Grades Of Microcrystalline Cellulose Research Articles

The Effect of Microcrystalline Cellulose-CaHPO4 Mixtures in Different Volume Ratios on the Compaction and Structural-Mechanical Properties of Tablets.

Using microcrystalline cellulose (MCC) with plastic behaviour and calcium phosphate anhydrous (CaHPO4) with brittle behaviour under compaction is very popular in the pharmaceutical industry for achieving desirable structural-mechanical properties of tablet formulations. Thus, mixtures of specific grades of MCC and CaHPO4 were tested in volume proportions of 100-0, 75-25, 50-50, 25-75, and 0-100 at a constant weight-by-weight concentration of sodium stearyl fumarate lubricant, utilizing a state-of-the-art benchtop compaction simulator (STYL'One Nano). Tablet formulations were prepared at 100, 150, 250, 350, 450, and 500 MPa, and characterized by tabletability profile, ejection force profile, proportion-tensile strength relationship, proportion-porosity relationship, pressure-displacement, and elastic recovery profiles, as well as by in-/out-of-die Heckel plots and yield pressures. Interestingly, the 25-75 formulation demonstrated a two-stage out-of-die Heckel plot and was additionally investigated with X-ray micro-computed tomography (µCT). By post-processing the µCT data, the degree of brittle CaHPO4 particles falling apart, along with the increasing compression pressure, was quantified by means of the surface area to volume (S/V) ratio. For the 25-75 formulation, the first stage (up to 150 MPa) and second stage (above the 150 MPa) of the out-of-die Heckel plot could be attributed to predominant MCC and CaHPO4 deformation, respectively.

Effect of particle size on the dispersion behavior of magnesium stearate blended with microcrystalline cellulose

The majority of tablets manufactured contain lubricants to reduce friction during ejection. However, especially for plastically deforming materials, e.g., microcrystalline cellulose (MCC), the internal addition of lubricants is known to reduce tablet tensile strength. This reduction is caused by the surface coverage by lubricant particles, the extent of which depends on both process and formulation parameters. Previously published models to predict the lubrication effect on mechanical strength do not account for changes in the excipient particle size. In this study, the impact of both lubricant concentration and mixing time on the tensile strength of tablets consisting of three different grades of MCC and four grades of magnesium stearate (MgSt) was evaluated. By taking into account the particle size of the applied excipients, a unifying relationship between the theoretically estimated surface coverage and compactibility reduction was identified. Evaluating the dispersion kinetics of MgSt as a function of time reveals a substantial impact of the initial surface coverage on the dispersion rate, while the minimal tensile strength was found to be comparable for the majority of formulations. In summary, the presented work extends the knowledge of lubricant dispersion and facilitates the reduction of necessary experiments during the development of new tablet formulations.

An evaluation of microcrystalline cellulose attributes affecting compaction-induced pellet coat damage through a multi-faceted analysis

Pellet coat damage in multi-unit pellet system (MUPS) tablets has previously been studied and addressed with limited success. The effects of lactose filler material attributes on pellet coat damage have been relatively well-studied but a similar understanding of microcrystalline cellulose (MCC) is lacking notwithstanding its high cushioning potential. Hence, the relationships between MCC attributes and pellet coat damage were investigated. Single pellet in minitablets (SPIMs) were used to isolate pellet-filler effects and reveal the under-unexplored impact of risk factors found in MUPS tablets. MUPS tablets and SPIMs were prepared with various grades of MCC and pellets with an ethylcellulose or acrylic coat at various compaction pressures. Subsequently, the extent of pellet coat damage was determined by dissolution test and quantified using two indicators to differentiate the nature of the damage. A multi-faceted analytical approach incorporated linear regression, correlations and a classification and regression tree algorithm and evaluated how MCC attributes, such as flowability, particle size and plastic deformability, exert various influences on the extent of ethylcellulose and acrylic pellet coat damage. This analysis improved the understanding of the different mechanisms by which pellet coat damage to these two polymer types occurs which can help enhance future pellet coat damage mitigation strategies.

