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1.  From Heuristic to Mathematical Modeling of Drugs Dissolution Profiles: Application of Artificial Neural Networks and Genetic Programming 
The purpose of this work was to develop a mathematical model of the drug dissolution (Q) from the solid lipid extrudates based on the empirical approach. Artificial neural networks (ANNs) and genetic programming (GP) tools were used. Sensitivity analysis of ANNs provided reduction of the original input vector. GP allowed creation of the mathematical equation in two major approaches: (1) direct modeling of Q versus extrudate diameter (d) and the time variable (t) and (2) indirect modeling through Weibull equation. ANNs provided also information about minimum achievable generalization error and the way to enhance the original dataset used for adjustment of the equations' parameters. Two inputs were found important for the drug dissolution: d and t. The extrudates length (L) was found not important. Both GP modeling approaches allowed creation of relatively simple equations with their predictive performance comparable to the ANNs (root mean squared error (RMSE) from 2.19 to 2.33). The direct mode of GP modeling of Q versus d and t resulted in the most robust model. The idea of how to combine ANNs and GP in order to escape ANNs' black-box drawback without losing their superior predictive performance was demonstrated. Open Source software was used to deliver the state-of-the-art models and modeling strategies.
PMCID: PMC4460208  PMID: 26101544
2.  Coherent anti-Stokes Raman Scattering (CARS) Microscopy Visualizes Pharmaceutical Tablets During Dissolution 
Traditional pharmaceutical dissolution tests determine the amount of drug dissolved over time by measuring drug content in the dissolution medium. This method provides little direct information about what is happening on the surface of the dissolving tablet. As the tablet surface composition and structure can change during dissolution, it is essential to monitor it during dissolution testing. In this work coherent anti-Stokes Raman scattering microscopy is used to image the surface of tablets during dissolution while UV absorption spectroscopy is simultaneously providing inline analysis of dissolved drug concentration for tablets containing a 50% mixture of theophylline anhydrate and ethyl cellulose. The measurements showed that in situ CARS microscopy is capable of imaging selectively theophylline in the presence of ethyl cellulose. Additionally, the theophylline anhydrate converted to theophylline monohydrate during dissolution, with needle-shaped crystals growing on the tablet surface during dissolution. The conversion of theophylline anhydrate to monohydrate, combined with reduced exposure of the drug to the flowing dissolution medium resulted in decreased dissolution rates. Our results show that in situ CARS microscopy combined with inline UV absorption spectroscopy is capable of monitoring pharmaceutical tablet dissolution and correlating surface changes with changes in dissolution rate.
PMCID: PMC4211842  PMID: 25045833
Physics; Issue 89; Coherent anti-Stokes Raman scattering; microscopy; pharmaceutics; dissolution; in situ analysis; theophylline; tablet
3.  Experimental Analysis of Tablet Properties for Discrete Element Modeling of an Active Coating Process 
AAPS PharmSciTech  2013;14(1):402-411.
Coating of solid dosage forms is an important unit operation in the pharmaceutical industry. In recent years, numerical simulations of drug manufacturing processes have been gaining interest as process analytical technology tools. The discrete element method (DEM) in particular is suitable to model tablet-coating processes. For the development of accurate simulations, information on the material properties of the tablets is required. In this study, the mechanical parameters Young’s modulus, coefficient of restitution (CoR), and coefficients of friction (CoF) of gastrointestinal therapeutic systems (GITS) and of active-coated GITS were measured experimentally. The dynamic angle of repose of these tablets in a drum coater was investigated to revise the CoF. The resulting values were used as input data in DEM simulations to compare simulation and experiment. A mean value of Young’s modulus of 31.9 MPa was determined by the uniaxial compression test. The CoR was found to be 0.78. For both tablet–steel and tablet–tablet friction, active-coated GITS showed a higher CoF compared with GITS. According to the values of the dynamic angle of repose, the CoF was adjusted to obtain consistent tablet motion in the simulation and in the experiment. On the basis of this experimental characterization, mechanical parameters are integrated into DEM simulation programs to perform numerical analysis of coating processes.
PMCID: PMC3581635  PMID: 23354469
active film coating; DEM simulation; dynamic angle of repose; tablet coating; tablet mechanical properties
4.  Compaction Behavior of Isomalt after Roll Compaction 
Pharmaceutics  2012;4(4):494-500.
