Impact of the digital revolution on the future of pharmaceutical formulation science.

The ongoing digital revolution is no longer limited to the application of apps on the smart phone for daily needs but starts to affect also our professional life in formulation science. The software platform F-CAD (Formulation-Computer Aided Design) of CINCAP can be used to develop and test in silico capsule and tablet formulations. Such an approach allows the pharmaceutical industry to adopt the workflow of the automotive and aircraft industry.

An attempt to calculate in silico disintegration time of tablets containing mefenamic acid, a low water-soluble drug.

Based on a Quality by Design (QbD) approach, it is important to follow International Conference on Harmonization (ICH) guidance Q8 (R2) recommendations to explore the design space. The application of an experimental design is, however, not sufficient because of the fact that it is necessary to take into account the effects of percolation theory. For this purpose, an adequate software needs to be applied, capable of detecting percolation thresholds as a function of the distribution of the functional powder particles.

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.

Development of push-pull osmotic tablets using chitosan-poly(acrylic acid) interpolymer complex as an osmopolymer.

The objectives of this study were to prepare push-pull osmotic tablets (PPOT) of felodipine using an interpolymer complex of chitosan (CS) and poly(acrylic acid) (PAA) as an osmopolymer, and to study the mechanisms of drug release from these tablets. The interpolymer complexes were prepared with different weight ratios of CS to PAA. Preparation of PPOT involved the fabrication of bilayered tablets with the drug layer, containing felodipine, polyethylene oxide, and the polymeric expansion layer, containing the CS-PAA complex.

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.

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.

Terahertz pulsed imaging and near infrared imaging to monitor the coating process of pharmaceutical tablets.

Terahertz pulsed imaging (TPI) and near infrared (NIR) imaging were used to non-destructively monitor the coating process of film-coated tablets. Samples that were taken from a pan coater at different time points were analyzed by both methods. TPI provided coating thickness maps over the whole surface of the tablets, determining the thickness of the coating at each point of the sample surface in mum, this way also giving information about the coating uniformity.

Influence of loading volume of mefenamic acid on granules and tablet characteristics using a compaction simulator.

Mefenamic acid (MA), a poorly water-soluble drug, was used as a model substance to investigate granules and tablet characteristics to be optimized for the loading volume of MA (0-74.1% v/v) in the formulation including lactose monohydrate/maize starch (7/3) as excipients. The compactibility of granules increased with loading volume of MA.

Influence of loading volume of mefenamic acid on granules and tablet characteristics using a compaction simulator.

Mefenamic acid (MA), a poorly water-soluble drug, was used as a model substance to investigate granules and tablet characteristics to be optimized for the loading volume of MA (0-74.1% v/v) in the formulation including lactose monohydrate/maize starch (7/3) as excipients. The compactibility of granules increased with loading volume of MA.

Preference of dairy cows for ryegrass, white clover and red clover, and its effects on nutrient supply and milk quality.

Two experiments were conducted with 30 dairy cows each, to study the preference for fresh (Experiment 1) and ensiled (Experiment 2) ryegrass, white and red clover. Both experiments consisted of three choice diets with white or red clover or both, offered with ryegrass, and two diets with ryegrass mixed with white or red clover (40% clover). Cows consumed diets with 37.

Rational estimation of the optimum amount of non-fibrous disintegrant applying percolation theory for binary fast disintegrating formulation.

The purpose of this study was to propose a method of determining the exact value of disintegrant ratio in a binary drug-disintegrant compacted mixture for a minimum disintegration time in the case of spherical particles. Disintegration is a limiting factor in dissolution process of compact for low water soluble active ingredients. As disintegration time is shortest at a certain ratio of disintegrant, a calculation of this value is important for solid dosage from design to enhance disintegration and dissolution process.

Percolation theory and the role of maize starch as a disintegrant for a low water-soluble drug.

The objective of the present work is to investigate the presence or absence of a critical concentration of maize starch according to the percolation theory for a truly ternary system with respect to a minimum disintegration time. The results of this study show that the application of percolation theory is not limited to the study of binary systems. In this work it is shown how it can be used to analyze the behavior of binary and ternary systems for caffeine and mefenamic acid formulations containing a starch-based disintegrant.

The characterization of aprotic polar liquids and percolation phenomena in DMSO/water mixtures.

In the previous papers of our research group it was shown, that the Clausius-Mossotti-Debye equation for the quasi-static dielectric constant (epsilonr) can be extended to liquids if the parameter Ei/E is introduced. Thus, it is possible to characterize polar liquids with the easily accessible parameter Ei/E. This property is also reflected by the fact that the parameter Ei/E can be directly related to the empirical ET(30) and the normalized ETN parameter to describe the polarity of liquids proposed by Reichardt (Chem.

