Effects of pigeon pea and plantain starches on the compressional, mechanical, and disintegration properties of paracetamol tablets

A study has been made of the effects of pigeon pea starch obtained from the plant Cajanus cajan (L) Millisp. (family Fabaceae) and plantain starch obtained from the unripe fruit of Musa paradisiaca L. (family Musaceae) on the compressional, mechanical, and disintegration properties of paracetamol tablets in comparison with official corn starch BP. Analysis of compressional properties was done by using density measurements, and the Heckel and Kawakita equations, whereas the mechanical properties of the tablets were evaluated by using tensile strength (T--a measure of bond strength) and brittle fracture index (BFI--a measure of lamination tendency). The ranking for the mean yield pressure, P(y), for the formulations containing the different starches was generally corn < pigeon pea < plantain starch while the ranking for P(k), an inverse measure of the amount of plasticity, was pigeon pea < plantain < corn starch, which indicated that formulations containing corn starch generally exhibited the fastest onset of plastic deformation, whereas those formulations containing pigeon pea starch exhibited the highest amount of plastic deformation during tableting. The tensile strength of the tablets increased with increase in concentration of the starches while the Brittle Fracture Index decreased. The ranking for T was pigeon pea > plantain > corn starch while the ranking for BFI was corn > plantain > pigeon pea starch. The bonding capacity of the formulations was in general agreement with the tensile strength results. The disintegration time (DT) of the formulation increased with concentration of plantain and corn starches but decreased with concentration of pigeon pea starch. The general ranking of DT values was plantain < pigeon pea < corn starch. Notably, formulations containing pigeon pea starch exhibited the highest bond strength and lowest brittleness, suggesting the usefulness of pigeon pea starch in producing strong tablets with minimal lamination tendency. Plantain starch, on the other hand, would be more useful where faster disintegration of tablet is desired. The results show that the starches could be useful in various formulations depending on the intended use of the tablets with the implication that the experimental starches can be developed for commercial purposes.     

Effects of Pigeon Pea and Plantain Starches on the Compressional,Mechanical, and Disintegration Properties of Paracetamol Tablets

ABSTRACT

A study has been made of the effects of pigeon pea starch obtained from the plant Cajanus cajan (L) Millisp. (family Fabaceae) and plantain starch obtained from the unripe fruit of Musa paradisiaca L. (family Musaceae) on the compressional, mechanical, and disintegration properties of paracetamol tablets in comparison with official corn starch BP. Analysis of compressional properties was done by using density measurements, and the Heckel and Kawakita equations, whereas the mechanical properties of the tablets were evaluated by using tensile strength (T-a measure of bond strength) and brittle fracture index (BFI-a measure of lamination tendency). The ranking for the mean yield pressure, P_y, for the formulations containing the different starches was generally corn < pigeon pea < plantain starch while the ranking for P_k, an inverse measure of the amount of plasticity, was pigeon pea < plantain < corn starch, which indicated that formulations containing corn starch generally exhibited the fastest onset of plastic deformation, whereas those formulations containing pigeon pea starch exhibited the highest amount of plastic deformation during tableting. The tensile strength of the tablets increased with increase in concentration of the starches while the Brittle Fracture Index decreased. The ranking for T was pigeon pea > plantain > corn starch while the ranking for BFI was corn > plantain > pigeon pea starch. The bonding capacity of the formulations was in general agreement with the tensile strength results. The disintegration time (DT) of the formulation increased with concentration of plantain and corn starches but decreased with concentration of pigeon pea starch. The general ranking of DT values was plantain < pigeon pea < corn starch. Notably, formulations containing pigeon pea starch exhibited the highest bond strength and lowest brittleness, suggesting the usefulness of pigeon pea starch in producing strong tablets with minimal lamination tendency. Plantain starch, on the other hand, would be more useful where faster disintegration of tablet is desired. The results show that the starches could be useful in various formulations depending on the intended use of the tablets with the implication that the experimental starches can be developed for commercial purposes.     

