High-speed Tablet Research Articles

FLOWABILITY PROPERTIES OF BINARY POWDER MIXTURES CONTAINING DATES POWDER (PHEONIX DACTYLIFERA) MIXED WITH LACTOSE MONOHYDRATE AND MICROCRYSTALLINE CELLULOSE BASED EXCIPIENTS

Powder flow is important in powder processing industries to obtain a quality by design product and efficient manufacturing process. Poor powder flowability can cause problems especially during high speed tableting and capsule filling processes. In this study, dates powder (DP), lactose monohydrate powder, and two types of microcrystalline-based powder excipients evaluated for their flow properties as a binary mixture. Angle of repose (AoR), Hausner ratio (HR) and Carr index (CI) were used to characterize the extent of the powder cohesion. The results show that generally, as particle size increases, values of AoR generally decreases, depicting lower flowability characteristics with decreasing binary mixture particle size. However, HR and CI flowability indicators give contrasting flowability characteristics for the binary mixture containing lactose monohydrate and dates powder.

High-Speed Tableting of High Drug-Loaded Tablets Prepared from Fluid-Bed Granulated Isoniazid.

The aim of this feasibility study was to investigate the possibility of producing industrial-scale relevant, robust, high drug-loaded (90.9%, w/w) 100 mg dose immediate-release tablets of isoniazid and simultaneously meet the biowaiver requirements. With an understanding of the real-life constrictions on formulation scientists during product development for the generic industry, this study was done considering a common set of excipients and manufacturing operations, as well as paying special attention to the industrial-scale high-speed tableting process as one of the most critical manufacturing operations. The isoniazid substance was not applicable for the direct compression method. Thus, the selection of granulation method was logically justified, and it was fluid-bed granulated with an aqueous solution of Kollidon® 25, mixed with excipients, and tableted with a rotary tablet press (Korsch XL 100) at 80 rpm (80% of the maximum speed) in the compaction pressure range 170-549 MPa monitoring of ejection/removal forces, tablet weight uniformity, thickness, and hardness. Adjusting the main compression force, the Heckel plot, manufacturability, tabletability, compactability, and compressibility profiles were analysed to choose the main compression force that resulted in the desirable tensile strength, friability, disintegration, and dissolution profile. The study showed that highly robust drug-loaded isoniazid tablets with biowaiver requirements compliance can be prepared with a common set of excipients and manufacturing equipment/operations incl. the industrial-scale high-speed tableting process.

An update on advancements in tablet tooling technology

The pharmaceutical companies are paying more attention to tablet tooling to establish a strong brand identity for their tablet products and to maintain the quality of tablets, while at the same time ensuring that the design can function in a high speed tablet production environment. Advanced tablet tooling design has the potential to produce robust tablets using high speed tablet press minimizing the production cost. Innovative tooling design mainly relies on modification of the punches and dies. A recent advanced tooling design includes multi-tip punches and dies table segments which are more efficient and increases the productivity of tablets. On the other hand, quick-release tooling is engineered to test different dwell times during the research process and to resolve the operational differences. Other developments like various punch and die configurations, and coated punches are responsible for maintaining the quality of tablets as well as extending the tool life. This article highlights the various tooling considerations and also includes innovative approaches to tooling solutions.

High-Speed Tableting of High Drug-Loaded Tablets Prepared from Fluid-Bed Granulated Isoniazid

High-Speed Tableting of High Drug-Loaded Tablets Prepared from Fluid-Bed Granulated Isoniazid

DIRECT COMPRESSIBLE AND CO-PROCESSED EXCIPIENTS- A REVIEW

The demands on the functionality of excipients are increasing day by day because of the emergence of high-speed tableting machines and the use of direct compression methods for tableting. Direct compressible is the preferred method for the preparation of tablet. Excipient play an important role in formulating a dosage form. these are the ingredient which along with active pharmaceutical ingredient make up the dosage forms. Excipient act as protective agent, bulking agent and can also be used sources of excipients along with their uses, and these Can be used for different activities. The current review article highlights the information about Direct compressible and co-processing excipients and their advantages. Also, the recent developments in excipient technology with special emphasis on natural combinations that could be used as co-processed excipients are briefly discussed.