The suitability of the new isomalt grade galenIQ™ 801 for dry granulation and following tableting is evaluated in this study. Isomalt alone, as well as a blend of equal parts with dibasic calcium phosphate, is roll compacted and tableted. Particle size distribution and flowability of the granules and friability and disintegration time of the tablets are determined. Tensile strength of tablets is related to the specific compaction force during roll compaction and the tableting force. In all cases, the tensile strength increases with raising tableting forces. The specific compaction force has a different influence. For isomalt alone the tensile strength is highest for tablets made from granules prepared at 2 kN/cm and 6 kN/cm and decreases at higher values, i.e., >10 kN/cm. Tensile strength of the blend tablets is almost one third lower compared to the strongest tablets of pure isomalt. Friability of pure isomalt tablets is above the limit. Disintegration time is longest when the tensile strength is at its maximum and decreases with higher porosity and lower tensile strengths. Isomalt proves to be suitable for tableting after roll compaction. Even though the capacity as a binder might not be as high as of other excipients, it is a further alternative for the formulation scientist.
PMCID: PMC3834925  PMID: 24300366
isomalt; roll compaction; work hardening; recompression; compactibility
5.  From Mini to Micro Scale—Feasibility of Raman Spectroscopy as a Process Analytical Tool (PAT) 
Pharmaceutics  2011;3(4):723-730.
Active coating is an important unit operation in the pharmaceutical industry. The quality, stability, safety and performance of the final product largely depend on the amount and uniformity of coating applied. Active coating is challenging regarding the total amount of coating and its uniformity. Consequently, there is a strong demand for tools, which are able to monitor and determine the endpoint of a coating operation. In previous work, it was shown that Raman spectroscopy is an appropriate process analytical tool (PAT) to monitor an active spray coating process in a pan coater [1]. Using a multivariate model (Partial Least Squares—PLS) the Raman spectral data could be correlated with the coated amount of the API diprophylline. While the multivariate model was shown to be valid for the process in a mini scale pan coater (batch size: 3.5 kg cores), the aim of the present work was to prove the robustness of the model by transferring the results to tablets coated in a micro scale pan coater (0.5 kg).
Coating experiments were performed in both, a mini scale and a micro scale pan coater. The model drug diprophylline was coated on placebo tablets. The multivariate model, established for the process in the mini scale pan coater, was applied to the Raman measurements of tablets coated in the micro scale coater for six different coating levels. Then, the amount of coating, which was predicted by the model, was compared with reference measurements using UV spectroscopy.
For all six coating levels the predicted coating amount was equal to the amounts obtained by UV spectroscopy within the statistical error. Thus, it was possible to predict the total coating amount with an error smaller than 3.6%. The root mean squares of errors for calibration and prediction (root mean square of errors for calibration and prediction—RMSEC and RMSEP) were 0.335 mg and 0.392 mg, respectively, which means that the predictive power of the model is not dependent on the scale or the equipment.
The scale-down experiment showed that it was possible to transfer the PLS model developed on a mini scale coater to a micro scale coater.
PMCID: PMC3857055  PMID: 24309305
mini scale; micro scale; active coating; Raman spectroscopy; PAT tool
6.  Improvement of Dissolution Behavior for Poorly Water-Soluble Drug by Application of Cyclodextrin in Extrusion Process: Comparison between Melt Extrusion and Wet Extrusion 
AAPS PharmSciTech  2010;11(2):885-893.
The purpose of this study was to improve dissolution behavior of poorly water-soluble drugs by application of cyclodextrin in extrusion processes, which were melt extrusion process and wet extrusion process. Indomethacin (IM) was employed as a model drug. Extrudates containing IM and 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD) in 1:1 w/w ratio were manufactured by both melt extrusion process and wet extrusion process. In vitro drug release properties of IM from extrudates and physiochemical properties of extrudates were investigated. The dissolution rates of IM from extrudates manufactured by melt extrusion and wet extrusion with HP-β-CyD were significantly higher than that of the physical mixture of IM and HP-β-CyD. In extrudate manufactured by melt extrusion, γ-form of IM changed to amorphous completely during melt extrusion due to heating above melting point of IM. On the other hand, in extrudate manufactured by wet extrusion, γ-form of IM changed to amorphous partially due to interaction between IM and HP-β-CyD and mechanical agitating force during process. Application of HP-β-CyD in extrusion process is useful for the enhancement of dissolution rate for poorly water-soluble drugs.