Crosslinked Starch as Sustained Release Agent

Different types of crosslinked starches and pregelatinized-crosslinked starches were evaluated for their use as hydrophilic matrices. Some fundamental properties of these chemically modified starches, e.g. granule swelling power and viscosity of the dispersion in function of pH and ionic strength, were studied. Dissolution tests and the rate and amount of water uptake were evaluated on tablets containing theophylline and modified starch (40/60 w/w), compressed on an instrumented tablet press at three different pressures (50,200 and 300 MPa.). Theophylline releasing profiles were determined using the paddle system at a rotational speed of 50 rpm Water, simulated gastric fluid, and simulated intestinal fluid were used as dissolution media. Crosslinked starches showed a poor swelling power and dispersion viscosity in comparison to pregelatinized starch and pregelatinized-crosslinked starches. The pregelatinized-crosslinked starches developed less swelling power than the pregelatinized starch, but they showed higher dispersion viscosity than the pregelatinized starch. The viscosity of all starch dispersions was not affected by ionic strength. An alkaline pH dramatically increased the dispersion viscosity of pregelatinized starch and pregelatinized-crosslinked starches. Drug dissolution rate was lower for tablets containing pregelatinized starch than for tablets containing pregelatinized-crosslinked starches. This phenomenon can be related to the rate and amount of water uptake. The dissolution rate seemed not to be influenced by the compression force nor by the composition of the dissolution media. The results indicate that crosslinked starches, either pregelatinized or not, are not suitable as sustained release agents.     

Effects of Temperature,Humidity, and Aging on the Disintegration and Dissolution of Acetaminophen Tablets

Abstract

The effect of storage for 8 weeks at 40°C in moderate and high humidity on acetaminophen tablets prepared by the wet granulation method using povidone or pregelatinized starch as a binder was studies. Storage at 52% relative humidity produced an increase in hardness of acetaminophen tablets and storage at 94% relative humidity caused a decrease in hardness. In all cases tablets granulated with pregelatinized starch were less susceptible to change caused by humidity than tablets granulated with povidone. The disintegration of tablets containing starch or povidone was slowed as the humidity was increased. Tablets stored at 40 =C and 94 V. relative humidity showed a substantial slowing of dissolution, but there was little change of dissolution of tablets when aged at 40 -C / 52% relative humidity. In comparing starch and povidone as binders, acetaminophen tablets prepared with pregelatinized starch were less effected by high humidity than tablets prepared with povidone.     

Indices of Tableting Performance for Acrylic Resin Polymers with Plastic and Brittle Drugs

Abstract

The indices of tableting performance were used to investigate the compaction properties of two methacrylate ester copolymers (Eudragit® RS PM and RL PM) and three methacrylic acid copolymers (Eudragit® S 100, L 100, and L 100–55). These polymers were designed to be incorporated directly into solid dosage forms for controlled-release purposes. The polymers were combined in the dry state with either sodium sulfathiazole (a brittle drug) or theophylline (a plastic drug) at concentrations ranging from 0 to 100% polymer. All powders were blended for 15 minutes and compacts measuring 1 inch square and weighing 5 g each were made using a die that decompressed triaxially and a Carver® press equipped with a strain gauge. Solid fractions were kept constant at 0.81. Two of the tableting indices, the bonding index (BI) and brittle fracture index (BFI), were studied for all mixtures. The BFI of the sulfonamide (0.49) was nearly three times greater than the BFI for theophylline(0.17) The three methacrylic acid copolymers had high BFI values ranging from 0.99 to 1.60, demonstrating the brittle characteristics of these polymers. The BFI decreased with increasing drug content in all cases. Of the five polymers, the BI was greatest for Eudragit® L 100–55 with both drugs, especially at the 20% drug concentration, followed by Eudragits L 100 and S 100. These three resins were prepared by a spray-drying process. The strongest interactions (positive deviations for the BFI; negative deviations for indentation hardness and BI) of either drug with the polymers were always seen with the spray-dried materials. Low bonding indices were obtained for both of the methacrylate ester copolymers. However, all mixtures of both drug with these milled polymers (RL PM and RS PM) formed successful tablets.     

The 3D model: explaining densification and deformation mechanisms by using 3D parameter plots