Comparative evaluation of mechanical properties of lactose-based excipients co-processed with lipophilic glycerides as meltable binders

The introduction of the high-speed tableting machines and the lack of excipients with good flow and compaction properties required for direct compression process have increased research interest in the development of co-processed excipients. Melt granulation, as an environmentally friendly and cost-effective method, has recently been recognized as a promising co-processing technique. The aim of the present study was to prepare lipid-based co-processed excipients by in situ fluidized bed melt granulation and to investigated their suitability for direct compression process. Lactose monohydrate was co-processed with glyceryl dibehenate (Compritol® 888 ATO) or glyceryl palmitostearate (Precirol® ATO 5), as lipophilic meltable binders. Besides the flowability testing, dynamic compaction analysis was applied for thorough investigation into the tableting properties of developed co-processed excipients. Solid state characterization, performed by means of XRPD and DRIFT, confirmed the absence of chemical changes of the single components of co-processed excipients. Co-processed excipients showed improved flowability in comparison with single ingredients and corresponding physical mixtures. Novel co-processed excipients were found to have better tabletability profiles than physical mixtures of the ingredients, and were able to retain acceptable tensile strength values at high content of paracetamol in tableting mixture. Tablets with high tensile strength could be obtained with less work of compression needed in comparison with the commercial lactose-based excipients. Furthermore, novel lipid-based co-processed excipients were found to be highly superior regarding the antiadhesive and lubricating properties, with no additional lubricants required.

A Review on Multifunctional Excipients with Regulatory Considerations

The practice of multifunctional excipients is gaining more and more attention as it simplifies the process of drug formulation by substituting the necessity of using mixture of many excipients. The multifunctional excipients are the class of excipients which includes pre-–processed and co-processed excipients and it provides added functionalities to the formulation. Functionality of an excipient is a useful property which helps in manufacturing and improves quality as well as applicability of the material. Researchers have identified that single component excipients may not always give the required results during development and manufacturing of definite API, hence they are concentrating to develop multifunctional excipients which will have improved quality that will fulfil the requirements of the formulation experts in terms of cost. The cost of new excipient development is very high as it demands toxicity studies, hence the industry is now focusing on co-processing of approved materials. The demand for directly compressible co-processed excipients has also increased due to the availability of high-speed tableting machines, time saving in Abbreviated New Drug Application (ANDA), simplified validation and stability of active ingredients. The intention of this review article is to highlight applicability and increasing attention focusing the benefits of co-processed excipients. Their advantages over conventional blend of excipients include development methods, testing and also highlighting their regulatory consideration.

Real-time monitoring of tablet surface temperature during high-speed tableting by infrared thermal imaging

The effect of tableting speed on the surface temperature of tablets during the high-speed tablet manufacturing process was monitored using an infrared (IR) thermal imaging camera. The direct compression prescription powder was tableted using a practical rotary-tableting machine at 10, 25, and 40 rpm with a compression force of 9 kN to produce 200 mg tablets over 30 min. Subsequently, the weight and hardness of the tablets were measured to determine their pharmaceutical properties. The surface temperatures of the tablets were continuously measured using an IR camera, and the relative frequency distribution (RFD) and cumulative relative frequency distribution (CRFD) of the surface temperature of the entire tablet, compression surface, and side surface were obtained from the IR image. The IR thermal imaging parameters, such as the maximum surface temperature (Tmax), mode temperature (Tmo), increasing temperature of the tablet after tableting compression (ΔT), 50% temperature of the ΔT RFD (ΔT50%), and thermal energy parameter for tableting compression (ΔQ’) were evaluated based on the RFD and CRFD. These parameters indicated that the thermal behaviors of the top and side surfaces of the tablets were considerably different depending on the tableting speed. At a tableting speed of 10 rpm, the temperature of the top surface of the tablet was higher than that of the side surface; however, at 25 and 40 rpm, the temperature of the side surface of the tablet was higher than that of the top surface. The weight and hardness of the tablets tended to decrease with an increase in tableting time.

Optimization of Critical Quality Attributes in Tablet Film Coating and Design Space Determination Using Pilot-Scale Experimental Data.

