NMR imaging of high-amylose starch tablets. 1. Swelling and water uptake

Pharmaceutical tablets made of modified high-amylose starch have a hydrophilic polymer matrix into which water can penetrate with time to form a hydrogel. Nuclear magnetic resonance imaging was used to study the water penetration and the swelling of the matrix of these tablets. The tablets immersed in water were imaged at different time intervals on a 300 MHz NMR spectrometer. Radial images show clearly the swelling of the tablets and the water concentration profile. The rate constants for water diffusion and the tablet swelling were extracted from the experimental data. The water diffusion process was found to follow case II kinetics at 25 degrees C. NMR imaging also provided spin density profiles of the water penetrating inside the tablets.     

NMR imaging of high-amylose starch tablets. 2. Effect of tablet size

Carbohydrate polymers are widely used for pharmaceutical applications such as the controlled release of drugs. The swelling and water mobility in high-amylose starch tablets are important parameters to be determined for these applications. They have been studied at different time intervals by nuclear magnetic resonance imaging (NMRI) after the immersion of the samples in water. These tablets have a hydrophilic matrix, which swells anisotropically and forms a hydrogel in water. NMRI shows clearly the anisotropy of the water penetration and the swelling along the radial and axial dimensions of the tablets. Empirical relationships are established to describe the kinetics of water penetration and swelling of the tablets. Results show that water uptake and tablet swelling strongly depend on the size of the tablets. Gravimetric measurements of water uptake were also performed in comparison with the NMRI results.     

Membrane formation and drug loading effects in high amylose starch tablets studied by NMR imaging

Cross-linked high amylose starch is used as an excipient in the preparation of pharmaceutical tablets for the sustained release of drugs. NMR imaging with contrast enhanced by proton density and by self-diffusion coefficient was used to follow the water uptake and swelling, two critical parameters controlling the drug release of the cross-linked starch tablets containing 10 wt % of ciprofloxacin and of acetaminophen, respectively. The drug-loaded tablets were studied in a H2O/D2O mixture at 37 degrees C in comparison to the tablets without any drug loading. The diffusion of water in the tablets all showed a Fickian behavior, but the kinetics of water uptake was faster in the case of the drug-loaded tablets. The formation of a membrane at the water/tablet interface was observed.     

On the effect of surface active agents and their structure on the temperature-induced changes of normal and waxy wheat starch in aqueous suspension. Part II: A confocal laser scanning microscopy study

The location and penetration patterns of two fluorescently labelled, surface active molecules into normal and waxy wheat starch granules prior, during and after the temperature-induced gelatinization were studied by means of confocal laser scanning microscopy (CLSM). Amphiphilic dyes were found to have a tendency to penetrate wheat starch granules in aqueous suspension. The penetration patterns were however found to be dependent on the contact time, type of starch and the chain length (C₁₂ vs. C₁₆) of the amphiphilic dye. The penetration of amphiphilic dyes through the starch granule matrix proved to be less restricted in waxy than in normal wheat starch. For a given type of starch, the penetration of the longer chain dye was more constrained than that of the shorter chain one. The extent to which the dye diffuses into the granule matrix as it gelatinizes is also affected by the chain length of the dye, diffusion of the shorter chain dye occurring more profusely and at lower temperatures than for the longer chain one. These differences are suggested to be related to the dissociation temperature of the AM-amphiphilic dye complexes.     

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     

A study of water diffusion into a high-amylose starch blend: the effect of moisture content and temperature

The effect of moisture content and temperature on water diffusion into a modified high amylose (< or = 90%) maize thermoplastic starch blend was investigated. Gravimetric and magnetic resonance imaging (MRI) studies were conducted to elucidate the diffusion mechanism and diffusion coefficients for this system. The diffusion coefficient data demonstrated that the rate of water diffusion into this blend was significantly dependent upon temperature and moisture content. Water diffusion was faster at higher temperatures and generally for samples stored at higher relative humidity environments. It was revealed from the gravimetric data that water diffusion into this starch blend was Fickian; however, further analysis of the MRI images found that the water diffusion mechanism was exponentially dependent on the concentration. This result was determined by comparing experimental water concentration profiles to a theoretical model calculated using the implicit Crank-Nicolson finite difference method.     