The aim of the study was to analyze very differently deforming materials using 3D parameter plots and consequently to gain deeper insights into the densification and deformation process described with the 3D model in order to define an ideal tableting excipient. The excipients used were dicalcium phosphate dihydrate (DCPD), sodium chloride (NaCl), microcrystalline cellulose (MCC), xylitol, mannitol, alpha-lactose monohydrate, maltose, hydroxypropyl methylcellulose (HPMC), sodium carboxymethylcellulose (NaCMC), cellulose acetate (CAC), maize starch, potato starch, pregelatinized starch, and maltodextrine. All of the materials were tableted to graded maximum relative densities (rhorel, max) using an eccentric tableting machine. The data which resulted, namely force, displacement, and time, were analyzed by the application of 3D modeling. Different particle size fractions of DCPD, CAC, and MCC were analyzed in addition. Brittle deforming materials such as DCPD exhibited a completely different 3D parameter plot, with low time plasticity, d, and low pressure plasticity, e, and a strong decrease in omega values when densification increased, in contrast to the plastically deforming MCC, which had much higher d, e, and omega values. e and omega values changed only slightly when densification increased for MCC. NaCl showed less of a decrease in omega values than DCPD did, and the d and e values were between those of MCC and DCPD. The sugar alcohols, xylitol and mannitol, behaved in a similar fashion to sodium chloride. This is also valid for the crystalline sugars, alpha-lactose monohydrate, and maltose. However, the sugars are more brittle than the sugar alcohols. The cellulose derivatives, HPMC, NaCMC, and CAC, are as plastic as MCC, however, their elasticity depends on substitution indicated by lower (more elastic) or higher (less elastic) omega values. The native starches, maize starch and potato starch, are very elastic, and pregelatinized starch and maltodextrine are less elastic and exhibited higher omega values. Deformation behavior as shown in 3D parameter plots depends on particle size for polymers such as CAC and MCC; however, it does not depend on particle size for brittle materials such as DCPD. An ideally deforming tableting excipient should exhibit high e, d, and omega values with a constant ratio of e and omega at increasing densification.     

Indices of Tableting Performance for Acrylic Resin Polymers with Plastic and Brittle Drugs

The indices of tableting performance were used to investigate the compaction properties of two methacrylate ester copolymers (Eudragit® RS PM and RL PM) and three methacrylic acid copolymers (Eudragit® S 100, L 100, and L 100-55). These polymers were designed to be incorporated directly into solid dosage forms for controlled-release purposes. The polymers were combined in the dry state with either sodium sulfathiazole (a brittle drug) or theophylline (a plastic drug) at concentrations ranging from 0 to 100% polymer. All powders were blended for 15 minutes and compacts measuring 1 inch square and weighing 5 g each were made using a die that decompressed triaxially and a Carver® press equipped with a strain gauge. Solid fractions were kept constant at 0.81. Two of the tableting indices, the bonding index (BI) and brittle fracture index (BFI), were studied for all mixtures. The BFI of the sulfonamide (0.49) was nearly three times greater than the BFI for theophylline(0.17) The three methacrylic acid copolymers had high BFI values ranging from 0.99 to 1.60, demonstrating the brittle characteristics of these polymers. The BFI decreased with increasing drug content in all cases. Of the five polymers, the BI was greatest for Eudragit® L 100-55 with both drugs, especially at the 20% drug concentration, followed by Eudragits L 100 and S 100. These three resins were prepared by a spray-drying process. The strongest interactions (positive deviations for the BFI; negative deviations for indentation hardness and BI) of either drug with the polymers were always seen with the spray-dried materials. Low bonding indices were obtained for both of the methacrylate ester copolymers. However, all mixtures of both drug with these milled polymers (RL PM and RS PM) formed successful tablets.     

Evaluation of the effects of khaya gum on the mechanical and release properties of paracetamol tablets

A study of the comparative effects of khaya gum and two standard binding agents-polyvinylpyrrolidone (PVP) and gelatin--on crushing strength and friability, and the disintegration and dissolution characteristics of paracetamol tablets was made. The crushing strength-friability ratio (CSFR), the disintegration times, D, and the dissolution times t50, t90, and t1 (derived from the equation of Noyes and Whitney), all increased with an increase in binder concentration; however, the dissolution rate constants, k1 and k2, decreased. The ranking for the values of CSFR for tablets containing the different binders was PVP > gelatin > khaya gum. The ranking for D and the dissolution times was gelatin > khaya gum > PVP, whereas the ranking for the dissolution rate constants was PVP > khaya gum > gelatin. There were significant linear correlations between CSFR, D, t50, t90, and t1 for the tablets. There were also significant correlations between k1 and D, t50, t90, and t1, and between k2 and t90. The results suggest that khaya gum could be useful as an alternative binding agent to produce tablets with particular mechanical strength and drug release profiles.     

