Use of near-infrared spectroscopy to quantify drug content on a continuous blending process: influence of mass flow and rotation speed variations.

The aim of this study was to develop a quantitative Near-Infrared (NIR) method which monitors the homogeneity of a pharmaceutical formulation coming out of a continuous blender. For this purpose, a NIR diode array spectrometer with fast data acquisition was selected. Additionally, the dynamic aspects of a continuous blending process were studied; the results showed a well-defined cluster for the steady state, and the paths for the start-up and emptying stages were clearly identified.

Correlation between compactibility values and excipient cluster size using an in silico approach.

Background: In silico simulation and percolation theory are important tools in the study of physical and mechanical behavior of pharmaceutical compacts. The aim was to generate a new in silico simulation program that describes the mechanical structure of binary compacts formed from an excipient with excellent compactibility and a drug with null compactibility.

Materials And Methods: Paracetamol and microcrystalline cellulose powders were compressed under different pressures.

Assessing compressibility and compactibility of powder formulations with Near-Infrared Spectroscopy.

Context: The compressibility and compatibility of a powder formulation is usually determined by compaction and following destructive tensile strength and relative density measurement of the final compact.

Objective: In this study, a non-destructive method with Near-Infrared Spectroscopy (NIRS) was designed and evaluated for the measurement of powder compressibility and compactibility.

Materials And Methods: 12 different formulations with a wide range of difference in properties were investigated by compaction and analysis of the resulting tablets.

Optimization of matrix tablets controlled drug release using Elman dynamic neural networks and decision trees.

The main objective of the study was to develop artificial intelligence methods for optimization of drug release from matrix tablets regardless of the matrix type. Static and dynamic artificial neural networks of the same topology were developed to model dissolution profiles of different matrix tablets types (hydrophilic/lipid) using formulation composition, compression force used for tableting and tablets porosity and tensile strength as input data. Potential application of decision trees in discovering knowledge from experimental data was also investigated.

Recrystallization of commercial carbamazepine samples-a strategy to control dissolution variability.

Physical properties of commercial carbamazepine (CBZ) samples can significantly influence drug release and thereby jeopardize bioequivalence of the final dosage form. The aim of this study was to reduce variability in commercial CBZ samples by recrystallization. CBZ samples of four different suppliers were recrystallized in ethanol solution containing 1% polyvinylpyrrolidone (PVP).

Compressibility of binary powder formulations: investigation and evaluation with compaction equations.

The purpose of this work was to investigate and evaluate the powder compressibility of binary mixtures containing a well-compressible compound (microcrystalline cellulose) and a brittle active drug (paracetamol and mefenamic acid) and its progression after a drug load increase. Drug concentration range was 0%-100% (m/m) with 10% intervals. The powder formulations were compacted to several relative densities with the Zwick material tester.

Focused beam reflectance method as an innovative (PAT) tool to monitor in-line granulation process in fluidized bed.

Fluidized bed granulation is a commonly used unit operation in the pharmaceutical industry. But still to obtain and control the desired granule size is challenging due to many process variables affecting the final product. Focused beam reflectance measurement (FBRM, Mettler-Toledo, Switzerland) is an increasingly popular particle growth analysis technique.

Effect of crospovidone and hydroxypropyl cellulose on carbamazepine in high-dose tablet formulation.

Unlabelled: The aim of this study was to develop a high-dose tablet formulation of the poorly soluble carbamazepine (CBZ) with sufficient tablet hardness and immediate drug release. A further aim was to investigate the influence of various commercial CBZ raw materials on the optimized tablet formulation.

Materials And Methods: Hydroxypropyl cellulose (HPC-SL) was selected as a dry binder and crospovidone (CrosPVP) as a superdisintegrant.

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.

Drug release control and system understanding of sucrose esters matrix tablets by artificial neural networks.

Artificial neural networks (ANNs) were applied for system understanding and prediction of drug release properties from direct compacted matrix tablets using sucrose esters (SEs) as matrix-forming agents for controlled release of a highly water soluble drug, metoprolol tartrate. Complexity of the system was presented through the effects of SE concentration and tablet porosity at various hydrophilic-lipophilic balance (HLB) values of SEs ranging from 0 to 16. Both effects contributed to release behaviors especially in the system containing hydrophilic SEs where swelling phenomena occurred.

Analysis of fluidized bed granulation process using conventional and novel modeling techniques.

Various modeling techniques have been applied to analyze fluidized-bed granulation process. Influence of various input parameters (product, inlet and outlet air temperature, consumption of liquid-binder, granulation liquid-binder spray rate, spray pressure, drying time) on granulation output properties (granule flow rate, granule size determined using light scattering method and sieve analysis, granules Hausner ratio, porosity and residual moisture) has been assessed. Both conventional and novel modeling techniques were used, such as screening test, multiple regression analysis, self-organizing maps, artificial neural networks, decision trees and rule induction.

Investigating the effect of punch geometry on high speed tableting through radial die-wall pressure monitoring.

Dwell time mainly depends on punch geometry, so some tableting problems such as capping and lamination could occur at high speed compaction. Robust tools are required to monitor the interaction of punch tip and powder bed at these high speeds. Our aim was to investigate the effect of punch geometry (flat and standard concave) on powder compaction at high speed using radial die-wall pressure (RDWP) as a monitoring tool.

Investigation of compressibility and compactibility parameters of roller compacted Theophylline and its binary mixtures.

Roller compaction is a dry granulation method which results in tablets with inferior tensile strength comparing to direct compaction. The effect of roller compaction on compressibility and compactibility of tablets prepared from Theophylline anhydrate powder, Theophylline anhydrate fine powder and Theophylline monohydrate was investigated by measuring tensile strength of tablets as well as calculating compressibility and compactibility parameters by Leuenberger equation. The tablets under the same conditions were prepared by direct compaction and roller compaction.

