegrate within 30 minutes at all percentages of binder addition because in the case of the HPC, PVP, or PUL tablets in the dissolution medium, water scarcely penetrated into the inner region of the tablet, causing no disintegration. In the case of the AYC tablets, disintegration was not detected at 3% or less of AYC. When AYC was equal to or greater than 5%, AYC tablets disintegrated in approximately 4 minutes and rapid ASA release from the tablets was observed. These results may have been caused by the following. In the case of the AYC 3% granules, ungranulated aspirin powder remained, but in the case of the AYC 5% granules, ASA powder was granulated and covered with AYC. Water absorption was observed initially; however, a plateau was reached in the case of the AYC 3%-tablet. In contrast, in the cases of the AYC 5% and more tablets, water absorption was greater and increased with time. The angle of repose of the AYC 5% granules was 25.7°, which represented high fluidity. The tablets produced by compressing the granules demonstrated sufficient tensile strength greater than 0.8 MPa. The tablets rapidly disintegrated and rapid ASA release was obtained. AYC functioned as a binder at granulation; additionally, AYC served as a disintegrant in the dissolution of drug from the tablets. These results indicate that AYC affords high utility as a unique pharmaceutical additive possessing contrary functions such as binding and disintegration.     

Effects of varying levels and frequencies of irrigation on growth,yield, nutrient uptake and water use efficiency of maize and cowpeas on a sandy loam ultisol

Summary A greenhouse study was carried out on an Nsukka sandy loam Ultisol having low soil moisture retention capacity to investigate the soil moisture regime and irrigation frequency required for optimum growth, yield, nutrient uptake and water use efficiency of maize (Zea mays L.) and cowpeas (Vigna unguiculata L. Walp). Four irrigation amounts (400 cm³, 300 cm³, 200 cm³ and 100 cm³ equivalent to 100, 75, 50 and 25% of field capacity, respectively) and four irrigation frequencies (daily, 2-day, 3-day and 4-day intervals) were tested in a factorial randomized design with three replications.Growth of maize was best when irrigation with water equivalent to 75% field capacity at daily interval but the optimum yields and nutrient uptake of both crops as well as cowpea nodulation were obtained when irrigating with water equivalent to 100% field capacity at daily or 2-day interval. The optimum water use efficiency was, however, achieved when irragating with amount equivalent to 100% field capacity at a 2-day interval. Irrigation with water equivalent to 50 or 25% field capacity at any interval resulted in various degrees of moisture stress which manifested in poor crop performance.     

Influence of moisture, heat, and light stress on hydrogen fluoride fumigation injury to soybeans

Soybean (Glycine max (L) Merr.) plants were exposed to a single fumigation with hydrogen fluoride at concentrations sufficient to cause visible injury within 2 days. They were subjected to soil moisture or osmotic stress prior to, during, or after fumigation. Moisture stress before or during fumigation reduced injury because of stomatal closure and reduced fluoride uptake. Moisture stress after fumigation markedly accentuated the injury resulting from a single fumigation compared to plants kept continually under optimum soil moisture conditions. Full sunlight following the fumigation accentuated injury, while shade reduced it. Higher temperatures following fumigation also increased severity of symptoms.     

Preparation of Spherical Crystal Agglomerates of Naproxen Containing Disintegrant for Direct Tablet Making by Spherical Crystallization Technique

The purpose of this research was to obtain directly compressible agglomerates of naproxen containing disintegrant by spherical crystallization technique. Acetone–water containing hydroxypropyl celloluse (HPC) and disintegrant was used as the crystallization system. In this study croscarmellose sodium (Ac–Di–Sol) was employed as disintegrant. The agglomerates were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (XRPD), and scanning electron microscopy and were evaluated for flow, packing and tableting properties and drug release. The growth of particle size and the spherical form of the agglomerates resulted in formation of products with good flow and packing properties. The improved compaction properties of the agglomerated crystals were due to their fragmentation occurred during compression. DSC and XRPD studies showed that naproxen particles, crystallized in the presence of HPC and Ac–Di–Sol did not undergo structural modifications. The dissolution rate of naproxen from tablets made of naproxen–(Ac–Di–Sol) agglomerates was enhanced significantly because of including the disintegrant in to the particles. This was attributed to an increase in the surface area of the practically water insoluble drug is exposed to the dissolution medium. In conclusion the spherical crystallization technique developed in this study is suitable for obtaining agglomerates of drug with disintegrant.     