In this study, the novel high-speed tablet film coating process in the continuous manufacturing was investigated. The influence of key process variables (inlet air flow rate, inlet air temperature, and suspension spray rate) were investigated using a Box-Behnken experimental design method. Statistical regression models were developed to predict the outlet air temperature and relative humidity, the coating efficiency, the tablet moisture content, and coating uniformity. The effects of the three key process variables were comprehensively investigated based on mathematical analysis, contour plots, and interaction plots. The results indicate that all the process responses are affected by changing the inlet air flow rate, temperature, and suspension spray rate. A design space (DS) in terms of failure probability was determined based on specifications for tablet moisture content (< 3.5%) and coating uniformity (tablet weight standard deviation < 4mg for tablet weight of 200mg) using Monte Carlo simulations. Independent experiments were carried out and successfully validated the robustness and accuracy of the determined DS for the investigated tablet film coating process. All the data were generated using an industrial pilot-scale novel high-speed tablet coating unit from a continuous manufacturing line. The work facilitates the quality by design implementation of continuous pharmaceutical manufacturing.

Role of dwell on compact deformation during tableting: an overview

Tablet compaction is an important unit operation in the pharmaceutical industry. Among the compaction parameters, dwell time is a key parameter that has been consistently been shown to impact the mechanical quality of tablets. Compacts experience a state of relatively constant strain during the dwell phase and this allows time dependent reactions such as viscoelastic flow to take place within the tablet microstructure. The importance of time dependent compact deformation during the dwell phase has been extensively researched over the years. The amount of plastic flow during the dwell phase has been quantified by researchers by calculating the amount of compaction force decay from stress relaxation curves and by determining certain deformation parameters from compaction force–time profiles during high speed tableting. Dwell time prolongation often led to significant enhancements in the mechanical strength of the tablets, due to a favorable time-dependent shift in the elastic–plastic equilibrium in the compact. The influence of dwell phase on tablet properties is governed by the predominant deformation properties of constituents being compressed along with other coexisting compaction parameters such as strain rate during the consolidation phase of the compaction cycle. Research work on the impact of dwell time on tablet compaction in conjunction with formulation and process variables are useful as the findings that are representative of manufacturing conditions would be useful for understanding of the compaction process especially in high speed tableting. Press or tool designs may also be accentuated at increasing dwell time without compromising tablet production rate.

INFLUENCE OF FREE-FLOW EXCIPIENTS ON FUNCTIONAL PERFORMANCE OF NOVEONAA1 IN CONTROLLED-RELEASE TABLETS

&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The aim of this work is the assessment of an eventual improvement in flowability of free flowing excipients on formulations containing Noveon AA1 and their influence on compactibility and release profile.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Mixtures containing 20% Noveon AA1 and variable proportions of metronidazole and the free flowing excipients Prosolv EasyTab and GalenIQ 720 and 721were tested in their powder flow rate and the tablets compactibility and released profiles.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The powder flowability obtained with GalenIQ is about 20% better than that obtained with EasyTab. However, it is lesser than that considered as acceptable for a high-speed tableting machine. EasyTab reduces the drug release up to a half along with a continuing flattening of the release profile. This is attributed to an increasing tortuosity of the drug release path as the proportion EasyTab increases. GalenIQ restricts drug release in about a third with a lesser change in the release mechanism. This is attributed to competition for the available water inside the tablet, between the hydrating Noveon AA1 and the dissolving GalenIQ. The compactibility of the metronidazole/Noveon AA1 mixtures increases after addition of EasyTab in about 3.5 N per unit percentage of the added excipient while GalenIQ does it in about 2.6 N.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The powder flowability of mixtures of metronidazole with Noveon AA1 was not suited for direct compression after addition of 40% of the free-flow excipient. The free-flow excipients reduce the metronidazole release rate and increase its compactibility. It was not observed a different clear functioning between both types of GalenIQ.&lt;/p&gt;

Lubricant sensitivity in function of paddle movement in the forced feeder of a high-speed tablet press