Solubility and diffusion of nitrogen in maltodextrin/protein tablets

The gas transport properties of compacted tablets consisting of an amorphous mixture of maltodextrin and sodium caseinate were studied by dissolving nitrogen gas in the tablets and then determining the gas release over time as a function of temperature and water activity. Gas was dissolved in the tablet matrix by heating the tablets under pressure, generally to temperatures above the glass transition temperature of the matrix, holding them at these conditions for a specified time and then rapidly cooling them while maintaining the external pressure. The solubility of nitrogen was found to be largely determined by the free volume of the matrix, which in turn can be influenced to some degree by thermal and pressure treatments during gas loading. At the levels of free volume studied, the dissolved nitrogen is densely packed in the free volume, the packing density being virtually independent of the externally applied pressure. Release of gas from the tablets at temperatures below the glass transition temperature is generally well described by Fickian diffusion. The effective diffusion coefficient of gas release is strongly dependent on the microstructure and porosity of the tablet matrix, and an approximate model describing the relationship between tablet structure and rate of gas release is formulated. The model is in semiquantitative agreement with the rates of gas diffusion obtained for tablets and dense granules. Owing to the structural heterogeneity and variability of the tablets and the history-dependent properties of the tablet matrix, the effective diffusion coefficients of gas release from the tablets showed a relatively large spread. The temperature dependence of diffusional release follows an Arrhenius relation below the glass transition temperature. This allows the prediction of the nitrogen retention in the tablets as function of time, temperature and pressure.     

Heat-induced temperature sensitivity of outgrowing Bacillus cereus spores.

Inactivation of Bacillus cereus spores during cooling (10 degrees C/h) from 90 degrees C occurred in two phases. One phase occurred during cooling from 90 to 80 degrees C; the second occurred during cooling from 46 to 38 degrees C. In contrast, no inactivation occurred when spores were cooled from a maximum temperature of 80 degrees C. Inactivation of spores at a constant temperature of 45 degrees C was induced by initial heat treatments from 80 to 90 degrees C. The higher temperatures accelerated the rate of inactivation. Germination of spores was required for 45 degrees C inactivation to occur; however, faster germination was not the cause of accelerated inactivation of spores receiving higher initial heat treatments. Repair of possible injury was not observed in Trypticase soy broth (BBL Microbiology Systems), peptone, beef extract, starch, or L-alanine at 30 or 35 degrees C. Microscopic evaluation of spores outgrowing at 45 degrees C revealed that when inactivation occurred, outgrowth halted at the swelling stage. Inhibition of protein synthesis by chloramphenicol at the optimum temperature also stopped outgrowth at swelling; thus protein synthesis may play a role in the 45 degree C inactivation mechanism.     

Oxidized and acid thinned starch derivatives of hybrid maize: functional characteristics, wide-angle X-ray diffractometry and thermal properties

Starch isolated from hybrid maize (8535-23) was subjected to oxidation and acid thinning. Proximate analyses revealed that moisture, ash, protein, fat, fibre, and pH reduced after oxidation and acid thinning. Percentage amylose content reduced from 20.42% in native starch to 18.76 and 17.65% in oxidised and acid thinned starch derivatives, respectively. Wide-angle X-ray diffraction patterns indicated strong peaks at 15.9 degrees, 17.2 degrees, 18.8 degrees, and 25.0 degrees 2theta. No significant difference was observed between the X-ray pattern of the native and modified starches. Both swelling power and solubility increased with increase in temperature. Oxidation and acid thinning reduced swelling power and increased solubility starch. At all pHs, both oxidation and acid thinning reduced the swelling capacity of the native starch. Oxidation increased water and oil absorption capacity of the native starch, while both hydrophilic and hydrophobic properties reduced following acid thinning. Least gelation concentration reduced in acid thinned starch but increased in oxidised derivative. Pasting temperature (Tp), peak viscosity (Pv), hot paste viscosity (Hv), and viscosity after 30 min holding at 95 degrees C (H(v30)) reduced following both modifications. However, values for cold paste viscosity (Cv) and setback (SB) reduced in oxidised derivative and increased in acid thinned starch. Light transmittance of the starch pastes reduced with increase in storage days, however, reduction was more pronounced in native and acid thinned starches. Onset temperature (To), peak temperature (Tp) and conclusion temperature (Tc) of gelatinisation reduced in modified starches compared with native hybrid maize starch. Also, gelatinisation enthalpy reduced after oxidation and acid thinning. Enthalpy of regelatinisation increased as days of storage of starch paste increased.     

Identification of the thermal transitions in potato starch at a low water content as studied by preparative DSC

The aim of this work was to identify the transitions in the complex DSC profiles of potato starch at a low water content. Preparative DSC involves the thermal processing of samples in stainless steel DSC pans in a way that allows their subsequent structural characterization. The low temperature (LT), dual melting (M1–M2), and high temperature (HT) endotherms observed in DSC profiles of potato starch with 16% water were assigned to enthalpy relaxation, melting with preservation of granular identity, and transition of the melted granules into a molecular melt, respectively. Granular melting was accompanied by a strong reduction of swelling capacity. Significant molecular degradation was observed after the HT transition. There is evidence that HT does not represent a true thermodynamic transition, but is due to a volume change in the sample. In contrast to potato starch, maize starch with 16% water gave inhomogeneous samples after processing, presumably because of its low packing density.     