Control Strategy for Excipient Variability in the Quality by Design Approach Using Statistical Analysis and Predictive Model: Effect of Microcrystalline Cellulose Variability on Design Space.

Although various quality by design (QbD) approaches have been used to establish a design space to obtain robust drug formulation and process parameters, the effect of excipient variability on the design space and drug product quality is unclear. In this study, the effect of microcrystalline cellulose (MCC) variability on drug product quality was examined using a design space for immediate-release tablets of amlodipine besylate. MCC variability was assessed by altering the manufacturer and grade. The formulation was developed by employing the QbD approach, which was optimized using a D-optimal mixture design. Using 36 different MCCs, the effect of MCC variability on the design space was assessed. The design space was shifted by different manufacturers and grades of MCC, which resulted in associations between the physicochemical properties of MCC and critical quality attributes (CQAs). The correlation between the physicochemical properties of MCCs and CQAs was assessed through a statistical analysis. A predictive model correlating the physicochemical properties of MCCs with dissolution was established using an artificial neural network (ANN). The ANN model accurately predicted dissolution with low absolute and relative errors. The present study described a comprehensive QbD approach, statistical analysis, and ANN to comprehend and manage the effect of excipient variability on the design space.

A compactibility-based lubricant dispersion model describing the effect of formulation and paddle speed

In rotary tablet presses, the powder flow into the dies is typically facilitated by paddle feeder. For internally lubricated formulations, the shear forces exerted by the paddle rotation can result in a considerable decrease in tablet strength due to the dispersion of lubricant agglomerates. Available models to describe the lubricant dispersion in paddle feeder allow only a limited quantitative description and transferability of the process. This study introduces an empirical dispersion kinetic which is able to precisely describe the reduction of compactibility due to the shear stresses inside the paddle feeder, even for inhomogeneously flowing material. Additionally, by blending different grades of magnesium stearate at three levels of lubricant concentration with two different grades of microcrystalline cellulose, the impact of bulk properties on the lubrication dispersion in the feed frame was investigated. It was shown, that for a given formulation, the kinetics of compactibility reduction are comparable for different magnesium stearate concentrations. Additionally, the bulk properties of the applied magnesium stearate grade critically affect the dispersion kinetics as well as the maximum compactibility reduction inside the feed frame. In summary, the developed model represents a meaningful extension of the currently available process models for pharmaceutical tablet lubrication.

Influences of different microcrystalline cellulose (MCC) grades on tablet quality and compression behavior of MCC-lactose binary mixtures

Microcrystalline cellulose (MCC) is one of the most commonly used excipients in tablet formulations. At present, numerous grades of MCC are available for pharmaceutical manufacturing and significantly differ in particulate and powder properties. The choice of MCC is important to the development of a tablet formulation with satisfactory quality. In this paper, five commercial grades of MCC from the same manufacturer were systematically evaluated by combination with lactose to investigate their influences on tablet quality. Furthermore, the key compression parameters obtained from empirical compression equations were used to analyze the compression behavior of the tablet formulations. When the proportion of MCC was up to ∼50%, PH 102, PH 102SCG, and PH 112 showed good and similar abilities in improving tablet tensile strength followed by PH 200, and PH 302 did the weakest. All the MCC successfully decreased the tablet friability and disintegration time values. The improvement effect of MCC on tablet disintegration followed the descending order: PH 200 > PH 102SCG > PH 302 > PH 102 > PH 112. Besides, the different effects of MCC grades on tablet quality could be weakened by lubricants when the mixtures mainly underwent plastic deformation during compression process. In conclusion, a clear understanding of the influences of commonly used grades of MCC on tablet quality is critical for future tablet formulation efforts.