Context: The negative impact of magnesium stearate (MgSt) on the hardness of tablets is a well-known phenomenon, but the influence of paddle movement in the forced feeder on the lubricant effect during tablet compression is often neglected.Objective: The purpose of this research was to investigate the influence of paddle speed in the forced feeder on tablet tensile strength (TS).Materials and methods: Mixtures of microcrystalline cellulose (MCC) and MgSt (0.5%) were blended using different methods (low & high shear). After blending, the formulations were compressed into tablets. All parameters of the tableting cycle were kept constant except the speed of the paddles in the forced feeder.Results and discussion: The blending technique affected the sensitivity of the formulation to the paddle speed. The TS of pure MCC tablets did not change in function of paddle speed, while tablets prepared by low shear mixing became softer at higher paddle speed. The TS of tablets manufactured using the high-shear mixed blend was low and did not vary in function of paddle speed, suggesting that overlubrication already occurred during the initial blending step. Furthermore, analysis of the machine parameters allowed evaluation of the influence of the paddles on the flowability, initial packing, and compactability of the powder mixtures.Conclusion: The results elucidated that during manufacturing of tablets using MgSt-containing blends care should not only be taken during the blending step prior to tableting, but also during the tableting process itself, as paddle speed can affect tablet TS, a critical quality attribute.

Co-Processed Excipients: A Patent Review

The introduction of high speed tableting machines and the preference of direct compression as a method of tableting have increased the demands on the functionality of excipients mainly in terms of flowability and compressibility. Co-processed excipients, where in, excipients are combined by virtue of sub-particle level interaction have provided an attractive tool for developing high functionality excipients. The multifold advantages offered by co-processed excipients such as production of synergism in functionality of individual components, reduction of company's regulatory concern because of absence of chemical change during co-processing and improvement in physico-chemical properties have expanded their use in the pharmaceutical industry. In the recent years, there has been a spurt in the number of patents filed on co-processed excipients. Hence, the present review focuses on co-processed excipients and their application in pharmaceutical industry. The worldwide databases of European patent office (http://ep.espacenet.com) and United States patent office (www.uspto.gov) were employed to collect the patents and patent applications. The advantages, limitations, basis for the selection of excipients to be co-processed, methods of co-processing and regulatory perspective of co-processed excipients are also briefly discussed.

Enabling direct compression of formulated Danshen powder by surface engineering

Abstract The direct compression (DC) technology is increasingly popular in the manufacture of tablets due to its efficiency and economy. However, its use in the production of Traditional Chinese Medicine (TCM) tablets is often limited owing to poor powder flow and compaction properties of TCM powders. In this work, we aimed at improving properties of powders used in Fufang Danshen tablet, a popular TCM for treating angina pectoris, by particle surface engineering. Both the active ingredients (Danshen root, Notoginseng, and Borneol) and formulated Danshen mixture exhibit flowability too poor to be processed directly on a high speed tablet press. By dry coating with 1% silica nanoparticles, the flowability, tabletability, and fillability of these powders were adequately improved to be suitable for DC.

Preparation and Characterization of Surface-Engineered Coarse Microcrystalline Cellulose Through Dry Coating with Silica Nanoparticles

A popular grade of microcrystalline cellulose (MCC) exhibits excellent tabletability, but marginal flowability for high-speed tableting operations. Accordingly, an enhancement in flowability, while preserving its tabletability, will make it a more useful excipient in pharmaceutical tablet formulations, especially for the direct compression process. In this work, we show that surface coating by silica nanoparticles, using either a dry comilling process or simple mechanical blending, is a valid strategy for achieving the goal. The effects of milling intensity, either the number of comilling cycles or blending time, and silica loading level have been evaluated. Results show that surface deposition of 0.1% silica nanoparticles substantially improves the flowability of this grade of MCC while preserving a significant portion of its tabletability. Higher silica loading leads to better flowability, but at the cost of reduced tabletability. However, even up to 2.0% silica deposition, its tabletability remains superior.

Tableting Properties of Assam Bora Rice Starch

Starches are used as fillers, binders, and disintegrating agents in the tablet formulation due to their suitable physicochemical as well as mechanical properties. In the present investigation, a study has been done on the compaction properties of Assam Bora rice starch, and their physicochemical properties are evaluated. Assam Bora rice starch exhibit good flow properties. The influences of physical and geometrical properties of starch were evaluated with regard to their compression properties. Further compaction properties of the Assam Bora rice starch were evaluated by density measurement, Heckel and Kawakita equation. The result obtained shows that Assam Bora rice starch deforms mainly by plastic deformation. From the study it has been concluded that Assam Bora rice starch would be more useful in minimizing the problems of lamination and capping especially on high speed tableting machine with short dwelling time for the plastic deformation of material, on the other hand it would be more useful when high tensile strength of tablet is desirable.