Encapsulation of R. planticola Rs-2 from alginate-starch-bentonite and its controlled release and swelling behavior under simulated soil conditions

The plant growth-promoting bacteria (PGPR) Raoultella planticola Rs-2 was encapsulated with the various blends of alginate, starch, and bentonite for development of controlled-release formulations. The stability and release characteristics of these different capsule formulations were evaluated. The entrapment efficiency of Rs-2 in the beads (capsules) was more than 99%. The diameter of dry beads ranged from 0.98 to 1.41 mm. The bacteria release efficiency, swelling ratio, and biodegradability of the different bead formulations were enhanced by increasing the starch or alginate contents, but were impeded by higher bentonite content. The release kinetics of viable cells from capsules and the swelling ratio of capsules were studied in simulated soil media of varying temperature, moisture, pH, and salt content. The release of loaded Rs-2 cells and swelling of capsules are greatly affected by moisture, temperature, pH and salt content of the release medium. The release of viable Rs-2 cells from capsules was positively associated with the swelling properties of the capsules. The release of Rs-2 cells occurred through a Case II diffusion mechanism. In summary, this work indicates that alginate-starch-bentonite blends are a viable option for the development of efficient controlled-release formulations of Rs-2 biofertilizer, and which could have a promising application in natural field conditions.     

Permeation of volatile compounds through starch films

The aim of this study was to gain insight into the factors that affect the permeation of volatiles through starch films. These films were obtained by casting gelatinized starch/water/glycerol mixtures. The films were dried and conditioned under different conditions (temperature and relative humidity) resulting in films that vary in the degree of starch crystallinity and glycerol and water content. The permeation of two model volatiles (carvone and diacetyl) at 20 degrees C and at 30, 60, or 90% relative humidity (RH) was analyzed gravimetrically. Further, the solubility of the two model compounds (under conditions where the permeation experiments were carried out) was determined. From the obtained permeation and solubility data, the diffusion coefficients of these compounds in the different starch films were calculated. The crystallinity in the starch films increased with increasing water content of the films during preparation. The water content of the resulting films in turn increased with increasing glycerol and when the films were exposed to a higher RH during drying or conditioning. For films with the same composition, the flux for diacetyl was greater than for carvone. The solubilities of diacetyl and carvone were slightly dependent on the properties of the films. It was found that with increasing starch crystallinity the diffusion coefficient for both compounds decreases, which is probably due to the impermeability of starch crystallites. Interestingly, in films with about the same extent of crystallinity, the diffusion can be described with the free volume model, with water and glycerol determining the amount of free volume.     

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.     

Solvent Penetration Rate in Tablet Measurement Using Video Image Processing

We describe a simple technique for the measurement of solvent penetration rates into spray-dried lactose (DCL) tablets and tablets made of blended materials using digital video image processing. The results of the experimental study show that the penetration rate in some cases appears to be close to linear with time, which corresponds to non-Fickian or Case II-type diffusion. We discuss relevant capillary invasion models in order to explain the observed penetration rate. The proposed technique allows fast diffusion rate acquisition/processing and can be useful when designing immediate release tablets that require a large number of measurements corresponding to different formulations and processing parameters.     

Evaluation of Mimosa pudica Seed Mucilage as Sustained-Release Excipient

The present study was conducted to investigate the sustained-release properties of Mimosa pudica seed mucilage. Matrix tablets of diclofenac sodium containing different proportions of mucilage and dibasic calcium phosphate as diluent were formulated by wet granulation method. The tablets had uniform physical appearance, average weight, drug content, and adequate hardness. The results of in vitro release conducted using USP type II dissolution rate apparatus, in a dissolution media comprising of 900 mL of 0.1 N HCl for 2 h followed by phosphate buffer (pH 6.8) for 24 h at 37°C and 50 rpm, revealed that as the proportion of mucilage in the matrix was increased there was a corresponding decrease in the release of drug. Further, the matrix tablets were found to release the drug following Higuchi square root release kinetics, with the mechanism of release being diffusion for tablets containing higher proportion of mucilage and a combination of matrix erosion and diffusion for tablets containing smaller proportion of mucilage. The swelling and erosion studies revealed that, as the proportion of mucilage in tablets was increased, there was a corresponding increase in percent swelling and a decrease in percent erosion of tablets. The SEM photomicrographs showed gelling structures in tablets containing higher percentage of mucilage, while both pores and gelling structures were present on the surface of tablets containing smaller proportion of mucilage and commercial formulation. On comparative evaluation, the dissolution profile from formulation containing mucilage to drug in the proportion of 1:40 was found to be similar to the commercial sustained-release formulation of diclofenac.     

