An evaluation of starch obtained from pearl millet - Pennisetum typhoides. As a binder and disintegrant for compressed tablets

The binding and disintegrant properties of millet starch obtained from Pearl Millet - Pennisteum typhoides (Staph. Burn, and Hubb.) Fam. Gramineae have been evaluated using tablet formulations of four drugs.

The results showed that Millet starch compared favourably with Maize starch with regards to most of the parameters used to evaluate the tablets. It can be safely concluded that millet starch is suitable for use as a binder and disintegrant in tablet formulations.     

Carboxymethylstarches in Wet Granulation

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     

Comparison of Disintegrant and Binder Activity of Three Corn Starch Products

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

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.     

Factors Affecting Rate of Dissolution of Prednisone from Tablets

A study was carried out to evaluate some parameters which may have an effect on the dissolution rate of prednisone from tablets. The parameters examined involving formulation were: diluent proportion (Lactose-starch), dissintegrant type (starch, explotab (sodium starch glycolate) type of binder (starch paste, gelatine water solution and PVP alcoholic solution), lubricant, and dye concentration. The Manufacturing variables studied were: method of manufacture (wet granulation, direct compression and double compression), granule size in wet granulation and tablet hardness. dissolution profiles of tablets storaged 2 months at 45°C were compared with those of fresh samples. Tablets prepared with prednisone five years old, tablets with fresh active ingredient and tablets with two different prednisone concentrations (5 and 50 mg per tablet) were used for other evaluations.

In all cases micronized prednisone was used and all batches were physically and chemically evaluated before studying their dissolution following the USP basket method.

The parameters studied that affected significatively dissolution rate of prednisone were: type of binder, lubricant concentration, method of manufacture, active ingredient, age and prednisone concentration.     

An Evaluation of Hydroxypropyl Starch as Disintegrant and Binder in Tablet Formulation

Hydroxypropyl and pregelatinized hydroxypropyl starch were evaluated as disintegrant and binder in tablet formulations. The study showed that the use of pure hydroxypropyl starch showed no advantage as a disintegrant or binder over the actually available tablet ingredients. Pregelatinized hydroxypropyl starch showed some good disintegrating properties and could be used as a binder in wet granulation.     

Comparative evaluation of soy polysaccharide as direct compression excipient

Commercial soy polysaccharide (Emcosoy^R) has been evaluated as direct compression excipient in comparison with two frequently used materials, microcrystalline cellulose (Avicel pH 101) and pregelatinized maize starch (Sta-RX 1500).

Moisture sorption and desorption data analysed according to the Young and Nelson and the GAB equations and mechanical properties such as tensile strength, brittle fracture probensity, interparticle bonding isotropy and yield pressure of compacted excipients after storage at various environmental relative humidities are reported. Tableting characteristics such as punch force ratio, weight variation, tensile strength, friability, capping tendency, disintegration and dissolution of mixtures of the excipients and paracetamol are compared.

Emcosoy has been found to behave like Avicel as direct compression binder but like Sta-RX as disintegrant.     

Disintegrants in Solid Dosage Forms

The dynamic approach to tablet disintegration, which is based on the measurement of the force that develops inside the compact upon water entrance, is basically taken up.

The combined measurements of force development and water uptake, simultaneously effected on the same compact, provide a novel parameter that is proposed to quantify and compare the efficiency of disintegrants.

The new parameter, which is based on the “force-equivalent” concept, expresses the capability of a disintegrant of transforming water uptaken into swelling (or disintegrating) force. A few examples, that illustrate the usefulness of this parameter for disintegrant characterization, are given.

In parallel to the quantification of swelling (or disintegrating) efficiency inside compacts, attention is also being paid to the characterization of swelling disintegrants as pure materials.

In particular the case of the so-called limited swelling materials, for which the quantification of intrinsic swelling (particle volume increase in swelling media) is critical, is considered.

The applicability of an instrumental method, which is based on the employment of a Coulter Counter, is discussed alternatively to microscopic methods.

Disintegrant characterization may also be considered in view of new possible exploitations of the swelling properties of polymers in controlling drug release.     

Disintegration Mechanisms of Tablets Containing Starches. Hypothesis About the Particle-Particle Repulsive Force

The disintegration of a tablet immersed in a liquid appears to be essentially a mechanical phenomenon: penetration of liquid then destruction of compressed structure

For a number of authors, the starch granule swelling is the mechanical force which destroys the tablet.

Indeed, a study on a series of experimental carboxymethylstraches indicates that those that do not swell, show the same disintegration time to those that do swell.

We can also notice that the carboxymethylstarches wich swell much less in a gastric medium, produce even shorter disintegration times in this medium.

The destruction of the cohesion forces between the constitutive elements of the tablet under the action of water may be ascribed to the creation of a repulsive force when the elements of the tablet enter into contact with water, or to a simple annihilation of the hydrogen bonds or of the capillary cohesion forces.