Tableting Properties of Assam Bora Rice Starch

Starches are used as fillers, binders, and disintegrating agents in the tablet formulation due to their suitable physicochemical as well as mechanical properties. In the present investigation, a study has been done on the compaction properties of Assam Bora rice starch, and their physicochemical properties are evaluated. Assam Bora rice starch exhibit good flow properties. The influences of physical and geometrical properties of starch were evaluated with regard to their compression properties. Further compaction properties of the Assam Bora rice starch were evaluated by density measurement, Heckel and Kawakita equation. The result obtained shows that Assam Bora rice starch deforms mainly by plastic deformation. From the study it has been concluded that Assam Bora rice starch would be more useful in minimizing the problems of lamination and capping especially on high speed tableting machine with short dwelling time for the plastic deformation of material, on the other hand it would be more useful when high tensile strength of tablet is desirable. Keywords: Assam Bora rice starch, tableting properties, heckel plot, kawakita plot, compaction properties, plastic deformation, tapioca starch, corn starch

Predicting physical properties of pharmaceutical compacts using focused beam reflectance measurement (FBRM)

Fluid bed granulation is a dominant method used to produce granules in the pharmaceutical industry. However, controlling the various process parameters is still challenging and granule product quality has further impacts on the tableting process and final tablet quality. Focused beam reflectance measurement (FBRM) was implemented inside the vessel of a fluid bed granulator as a tool for monitoring in-line the particle growth during the granulation process. The main objective of our study was to investigate the relationship between the FBRM measurements of the granules with the physical properties of the compacted granules (tablets). Fifteen granulation experiments were performed under different process parameters in order to vary the dimension of the granules. After granulation, the mean granule size was measured using sieve analysis. Then, the granules were compacted using an instrumented compaction simulator in order to simulate high-speed tableting conditions. The breaking force, disintegration time, compactibility and compressibility of the tablets were analyzed. The results showed that granule size has a powerful influence on the physical properties of the final tablets and, thus, on the quality of the tablets. However, the prediction of those properties exhibited its dependency on the method used to determine particle size.

Profoundly improving flow properties of a cohesive cellulose powder by surface coating with nano‐silica through comilling

Poor flow properties hinder the easy handling of powders during industrial-scale processing. In this work, we show that powder flow can be substantially improved by reducing the cohesion of powders by coating them with nanosized guest particles. We further show that comilling is an efficient process for nanocoating. We have systematically investigated the effects of total number of comilling cycles (10-70 cycles) and silica loading (0-1.0 wt %) on the flow behavior of a highly cohesive and poorly flowing grade of microcrystalline cellulose powder (Avicel PH105). Optimum flow enhancement has been achieved with 1.0 wt % silica loading at 40 comilling cycles. The flow properties of nanocoated Avicel PH105 are comparable to those of Avicel PH102, which exhibits adequate flowability for processing on a high-speed tablet press. Comilling is fast and suitable for continuous processing. It shows potential for addressing industrial powder handling problems caused by poor powder flow properties.

Study of radial die-wall pressure during high speed tableting: effect of formulation variables

With high-speed compaction cycles as applied in pharmaceutical industrial presses, robust tools like radial die-wall pressure (RDWP) are required to monitor the deformation behavior of formulations under pressure and to avoid common problems such as capping. In this study, the effects of common formulation factors such as lubricant, binder, and drug loading on RDW were investigated. Compaction simulation using Presster™ was applied for five pharmaceutical fillers with different compaction behaviors. Two lubricants, two binders and paracetamol as a model drug were used. Residual die-wall (RDP) and other compaction parameters were measured. Lubricant reduced RDP for fillers with plastic/brittle behavior(s), (p < 0.05), while increased RDP for fillers with plastic/elastic behavior, (p < 0.05), leading to higher tendency for capping in the later fillers. Binder reduced RDP for the fillers, (p < 0.05), hence, decreased capping probability. By increasing drug loading for fillers with plastic/elastic behavior(s), RDP was increased, (p = 0.00001), leading to capping, especially at high compaction pressure and speed. Die-wall instrumentation was useful in investigating formulation variables and detecting capping during high speed tableting.