PMCID: PMC2902314  PMID: 20496019
2-hydroxypropyl-β-cyclodextrin; dissolution; extrusion; indomethacin; poor water-soluble drug
7.  Two-Step Solid Lipid Extrusion as a Process to Modify Dissolution Behavior 
AAPS PharmSciTech  2010;11(1):2-8.
Extrudates based on varying ratios of the triglyceride tripalmitin and the hydrophilic polymer polyethylene glycol as matrix formers were produced as oral dosage forms with controlled release characteristics. The extrudates were processed below the melting points of the excipients and contained the hydrophobic model drug chloramphenicol. The influence of the ratio of the matrix formers on drug dissolution was investigated, with an increase in the water-soluble polymer content increasing the drug release rate. In addition, the effect of varying the extrusion process on the extrudate structure and drug dissolution was investigated. Two-step extrusion was performed, which comprised an initial extrusion step of drug and one matrix component followed by milling these extrudates and a second extrusion step for the milled extrudates mixed with the second matrix component. Initial extrusion with polyethylene glycol led to increased dissolution rates, while initial extrusion with tripalmitin led to decreased dissolution rates compared to the dissolution characteristics of extrudates containing the same composition produced by one-step extrusion. Thus, two-step solid lipid extrusion can successfully be used as a process to modify the dissolution behavior of extrudates.
PMCID: PMC2850486  PMID: 20309654
dissolution; polyethylene glycol; process variations; solid lipid extrusion; triglyceride
8.  Investigating the Principles of Recrystallization from Glyceride Melts 
AAPS PharmSciTech  2009;10(4):1224-1233.
Different lipids were melted and resolidified as model systems to gain deeper insight into the principles of recrystallization processes in lipid-based dosage forms. Solid-state characterization was performed on the samples with differential scanning calorimetry and X-ray powder diffraction. Several recrystallization processes could be identified during storage of the lipid layers. Pure triglycerides that generally crystallize to the metastable α-form from the melt followed by a recrystallization process to the stable β-form with time showed a chain-length-dependent behavior during storage. With increasing chain length, the recrystallization to the stable β-form was decelerated. Partial glycerides exhibited a more complex recrystallization behavior due to the fact that these substances are less homogenous. Mixtures of a long-chain triglyceride and a partial glyceride showed evidence of some interaction between the two components as the partial glyceride hindered the recrystallization of the triglyceride to the stable β-form. In addition, the extent of this phenomenon depended on the amount of partial glyceride in the mixture. Based on these results, changes in solid dosage forms based on glycerides during processing and storage can be better understood.
PMCID: PMC2799577  PMID: 19862628
lipids; partial glycerides; polymorphism; recrystallization; triglycerides
9.  The 6th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology (PBP Meeting) April 7–10, 2008, Barcelona, Spain 
AAPS PharmSciTech  2008;9(3):828.
PMCID: PMC2977042  PMID: 18618267
Biopharmaceutics; Pharmaceutics; Pharmaceutical Technology; World Meeting
10.  Properties of pellets manufactured by wet extrusion/spheronization process using κ-carrageenan: Effect of process parameters 
AAPS PharmSciTech  2007;8(4):101-108.
The aim of this study was to systematically evaluate the pelletization process parameters of κ-carrageenan-containing formulations. The study dealt with the effect of 4 process parameters—screw speed, number of die holes, friction plate speed, and spheronizer temperature—on the pellet properties of shape, size, size distribution, tensile strength, and drug release. These parameters were varied systematically in a 24 full factorial design. In addition, 4 drugs—phenacetin, chloramphenicol, dimenhydrinate, and lidocaine hydrochloride—were investigated under constant process conditions. The most spherical pellets were achieved in a high yield by using a large number of die holes and a high spheronizer speed. There was no relevant influence of the investigated process parameters on the size distribution, mechanical stability, and drug release. The poorly soluble drugs, phenacetin and chloramphenicol, resulted in pellets with adequate shape, size, and tensile strength and a fast drug release. The salts of dimenhydrinate and lidocaine affected pellet shape, mechanical stability, and the drug release properties using an aqueous solution of pH 3 as a granulation liquid. In the case of dimenhydrinate, this was attributed to the ionic interactions with κ-carrageenan, resulting in a stable matrix during dissolution that did not disintegrate. The effect of lidocaine is comparable to the effect of sodium ions, which suppress the gelling of carrageenan, resulting in pellets with fast disintegration and drug release characteristics. The pellet properties are affected by the process parameters and the active pharmaceutical ingredient used.
