Mprovement in Pressure-Dependent Dissolution of Trepibutone Tablets by Using Intragranular Disintegrants

In developing compressed tablets trepibutone 40mg, dissolution studies indicated that the compression pressure applied exerted strong influence on drug dissolution from the tablets. It was found that the incorporation of disintegrants in the granular formulation prevented the decrease in dissolution rate of drug from tablets by compression. Instead of the intragranular disintegrants, incorporation of a rubber powder, which does not swell at all in water and has some elastic recoveries after compression, did not improve the drug dissolution from tablets. It was concluded that the addition of disintegrants in the granular formulation resulted in little prevention of the particle aggregation during compression. The swelling of disintegrant grains in water is considered to play an important part in the deaggregation of drug particles     

Investigation of Dissolution Enhancement of Nifedipine by Deposition on Superdisintegrants

In this study we aimed to investigate the dissolution enhancement of nifedipine by the solvent deposition technique using superdisintegrants including Ac-Di-Sol, Kollldon CL, and Explotab as excipients. The relative significance of action of solvent deposition (deposition of small drug particles on the excipient after solvent is evaporated) and action of superdislntegrant was investigated. The effect of solvent on dissolution of nifedipine in the solvent deposition system was also Investigated. Differential scanning calorlmetry (DSC) was used to study the interaction between nifedipine and superdisintegrants. Capsules and tablets of a physical mixture and a solvent deposition system of nifedipine were prepared. The dissolution rate of nifedipine of these capsules and tablets was studied. The results of this study show that solvent deposition system with lactose and super dlslntegrants in capsule and tablet dosage forms can significantly enhance dissolution rate of nifedipine. Both the action of superdislntegrant and solvent deposition contribute to the enhancement of the dissolution, but the solvent deposition is mainly responsible for this enhancement. The solvent and disintegrants used can influence the dissolution rate also. The solvent deposition system using both Kollldon CL as excipient and dichloromethane as solvent has the highest dissolution rate. DSC study indicated Kollldon CL has the strongest interaction with nifedipine also.     

The Effect of Recompression on the Dissolution of Wet Massed Tablets Containing 'Super' Disintegrants

The effect of recompression on the disintegration, and dissolution of tablets employing 'super' disintegrants within a wet-massed Avicel matrix is reported. Differences were found in the disintegration times of tablets containing intra-granular or extra-granular disintegrants (Polyplasdone XL, Explotab and Ac-di-sol), both between disintegrant type and within the same disintegrant system following rework.

In the case oE extra-granular disintegrant, reworked compacts dissolved faster than the first compression tablets, irrespective of disintegrant type. Thus, milling and dispersion of the drug during rework appear to dominate over the effects of impaired disintegration when 'super' disintegrants are present. The control compacts (no disintegrant), however, dissolved less quickly following rework, indicating that dissolution was controlled by disintegration.

Tablets with intra-granular Polyplasdone XL and Ac-di-sol dissolved less quickly following rework. Both disintegrants have poor intra-granular rework efficiencies. However, for Explotab, which has better rework intra-granular efficiency, reworked tablets dissolved faster than first compression compacts.     

Increasing Dissolution Rates of Poorly Soluble Drugs by Adsorption to Montnorillonith

The surface adsorption of griseofulvin, indomethacin and prednisone to colloidal magnesium aluminum silicate was shown to markedly improve the dissolution rates of there hydrophobic and party soluble drugs. The rapid release of drug from the surface of the clay was due to the weak physical bonding between the two materials and to the swelling of the clay in aqueous media. The hydrophilic and swelling properties of the montmorillonite clay in aqueous media also helped to facilitate the wetting of hydro-phobic drug substances. The equilibrating solvents employed in the preparation of the griseofulvin-clay adsorbates caused a significant variance in the dissolution profiles of griseofulvin. This did not occur with indomethacin. Dramatic increases in dissolution rates were seen with the prednisone adsorbates and 100 percent of the drug was present in solution from the 1:4 ad-sorbate after four minutes.     

蒸发速率对Si衬底上SSMBE外延SiC薄膜的影响

采用固源分子束外延（SSMBE）生长技术,用不同的蒸发速率,在Si（111）衬底上生长SiC薄膜。利用反射式高能电子衍射（RHEED）、X射线衍射（XRD）、原子力显微镜（AFM）等实验技术,对生长的样品的形貌和结构进行研究。结果表明,在优化的蒸发速率（1.0 nm·min^-1）下,所生长的薄膜质量最好。低的蒸发速率（0.25 nm·min^-1）难以抑制孔洞的形成,衬底的Si原子可通过这些孔洞扩散到样品表面,导致结晶质量变差。在高的蒸发速率（1.8 nm·min^-1）下,以岛状方式生长甚至以团簇聚集,表面的原子难以迁移到最佳取向的平衡位置,导致样品表面粗糙度变大,薄膜的结晶质量变差,甚至出现多晶。     

In Vivo Dissolution Rates: An Error Analysis

Abstract

The uncertainty associated with the determination of in vivo dissolution rates was determined by Monte Carlo simulation. Error was imposed upon sets of artificially generated data that simulated plasma drug levels after tablet and solution dosage from ingestion. Deconvolutions were performed on the data sets to determine how error in the plasma levels propagated into the in vivo dissolution determinations. Two approaches were taken in the performance of the deconvolution step of the simulation. In the first, a model was explicitly assumed for dissolution. In the second, deconvolution was accomplished by a mass balance approach in which no explicit model for dissolution was assumed.     