Water sorption studies of hybrid biofiber-reinforced natural rubber biocomposites

Hybrid biofibers (sisal and oil palm) were incorporated into natural rubber matrix. The water absorption characteristics of the composites were evaluated with reference to fiber loading. The influence of temperature on water sorption of the composites is also analyzed. Moisture uptake was found to be dependent on the properties of the biofibers. The mechanism of diffusion in the gum sample was found to be Fickian in nature, while in the loaded composites, it was non-Fickian. Sisal and oil palm fibers were subjected to different treatments such as mercerization and silanation. The effect of chemical modification on moisture uptake was also analyzed. Chemical modification was seen to decrease the water uptake in the composites. The thermodynamic parameters of the sorption process were also evaluated. Activation energy was found to be maximum for the gum sample.     

Functionality of Disintegrants and Their Mixtures in Enabling Fast Disintegration of Tablets by a Quality by Design Approach

Investigation of the effect of disintegrants on the disintegration time and hardness of rapidly disintegrating tablets (RDTs) was carried out using a quality by design (QbD) paradigm. Ascorbic acid, aspirin, and ibuprofen, which have different water solubilities, were chosen as the drug models. Disintegration time and hardness of RDTs were determined and modeled by executing combined optimal design. The generated models were validated and used for further analysis. Sodium starch glycolate, croscarmellose sodium, and crospovidone were found to lengthen disintegration time when utilized at high concentrations. Sodium starch glycolate and crospovidone worked synergistically in aspirin RDTs to decrease disintegration time. Sodium starch glycolate-crospovidone mixtures, as well as croscarmellose sodium-crospovidone mixtures, also decreased disintegration time in ibuprofen RDTs at high compression pressures as compared to the disintegrants used alone. The use of sodium starch glycolate in RDTs with highly water soluble active ingredients like ascorbic acid slowed disintegration, while microcrystalline cellulose and crospovidone drew water into the tablet rapidly and quickened disintegration. Graphical optimization analysis demonstrated that the RDTs with desired disintegration times and hardness can be formulated with a larger area of design space by combining disintegrants at difference compression pressures. QbD was an efficient and effective paradigm in understanding formulation and process parameters and building quality in to RDT formulated systems.KEY WORDS: disintegrants, quality by design, rapidly disintegrating tablets     

Impact of Physicochemical Environment on the Super Disintegrant Functionality of Cross-Linked Carboxymethyl Sodium Starch: Insight on Formulation Precautions

The aim of this work is to improve the understanding of the physicochemical mechanisms involved in the functionality of cross-linked carboxymethyl sodium starch (CCSS) as a tablet super disintegrant (SD). The behavior and properties of this SD (medium uptake, disintegration times, particle size, and rheology) was investigated in a wetting medium of different physicochemical properties. In particular, the relative permittivity (dielectric constant) of these media was intentionally modified for evaluating its effect on CCSS properties. Results showed different swelling behaviors of CCSS particles according to the relative permittivity of the tested media and allow to propose two underlying mechanisms that explain CCSS functionality. Both the intra-particular swelling and the inter-particular repulsion are affected by the relative permittivity of the media. Finally, disintegration test performed on tablets specially formulated with mannitol (used commonly as an excipient and known to modify relative permittivity) confirmed that the functionality of CCSS and therefore the disintegration of the tablet can be altered according to the mannitol content.KEY WORDS: cross-linked carboxymethyl sodium starch, disintegrant functionality, orally disintegrating tablets, relative permittivity, repulsive layers     

