An Investigation on the Relationship between Dust Emission and Air Flow as Well as Particle Size with a Novel Containment Two-Chamber Setup.

In the present study with a novel two-chamber setup (TCS) for dustiness investigations, the relationship between pressure differences as well as air velocities and the resulting dust emissions is investigated. The dust emissions of six particle size fractions of acetaminophen at pressure differences between 0 and 12 Pa are examined. The results show that both simulated and measured air velocities increase with increasing pressure difference.

Co-amorphous systems consisting of indomethacin and the chiral co-former tryptophan: Solid-state properties and molecular mobilities.

In this study the influence of an enantiomeric co-former and the preparation method on the solid-state properties and physical stability of co-amorphous systems were investigated. Co-amorphous systems consisting of indomethacin (IND) and chiral tryptophan (TRP) as co-former in its two enantiomeric forms, as racemate, and as conglomerate (equimolar mixture of D- and L-TRP) were prepared. Co-amorphization was achieved by ball milling (BM) and spray drying (SD).

A Novel Two-Chamber Setup for Containment Investigations with Special Focus on the Dustiness of Pharmaceutical Powders Depending on the Airflow.

In the present study, it was shown that a newly developed two-chamber setup (TCS) for containment investigations consisting of an emission and a detection chamber may serve to predict the dustiness of HPAPIs in a sealed system at different flow conditions. These flow conditions include the plain diffusive transport and the diffusive transport with the oppositely directed convective flow of airborne particles of the safe surrogate substance acetaminophen (ACAM). A linear correlation was found between an atomized amount of up to 400 mg of ACAM and the resulting dust emissions.

(Co-)amorphization of enantiomers - Investigation of the amorphization process, the physical stability and the dissolution behavior.

A novel approach for improvement of the aqueous solubility of poorly water soluble compounds applying co-amorphous systems was investigated by application of the enantiomers of the chiral amino acid tryptophan (TRP) as the model system. (Co-)amorphization of various forms of crystalline TRP was achieved by ball milling. Solid state analysis demonstrated significant differences in the amorphization tendency and physical stability between the two TRP enantiomers alone, the TRP racemate and an equimolar physical mixture of D- and L-TRP (TRP conglomerate).

Evaluation of the orally administered calcium alginate aerogel on the changes of gut microbiota and hepatic and renal function of Wistar rats.

The present study evaluates the effect of calcium alginate aerogel as a potential drug carrier, on the liver and kidney functions, and on the gut microbiota of Wistar rats. The studied alginate aerogel was prepared in the form of nanoparticles using the jet cutting technique, and they were characterized in terms of specific surface areas, outer morphology and particle size distribution. For the in vivo study, calcium alginate aerogel was administered orally, and liver and kidney functions were tested for one week and for four weeks in two distinct studies.

Pulmonary drug delivery with aerogels: engineering of alginate and alginate-hyaluronic acid microspheres.

In this study, the aerogel technology was used to prepare pulmonary drug carriers consisting of alginate and alginate-hyaluronic acid by an emulsion gelation technique and supercritical CO drying. During the preparation process, the emulsification rate and inner phase viscosity were varied to control the diameter of aerogel microspheres. Results showed that the aerogel microspheres were highly porous (porosity > 98%) with low densities in the range between 0.

Application of Aquasolv Lignin in ibuprofen-loaded pharmaceutical formulations obtained via direct compression and wet granulation.

AS (Aquasolv) Lignin produced via Liquid Hot Water Pretreatment and Enzymatic Hydrolysis has shown potential as an active pharmaceutical ingredient and/or excipient in solid dosage forms. Moreover, lignin is safe to consume and presents antioxidant and antidiabetic capacity, properties that can add to solid dosage forms in pharmaceuticals. This work aimed to evaluate the performance of tablets produced via direct compression and wet granulation when lignin is used in combination with commercial excipients.

Effect of Pullulan as Additive to the Synthetic Polymeric Coating Blend Eudragit® NM-L55 on the Properties of the Resulting Films.

The aim of the present study was to investigate the effect of pullulan as additive to Eudragit® NM-L55 blend film for modification of the resulting film properties with regard to future drug release studies. Films of the plain polymers as well as of those of their blends at different ratios were prepared by an aqueous casting method. Infrared, mechanical, thermogravimetric, water vapor permeance and swelling index studies were performed with blend films of Eudragit® NM-L55 and pullulan.