In Vivo Dissolution Rates: An Error Analysis

The uncertainty associated with the determination of in vivo dissolution rates was determined by Monte Carlo simulation. Error was imposed upon sets of artificially generated data that simulated plasma drug levels after tablet and solution dosage from ingestion. Deconvolutions were performed on the data sets to determine how error in the plasma levels propagated into the in vivo dissolution determinations. Two approaches were taken in the performance of the deconvolution step of the simulation. In the first, a model was explicitly assumed for dissolution. In the second, deconvolution was accomplished by a mass balance approach in which no explicit model for dissolution was assumed.     

Dissolution Rates of Commercial Phenylbutazone Tablets: Inter-And Intra-Brand Effects

Abstract

A study has been carried out to investigate the dissolution rate profiles of twelve batches of sugar-coated phenylbutazone tablets belonging to four commercial brands. Using the rotating basket method, significant inter-brand and inter-batch variations in dissolution rates were found. Only two batches of one brand passed the B.P. dissolution limit whilst other batches had percentages dissolution between 0.3 and 58 after 45 min. Batches with poor dissolution characteristics exhibited significant tablet-to-tablet variations in dissolution rates; a finding which was not observed in the relatively fast-dissolving batches. When the paddle method was substituted for the B.P. basket method, the dissolution rates were relatively faster but similar dissolution failure was found. However, the tablet-to-tablet dissolution variability was decreased in some of the batches. The observed differences in dissolution rates of the batches examined were unrelated to their disintegration times. Inspite of the poor dissolution characteristics of most of the batches studied, no apparent chemical degradation was found. It is recommended that when evaluating the dissolution rates of brands of phenylbutazone tablets, a number of batches from each brand should be tested.     

Dissolution Rates of Trimethoprim-Sulphamethoxazole and Trimethoprim Tablets in Aqueous Media

Abstract

Dissolution rates of trimethoprim and sulphamethoxazole from combination tablets showed a rapid release of trimethoprim in acid media from all formulations. Sulphamethoxazole showed a more variable release pattern and faster release in dilute acid medium compared with the less acidic simulated gastric fluid. Tablets containing only trimethoprim showed a release rate into hydrochloric acid media that was dependent upon pH. Approximately twice the amount of trimethoprim was released in twenty minutes at pH 1.32 compared with pH 6.50.     

Dissolution Rates of Commercial Phenylbutazone Tablets: Inter-And Intra-Brand Effects

A study has been carried out to investigate the dissolution rate profiles of twelve batches of sugar-coated phenylbutazone tablets belonging to four commercial brands. Using the rotating basket method, significant inter-brand and inter-batch variations in dissolution rates were found. Only two batches of one brand passed the B.P. dissolution limit whilst other batches had percentages dissolution between 0.3 and 58 after 45 min. Batches with poor dissolution characteristics exhibited significant tablet-to-tablet variations in dissolution rates; a finding which was not observed in the relatively fast-dissolving batches. When the paddle method was substituted for the B.P. basket method, the dissolution rates were relatively faster but similar dissolution failure was found. However, the tablet-to-tablet dissolution variability was decreased in some of the batches. The observed differences in dissolution rates of the batches examined were unrelated to their disintegration times. Inspite of the poor dissolution characteristics of most of the batches studied, no apparent chemical degradation was found. It is recommended that when evaluating the dissolution rates of brands of phenylbutazone tablets, a number of batches from each brand should be tested.     

Stability and Dissolution Rates of Corticosteroids in Polyethylene Glycol Solid Dispersions

Abstract

A study has been made to examine the stability and dissolution rates of prednisolone, prednisone and hydrocortisone formulated as solid dispersions in polyethylene glycols. Of the five PEG samples used, three enhanced the chemical instability of the steroids; the effect being dependent on the PEG sample and storage conditions of the solid dispersions. Dissolution rates of the steroids were relatively fast from the solid dispersions and showed no significant changes upon storage. Using two methods of analysis (direct UV spectrophotometry and the USP blue tetrazolium method), it is concluded that the chemical instability of the steroids in some PEG samples was due to alterations in the dihydroxy acetone side chain. One of the decomposition products found appeared to be an acidic compound resulting from oxidation of the C₁₇ side chain. The oxidation is presumably accelerated by a peroxide impurity in PEG samples.     