PMCID: PMC2750681  PMID: 18181555
Pellets; carrageenan; extrusion; spheronization; process parameters; experimental design
11.  Influence of chitosan type on the properties of extruded pellets with low amount of microcrystalline cellulose 
AAPS PharmSciTech  2007;8(3):E99-E109.
The purpose of this research was to study the influence of type of chitosan with different molecular weights, ie, 190 and 419 kDa, on properties of pellets prepared by extrusion/ spheronization. The formulations, consisting of acetaminophen as model drug, chitosan, microcrystalline cellulose (MCC), and dibasic calcium phosphate dihydrate with/without sodium alginate, were extruded using a twin-screw extruder and water as the granulating liquid. With 30% wt/wt MCC and no added sodium alginate, spherical pellets were produced containing low and high molecular weight chitosan at a maximum amount of 60% and 40% wt/wt, respectively. With sodium alginate (2.5% wt/wt), pellets with either type of chitosan (60% wt/wt), MCC (17.5% wt/wt), and acetaminophen (20% wt/wt) could be produced indicating an improved pelletforming ability. Type and amount of chitosan and added sodium alginate affected physical properties of pellets including size, roundness, crushing force, and drug release. Low molecular weight chitosan produced pellets with higher mean diameter, sphericity, and crushing force. Additionally, the pellets made of low molecular weight chitosan and added sodium alginate showed faster drug release in 0.1 N HCl but had slower drug release in pH 7.4 phosphate buffer. This indicated that drug release from pellets could be modified by the molecular weight of chitosan. In conclusion, the molecular weight of chitosan had a major influence on formation, physical properties, and drug release from the obtained pellets.
PMCID: PMC2750560  PMID: 18181559
Chitosan; sodium alginate; pellets; extrusion/spheronization; drug release
12.  Comparison of a laboratory and a production coating spray gun with respect to scale-up 
AAPS PharmSciTech  2007;8(1):E21-E31.
A laboratory spray gun and a production spray gun were investigated in a scale-up study. Two Schlick spray guns, which are equipped with a new antibearding cap, were used in this study. The influence of the atomization air pressure, spray gun-to tablet bed distance, polymer solution viscosity, and spray rate were analyzed in a statistical design of experiments. The 2 spray guns were compared with respect to the spray width and height, droplet size, droplet velocity, and spray density. The droplet size, velocity, and spray density were measured with a Phase Doppler Particle Analyzer.
A successful scale-up of the atomization is accomplished if similar droplet sizes, droplet velocities, and spray densities are achieved in the production scale as in the laboratory scale. This study gives basic information for the scale-up of the settings from the laboratory spray gun to the production spray gun. Both spray guns are highly comparable with respect to the droplet size and velocity. The scale-up of the droplet size should be performed by an adjustment of the atomization air pressure. The scale-up of the droplet velocity should be performed by an adjustment of the spray gun to tablet bed distance. The presented statistical model and surface plots are convenient and powerful tools for scaling up the spray settings if the spray gun is changed from laboratory spray gun to the production spray gun.
PMCID: PMC2750438  PMID: 17408226
Atomization; film coating; spray gun; scale-up; design of experiments
13.  Mathematical modeling of an aqueous film coating process in a Bohle Lab-Coater, Part 1: Development of the model 
AAPS PharmSciTech  2006;7(2):E79-E86.
The purpose of this study was to develop a model to predict (1) air and product temperatures, (2) product moisture, and (3) air humidity during an aqueous coating process using a Bohle Lab-Coater. Because of the geometrical properties and the airflow, the drum of the Bohle Lab-Coater can in principle be divided into 2 zones of equal size—the drying and the spraying zones. For each zone, 4 balance equations could be set up describing the change of the air humidity, the product moisture, the enthalpy of the air, and the enthalpy of the product in each zone. For this purpose, knowledge regarding heat and mass transfer and also the motion of the tablets in drums was used. Based on the considerations of the heat and mass transfer, a set of first-order coupled ordinary differential equations (ODEs) was developed. This set of ODEs can be solved numerically. In this part, the development of the model is described in detail, whereas the application of the model can be found in part 2.