A novel approach to avoid capping and/or lamination by application of external lower punch vibration.

Capping as well as lamination are two common problems, which affect the resulting product quality of the tablet. Usually, capping and lamination occur during or after tablet manufacturing, and may therefore influence follow-up processes such as the coating. In this context, there is an urgent need for approaches to overcome the occurrences of capping and lamination.

Application of Externally Applied Lower Punch Vibration and its Effects on Tablet Manufacturing.

Purpose: In the present study the influence and application of a newly developed external lower punch vibration system for an improved die filling on a running rotary tablet press was investigated.

Methods: Tablets were manufactured at different conditions (with and without vibration) and characterized regarding their direct compressibility and mechanical stability. Thus, two typical pharmaceutical binders for direct compression (Parmcel 102 and Tablettose® 80) were compared with two binders unsuitable for direct compression (Ceolus® KG1000 and GranuLac® 200).

Combination of a hot-melt subcoating and an enteric coating for moisture protection of hygroscopic Sennae fructus tablets.

The objective of this study was to investigate the efficiency of moisture protection of hot-melt coatings solely and in combination with an enteric coating on hygroscopic tablet cores containing a spray-dried Sennae fructus extract. Tablet cores were subcoated with different hot-melt coating materials: medium chain tryglycerides, stearic acid, Precirol ATO 5, and Compritol 888 ATO, at varying amounts and coated with Eudragit L 30D-55 for enteric resistance. Subcoating penetration, tablet disintegration, dissolution times, tablet hygroscopicity, and tablet properties such as weight, height, diameter, and hardness were analyzed.

Performance Characteristics of a Novel Vibration Technique for the Densification of a Powder Bed within a Die of a Rotary Tablet Press - a Proof of Concept.

The aim of this study was to investigate the concept of lower punch vibration as a possible approach to densify the powder bed within the die of a rotary tablet press. Therefore, a laboratory vibration equipment was developed to obtain a better understanding of the performance characteristics and effects of a pneumatically generated vibration system on pharmaceutical powders. For this purpose, two widely used pharmaceutical powders, basic magnesium carbonate (Pharmagnesia MC Type F) and microcrystalline cellulose (Ceolus® KG1000), both with different physical properties, were investigated.

Comparison of two paddle wheel geometries within the filling chamber of a rotary tablet press feed frame with regard to the distribution behavior of a model powder and the influence on the resulting tablet mass.

The purpose of this study was to compare the influence of two different paddle wheel geometries on the distribution behavior of a model powder within the filling chamber of the modified feed frame of a rotary tablet press. Moreover, both paddle wheels were compared regarding their influence on the resulting tablet mass during the tableting process. Insights are provided regarding the influence of the paddle wheel geometry on the powder distribution to optimize the die filling process.

In situ co-amorphisation in coated tablets - The combination of carvedilol with aspartic acid during immersion in an acidic medium.

In the present study the feasibility of an in situ co-amorphisation of the basic drug carvedilol with the acidic co-former aspartic acid was investigated by immersion of film-coated tablets consisting of the two compounds in 0.1 MHCl. Tablets containing either crystalline carvedilol with aspartic acid or only crystalline carvedilol were prepared and coated with a gastro-resistant but water-permeable coating of a methacrylic acid - ethyl acrylate copolymer (Eudragit®L55).

In situ co-amorphisation of arginine with indomethacin or furosemide during immersion in an acidic medium - A proof of concept study.

The concept of controlled in situ amorphisation of drug/polymer mixtures has been introduced previously with indomethacin-Eudragit E and naproxen-Eudragit E compacts. In the present study, the feasibility of in situ amorphisation of a crystalline API with the low molecular weight coformer arginine was investigated. This research was based on a previous study, which showed that a high relative humidity (75% RH) may induce co-amorphisation of indomethacin with arginine.

Factors influencing the properties and the stability of spray-dried Sennae fructus extracts.

Objective: The objective of this study was to characterize the properties of aqueous Sennae fructus extracts prepared by spray-drying at varying process conditions.

Significance: From an industrial point of view it is essential to develop a formulation which has a constant quality over the whole period of its specified shelf-life.

Method: Sennae fructus extracts were spray-dried with different atomizing gas pressures, pump feed rates, and inlet temperatures.

Undesired co-amorphisation of indomethacin and arginine during combined storage at high humidity conditions.