Effect of Polacrilin Potassium as Disintegrant on Bioavailability of Diclofenac Potassium in Tablets : a Technical Note

Polacrilin potassium is an ion exchange resin used in oral pharmaceutical formulations as a tablet disintegrant. It is a weakly acidic cation exchange resin. Chemically, it is a partial potassium salt of a copolymer of methacrylic acid with divinyl benzene. It ionizes to an anionic polymer chain and potassium cations. It was hypothesized that polacrilin potassium may be able to improve the permeability of anionic drugs according to the Donnan membrane phenomenon. The effect of polacrilin potassium on the permeability of diclofenac potassium, used as a model anionic drug, was tested in vitro using diffusion cells and in vivo by monitoring serum levels in rats. The amount of drug permeated across a dialysis membrane in vitro was significantly more in the presence of polacrilin potassium. Significant improvement was found in the extent of drug absorption in vivo. It could be concluded that polacrilin potassium may be used as a high-functionality excipient for improving the bioavailability of anionic drugs having poor gastrointestinal permeability.     

A study on moisture isotherms of formulations: the Use of polynomial equations to predict the moisture isotherms of tablet products

The objectives of this study were to investigate the effects of manufacturing parameters on the moisture sorption isotherms of some tablet formulations and to predict the moisture isotherms of the final formulations using polynomial equations. Three tablet formulations including a placebo and 2 drug products were prepared through wet granulation, drying, compression, and coating processes. Equilibrium moisture content of excipients and granules at 25°C with different relative humidities were determined using a dynamic moisture sorption microbalance, while such data for tablets were determined using desiccators. Moisture sorption isotherms were expressed in polynomial equations. Excipient isotherms were used to predict the moisture sorption isotherms of the 3 tablet products. Results showed that different physical properties of granules and tablets, such as particle size distribution, density, and porosity resulting from different granulation and compression conditions did not have significant effect on the moisture isotherms of the materials. Changing coating materials from a powder mixture to a film also did not change the moisture sorption characteristics significantly. The predicted moisture sorption isotherms of the formulations agreed well with the experimental results. These results show that moisture isotherms of solid pharmaceutical products manufactured with conventional processes may be predicted using the isotherms of excipients, and polynomial equations may be used as a tool for the prediction of moisture isotherms.     

An examination of the moisture sorption characteristics of commercial magnesium stearate

The objective of this study was to characterize the moisture sorption of magnesium stearate and the morphological changes, if any, resulting from moisture sorption. Six samples of commercial magnesium stearate USP were examined. Moisture sorption isotherms were obtained at 25°C and 5% to 98% relative humidity (RH) using a moisture balance. Changes in crystal form resulting from moisture sorption were determined by x-ray diffraction. There were differences in the shape of the isotherm, reversibility of moisture uptake, and shape of the hysteresis loop in the isotherms of crystalline and amorphous magnesium stearates. The isotherm of crystalline magnesium stearate was almost parallel to the pressure axis until and RH of ∼80%. The isotherm of the amorphous sample was characterized by continuous uptake of water over the entire range of RH. Exposure of amorphous magnesium stearate to RH greater than 70% resulted in the formation of the trihydrate. The trihydrate was converted into the anhydrous form when heated to a temperature of 100°C to 105°C. The trihydrate could be generated by exposing the anhydrate to RH higher than 70%.     

Relation of soil moisture and air conditioning irrigation to plant water balance,growth characteristics and nutrients uptake in rye and wheat

The results of experiments conducted with autumn rye and summer wheat on sandy loam soil at the Institute for Cereal Production of the Martin-Luther University, Halle-Wittenberg (G.D.R.) have revealed that an increase in soil moisture improved the plant water balance, width of stomata, shoot growth, tiller density, leaf area and growth rate. Net assimilation rate, however, decreased with the increase in soil moisture above 50 per cent water holding capacity. Increased soil moisture improved contents of nitrogen, potassium and phosphorus only during early stages of growth, but their uptake was not reduoed at maturity. Air conditioning irrigation proved superior in respect to all above mentioned characteristics, except the uptake of potassium, which decreased with air conditioning irrigation at higher soil moisture relations.     

