A validation of discrete-element model simulations for predicting tablet coating variability.

Achieving an even coating distribution on tablets during the coating process can be challenging, not to mention the challenges of accurately measuring and quantifying inter-tablet coating variability. Computer simulations using the Discrete Element Method (DEM) provide a viable pathway towards model-predictive design of coating processes. The purpose of this study was to assess their predictivity accounting for both experimental and simulation input uncertainties.

Predicting Drug Release Rate of Implantable Matrices and Better Understanding of the Underlying Mechanisms through Experimental Design and Artificial Neural Network-Based Modelling.

There is a growing interest in implantable drug delivery systems (DDS) in pharmaceutical science. The aim of the present study is to investigate whether it is possible to customize drug release from implantable DDSs through drug-carrier interactions. Therefore, a series of chemically similar active ingredients (APIs) was mixed with different matrix-forming materials and was then compressed directly.

Self-microemulsifying tablets prepared by direct compression for improved resveratrol delivery.

The purpose of this study was to develop self-microemulsifying (SME-) tablets to improve resveratrol solubility whilst delivering resveratrol in a preferred tablet dosage form. Resveratrol was dissolved in liquid self-microemulsifying drug delivery system (SMEDDS) (10% w/w) and solidified through adsorption on several different solid carriers. Two ranges of synthetic amorphous silica (Sylysia® 290, 350, 470, 580; Syloid® 244FP, AL-1FP) as well as granulated magnesium aluminometasilicate (Neusilin® US2) were screened for their SMEDDS adsorbent capacity.

Modified equation for particle bonding area and strength with inclusion of powder fragmentation propensity.

The paper considers a novel, modified equation for evaluation of relationship between tablet tensile strength, bonding area and bonding strength with inclusion of fragmentation as particle deformation mechanism. Four types of lactose particles for direct compression were assessed for their micromeritic and mechanical properties (compressibility and compactibility), with particular focus on fragmentation behaviour, bonding area and bonding strength. Compressibility properties were assessed using three established models.

Spherical agglomerates of lactose with enhanced mechanical properties.

The aim of this study was to prepare spherical agglomerates of lactose and to evaluate their physicochemical properties, flow properties, particle friability and compaction properties, and to compare them to commercially available types of lactose for direct compression (spray-dried, granulated and anhydrous β-lactose). Porous spherical agglomerates of α-lactose monohydrate with radially arranged prism-like primary particles were prepared exhibiting a high specific surface area. All types of lactose analysed had passable or better flow properties, except for anhydrous β-lactose, which had poor flowability.

Flow and compaction properties of hypromellose: new directly compressible versus the established grades.

Context: Information about flow and compaction properties of hypromellose (HPMC) polymers is essential for the technologists who are facing challenges regarding poor flow and compaction while developing new controlled release matrix tablets. There is a profound lack of studies in this field and none of the published ones deal with the compaction of the newly introduced HPMC grades specifically designed for direct compression (DC).

Objective: The objective behind this study was the evaluation of flow and compaction properties of six different grades of HPMC substitution type 2208 polymers, including two second generation directly compressible grades from Dow Chemical Company (K100LV, K15M, K4M CR, K4M DC, K100M CR and K100M DC).

Effect of the surface free energy of materials on the lamination tendency of bilayer tablets.

Dosage forms with fixed dose combinations of drugs is a frequent and advantageous mode of administration, but their production involves a number of technological problems. Numerous interactions in a homogeneous vehicle may be avoided through the use of layered tablets. The mechanical properties of these dosage forms depend on numerous process parameters and material characteristics.

Impact of microcrystalline cellulose material attributes: a case study on continuous twin screw granulation.

The International Conference on Harmonisation (ICH) states in its Q8 'Pharmaceutical Development' guideline that the manufacturer of pharmaceuticals should have an enhanced knowledge of the product performance over a range of material attributes, manufacturing process options and process parameters. The present case study evaluates the effect of unspecified variability of raw material properties upon the quality attributes of granules; produced using a continuous from-powder-to-tablet wet granulation line (ConsiGma™ 25). The impact of different material attributes of six samples of microcrystalline cellulose (MCC) was investigated.

Nanomechanical properties of selected single pharmaceutical crystals as a predictor of their bulk behaviour.

Purpose: The main goal of this research was to assess the mechanical properties of APIs' polymorphic forms at the single-crystal level (piroxicam, famotidine, nifedipine, olanzapine) in order to predict their bulk deformational attributes, which are critical for some pharmaceutical technology processes.

Methods: The mechanical properties of oriented single crystals were determined using instrumented nanoindentation (continuous stiffness measurement). All polymorphic forms investigated were previously identified using a combination of calorimetric and spectroscopic techniques.