Effect of deaeration on processability of poorly flowing powders by roller compaction

Roller compaction (RC) is a common granulation process for manufacturing solid dosage forms. However, its applicability to the growing number of powders with very low bulk densities and high cohesiveness can be limited due to poor powder feeding. Although deaeration with a vacuum in the feeding line is an effective approach to enhance the powder feeding performance, a systematic assessment of its effects on RC process is lacking. In this work, we have examined the effect of vacuum on the processability of RC using an extremely poorly flowing powder, colloidal silica, and two grades of microcrystalline cellulose (MCC). A processable range is defined by roll speed and screw speed that attain stable feeding under the roller-gap controlled mode. A 0.35 barg vacuum level was sufficient to make the colloidal silica processable and a higher vacuum level solved the subfeeding issue and significantly expanded the RC operation range. In contrast, deaeration slightly narrowed the processable range for MCC PH105 and PH101, while only minimally affects the relationship between roll speed and screw speed. The effects of vacuum on the processability of these materials qualitatively correlated with the sensitivity of their bulk densities to pressure. A better understood effects of material properties (bulk density), process parameters (roller gap), and deaeration (vacuum level) on RC processability of powders help to determine an appropriate use of a vacuum line to improve the RC process.

Improving the Effectiveness of the Conical Screen Mill as a Dry-Coating Process at Lab and Manufacturing Scale.

The conical screen mill (comill) is investigated as a dry-coating process for flowability and bulk density enhancement of pharmaceutical powders. In this study, the effectiveness of the comill is improved by using modified screens with reduced open area. In comparison to the screens provided by the comill manufacturer, the modified screens increase mean residence time of the process and improve the extent of flowability and bulk density enhancement. The effectiveness of the comill as a dry-coating process is demonstrated using Avicel PH 105, a fine grade of microcrystalline cellulose, as a model cohesive powder. The process is evaluated thoroughly using a lab scale comill and scalability is demonstrated using a manufacturing scale model. The use of the modified screens is also compared against the so-called "multi-pass" approach in which material is passed through the comill, collected, and passed through once or several times. While the "multi-pass" approach is offered as a simple method to increase mean residence time and to improve process effectiveness, the use of the modified screens is shown to be the superior approach. Due to the ubiquitous use of the comill and the improvement in effectiveness attained in this study, dry-coating is shown to be a practical and readily implemented process for the pharmaceutical industry.

Modeling of High-Density Compaction of Pharmaceutical Tablets Using Multi-Contact Discrete Element Method.

The purpose of this work is to simulate the powder compaction of pharmaceutical materials at the microscopic scale in order to better understand the interplay of mechanical forces between particles, and to predict their compression profiles by controlling the microstructure. For this task, the new framework of multi-contact discrete element method (MC-DEM) was applied. In contrast to the conventional discrete element method (DEM), MC-DEM interactions between multiple contacts on the same particle are now explicitly taken into account. A new adhesive elastic-plastic multi-contact model invoking neighboring contact interaction was introduced and implemented. The uniaxial compaction of two microcrystalline cellulose grades (Avicel® PH 200 (FMC BioPolymer, Philadelphia, PA, USA) and Pharmacel® 102 (DFE Pharma, Nörten-Hardenberg, Germany) subjected to high confining conditions was studied. The objectives of these simulations were: (1) to investigate the micromechanical behavior; (2) to predict the macroscopic behavior; and (3) to develop a methodology for the calibration of the model parameters needed for the MC-DEM simulations. A two-stage calibration strategy was followed: first, the model parameters were directly measured at the micro-scale (particle level) and second, a meso-scale calibration was established between MC-DEM parameters and compression profiles of the pharmaceutical powders. The new MC-DEM framework could capture the main compressibility characteristics of pharmaceutical materials and could successfully provide predictions on compression profiles at high relative densities.