土壤水分遥感反演研究进展

土壤水分精确反演对于理解和解决农业生产、生态规划以及水资源管理中的科学与实际问题至关重要。目前,大量的反演算法被广泛用于土壤水分估算,全球土壤水分遥感反演产品不断发布,反演算法与产品数据集的应用前景亟待系统梳理。基于不同谱段遥感探测技术中的土壤水分反演方法存在各自的特点、优势和局限性。除反演方法研究外,土壤水分遥感反演研究热点可被归纳为遥感土壤水分产品评估、在相关领域的应用、数据同化3个方面。大量研究表明土壤水分遥感反演产品在生态、水文、干旱等研究中表现出巨大的潜力,且在部分研究中已经得到应用。但目前土壤水分的遥感观测与应用需求仍存在一定的差距,因此最后对土壤水分遥感反演在探测的精度和准确度两个方面及其解决方案进行了总结与展望。     

Phytoextraction of nitrogen and phosphorus by crops grown in a heavily manured Dark Brown Chernozem under contrasting soil moisture conditions

Phytoextraction of excess nutrients by crops in soils with a long history of manure application may be a viable option for reducing the nutrient levels. This greenhouse study examined the effectiveness of six growth cycles (40 d each) of barley, canola, corn, oat, pea, soybean, and triticale at extracting nitrogen (N) and phosphorus (P) from a Dark Brown Chernozem that had received 180 Mg ha^?1 (wet wt.) of beef cattle feedlot manure annually for 38 years. Moisture content during the study was maintained at either 100% or 50% soil field capacity (SFC). Repeated cropping resulted in an overall decrease in dry matter yield (DMY). The decrease in N and P uptake relative to Cycle 1 was fastest for the cereal grains and less pronounced for the two legumes. However, cumulative N uptake values were significantly greater for corn than the other crops under both moisture regimes. The reduction in soil N was greater under the 100% than the 50% SFC. These results indicate that repeated cropping can be a useful management practice for reducing N and P levels in a heavily manured soil. The extent of reduction will be greater for crops with high biomass production under adequate moisture supply.     

Effect of soil moisture stress on legume-rhizobium symbiosis in soybeans

Summary In a pot culture experiment, the influence of soil moisture stress at different physiological stages of soybean, cv. Hark, on nodulation, symbiosis and nitrogen accumulation was studied. Moisture stress reduced leghemoglobin content of root nodules and nitrogen uptake by plants. It had no effect on number of bacteroids. Stress at mid bloom and rapid pod filling stages reduced yield and seed protein content. However, these parameters were not affected by stress at nodule initiation and early flowering stages, though, flower initiation and maturity of the plant were delayed. Moisture stress at any stage did not alter nitrogen status of roots.     

A quantitative analysis of varietal and moisture status effects on the growth of Vicia faba in relation to radiation absorption

Growth of two cultivars of Vicia faba, under various conditions of moisture status, was analysed in terms of solar radiation absorbed by their foliage. The relationship between dry-matter production and absorbed photosynthetically active radiation was linear throughout the growing season for both cultivars (Minica and Alfred) and for all levels of soil moisture status. A straight line was used, the slope of which represented a constant mean seasonal ‘efficiency’ of conversion of radiation into biomass. Moisture stress reduced both the amount of radiation intercepted, by limiting the size of the canopy, and the efficiency of its conversion into dry matter. Efficiency of both cultivars grown under optimal water regimes was similar, however, drought had a more drastic effect on conversion efficiency of Minica. Mean crop growth rates were highly dependent upon both absorption and efficiency, as were maximum crop growth rates during the linear portion of growth. Reductions in seed yield were similar to trends in total biomass production. Harvest index was reduced by moisture stress in Minica, and increased to compensate for dry-matter loss in Alfred.