PMCID: PMC2750293  PMID: 16796359
film coating; mathematical modeling; heat and mass transfer; convection; particle movement
14.  Mathematical modeling of an aqueous film coating process in a Bohle Lab-Coater: Part 2: Application of the model 
AAPS PharmSciTech  2006;7(2):E87-E94.
For the prediction of the air and product temperatures, the product moisture, and the air humidity during a coating process in a Bohle Lab-Coater, a model was developed. The purpose of this work was to determine the limit moisture, the critical moisture, and the constant for the exchange rate between both zones and to use these values for other sets of experiments to test the model. The adaptation of the 3 parameters (limit moisture, critical moisture, and exchange rate constant), was done by calculation of the product temperature in both zones for several sets of parameters in order to minimize the sum of square deviation between the calculated and the measured product temperatures. This set of parameters was used to test the validity of the model. By applying the model, the product temperature could be predicted based on the product, process, and equipment-related parameters. Hence, the model can be used to theoretically investigate the influence of different process paramaters. The mean difference between the predicted, and measured product temperatures in the steady state is ≈2 up to 3 K using the determined parameter set for the limit moisture, the critical moisture, and the exchange rate constant. The model is useful for the prediction of the air and product temperatures, the product moisture, and air humidity during a coating process in the Bohle Lab-Coater using round, biconvex tablets.
PMCID: PMC2750294
film coating; mathematical modeling; heat and mass transfer; convection; particle movement
15.  Properties of microcrystalline cellulose and powder cellulose after extrusion/spheronization as studied by fourier transform Raman spectroscopy and environmental scanning electron microscopy 
AAPS PharmSci  2003;5(4):77-89.
In this study, the effect of powder cellulose (PC) and 2 types of microcrystalline cellulose (MCC 101 and MCC 301) on pellet properties produced by an extrusion/spheronization process was investigated. The different investigated types of cellulose displayed different behavior during the extrusion/spheronization process. Pure PC was unsuitable for extrusion, because too much water was required and the added water was partly squeezed during the extrusion process. In contrast, MCC 101 and MCC 301 were extrudable at a wide range of water content, but the quality of the resulting products varied. In the extrusion/spheronization process, MCC 101 was the best substance, with easy handling and acceptable product properties. The properties of the extrudates and pellets were determined by Fourier transform (FT) Raman spectroscopy and environmental scanning electron microscopy (ESEM). FT-Raman spectroscopy was able to distinguish between the original substances and also between the wet and dried extrudates. The particle sizes of the raw material and of the extrudates were determined by ESEM without additional preparation. For MCC, the size of the resulting particles within the extrudate or pellet was smaller. However, in the extrudates of PC, changes in particle size could not be observed.
PMCID: PMC2750993  PMID: 15198519
powder cellulose; microcrystalline cellulose; pellet; Raman spectroscopy; environmental scanning electron microscopy; extrusion/spheronization
16.  Extrusion/spheronization of pectin-based formulations. I. Screening of important factors 
AAPS PharmSciTech  2001;2(4):54-62.
This study investigated the possibility of producing pectin-based pellets by extrusion/spheronization. The study also identified factors influencing the process and the characteristics of the resulting product. Three types of pectin with different degrees of amid and methoxyl substitution were studied in combination with different granulation liquids (water, calcium chloride, citric acid, and ethanol) and/or microcrystalline cellulose. Pellets were prepared in a power-consumption-controlled, twinscrew extruder; then they were spheronized and dried. The products were characterized by image analysis, sieving analysis, and disintegration and dissolution tests. The results were evaluated by multivariate analysis. Different additives, either in the granulation liquid or in the powder mixture, influenced the ability of the extruded mass to form pellets (the processability) with this technique. However, the various pectin types responded to modifications to a different extent. Short, nearly spherical pellets are obtained with granulation liquids, such as ethanol, that reduce the swelling ability of pectin. Pellets produced with ethanol are, however, mechanically weak and tend to ditintegrate. Pectin molecules with a high degree of free carboxylic acid groups seem to be more sensitive to changes in the granulation liquid. Addition of microcrystalline cellulose as an extrusion aid generally resulted in improvements in shape and size. It was demonstrated that the processability of pectin as well as the characteristics of the products can be influenced in different ways during the process (eg, adding substances to the granulation liquid or to the powder mixture).
