Kollidon CL Research Articles

Fast dispersible/slow releasing ibuprofen tablets

Eight formulations were developed containing ibuprofen in the form of orally disintegrating tablets. To prevent bitter taste and side effects of the drug, the drug was associated with Phospholipon 80H, a saturated lecithin, by wet granulation. The granules were then coated using different film forming agents (Kollicoat SR 30, Amprac 01, Kollidon 90F, Eudragit RD 100) obtaining four lots 1–4. Coated granules were then formulated with a sweetener (Aspartame), a mannitol-based diluent (Pearlitol SD 200) and Kollidon CL (1-4K) or Explotab (1-4E) were added as superdisintegrants and compacted under low compression force. The eight lots of tablets, 1-4K and 1-4E, were assessed if suitable as oral disintegrating tablets by determination of a range of technological parameters. Wetting and disintegregation time matched with the requirements of EP IV Ed., for almost all these formulations. Dissolution profiles suggested that the combined action of the hydrophobic lecithin and the coating delay the release of the drug from tablets with respect to when it is free or in the form of simple granules. By an appropriate combination of excipients it was thus possible to obtain orally disintegrating tablets and a delayed release of ibuprofen using simple and conventional techniques.

The use of extragranular disintegrants in multiple-unit tablet formulations: effect on compressibility, compactibility and disintegration

Multiple-unit tablets formed from mixtures of microcrystalline cellulose pellets and disintegrants (Ac-Di-Sol, Primojel or Kollidon CL) by compaction were investigated with the aim of controlling tablet tensile strength and disintegration time. The effects of pellet porosity, compaction pressure, and type and amount of disintegrant were studied. Primojel made the pellets less prone to deformation during compression, while the other two disintegrants had very minor effects on the compression behavior. Ac-Di-Sol and Primojel generally increased the tablet tensile strength, whereas the effect of Kollidon CL was dependent on the initial pellet porosity. Kollidon CL was found to significantly reduce the disintegration time, but the other two disintegrants had variable efficacy, and for the low-porosity pellets significantly increased the disintegration time. These results are interpreted as resulting from the interplay between the mechanical characteristics of the pellets and the mechanisms of action of the disintegrants.

Preparation and Evaluation of Ibuprofen Solid Dispersion Systems with Kollidon Particles Using a Pulse Combustion Dryer System

Solid dispersions (SDs) of ibuprofen (IBU) were prepared with four carriers: Kollidon 25, Kollidon 30, Kollidon VA64, and Kollidon CL, using a newly developed pulse combustion dryer system, HYPULCON. Physicochemical properties of the SDs obtained were investigated by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), scanning electron microscope (SEM), and Fourier transformation IR spectroscopy (FT-IR). Powder X-ray diffraction (PXRD) showed that the crystal diffraction peaks of IBU in SDs disappeared completely, and in differential scanning calorimetry (DSC) curves, the endothermic peaks of IBU in SDs were not observed. Fourier transformation IR spectroscopy (FT-IR) proved that interactions between the drug and carrier existed. These findings demonstrated that IBU changed to an amorphous form in the SDs with the four carriers using the pulse combustion dryer system. The dissolution property of IBU in the SDs was markedly enhanced. The dissolution test showed that after 5 min of dissolution, the concentrations of IBU in the SDs with Kollidon CL as the carrier was 43.81 mug/ml, corresponding to 13.0 times that of pure IBU. So, it is demonstrated that the pulse combustion dryer system is very useful for preparing SDs of IBU with Kollidon of different grades as carriers.

Spray Dried Excipient Base: A Novel Technique for the Formulation of Orally Disintegrating Tablets

Orally disintegrating tablets (ODT) are gaining popularity over conventional tablets due to their convenience in administration and suitability for patients having dysphagia. Moreover no water is required for swallowing the tablets and hence suitable for geriatric, pediatric and traveling patients. The purpose of this study is to assess the suitability of spray dried excipient base in the formulation of ODTs of Valdecoxib (low aqueous solubility) and Metoclopramide (high aqueous solubility). Spray dried excipient base was prepared using Scientech spray drier. Super disintegrants (such as Ac-Di-Sol, Kollidon CL, sodium starch glycolate), diluent (mannitol) alongwith sweetening agent (aspartame) were used in the formulation of tablets. The tablets were evaluated for hardness, friability, water absorption ratio, disintegration time (DT) and in vitro drug release. Using the same excipients, the tablets were prepared by direct compression and were evaluated in the similar way. Maximum drug release and minimum DT were observed with Kollidon CL excipient base as compared to tablets prepared by direct compression, showing the superiority of the spray dried excipient base technique over direct compression technique.