Influence of the physiological variability of fasted gastric pH and tablet retention time on the variability of in vitro dissolution and simulated plasma profiles.

The aim of the present study was to show that the physiological variability of fasted gastric pH and tablet gastric retention time contributes to the overall variability of simulated plasma profiles of diclofenac. Those two parameters were implemented into dissolution study and plasma profiles were simulated under assumptions that in vitro dissolution well represents that occurring in vivo, and that absorption profiles are identical to dissolution profiles, as diclofenac is a highly permeable drug. Dissolution experiments were performed using USP 2 apparatus and two consecutive dissolution media, namely, an acidic medium of various pH (ranging from 1-3), where tablets were kept for a certain time (10-200 min), and phosphate buffer (pH 6.

In silico modeling of in situ fluidized bed melt granulation.

Fluidized bed melt granulation has recently been recognized as a promising technique with numerous advantages over conventional granulation techniques. The aim of this study was to evaluate the possibility of using response surface methodology and artificial neural networks for optimizing in situ fluidized bed melt granulation and to compare them with regard to modeling ability and predictability. The experiments were organized in line with the Box-Behnken design.

A compressibility and compactibility study of real tableting mixtures: the effect of granule particle size.

This study investigates the effect of particle size on the compression characteristics of wet- (fluid-bed granulation - FBG) and dry-granulated (slugging - DGS) tableting mixtures. Particle-size distribution, flowability, compressibility, using the Heckel and Walker model, compactibility and elastic recovery as well as friability and disintegration were determined and compared between the two particle size fractions (180-400 μm, 400-710 μm) and initial unsieved mixtures. The results showed that the particle size of granules had no effect on the compressibility of the FBG and DGS mixtures, due to the high fragmenting nature of the formulation used in this study.

Application of physicochemical properties and process parameters in the development of a neural network model for prediction of tablet characteristics.

The importance of in silico modeling in the pharmaceutical industry is continuously increasing. The aim of the present study was the development of a neural network model for prediction of the postcompressional properties of scored tablets based on the application of existing data sets from our previous studies. Some important process parameters and physicochemical characteristics of the powder mixtures were used as training factors to achieve the best applicability in a wide range of possible compositions.

Deformation properties of pharmaceutical excipients determined using an in-die and out-die method.

This study investigated deformation mechanisms of some commonly used pharmaceutical fillers, such as microcrystalline cellulose, lactose, dicalcium phosphate, isomalt and cornstarch, using a combination of the in-die and out-die method with the Heckel and Walker models. The tableting mixtures contained of 98.5% (w/w) filler, the rest consisted of dry binder and an antiadhesive agent.

Melt granulation in fluidized bed: a comparative study of spray-on versus in situ procedure.

Objective: The aim of this study was to investigate the influence of process parameters, binder content and binder addition method on characteristics of the granules obtained by melt granulation (MG) in fluidized bed.

Methods: Spray-on experiments were performed according to 2(3) full factorial design. The effect of binder content, molten binder feed rate, and spray air pressure on granule size and size distribution, granule shape, flowability and drug release rate was investigated.

An investigation into the effect of formulation variables and process parameters on characteristics of granules obtained by in situ fluidized hot melt granulation.

The aim of this study was to investigate the influence of binder content, binder particle size, granulation time and inlet air flow rate on granule size and size distribution, granule shape and flowability, as well as on drug release rate. Hydrophilic (polyethyleneglycol 2000) and hydrophobic meltable binder (glyceryl palmitostearate) were used for in situ fluidized hot melt granulation. Granule size was mainly influenced by binder particle size.

A compressibility and compactibility study of real tableting mixtures: the impact of wet and dry granulation versus a direct tableting mixture.

The purpose of this study was to investigate the influence of various powder agglomeration processes on tableting mixture flow and compaction properties. Four different granulation methods of the same model placebo formulation were tested at a semi-industrial scale and their properties were compared to those of the directly compressed mixture. The wet granulated mixtures had superior flow properties compared to other mixtures and showed better compressibility, measured by the Heckel and Walker models.

Development of a multiple-unit tablet containing enteric-coated pellets.

Film coating of pellets is a common way to design modified-release systems. The aim of this study was to produce a multiple-unit tablet compressed from enteric-coated pellets. The dosage form should comply with Pharmacopoeial demands, especially regarding dissolution, but preferably also all other parameters, including sufficient hardness for packaging procedures.

The compressibility and compactibility of different types of lactose.

Objective: The purpose of this study was to investigate and quantify flow properties, compressibility, and compactibility of various pharmaceutical lactose powders found on the market today (DCL-11, DCL-21, M-200, Flowlac-100, and Tablettose 70, 80, and 100).

Methods: Flow properties were estimated by measuring flow time, angle of repose, and the Hausner ratio. Particle rearrangement was studied using Kawakita's linear model.