Structural, morphological and thermal properties of microcrystalline cellulose extracted from coconut husk fiber

In this work, chemically treated microcrystalline cellulose (MCC-C) was extracted from coconut husk fiber. In order to extract hemicellulose, the sieved coconut husk fiber was treated with sodium hydroxide (NaOH) for dewaxing and acidified using sodium chlorite (NaClO2) to extract the residual lignin (bleaching process). The obtained lignin-free cellulose was then treated with potassium hydroxide (KOH). The characterizations used to equate the MCC-C with commercial grade microcrystalline cellulose (MCC) are solubility test, X-ray diffractogram (XRD), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). The XRD showed that the crystallinity of MCC and MCC-C increased significantly by 80.15% and 71.8% by chemical treatments. TGA found that the active removal of lignin-hemicelluloses and the thermal stability of the material were about 350–500°C and 300–500°C. The morphology of the fiber confirmed that there is an irregular cross-section, non-uniform surface, a large amount of short microfibrils and some impurities on the surface of the coconut husk fiber. The findings showed that microcrystalline cellulose has been successfully extracted from coconut husk fiber and that it can be used further.

Quantification of swelling characteristics of pharmaceutical particles.

Particle swelling is a crucial component in the disintegration of a pharmaceutical tablet. The swelling of particles in a tablet creates stress inside the tablet and thereby pushes apart adjoining particles, eventually causing the tablet to break-up. This work focused on quantifying the swelling of single particles to identify the swelling-limited mechanisms in a particle, i.e. diffusion- or absorption capacity-limited. This was studied for three different disintegrants (sodium starch glycolate/SSG, croscarmellose sodium/CCS, and low-substituted hydroxypropyl cellulose/L-HPC) and five grades of microcrystalline cellulose (MCC) using an optical microscope coupled with a bespoke flow cell and utilising a single particle swelling model. Fundamental swelling characteristics, such as diffusion coefficient, maximum liquid absorption ratio and swelling capacity (maximum swelling of a particle) were determined for each material. The results clearly highlighted the different swelling behaviour for the various materials, where CCS has the highest diffusion coefficient with 739.70 μm2/s and SSG has the highest maximum absorption ratio of 10.04g/g. For the disintegrants, the swelling performance of SSG is diffusion-limited, whereas it is absorption capacity-limited for CCS. L-HPC is both diffusion- and absorption capacity-limited. This work also reveals an anisotropic, particle facet dependant, swelling behaviour, which is particularly strong for the liquid uptake ability of two MCC grades (PH101 and PH102) and for the absorption capacity of CCS. Having a better understanding of swelling characteristics of single particles will contribute to improving the rational design of a formulation for oral solid dosage forms.

Application of percolation threshold to disintegration and dissolution of ibuprofen tablets with different microcrystalline cellulose grades.

The study presented was conducted to determine whether a percolation threshold value, previously determined for ibuprofen/microcrystalline cellulose (MCC) blends using percolation theory and compression data (Queiroz et al., 2019), could translate to tablet disintegration and dissolution data. The influence of MCC grade (air stream dried versus spray dried) on tablet disintegration and dissolution was also investigated. Complementary to conventional disintegration and dissolution testing, Raman imaging determined drug distribution within tablets, and in-line particle video microscopy (PVM) and focused-beam reflectance measurement (FBRM) monitored tablet disintegration. Tablets were prepared containing 0-30% w/w ibuprofen. Raman imaging confirmed the percolation threshold by quantifying the number and equivalent circular diameters of ibuprofen domains on tablet surfaces. Across the percolation threshold, a step change in dissolution behaviour occurred, and tablets containing air stream dried MCC showed slower disintegration rates compared to tablets containing spray dried MCC. Dissolution measurements confirmed experimentally a percolation threshold in agreement with that determined using percolation theory and compression data. An increase in drug domains, due to cluster formation, and less efficient tablet disintegration contributed to slower ibuprofen dissolution above the percolation threshold. Slower dissolution was measured for tablets containing air stream dried compared to spray dried MCC.

Image-based characterization of powder flow to predict the success of pharmaceutical minitablet manufacturing.