The hydrophilic nature of starch seems to be determinant: water penetrates into the tablet owing to hydrophilic porosity under the action of an important hydrostatic pressure.     

Investigation of Prolonged Drug Release from Matrix Formulations of Chitosan

A hydrocolloidal matrix system containing complexes of chitosan was investigated for preparation of sustained release tablets and examined in-vitro.

Theophylline tablets using chitosan as a sustained release base were evaluated. It was found that when chitosan is used in a concentration of more than 50% of tablet weight, an insoluble non-erosion type matrix was formed. Tablets prepared with a chitosan concentration of less than 33% were fast releasing.

Chitosan used in a concentration of about 10% acted as a disintegrant and the drug was dissolved within an hour.

Citric acid slowed down the release rates of chitosan based theophylline tablets. Theophylline tablets using carbomer-934P as a sustained release base were evaluated. Carbomer-934P in lower concentrations forms an erosion type matrix. In order to produce a twenty-four (24) hour sustained release tablet, more than 10% concentration of carbomer-934P is needed. Combination with chitosan and carbomer-934P produced slower releasing tablets.

A hydrocolloidal erosion type matrix was formulated using chitosan, carbomer-934Pand citric acid. Only 10% of chitosan was needed to prepare theophylline sustained release tablets in these mixtures.

The dose dumping potential of chitosan tablets due to rapid disintegration in alkaline media was eliminated by preparing hydrated erosion type matrix systems.     

An evaluation of starch obtained from pearl millet - Pennisetum typhoides. As a binder and disintegrant for compressed tablets

Abstract

The binding and disintegrant properties of millet starch obtained from Pearl Millet - Pennisteum typhoides (Staph. Burn, and Hubb.) Fam. Gramineae have been evaluated using tablet formulations of four drugs.

The results showed that Millet starch compared favourably with Maize starch with regards to most of the parameters used to evaluate the tablets. It can be safely concluded that millet starch is suitable for use as a binder and disintegrant in tablet formulations.     

Studies of Hie Effect of Powder Moisture Content on Drug Release from Hard Gelatin Capsules

The in vitro dissolution of model formulations from hard gelatin capsules containing drug: diluent powder mixtures at different moisture levels has been studied. The capsules were filled to a constant porosity of 50%. to contain either sodium barbitone or barbitone in 50:50 mixture with lactose or maize starch, the latter at one of three moisture levels. In addition, capsules containing drug alone were examined. The wettability and polarity indeces of the individual powders and binary mixtures, as well as the permeability and liquid penetration rates of powder beds were also determined.

The presence of either excipient was found to modify the time for 50% drug dissolution (t₅₀) compared with drug alone for all formulations examined, apart from the sodium barbitone: lactose capsules. The rate of drug dissolution was also dependent on the initial powder moisture content for the drug:starch formulations. Open storage of capsules at 20^%/75%. R.lt. generally increased t₅₀figures.

The findings are discussed in terms of the nature of the surfaces of the powder particles, moisture sorption phenomena and factors such as powder bed permeability and water penetitration lates.     

Disintegrating Force and Tablet Properties

The development of a disintegrating force inside the tablet due to the liquid/solid contact depends on a proper wetting of the material and occur according to saturation kinetics.

The aim of the present work is the evaluation of such a force development in relation to the characteristics of the tablet in particular to the compression force.

For this purpose, the disintegrating force of different tablets formulations has been measured by means of a previously described apparatus.

The results obtained show that a new evaluation of a compact disintegration characteristics may be obtained through the determination of such parameters as the maximum force developed (y₀) and the time of the half maximum force development (b).     

A Comparative Evaluation of the Properties of some Tablet Disintegrants

The subject of the study is a cooperative evaluation of the properties of different disintegrants: starches (corn, maize, potatoe, rice) and derivatives (STARX 1500, carboxymethylstarches as PRIMOJEL or EXPLOTAB); celluloses (AVICEL, ELCEMA) and derive ted products as methylcellulose (METHOCEL), carboxymethylcellu-lose (sodium salt, NYMCEL, AC DI SOL), low substituted hydroxy-propylcellulose (L-HPC); macromolecules (Alginic acid, AMBERLITE IRP 88, ESMA SPRENG, Pectins, a.s.o.); finely divided solids (AEROSIL, VEEGUM). To realise this comparative study, different methods of evaluation of disintegrants physical properties are choosen, and wettability (contact angle), water uptake and swelling of the products measured. The disintegrants are also included in a calcium phosphate based tablet formula, and the disintegration is studied. The mechanism of action of the disintegrants is shortly discussed, and an approximate price/efficiency ratio given.

The results of the work permit a better choice of an appropriated disintegrant.

Purpose of tablets formulation is now Co obtain very short disintegrating times so that to that liberation of drug can begin without delay as soon as tha tablet is in contact with gastric juice.

Therefore, it is now iaportant to look for the sure efficient disiutugrauts, and so, many Materials are avalaible from industry.