PMCID: PMC2784841  PMID: 14727863
Pectin; Pellets; Extrusion; Spheronization; Multivariate analysis
17.  Extrusion/spheronization of pectin-based formulations. II. Effect of additive concentration in the granulation liquid 
AAPS PharmSciTech  2001;2(4):63-72.
Purpose. The aim of this study was to improve the formation of spherical pectin pellets by investigating the effect of additive concentration in the granulation liquid on the shape and size of the products as well as by identifying an optimal additive concentration.Methods. High-methoxylated, low-methoxylated, and amidated low-methoxylated pectin types were evaluated in combination with different concentrations of methanol, ethanol, citric acid, lactic acid, and calcium chloride. Pellets were prepared in a power-consumption-controlled twin-screw extruder, then spheronized and dried. The moisture content of the extrudate was determined, and the final products were characterized by image analysis and sieving analysis. A cloud point test was employed for the identification of an optimal additive concentration.Results. The concentration of additive in the granulation liquid affected the moisture content of the extrudate and the shape, size, and mechanical stability of the pectin pellets. Improvements in the pellet characteristics are dependent on the pectin type employed. The 2 low-methoxylated pectins were more sensitive to concentration changes than was the high-methoxylated type. Above a certain threshold concentration, the quality of the pellets are improved. This additive concentration differs according to type of pectin and type of additive.Conclusion. It was demonstrated that there is a concentration-dependent interaction between pectin and substances added to the granulation liquid that can be utilized to improve the formation of spherical pectin pellets.
PMCID: PMC2784842
Extrusion; Spheronization; Pectin; Granulation Liquid; Concentration Effects
18.  Direct pelletization in a rotary processor controlled by torque measurements. II: Effects of changes in the content of microcrystalline cellulose 
AAPS PharmSci  2000;2(3):45-52.
In the present study we investigated the effect of changes in the content of microcrystalline cellulose (MCC) on a direct pelletization process in a rotary processor in which the liquid addition was terminated once a certain increase in torque was produced. Nine different mixtures of MCC and lactose with MCC contents varying from 10% to 100% (w/w) were pelletized using 6 different torque increase levels, and the changes in pellet characteristics were investigated. The pellet characteristics investigated were pellet shape, size, and size distribution as well as the water content of the pellets at the end of liquid addition. To produce spherical agglomerates with suitable characteristics in a reproducible way, a content of a least 20% (w/w) MCC was found necessary. Linear correlations were found between the MCC content and the water content and between the torque incraase and the water content, showing that the torque increase is suitable to control the process. A higher torque increase or a higher MCC content was found to increase the water content independently of each other.
PMCID: PMC2761135  PMID: 11741240
19.  Influence of degree of polymerization on behavior of cellulose during homogenization and extrusion/spheronization 
AAPS PharmSci  2000;2(3):18-27.
The study objective was to investigate the influence of the degree of polymerization (DP) of cellulose materials (microcrystalline cellulose [MCC] and powder cellulose [PC]) on the behavior of these materials during homogenization and extrusion/spheronization processes. Suspensions of the cellulose types with different DP values were homogenized using a high-pressure homogenizer. The particle size, agglomeration index, and apparent viscosity of these suspensions was determined at different times after pouring. Additionally, these different cellulose types were processed into pellets using the extrusion/spheronization, method, and the water content and power consumption as a function of the DP were determined. Cellulose types with a high DP value showed greater particle size after homogenization, than the types with a low DP value. In contrast, no relevant relationship between the apparent viscosity and DP could be observed. During the extrusion process, water content in the extrudate and pellet porosity were increased as the DP was increased for the extrudates produced at the same level of power consumption. MCC types with various DPs compared with PC provided a novel way of understanding the role of cellulose in the extrusion process. The DP showed a remarkable influence on the physicochemical properties of the cellulose materials and, consequently, on the behavior of these materials during the extrusion/spheronization process. It is postulated that the sponge model is more appropriate for the cellulose type with high DP (PC), whereas the gel model is more applicable to cellulose types with lower DP (MCC).
PMCID: PMC2761132  PMID: 11741237

Results 1-19 (19)