Powder flowability plays an important role in die filling during tablet manufacturing. The present study introduces a novel small-scale measuring technique for powder flow. Based on image analysis, the flow was defined depending on the variation of luminous intensity and the movement of powder inside the measurement cuvette. Using quantities around 100mg it was possible to characterize a wide range of common pharmaceutical powders, especially in distinguishing subtle differences in flow caused by minor changes in samples characteristics. The method was compared with powder rheometry, which is widely used in the pharmaceutical literature, and showed a significant improvement in predicting the success of pharmaceutical minitablet manufacture (d=5mm). Tablet weight variation (RSD) was defined as the most efficient way to assess relevant powder flow behaviour in tablet production when using the novel device. The proposed method was distinguished from others by its ability to classify different grades of microcrystalline cellulose in the die-filling process. Subsequently, eight common pharmaceutical powders, both excipients and APIs, were properly ranked as a function of flowability based on their physical properties. The method showed a high repeatability, with a relative standard deviation not more than 10%.

Microcrystalline cellulose production from sugarcane bagasse: Sustainable process development and life cycle assessment

Sugarcane bagasse (SCB), a major and abundantly available byproduct of sugarcane processing industries is presently being used for energy generation. However, its rich resource content makes it a perfect feedstock for the production of various value-added products. In this communication, Microcrystalline Cellulose (MCC), a partially depolymerized cellulose is in vogue due to its versatile physical properties which holds substantial applications in the pharmaceutical industries, was produced from the surplus available SCB. Experiments were designed to optimize MCC production from SCB using three different chemical methods namely MCC1, MCC2 and MCC3 by varying the reaction conditions. Relatively higher yield of cellulose (0.34 g/g SCB) and MCC (0.32 g/g SCB) were observed with MCC2 method, followed by MCC3 (cellulose 0.32 g/g SCB; MCC 0.31 g/g SCB) and MCC1 (cellulose 0.30 g/g SCB; MCC 0.28 g/g SCB). Fourier transform infrared spectroscopy (FT-IR) showed good correlation with commercial grade MCC for the presence of characteristic functional groups. X-ray diffractograms (XRD) showed 79.8%, 84.1% and 87.4% crystallinity for MCC1, MCC2 and MCC3, respectively. The morphological analysis of all the three MCC samples correlated well with the standard MCC. EcoScale analysis awarded scores greater than 75 for the three MCC methods, in which MCC2 scored the maximum (84). Life cycle analysis depicted the impacts of MCC production methods on various environmental impact categories, where MCC3 method showed relatively less environmental impact in terms of global warming (27% less than MCC2). MCC3 further characterized with X-Ray Photoelectron Spectroscopy, Thermogravimetry analysis (TGA), Differential thermal analysis (DTA) and Differential scanning calorimetry (DSC) depicted its characteristic properties. Additionally, the sustainability analysis functioned as a valuable tool to assess the environmental impact of the process, prior to scaling up.

The Role of Particle Surface Area and Adhesion Force in the Sticking Behavior of Pharmaceutical Powders

The effect of particle surface area and adhesion force on sticking behavior for a model pharmaceutical blend was studied. Various lots of an active pharmaceutical ingredient (API) differing in particle size distribution and surface area were blended with commercial grades of microcrystalline cellulose ranging in size from 20 to 110 μm. A dry-coating technique was also used to modify the surface of microcrystalline cellulose to reduce its adhesion force. This allowed study of sticking behavior due to effects associated with particle adhesion force independently from effects associated with surface area. Using a removable-tip experiment to quantify the mass of adhered material to a tablet punch, this study concludes that both particle surface area and adhesion force significantly affect sticking behavior. Tablets with higher tensile strength comprised of API with lower surface area relative to the excipient surface area resulted in less sticking. This study found that the difference between the tablet tensile strength of the blend and that of the API normalized by the surface area fraction of API in the blend correlates well with the rate of mass adhered to the punch. This quantity, referred to as the sticking index, can be used to assess sticking propensity for a pharmaceutical blend.