The use of co-amorphous systems for solubility enhancement of poorly water-soluble drugs has recently gained interest in the field of pharmaceutical technology. However, undesired co-amorphisation of a drug may lead to an alteration of the performance of the drug product, e.g.

A comparative study on the sticking tendency of ibuprofen and ibuprofen sodium dihydrate to differently coated tablet punches.

In the present study, the sticking tendencies of ibuprofen and ibuprofen sodium dihydrate as model substances for a lipophilic and a hydrophilic sticky API to differently coated punches were investigated. Increased sticking was observed with the more polar ibuprofen sodium dihydrate than with the less polar ibuprofen. Interestingly, the anti-sticking performance of the punch coatings proved to be independent of the APIs' polarity.

Investigation of the tableting behavior of Ibuprofen DC 85 W.

The aim of the present study was to investigate the tableting behavior of Ibuprofen DC 85 W with special focus on the tablet disintegration time, the tablet crushing strength, and the sticking tendency to punch surfaces. To simulate production conditions, tableting was conducted on a rotary press, equipped with three compaction stations. An I-optimal design of experiments was used to analyze the influence of the pre-compaction, the intermediate compaction, and the main compaction force on the two responses: tablet disintegration time and crushing strength.

A non-destructive method for quality control of the pellet distribution within a MUPS tablet by terahertz pulsed imaging.

Terahertz pulsed imaging (TPI) was applied to analyse the inner structure of multiple unit pellet system (MUPS) tablets. MUPS tablets containing different amounts of theophylline pellets coated with Eudragit® NE 30 D and with microcrystalline cellulose (MCC) as cushioning agent were analysed. The tablets were imaged by TPI and the results were compared to X-ray microtomography.

UV imaging of multiple unit pellet system (MUPS) tablets: A case study of acetylsalicylic acid stability.

The applicability of multispectral ultraviolet (UV) imaging in combination with multivariate image analysis was investigated to monitor API degradation within multiple unit pellet system (MUPS) tablets during storage. For this purpose, acetylsalicylic acid (ASA) layered pellets were coated with Eudragit® RL PO and compressed to MUPS tablets. These tablets were stored under four different conditions with different levels of relative humidity (0 and 75%) and temperature (21 and 40°C) and analysed at seven storage time points (0, 15, 40, 140, 165, 265, and 330d).

A novel technique for the visualization of tablet punch surfaces: Characterization of surface modification, wear and sticking.

The surface quality of tablets is strongly related to the surface quality of the tablet punch. Therefore, regular control of the punch surfaces is needed to determine the surface properties, the wear status and sticking tendency of the punches. The aim of the present study was to develop and evaluate a new technique to visualize and evaluate tablet punch surfaces using high-resolution impression molding combined with 3D surface analysis.

Solid state properties and drug release behavior of co-amorphous indomethacin-arginine tablets coated with Kollicoat® Protect.

A promising approach to improve the solubility of poorly water-soluble drugs and to overcome the stability issues related to the plain amorphous form of the drugs, is the formulation of drugs as co-amorphous systems. Although polymer coatings have been proven very useful with regard to tablet stability and modifying drug release, there is little known on coating co-amorphous formulations. Hence, the aim of the present study was to investigate whether polymer coating of co-amorphous formulations is possible without inducing recrystallization.

Improvement of the physicochemical properties of Co-amorphous naproxen-indomethacin by naproxen-sodium.

Improvement of the physicochemical properties of amorphous active pharmaceutical ingredients (APIs) applying the concept of co-amorphisation is a promising alternative to the use of polymer glass solutions. In co-amorphous systems, the physical stability and the dissolution rate of the involved components may be improved in comparison to the respective single amorphous phases. However, for the co-amorphous naproxen-indomethacin model system it has been reported that recrystallization could not be prevented for more than 112days regardless of the applied preparation method and blend ratio In the present study, it was thus tested if the physicochemical properties of co-amorphous naproxen-indomethacin could be optimized by incorporation of the naproxen sodium into the system.

Multispectral UV Imaging for Determination of the Tablet Coating Thickness.

The applicability of off-line multispectral UV imaging in combination with multivariate data analysis was investigated to determine the coating thickness and its distribution on the tablet surface during lab-scale coating. The UV imaging results were compared with the weight gain measured for each individual tablet and the corresponding coating thickness and its distribution measured by terahertz pulsed imaging (TPI). Three different tablet formulations were investigated, 2 of which contained UV-active tablet cores.