Evaluation of Different Fast Melting Disintegrants by Means of a Central Composite Design

Fast-disintegration technologies have encountered increased interest from industries in the past decades. In order to orientate the formulators to the choice of the best disintegrating agent, the most common disintegrants were selected and their ability to quickly disintegrate direct compressed tablets was evaluated. For this study, a central composite design was used. The main factors included were the concentration of disintegrant (X1) and the compression force (X2). These factors were studied for tablets containing either Zeparox® or Pearlitol 200® as soluble diluents and six different disintegrants: L-HPC® LH11 and LH31, Lycatab PGS®, Vivasol®, Kollidon CL®, and Explotab®. Their micromeritics properties were previously determined. The response variables were disintegration time (Y1), tensile strength (Y2), and porosity (Y3). Whatever the diluent, the longest disintegration time is obtained with Vivasol® as the disintegrant, while Kollidon CL® leads to the shortest disintegration times. Exception for Lycatab PGS® and L-HPC LH11®, formulations with Pearlitol 200® disintegrate faster. Almost the same results are obtained with porosity: no relevant effect of disintegrant concentration is observed, since porosity is mainly correlated to the compression force. In particular, highest values are obtained with Zeparox® as the diluent when compared to Pearlitol 200® and, as the type of disintegrant is concerned, no difference is observed. Tensile strength models have been all statistically validated and are all highly dependent on the compression force. Lycatab PGS® concentration does not affect disintegration time, mainly increased by the increase of compression pressure. When Pearlitol 200® is used with Vivasol®, disintegration time is more influenced by the disintegrant concentration than by the compression pressure, an increase in concentration leading to a significant and relevant increase of the disintegration time. With Zeparox®, the interaction between the two controlled variables is more complex: there is no effect of compression force on the disintegration time for a small amount of disintegrant, but a significant increase for higher concentrations. With Kollidon CL®, the main factor influencing the disintegration time is the compression force, rather than the disintegrant concentration. Increasing both the compression force and the disintegrant concentration leads to an increase of the disintegration time.For lower Kollidon CL® percentages, the compression pressure increases dramatically the tablet disintegration. With the Explotab®, whatever the increase of compression force, the disintegrant concentration leads to an increase of the disintegration time. According to Student's t-test, only the compression force significantly and strongly influences the disintegration time when Pearlitol 200® is used. A slight interaction and some trends nevertheless appear: above 150 MPa, increasing the disintegrant concentration leads to a shortened disintegration time, below this limit the opposite effect is observed.

Compaction of enteric-coated pellets: influence of formulation and process parameters on tablet properties and in vivo evaluation.

The aim of this study was to investigate the influence of formulation and compression parameters on the properties of tablets, containing enteric-coated pellets, and on the integrity of the enteric polymer of the individual pellets after compression. In addition the piroxicam plasma concentrations were determined after single and multiple oral administration of powder, pellet and tablet formulations at a dose of 0.3 mg piroxicam/kg bodyweight to dogs. Tablets consisted of enteric-coated pellets (containing 2.5% (w/w) piroxicam in combination with microcrystalline cellulose and sodium carboxymethylcellulose (using Avicel PH 101 and Avicel CL 611 in a ratio of 1-3), cushioning waxy pellets and 10% Kollidon CL (as an external disintegrator). From the D-optimality experimental design it was concluded that the ratio of coated pellets to cushioning pellets (CoP/CuP) affected all tablet properties evaluated. Variation of the pellet size and the CoP/CuP ratio resulted in different in vitro tablet disintegration times. Enteric coating of the pellets or compression of the coated pellets did not have a significant influence (P >0.05) on AUC(0-->72 h). Cmax values obtained after oral administration of coated pellets and compressed coated pellets were significantly lower than for the other formulations. Differences in in vitro tablet disintegration times were not reflected in the onset of the piroxicam plasma concentrations. A dosing interval of 48 h prevented piroxicam accumulation following multiple dose administration.

Investigation of Dissolution Enhancement of Itraconazole by Solid Dispersion in Superdisintegrants

Solid dispersions of itraconazole (ITR) in lactose, microcrystalline cellulose (MCC), and three superdisintegrants (Primogel, Kollidon CL, and Ac-Di-Sol) and their formulation into tablets were investigated with an objective of enhancing the dissolution rate of ITR from tablet formulations. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) were used to characterize the dispersions. A marked enhancement in the dissolution rate of ITR was observed with all the excipients. The order for the excipients to enhance the dissolution rate was Ac-Di-Sol > Kollidon CL > Primogel > MCC > lactose. Solid dispersions in superdisintegrants gave much higher rates of dissolution than the dispersions in other excipients. Ac-Di-Sol gave the most improvement (28-fold) in the dissolution rate of ITR at a 1:1 drug: excipient ratio. Solid dispersions in superdisintegrants could be formulated into tablets. These tablets, apart from fulfilling all official and other specifications, exhibited higher rates of dissolution and dissolution efficiency (DE) values. XRD indicated the presence of ITR in amorphous form in the dispersions. DSC indicated a weak interaction between ITR and the excipients. Micronization and conversion of the drug into the amorphous form and the fast disintegrating and dispersing action of the superdisintegrants contribute to the enhancement of the dissolution rate of ITR from its solid dispersions in superdisintegrants and their corresponding tablet formulations.

Particle Design for Antidiabetic Drugs by the Spherical Crystallization Technique. IV. Assessment of Compressibility of Agglomerated Tolbutamide Crystals Prepared by Crystallization Technique.