English

Microcrystalline cellulose (MCC) is an important ingredient in pharmaceutical, food, cosmetic and other industries. In this research work, microcrystalline cellulose was synthesized from the alpha cellulose content of pretreated palm kernel de-oiled cake. The microcrystalline cellulose from palm kernel cake was obtained through acidified sodium chlorite, sodium hydroxide delignification followed by hydrogen peroxides bleaching and finally acid hydrolysis. The prepared microcrystalline cellulose was characterized by determining some physicochemical properties such as pH, bulk density, tap density, moisture content, ash content, Carrs compressibility index, Hausners ratio, powder porosity, angle of repose and compared with commercial-grade microcrystalline cellulose that is used in pharmaceutical industry as excipient. FT-IR was employed to expose the functional groups and the wavelength inherent by both the produced and commercial microcrystalline cellulose. The swelling property of MCC product was determined based on hydration capacity, swelling capacity and moisture sorption capacity. The results of the physicochemical parameters were given as pH (7.75 ± 0.40), bulk density (0.49 ± 0.67 gcm-3), tapped density (0.54 ± 0.03 gcm-3), moisture content (1.00 ± 0.5%), ash content (4.30 ± 0.35%), Carrs compressibility index (12.96 ± 0.27), Hausners ratio (1.15 ± 0.01), powder porosity (18.8 ± 0.55), angle of repose (27.4 ± 0.26), respectively. The swelling properties were also determined and compared favorably with the commercial grade of microcrystalline cellulose (p>0.05). The findings suggest that palm kernel cake can not only be used as feeds for animals but also a better source of cellulose for the production of microcrystalline cellulose for the industry owing to its availability and cost managements. Key words: Microcrystalline cellulose, palm kernel de-oiled cake, commercial grade, carr’s compressibility index, pharmaceutical excipient.

The application of percolation threshold theory to predict compaction behaviour of pharmaceutical powder blends

Percolation theory provides a statistical model which can be used to predict the behaviour of powder blends based on particle-particle interactions. The aim of this study was to investigate if percolation theory could be used to predict the drug loading concentration of pharmaceutical tablets, and the relative density of a blend, above which tablet tensile strength is reduced, resulting in the production of unsatisfactory products. The model blend studied contained ibuprofen as the API, which exhibits poor flow and compressibility, and microcrystalline cellulose (MCC) as the excipient, which exhibits good flowability and compressibility. Two MCC grades with differing physical properties were investigated, Vivapur® 102 (air streamed dried quality), and Emcocel® 90 (spray dried quality) to test the theory. Blends containing 2.5 to 40% w/w of ibuprofen were compacted at a range of pressures and the values of the powder true density, compaction pressure, tablet envelope density, and tablet tensile strength were used to calculate the percolation thresholds mathematically. The drug loading threshold values predicted with the model (19.08% w/w and 17.76% w/w respectively for Vivapur® 102 and Emcocel® 90) were found to be in good agreement when compared to experimental data and the infinite cluster of drug was visually confirmed on the surface of tablets using Raman imaging. The capability of multivariate analysis to predict the drug loading threshold was also tested. Principal component analysis was unable to identify the threshold, but provided an overview of the changes of the analysed properties as ibuprofen drug loading increased. It was also able to identify differences between blends containing Vivapur® or Emcocel®. In conclusion, percolation theory was able to predict the maximum acceptable drug loading for this binary system of API and excipient. This methodology could be employed for other binary systems to predict maximum drug loading potential without the need for time consuming and expensive tablet production.

Characterization of Mechanical Property Distributions on Tablet Surfaces.