Stability and Dissolution Rates of Corticosteroids in Polyethylene Glycol Solid Dispersions

A study has been made to examine the stability and dissolution rates of prednisolone, prednisone and hydrocortisone formulated as solid dispersions in polyethylene glycols. Of the five PEG samples used, three enhanced the chemical instability of the steroids; the effect being dependent on the PEG sample and storage conditions of the solid dispersions. Dissolution rates of the steroids were relatively fast from the solid dispersions and showed no significant changes upon storage. Using two methods of analysis (direct UV spectrophotometry and the USP blue tetrazolium method), it is concluded that the chemical instability of the steroids in some PEG samples was due to alterations in the dihydroxy acetone side chain. One of the decomposition products found appeared to be an acidic compound resulting from oxidation of the C₁₇ side chain. The oxidation is presumably accelerated by a peroxide impurity in PEG samples.     

Dissolution Rates of Carbamazepine and Nitrazepam Utilizing Sugar Solid Dispersion System

Abstract

The dissolution of carbamazepine and nitrazepam from Its solid dispersions using anhydrous lactose, mannitol, galactose, PEG 6000 and coprecipitate using polyvinylpyrrolidone (PVP) 40,000 was investigated. The dissolution process of capsules containing either carbamazepine or nitrazepam as solid dispersion or coprecipitate followed an apparent first order process. The combination of carbamazepine with sugars (mannitol, lactose, and galactose) caused, in every case, an increase in the dissolution rate of the drug. Carbamazepine-PVP coprecipitate gave the higher dissolution rate than that of the solid dispersions with sugars and PEG 6000. Nitrazepam-lactose system gave higher dissolution rate than the other dispersions and coprecipitate. This enhancement in dissolution rate was much more obvious for the solid dispersions and coprecipitate than for the physical mixtures.     

不同沉积速率微晶硅薄膜生长模式的蒙特卡洛模拟研究

采用标度理论比较了不同速率下微晶硅薄膜的生长模式。结果是:低速时薄膜的生长指数为0.19,高速时薄膜的生长指数为0.61,两者生长机理明显不同。通过蒙特卡洛模拟薄膜生长过程,结果表明:生长基元的粘附系数和扩散能力对不同生长速率下薄膜的生长有较大的影响。     

Chemometric Modelling of Dissolution Rates of Griseofulvin From Solid Dispersions With Polymers

The quantitative relationship between the release rate of griseofulvin and the chemical and physical properties of a series of polymers, used for the preparations of solid dispersions, was investigated by the application of multiple regression analysis (MRA), partial least square analysis (PLS) and a new non linear chemometric procedure called CARSO (Computer Aided Response Surface Optimization).

It was confirmed that the degree of crystallinity of griseofulvin and the wettability of the powder samples are important in the dissolution mechanism and in the prediction of dissolution profiles of griseofulvin from these solid dispersions.     

Chemometric Modelling of Dissolution Rates of Griseofulvin From Solid Dispersions With Polymers

Abstract

The quantitative relationship between the release rate of griseofulvin and the chemical and physical properties of a series of polymers, used for the preparations of solid dispersions, was investigated by the application of multiple regression analysis (MRA), partial least square analysis (PLS) and a new non linear chemometric procedure called CARSO (Computer Aided Response Surface Optimization).

It was confirmed that the degree of crystallinity of griseofulvin and the wettability of the powder samples are important in the dissolution mechanism and in the prediction of dissolution profiles of griseofulvin from these solid dispersions.     

Powder Compaction Properties of Sodium Starch Glycolate Disintegrants

ABSTRACT

The compaction behavior of three “as supplied” commercially available grades of sodium starch glycolate (SSG), Explotab, Primojel, and Vivastar P, was investigated at compression speeds of 0.17 and 30 mm/sec. The results suggested that the three “as supplied” materials exhibit different compression and compaction behavior. Primojel and Explotab exhibited similar compactibility, whereas Vivastar P produced compacts of poor integrity. This behavior was not mirrored in the compressibility of the powders, where Vivastar P and Explotab exhibited similar performance. The materials were studied using x-ray diffraction, scanning electron microscopy, Carr's compressibility index, and swelling volume. In terms of material characteristics, all the products exhibited similar swelling in water. Primojel and Explotab retained most of the crystallographic order from the parent potato starch and exhibited comparable particle surface topographies. Vivastar P contained the lowest moisture level. However, it is not clear if the poor compactibility of Vivastar P is due to differences in moisture content, the reduced surface topography, or subtle differences in the SSG polymer structures (substitution, cross-linking, and crystallinity). Overall, even though the three commercial grades of sodium starch glycolate are successfully used as disintegrants, they do exhibit differences in their “as supplied” powder mechanical properties: Primojel and Explotab exhibit similar compactibility, whereas Vivastar P is poorly compactable but exhibits similar compressibility to Explotab. These observations may have implications when formulating poorly compactable or moisture-sensitive drugs.     

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.     

Effect of Drug Solubility in Wet Granulation Fluids on the Dissolution Rates of the Resulting Tablets

One factor in wet granulation processes which affects dissolution rates of the final tablets is shown to be the solubility of the drug substance in the granulating liquid. The relationship is not a direct correlation and a feasible explanation is offered.