In vivo comparison of various liposome formulations for cosmetic application.

The interaction of liposome formulations, prepared with phospholipids of different origins (egg and soya), with skin were compared in terms of their effects on skin water content, skin barrier function, and skin elasticity. Short-term effect of four different liposome formulations and two references during 3.5 h was investigated non-occlusively on the volar side of the forearm of 10 volunteers, ranging in age from 24 to 32 years.

Preparation of dry powder inhalation with lactose carrier particles surface-coated using a Wurster fluidized bed.

An attempt was made to produce carrier particles for dry powder inhalation with lactose carrier particles surface-coated using a Wurster fluidized bed. The lactose carrier particles were coated with lactose aqueous solution containing hydroxypropyl methyl cellulose (HPMC) as a binder using a Wurster coating apparatus. Drug/carrier powder mixtures were prepared consisting of micronized salbutamol sulfate and lactose carriers under various particle surface conditions.

Detection of percolation phenomena in binary polar liquids by broadband dielectric spectroscopy.

In the previous papers [Stengele, A., Rey, St., Leuenberger, H.

Towards a better understanding of the parameter Ei/E in the characterization of polar liquids.

In the two previous papers [Stengele, A., Rey, St., Leuenberger, H.

Search for technological reasons to develop a capsule or a tablet formulation with respect to wettability and dissolution.

Proquazone, a poorly wettable compound, was used as a model drug in the search for reasons to develop a capsule or tablet formulation. The capsules were filled with proquazone as active ingredient, with lactose monohydrate (200 mesh) as filler and with magnesium stearate as lubricant. The tablet was made out of a granulate as internal phase which consisted of proquazone as active ingredient, lactose as filler, corn starch as disintegrant and PVP as a binding agent.

Comparative evaluation of the powder properties and compression behaviour of a new cellulose-based direct compression excipient and Avicel PH-102.

This study compares the compression behaviour of a new cellulose-based tableting excipient, hereinafter referred to as UICEL-A/102, and Avicel PH-102, a commercial direct compression excipient commonly referred to as microcrystalline cellulose (MCC). UICEL-A/102 shows the cellulose II lattice, while Avicel PH-102 belongs to the cellulose I polymorphic form. The median particle diameters of UICEL-A/102 and Avicel PH-102 fractions used in the study were 107 and 97 microm, respectively.

Power consumption measurement and temperature recording during granulation.

This study was performed to elucidate the influences of process and formulation design using power consumption and temperature measurements during granulation. Power consumption was recorded "in process" using a previously introduced computer program for optimal end-point detection at an early stage. The temperature increase (DeltaT) during granulation was recorded using a temperature sensor.

Aluminium in over-the-counter drugs: risks outweigh benefits?

In the early 1970s, aluminium toxicity was first implicated in the pathogenesis of clinical disorders in patients with chronic renal failure involving bone (renal osteomalacia) or brain tissue (dialysis encephalopathy). Before that time the toxic effects of aluminium ingestion were not considered to be a major concern because absorption seemed unlikely to occur. Meanwhile, aluminium toxicity has been investigated in countless epidemiological and clinical studies as well as in animal experiments and many papers have been published on the subject.

Batch and continuous processing in the production of pharmaceutical granules.

A quasicontinuous granulation and drying process to avoid scale-up problems is introduced in this work. Consistent and reproducible granule quality is a key factor in robust dosage form design and fits ideally the prerequisites of a drug quality system for the twenty-first century and the Food and Drug Administration's Process Analytical Technology (PAT) initiative. In scale-up, factors that simulate or reproduce the laboratory scale must be considered.

Compression behaviour of the enzyme beta-galactosidase and its mixture with microcrystalline cellulose.

The behaviour of beta-galactosidase powder under compaction was investigated to get more information on powder properties and to further characterise tablet excipients. The enzyme beta-galactosidase, the model excipient microcrystalline cellulose and several mixtures of these two substances were compressed at different compaction forces. The relative density of the obtained tablets was calculated and the Heckel equation as well as the modified Heckel equation was used to characterise the bulk powders and their mixtures.

Concentrate feeding strategy in lactating dairy cows: metabolic and endocrine changes with emphasis on leptin.

This study aimed to evaluate metabolic and endocrine adaptations to energy intake in multiparous Holstein cows (n = 90; mean 9434 kg energy-corrected milk yield/305 d) over the first 20 wk postpartum and to assess the association of leptin with metabolic, endocrine, and zootechnical traits. Concentrates were fed automatically for 24 h at 30% (C30) or 50% (C50) of total dry matter intake (DMI) from wk 1 to 10 postpartum and at linearly reduced amounts thereafter. Roughage was fed for ad libitum intake.