Comparison of Disintegrant and Binder Activity of Three Corn Starch Products

Abstract

This study demonstrates the differences obtained when using different corn starch products as both binder and disintegrant in pharmaceutical tablets. Formulations made with Fluftex W, Tablet White and Purity 21 starches were compared. In addition, Avicel PH101 was used in this study as a benchmark component whose properties are well understood.

Four test formulations containing hydrochlorothiazide were prepared by wet granulation. Starch was incorporated in both powder and paste form. All granulations were found to possess similar traits when evaluated based upon geometric mean diameter, particle size distribution, bulk/tap densities, powder flow rate and surface characteristics.

Tablets prepared from these granulations were shown to be similar when evaluated for degree of friability, weight and content uniformity. All starch formulations disintegrated within 30 seconds and produced similar dissolution profiles. Tablets produced with Avicel, however, were found to exhibit significantly longer disintegration times than the starch formulations. In addition, these tablets displayed a dissolution profile that was significantly different than the starch formulations, particularly during the earlier stages of the dissolution process.

When monitoring compression and ejection forces required to produce tablets of the same degree of hardness (≈6kg), Fluftex W and Tablet White granulations were found to use significantly lower forces than the Purity 21 granulation. This may be indicative of Fluftex W and Tablet White's superiority over Purity 21 in terms of binder capacity.     

Comparison of Disintegrant and Binder Activity of Three Corn Starch Products

Abstract

This study demonstrates the differences obtained when using different corn starch products as both binder and disintegrant in pharmaceutical tablets. Formulations made with Fluftex W, Tablet White and Purity 21 starches were compared. In addition, Avicel PH101 was used in this study as a benchmark component whose properties are well understood.

Four test formulations containing hydrochlorothiazide were prepared by wet granulation. Starch was incorporated in both powder and paste form. All granulations were found to possess similar traits when evaluated based upon geometric mean diameter, particle size distribution, bulk/tap densities, powder flow rate and surface characteristics.

Tablets prepared from these granulations were shown to be similar when evaluated for degree of friability, weight and content uniformity. All starch formulations disintegrated within 30 seconds and produced similar dissolution profiles. Tablets produced with Avicel, however, were found to exhibit significantly longer disintegration times than the starch formulations. In addition, these tablets displayed a dissolution profile than was significantly different than the starch formulations, particularly during the earlier stages of the dissolution process.

When monitoring compression and ejection forces required to produce tablets of the same degree of hardness (≈6kg), Fluftex W and Tablet White granulations were found to use significantly lower forces than the Purity 21 granulation. This may be indicative of Fluftex W and Tablet White's superiority over Purity 21 in terms of binder capacity.     

Compressional Behaviour of an Agglomerated Cellulose Powder

Abstract

The ability of an agglomerated cellulose powder to total and plastic deformation was evaluated and compared with those of Avicel PH 101, Emcocel and an experimental depolymerized cellulose powder. The elastic recovely of compressed cellulose tablets was also measured. The effects of deformation of the material during the tableting process and recovery of tablet after maximum compression on the mechanical strength of tablets were also discussed.

The apparent net work done into tablets during compression as well as the yield pressures to total and plastic deformation, determined from the Heckel treatment, showed no great differences between the agglomerated cellulose powder and the other cellulose powders. Thus all the cellulose materials studied had rather similar ability to total, i.e. elastic and plastic, deformation and to permanent, i.e. pure plastic, deformation. The obvious fragmentation of the agglomerated cellulose powder already at low compressional pressure, however, seemed to be advantageous for the formation of strong compacts.     

Directly Compressible Acetaminophen Compositions Prepared by Fluidized-Bed Granulation

Abstract

Polyvinylpyrrolidone (PVP) in aqueous solution was used as a binding agent in a fluidized-bed system to agglomerate acetaminophen powder into directly compressible granules. It was found that a minimal amount of 5% w/w PVP in a concentration of 7.5% w/v or less was needed to produce granules with an acceptable flow and the corresponding tablets having enough hardness without capping. There was a strong correlation between the time for 80% dissolved (T₈₀) and the logarithm of granule volume-surface mean diameter. A directly compressible acetaminophen composition to manufacture tablets having a T₈₀ value less than 30 min can be prepared simply by adding an appropriate amount of disintegrant (crospovidone, sodium starch glycolate, or pregelatinized starch) to the agglomerated granules.     