Powder densification through uniaxial compaction is governed by a number of simultaneous processes taking place on a reduced time as the result of the stress gradients within the packing, as well as the frictional and adhesive forces between the powder and the die walls. As a result of that, a density and stiffness anisotropy is developed across the axial and radial directions. In this study, microindentation has been applied to assess and quantify the variation of the module of elasticity () throughout the surface of cylindrical tablets. A representative set of deformation behaviors was analyzed by pharmaceutical excipients ranging from soft/plastic behavior (microcrystalline cellulose) over medium (lactose) to hard/brittle behavior (calcium phosphate) for different compaction pressures. The results of the local stiffness distribution over tablet faces depicted a linear and directly proportional tendency between a solid fraction and for the upper and lower faces, as well as remarkable stiffness anisotropy between the axial and radial directions of compaction. The highest extent of the stiffness anisotropy that was found for ductile grades of microcrystalline cellulose (MCC) in comparison with brittle powders has been attributed to the dual phenomena of overall elastic recovery and Poisson’s effect on the relaxation kinetics. As a reinforcement of this analysis, the evolution of the specific surface area elucidated the respective densification mechanism and its implementations toward anisotropy. For ductile excipients, the increase in the contact surface area as well as the reduction and closing of interstitial pores explain the reduction of surface area with increasing compaction pressure. For brittle powders, densification evolves through fragmentation and the subsequent filling of voids.

Evaluation of a Dry Coating Technology as a Substitute for Roller Compaction for Dry Agglomeration Applications in the Pharmaceutical Industry

A dry coating technology has been evaluated as a dry agglomeration technique for a typical pharmaceutical formulation. Its efficiency was compared with that of the more commonly used roller compaction dry granulation. A commercially available system was selected as a representative technology. The selection was based on batch size, processing time, unit size, vendor support, preventive maintenance requirements, development stage, and maturity for pharmaceutical industry requirements. The comparison targets the behavior of the resulting materials in terms of flowability, compressibility, mixing efficiency, and prevention of segregation. Particle size distribution, bulk density, scanning electron microscopy, FT4 powder rheometer, and hardness were used for the characterization of the powders. A design of experiment was used to evaluate the impact of the dry coating equipment operating parameters (rotor speed and processing time) as well as the impact of formulation (grade of microcrystalline cellulose and ratio between dibasic calcium phosphate and lactose). The tested dry coating technology shows (1) an improved compressibility, (2) that the powders are homogenous, and (3) that they do not have a tendency to segregate in downstream process steps and during handling and storage. The impact of the rotor speed is proven statistically not significant, but it seems that a lower rotor speed might lead to less attrition and better flow properties. Processing time does not seem to have an impact for the range of processing times evaluated. Compared to roller compaction, the main advantages of the tested technology are the shape and surface enhancement and the absence of work hardening. This work has shown that the blends produced by the targeted dry coating equipment has equal or better results than the powders processed by roller compaction for all the critical quality attributes that were evaluated.

Formulation and Evaluation of Nelfinavir Extended Release Trilayer Matrix Tablets by Design of Experiment

The present study was aimed to develop once-daily controlled release trilayer matrix tablets of nelfinavir to achieve zero-order drug release for sustained plasma concentration. Nelfinavir trilayer matrix tablets were prepared by direct compression method and consisted of middle active layer with different grades of hydroxypropyl methylcellulose (HPMC), PVP (Polyvinyl Pyrrolidine) K-30 and MCC (Micro Crystalline Cellulose). Barrier layers were prepared with Polyox WSR-303, Xanthan gum, microcrystalline cellulose and magnesium stearate. Based on the evaluation parameters, drug dissolution profile and release drug kinetics DF8 were found to be optimized formulation. The developed drug delivery system provided prolonged drug release rates over a period of 24 h. The release profile of the optimized formulation (DF8) was described by the zero-order and best fitted to Higuchi model. FT-IR studies confirmed that there were no chemical interactions between drug and excipients used in the formulation. These results indicate that the approach used could lead to a successful development of a controlled release formulation of nelfinavir in the management of AIDS.