Three different crystallization methods, i.e., the solvent change (SC) method, neutralization (NT) method and quasi-emulsion solvent diffusion (QESD) method, were employed to prepare agglomerated tolbutamide crystals (referred to as SC-A, SC-B, NT and QESD). Each of the agglomerated crystals or unagglomerated tolbutamide crystals (abbreviated as bulk) alone (single formulation), magnesium stearate (MgSt; a lubricant)-added single formulation sample (formulation A), and Kollidon CL (a disintegrating agent)-added formulation A samples (formulation B) were compacted into tablets by the direct tableting method. With the objective of elucidating the compressibility of these samples, the following parameters were analyzed : (1) the course of change in the powder bed volume as a function of the applied compression pressure, (2) the pressure-transmission ratio from the upper punch to the lower punch, (3) the course of decompression (ejection force) and (4) the tensile strength of the tablets determined by the diametric compression method. The results of each sample were compared.For each of the single-formulations, formulation A and formulation B, Kawakita's equation was able to be applied to each stage of the compaction process over the tested compression pressure range of 50-1500kg/cm2. The limiting value of the compaction ratio of the samples was higher in the order of SC-B>NT>SC-A>QESD>bulk, and each agglomerate showed much higher compressibility than the bulk. Although the agglomerates and bulk showed the same pressure-transmission ratio from the upper punch to the lower punch, the bulk showed a smaller ejection force during decompression. The agglomerates, whose primary crystal diameter is small, showed much larger tensile strength of the compacted tablet than the bulk. The addition of MgSt improved the compaction process, but it weakened the tensile strength of the compacted tablets, especially in the case of the bulk. The addition of Kollidon CL decreased the ejection force due to a decrease in the adhesion force of the tablet to the surface of the die wall. Because Kollidon CL suppressed the effect of MgSt, the tensile strength of the compacted tablets was increased.The above results revealed that the compressibility of the agglomerates, especially SC-B and NT, is much superior to that of the bulk, and that these agglomerates have the properties necessary for direct tableting. Moreover, formulation B was suggested to be useful as a practical formulation for direct tableting.

Preparation and Properties of Tablets Prepared from Furosemide-PVP Solid Dispersion Systems

AbstractTablets were prepared from the solid dispersion of furosemide: PVP by using different techniques such as direct compression and double compression. The results were compared with similar tablets prepared by physical mixture. Direct compression was much prefered, as it provided tablets with acceptable mechanical and physical qualities. On the other hand, the choice of disintegrant is very important in the formulation of furosemide: PVP solid dispersed tablets. With Kollidon CL, the best result was obtained. Disintegration mechanism of this system was also discussed. The other effective factor is the particle sizes of coprecipitates. Fine particle exhibited compression difficulty. The drug release from these tablets was 17 times greater than that from tablets prepared from physical mixture.

Influence of drug amount and dioctyl sodium sulfosuccinate on dissolution of propyphenazone tablets

A number of researchers have reported the results of investigating the influence of the amount of slightly soluble drugs on the disintegration and dissolution rate, but the drug content of these tablets seldom exceeded 30%, and even more rarely 50% (Rudnic et al. 1980, Graf et al. 1981; Kitamori and Makino 1982). The aim of this work was to investigate the influence of different, even large amounts of propyphenazone on tablet disintegration and drug dissolution rate in the presence of surfactant. Two kinds of tablets were prepared: tablets I containing lo-85% w/w propyphenazone (Hofmann-la Roche) and 0.5% dioctyl sodium sulfosuccinate (DSS; American Cyanamid Company) calculated on the total mass of tablet, and tablets II prepared with 1% DSS. Tablets were made by a wet granulation procedure. Dry Kollidon 25 (BASF) was used as the tablet binder in a concentration of 4%, calculated on the mass of active substance. The powder was wetted by concentrated ethanol in which the surfactant was dissolved. Avicel PH 101 (Select Chemie), Kollidon CL (BASF) and magnesium stearate (Ph-

Preparation of Rapidly Disintegrating Glipizide Tablets by Surface Solid Dispersion through Superdisintegrants

The objective of this investigation was to enhance the dissolution of glipizide using solid dispersions containing different superdisintegrants and to prepare rapidly disintegrating glipizide tablets with rapid absorption through the oral cavity by direct compression of the prepared solid dispersion. Primojel, Ac-Di-Sol and Kollidon CL were used as superdisintegrants. These excipients were used in different ratios and by using solvent evaporation method, rapidly disintegrating glipizide tablets were prepared by direct compression of the prepared solid dispersion, as well as, by camphor sublimation method aiming for more enhancing of tablet disintegration. Glipizide loaded with Kollidon CL showed the best dissolution properties compared to the other tested excipients. The physical properties of all the prepared GZ tablet formulations were found to be acceptable according to USP/NF2002. Kollidon CL containing formulations showed the most rapid disintegration time values reaching one second in tablets prepared by camphor sublimation method. The most effective formula in decreasing the blood glucose level was that containing glipizide loaded with Kollidon CL, with significant difference from the physically mixed ingredients or the pure GZ powder depending on Student’s T-test for area above the blood glucose level.