The Effect of Compaction Force and Type of Pregelatinized Starch on the Dissolution of Acetaminophen

Abstract

The influence of four pregelatinized starches—National® 1551, Lycatabps, Pregeflo®M, and Starch 1500®—as binders, on the dissolution of acetaminophen was evaluated in a model wet-granulated system. Systems containing 82% acetaminophen were prepared under the same processing conditions and compacted to three target tablet thicknesses. The dissolution performance was assessed using a point estimate of percent dissolved at 30 min (%T₃₀) as well as dissolution eflciency through 30 min (DE₃₀). All four binders evaluated meet USP requirements for purity. National 1551, Lycatab PGS, and Starch 1500 were not affected by compaction force in terms of dissolution performance. Differences were observed between the fully pregelatinized systems of National 1551 and Lycatab PGS, in comparison to the partially pregelatinized system, Starch 1500. The Pregeflo M starch produced a system with delayed drug dissolution and was influenced by compaction force.     

Acetylation enhances the tabletting properties of starch

The aim of this study was the evaluation of starch acetate (SA) powders used as tablet excipients. Deformation during powder volume reduction, strain-rate sensitivity, intrinsic elasticity of the materials, and tensile strength of the tablets were examined. Results showed that SA with the lowest degree of substitution (ds) still possessed characteristics of native starch granules. Due to dissolution in synthesis, the properties of higher ds SAs depended on precipitation and drying processes. The acetate moiety, perhaps in combination with existing hydroxyl groups, was a very effective bond-forming substituent. The formation of strong molecular bonds increased, leading to a very firm and intact tablet structure. Small changes existed in compression-induced deformation due to acetylation. Some fragmentation was induced due to the slightly harder and more irregular shape of high-substituted SA particles. The plastic flow under compression was enhanced. Acetylated material was slightly less sensitive to fast elastic recovery in-die, but somewhat more elastic out-of-die. In spite of their superior bonding, SAs under compression behaved similarly to native starches. It was concluded that deformation properties were more the consequence of the molecular chain structure properties of the starch polymer than the effect of the acetate moiety itself. In contrast, the opposite seemed to be the case with the extensive improvement in bond-forming properties.     

Evaluation of the emulsifying properties of some cationic starches

Different cationic potato, maize, and waxy maize starches were evaluated for their emulsifying properties. Emulsions were prepared using 20% (w/w) arachidic oil and 80% (w/w) water. Emulsions with the cationic starches as emulsifier in a concentration ranging from 1% to 5% (w/w) were prepared and characterized by droplet size and viscosity measurements, and the stability was evaluated visually and by electrical conductance measurements. None of the cationic potato, waxy maize starches, and maize starches with a low degree of substitution (DS) showed adequate emulsifying properties. Emulsions prepared using non-pregelatinized (C ☆ bond 05914, 2% and 5% w/w; C ☆ bond 05907, 5% w/w) and pregelatinized (C ☆ bond 12504, 5% w/w) cationic maize starches with high-DS were visually stable. The initial mean droplet volume diameter of the emulsions prepared with these cationic starches in a 5% (w/w) concentration was similar and ranged from 2.40 to 2.84 μm however, there was an important difference in droplet size distribution. The droplet size distribution of the emulsions prepared using the non-pregelatinized high-DS cationic starches was markedly narrower than in the case of the emulsions prepared using the pregelatinized high-DS cationic starches. The droplet size of the emulsions remained almost constant during 120 days of storage. Visual inspection and electrical conductance measurements showed that these emulsions were stable for at least 120 days.     

Spray-Dried Rice Starch: Comparative Evaluation of Direct Compression Fillers

Abstract

Spray-dried rice starch (SDRS), microcrystalline cellulose (MCC), lactose (L), pregelatinized starch (PS), and dibasic calcium phosphate (DCP) were studied for their flow behaviors and tableting properties. Both flow rate and percent compressibility values indicated that SDRS exhibited excellent flowability. The increase in magnesium stearate content reduced the hardness of MCC and SDRS tablets; however, general tablet properties were still acceptable while the PS tablets were unsatisfactory at high lubricant concentrations. The hardness of L or DCP tablets was not affected by the lubricant. The disintegration of L tablets was prolonged with the increased lubricant concentration while that of PS tablets seemed to be decreased due to softened tablets. The disintegration times of MCC and SDRS tablets seemed to be independent of the lubricant added. With respect to the dissolution, SDRS-based tablets offered fast and complete release of the drug regardless of its solubility. SDRS, L, and DCP exhibited comparable carrying capacity for ascorbic acid. The best dilution potential was obtained with MCC while the worst was obtained with PS.     