Purpose of present study was to compare some physical properties of these different disintegranta.     

A Combination Disintegration-Dissolution Apparatus for Fast-Disintegrating

A combination disintegration-dissolution apparatus for fast disintegrating tablets is described. Preliminary investigation using sodium carboxymethyl starch as the disintegrant indicated that the apparatus was capable of detecting differences in the disintegration time both due to disintegrant concentration as well as due to the intensity of agitation used in the apparatus. No difference in the disintegration times could be observed when similar tablets were evaluated using the existing disintegration apparatus.

The combination apparatus described is simple in construction and design and can be fabricated quite easily and economically in the laboratory. Due to the anticipated increase in the availability of fast-disintegrating tablets, this apparatus will be useful to the pharmaceutical formulator as a valuable quality control tool. In addition, the apparatus is adaptable to various other agitational systems in common usage and can be used by laboratories carrying out combined disintegration and dissolution tests using automated equipment.     

Dissolution Characteristics of Pharmaceutical Equivalents

The in-vitro release of diltiazem from pharmaceutical equivalents of sustained release tablets, commercially available in Italy, was studied.

The in-vitro release profiles were determined by means of different methods and apparatus. Paddle, basket, Poole, Diffutest and Stricker methods were compared.

The absorption rates in artificial gastric and enteric juices by means of lipid barriers were calculated.

Some preparations showed a diffusion mechanism, some a first-order release.

The differences among the dissolution profiles of the formulations were enhanced with the Strieker method.     

Effects of Binders and Moisture Content on the Disintegration, Hardness and Friability of Paracetamol and Orphenadrine Citrate Tablets

The effects of binders and moisture content on the disintegration time, friability and hardness of paracetamol and orphenadrine citrate tablets at different storage conditions were investigated. These parameters were determined after one, four and sixteen weeks of storage

The use of starch, ethocel or CMC Na as binders gave unsatisfactory tablets because of their high friability. Unacceptably high disintegration times were obtained, particularly at higher storage temperatures when PVP was used. Capping and yellow spotting observed in gelatin formulations makes this binder unsuitable for use. Methocel granulations yielded satisfactory tablets with acceptable disintegration time, hardness and friability and were unaffected by storage at different conditions of temperature and humidity     

The Binding and Disintegrant Properties of the Corn Starch Fractions: Amylose and Amylopectin

Corn Starch USP consists of the two glucose polymers, amylose and amylopectin, whose normal ratio is 27%:73%. This study was initiated to determine whether a variation in this ratio would have any benefit in pharmaceutical granulations. Starch pastes prepared by varying the amylose/amylopectin ratio were used to granulate a dicalcium phosphate system and the resulting tablet properties were evaluated.

Physical mixtures of the polymers and also special hybrid polymer mixtures were studied. Binding and disintegrant properties of the starch fractions do vary with the amylose/ amyloptectin ratio and with the degree of starch hydrolysis during the heating (cooking) phase of starch paste preparation. The results of this study give some indication as to the binding and disintegrant activity of starch and its fractions.     

Optimization of Direct Compression Tablet Formulations for Use in Tropical Countries

With the aid of a combined mixture- and factorial- design, 2 standard tablet formulations were selected suitable for use in tropical countries. The formulations were based on native ingredients or ingredients that are available worldwide. The selection of the standard formulations was based on both the initial tablet properties of the formulations one day after preparation as well as the physical stability after storage under tropical conditions.

The selected formulations were evaluated by adding model drugs (diazepam, 2 mg per tablet or hydrochlorthiazide, 100 mg per tablet) and measuring tablet properties, not only one day after preparation, but also after storage under tropical conditions. Both selected tablet formulations were suitable standard formulations for tablets prepared by direct compression for use in tropical countries.     

The Effect of Recompression on the Swelling Kinetics of Wet Massed Tablets, Containing 'Super' Disintegrants

The effect of recompression on the swelling force kinetics of tablets employing a wet massed Avicel matrix and those containing extra-granular super disintegrants has been investigated. Explotab, unlike the Ac-Di-Sol and Polyplasdone XL systems, was found to give a high initial compact swelling force at low tablet porosities, but the rework process reduced the maximal swelling forces for all systems. However, the measured maximal swelling forces did not correlate with tablet disintegration time.

The rate of fluid penetration into the compacts was found to be controlled by tablet porosity but the penetration rates for all disintegrant systems were essentially identical. However the penetration rates for reworked compacts were significantly lower than those for tablets produced by first compression possibly due to the effects of increased lubricant distribution and relubrication causing poorer wettability.

Tablet disintegration times were found to correlate with a fluid penetration kinetic function involving lag time and time for 50% tablet swelling. Also, the retention of disintegration efficiency following rework correlated with the retention of the rate of fluid penetration. It is concluded that lubricants can play an important role in the efficiency of compact disintegration following tablet rework.