Evaluation of roll compaction as a preparation method for hydroxypropyl cellulose-based matrix tablets.

Roll compaction was applied for the preparation of hydroxypropyl cellulose (HPC)-based sustained-release matrix tablets. Matrix tablets made via roll compaction exhibited higher dosage uniformity and faster drug release than direct-compacted tablets. HPC viscosity grade, roll pressure, and milling speed affected tablet properties significantly.

A novel tool for the prediction of tablet sticking during high speed compaction.

During tableting, capping is a problem of cohesion while sticking is a problem of adhesion. Sticking is a multi-composite problem; causes are either material or machine related. Nowadays, detecting such a problem is a pre-requisite in the early stages of development.

Investigating the effect of particle size and shape on high speed tableting through radial die-wall pressure monitoring.

Investigating particle properties such as shape and size is important in understanding the deformation behavior of powder under compression during tableting. Particle shape and size control the pattern of powder rearrangement and interaction in the die and so the final properties of the compact. The aim of this study was to examine the effect of particle size and shape on compactability.

Radial die-wall pressure as a reliable tool for studying the effect of powder water activity on high speed tableting.

The effect of moisture as a function of water activity (Aw) on the compaction process is important to understand particle/water interaction and deformation. Studying powder/moisture interaction under pressure with radial die-wall pressure (RDWP) tool was never done. The aim of our study was to use this tool to study this interaction at high compression pressure and speed.

Study of radial die-wall pressure changes during pharmaceutical powder compaction.

Context: In tablet manufacturing, less attention is paid to the measurement of die-wall pressure than to force-displacement diagrams.

Objective: Therefore, the aim of this study was to investigate radial stress change during pharmaceutical compaction.

Materials And Methods: The Presster(TM), a tablet-press replicator, was used to characterize compaction behavior of microcrystalline cellulose (viscoelastic), calcium hydrogen phosphate dihydrate (brittle), direct compressible mannitol (plastic), pre-gelatinized starch (plastic/elastic), and spray dried lactose monohydrate (plastic/brittle) by measuring radial die-wall pressure; therefore powders were compacted at different (pre) compaction pressures as well as different speeds.

Variability in commercial carbamazepine samples--impact on drug release.

The aim of this study was to characterize the variability of commercial carbamazepine (CBZ) samples and to investigate the influence of two commonly used tablet fillers, i.e., mannitol and microcrystalline cellulose (MCC) on the CBZ sample variability.

Assessment of diffuse transmission and reflection modes in near-infrared quantification, part 2: DIFFuse reflection information depth.

Near-infrared spectroscopy offers tremendous advantages for pharmaceutical manufacturing as a fast and nondestructive method of quantitative and qualitative analysis. Content uniformity (end-product analytics) and process analytics are two important applications of the method. Diffuse reflection (DR) information depth (vertical sampling span) assessment is of equal importance in content prediction applications and to understand the effect of inhomogeneities in the sample.

Permeation studies of novel terbinafine formulations containing hydrophobins through human nails in vitro.

Existing treatments of onychomycosis are not satisfactory. Oral therapies have many side effects and topical formulations are not able to penetrate into the human nail plate and deliver therapeutical concentrations of active agent in situ. The purpose of the present study was to determine the amount of terbinafine, which permeates through the human nail plate, from liquid formulations containing enhancers, namely hydrophobins A-C in the concentration of 0.

Roller compaction of different pseudopolymorphic forms of theophylline: Effect on compressibility and tablet properties.

The effect of roller compaction on disintegration time, dissolution rate and compressibility of tablets prepared from theophylline anhydrate powder, theophylline anhydrate fine powder and theophylline monohydrate was studied. In addition, the influence of adding microcrystalline cellulose, a commonly used excipient, in mixtures with these materials was investigated. Theophylline anhydrate powder was used as a model drug to investigate the influence of different compaction pressures on the tablet properties.

Optimization of drug release from compressed multi unit particle system (MUPS) using generalized regression neural network (GRNN).

The purpose of this study was development of diclofenac sodium extended release compressed matrix pellets and optimization using Generalized Regression Neural Network (GRNN). According to Central Composite Design (CCD), ten formulations of diclofenac sodium matrix tablets were prepared. Extended release of diclofenac sodium was accomplished using Carbopol 71G as matrix substance.

Investigation of different formulations for drug delivery through the nail plate.

Topical therapies for nail diseases are limited by keratinized cells in the human nail plate. An optimal permeation enhancer would not only improve drug delivery through the nail plate, but would also open new possibilities for treating neighboring target sites if systemic circulation is reached. The aim of the present work was to identify permeation enhancers and to improve the understanding of physicochemical parameters that influence drug permeation.

Investigation of intrinsic dissolution behavior of different carbamazepine samples.

The aim of the present study was to investigate the effect of the variability of commercially available carbamazepine (CBZ) samples on the intrinsic dissolution behavior in order to recommend a strategy to maintain product quality by monitoring the variability of critical parameters of the bulk drug. Extensive physical characterization of nine anhydrous CBZ samples from three different sources and their respective dihydrates showed that the commercial anhydrous CBZ samples exhibited the same polymorphic form, but different morphology and particle size distribution which led to a variation in the kinetics of conversion from anhydrous to the dihydrate CBZ and therefore to variation in the kinetics of solubility. Disc intrinsic dissolution rate (DIDR) tests showed different intrinsic dissolution behavior of the samples, whereby the transition points of anhydrous to dihydrate conversion varied between 15 and 25 min.