Optimization of Tablet Formulations Based on Starch/Lactose Granulations for Use in Tropical Countries

Abstract

Several granulations consisting of α-lactose monohydrate 200 mesh and native starch (corn, potato, rice or tapioca) were prepared. The influence of starch concentration, storage temperature and relative humidity on the physical properties of the tablets prepared from these granulations was estimated. Two granulations, which resulted in tablets with adequate initial values of crushing strength and disintegration time and with an acceptable physical stability were selected as standard granulations. The selected standard granulations were evaluated by incorporating a drug (diazepam, 2 mg or mebendazole, 100 mg). The tablet properties were determined one day after preparation. The crushing strength, the disintegration time and the microbiological quality were also measured after storage under tropical conditions. Both selected formulations proved to be adequate for the preparation of tablets by wet granulation, suitable for use in tropical countries.     

A Comparative Study of the use of Enset and Potato Starches in Tablet Formulations

Enset and potato starches have been compared as binding agents and disintegrants in tablets made with paracetamol and chloroquine phosphate. Tablet crushing strengths, friabilities and disintegration times have been measured. The results show that enset starch can be used both as a binding agent and disintegrant. It has a better binding ability than potato starch, giving tablets of lower porosity. However because of this, tablets containing enset starch disintegrate more slowly.     

Characterization of khaya gum as a binder in a paracetamol tablet formulation

The influence of khaya gum, a binding agent obtained from Khaya grandifolia (Meliaceae family), on the bulk, compressional, and tabletting characteristics of a paracetamol tablet formulation was studied in comparison with the effects of two standard binders: polyvinylpyrrolidone (PVP; molecular weight 40,000) and gelatin. The relative ability of khaya gum to destroy any residual microbial contamination in the binder or in the formulation during tabletting was also studied using Bacillus subtilis spores as a model. Formulations containing khaya gum exhibited more densification than formulations containing PVP and gelatin during die filling, but less densification due to rearrangement at low pressures. The mean yield pressure of the formulation particles obtained from Heckel plots, and another pressure term, also inversely related to plasticity, obtained from Kawakita plots, showed dependence on the nature and concentration of the binder, with formulations containing khaya gum exhibiting the lowest and highest values respectively. The values of the pressure terms suggest that the yield pressure relates to the onset of plastic deformation during compression, while the Kawakita pressure relates to the total amount of plastic deformation occurring during the compression process. Tablets made from formulations containing khaya gum had the lowest tensile strength values but also the lowest tendency to laminate or cap, as indicated by their lowest brittleness. All the tablets had friability values < 1% at higher concentrations of the three binders. In addition, khaya gum demonstrated a comparable ability to destroy microorganisms in the formulation during tabletting as the two binders. The characterization of the formulations suggests that khaya gum can be developed into a commercial binding agent for particular tablets.     

Carboxymethylstarches in Wet Granulation

Abstract

Commercialized carboxymethystarches (CMS) are both carboxyme-thylated and cross linked potato starch.

The influence of carboxymethylation and cross linkage on the disintegrating properties of starch are studied.

Tablets are made with acetaminophen as drug, Emcompress as diluant, Magnesium stearat as lubricant, and potato starch or its derivatives as disintegrants.

Tablets are prepared by direct compression or by wet granulation with the disintegrant intervening only in internal phasis.

Five disintegrants were studied, with two different concentrations:

native potato starch

potato starch simply cross linked

potato starch simply carboxymethylated

two potato starches both cross linked and carboxymethylated at two different degrees

Compressibility of powders blending and grain for compression are discussed.

The hardness, the tablet disintegration and the rate of drug dissolution are studied.

The results showed that the simply carboxymethylated starch has a totally different behaviour after direct compression or wet granulation. The poor results after wet granulation could be imputed to the bursting of starch granules during grain drying. Since it has lost its granular structure, the carboxymethylated starch will only allow a poor disintegration and a slow dissolution of the drug.

A very similar behaviour of native and simply cross linked starch: the results of which are bad for tablets either prepared by wet granulation or direct compression.

A very similar behaviour of the starches both carboxymethylated and cross linked, allowing a very good disponibility, either with tablets prepared by direct compression or wet granulation. These experiments prove :

the need for an sufficient cross linkage for CMS in a wet granulation process