Heat-induced temperature sensitivity of outgrowing Bacillus cereus spores

Inactivation of Bacillus cereus spores during cooling (10 degrees C/h) from 90 degrees C occurred in two phases. One phase occurred during cooling from 90 to 80 degrees C; the second occurred during cooling from 46 to 38 degrees C. In contrast, no inactivation occurred when spores were cooled from a maximum temperature of 80 degrees C. Inactivation of spores at a constant temperature of 45 degrees C was induced by initial heat treatments from 80 to 90 degrees C. The higher temperatures accelerated the rate of inactivation. Germination of spores was required for 45 degrees C inactivation to occur; however, faster germination was not the cause of accelerated inactivation of spores receiving higher initial heat treatments. Repair of possible injury was not observed in Trypticase soy broth (BBL Microbiology Systems), peptone, beef extract, starch, or L-alanine at 30 or 35 degrees C. Microscopic evaluation of spores outgrowing at 45 degrees C revealed that when inactivation occurred, outgrowth halted at the swelling stage. Inhibition of protein synthesis by chloramphenicol at the optimum temperature also stopped outgrowth at swelling; thus protein synthesis may play a role in the 45 degree C inactivation mechanism.     

Silicone Adhesive Matrix of Verapamil Hydrochloride to Provide pH-Independent Sustained Release

Providing pH-independent oral release of weakly basic drugs with conventional matrix tablets can be challenging because of the pH-dependent solubility characteristics of the drugs and the changing pH environment along the gastrointestinal tract. The aim of the present study was to use a hydrophobic polymer to overcome the issue of pH-dependent release of weakly basic model drug verapamil hydrochloride from matrix tablets without the use of organic buffers in the matrix formulations. Silicone pressure-sensitive adhesive (PSA) polymer was evaluated because of its unique properties of low surface energy, hydrophobicity, low glass transition temperature, high electrical resistance, and barrier to hydrogen ion diffusion. Drug release, hydrogen ion diffusion, tablet contact angle, and internal tablet microenvironment pH with matrix tablets prepared using PSA were compared with those using water-insoluble ethyl cellulose (EC). Silicone PSA films showed higher resistance to hydrogen ion diffusion compared with EC films. Verapamil hydrochloride tablets prepared using silicone PSA showed higher hydrophobicity and lower water uptake than EC tablets. Silicone PSA tablets also showed pH-independent release of verapamil and decreased in dimensions during drug dissolution. By contrast, verapamil hydrochloride tablets prepared using EC did not achieve pH-independent release.     

Characterization and in vitro evaluation of starch based hydrogels as carriers for colon specific drug delivery systems

A series of starch/methacrylic acid (MAAc) copolymer hydrogels of different compositions were synthesized using γ-rays induced polymerization and crosslinking. The effects of the preparation conditions such as the feed solution concentration, feed solution composition and irradiation dose on the gelation process of the synthesized copolymer were investigated. The swelling behavior of the starch/methacrylic acid (MAAc) copolymer hydrogels was characterized by studying the effect of the hydrogel composition on the time- and pH-dependent swelling. Swelling kinetics showed that the synthesized hydrogels possessed Fickian diffusion behavior at pH 1 and non-Fickian diffusion at pH 7 which recommend them as good candidate for colon specific drug delivery systems. The synthesized hydrogels were loaded with ketoprofen as a model drug to investigate the release behavior of the synthesized hydrogels. The results showed the ability of the hydrogels to keep the loaded drug at pH 1 and release it at pH 7. The data also showed that the release rate can be controlled by controlling the preparation conditions such as comonomer concentration and composition and irradiation dose.     

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     

THE KINETICS OF OSMOTIC SWELLING IN LIVING CELLS

The rate of swelling of unfertilized sea urchin eggs in hypotonic sea water was investigated. Analysis of curves leads to the following conclusions. 1. The rate of swelling follows the equation, See PDF for Equation where V _eq., V ₀, and V_t stand for volume at equilibrium, at first instant, and at time t, respectively, the other symbols having their usual significance. This equation is found to hold over a wide range of temperatures and osmotic pressures. This relation is the one expected in a diffusion process. 2. The rate of swelling is found to have a high temperature coefficient (Q ₁₀ = 2 to 3, or µ = 13,000 to 19,000). This deviation from the usual effect of temperature on diffusion processes is thought to be associated with changes in cell permeability to water. The possible influence of changes in viscosity is discussed. 3. The lower the osmotic pressure of the solution, the longer it takes for swelling of the cell. Thus at 15° in 80 per cent sea water, the velocity constant has a value of 0.072, in 20 per cent sea water, of 0.006.