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). The effects of chirality and preparation method on the solid-state properties and physical stabilities of the systems were investigated by XRPD, FTIR and mDSC. Differences in the BM process were caused by the enantiomeric properties of the co-former: The IND/TRP conglomerate (IND/TRPc) turned co-amorphous after 60 min. In contrast, co-amorphization of IND/L-TRP and IND/D-TRP required 80 min of ball milling, respectively, and the co-amorphous IND/TRP racemate (IND/TRPr) was obtained only after 90 min of ball milling. Although the intermolecular interactions of the co-amorphous systems prepared by BM and SD were similar (determined by FTIR), the Tg values differed (∼87 °C for the ball milled and âˆ¼62 °C for the spray dried systems). The physical stabilities of the ball milled co-amorphous systems varied between 3 and 11 months if stored at elevated temperature and dry conditions, with the highest stability for the IND/TRPc system and the lowest stability for the IND/TRPr system, and these differences correlated with the calculated relaxation times. In contrast, all spray dried systems were stable only for 1 month and their relaxation times were similar. It could be shown that the chirality of a co-former and the preparation method influence the solid-state properties, thermal properties and physical stability of IND/TRP systems.

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. The dust emission was reduced significantly by an oppositely directed convective flow. The results from the examinations, using either atomized ACAM or smoke for the determination of the evacuation time of the detection chamber, indicated that both methods are comparable. Furthermore, computational fluid dynamics (CFD) simulations were performed to determine the evacuation time. A time period of 9 min was sufficient for a reproducible evacuation and a reliable detection of most airborne ACAM particles within the detection chamber. CFD simulations were also carried out to simulate the air velocity resulting from various pressure differences and to visualize the flow of the airborne particles within the detection chamber.

(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). Ball milling for 6 h was required to obtain fully amorphous plain D- and L-TRP, whereas the TRP racemate and the TRP conglomerate were transformed into their amorphous forms already within 90 and 60 min of ball milling, respectively. Physical stability of the co-amorphous TRP conglomerate was observed for up to 60 d at ambient conditions as well as 40 °C/0 % RH. In contrast, the amorphous TRP racemate showed a reduced physical stability under ambient conditions. Interestingly, the intrinsic dissolution rates of the amorphous TRP conglomerate and racemate were not higher than those of the respective crystalline forms. In conclusion, applying two enantiomers of a chiral compound may be a promising approach for fast amorphization of an API and for improving the physical stability of the resulting amorphous form.

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. During the short-term in vivo study, feces samples were collected for bacterial DNA extraction followed by 16S rRNA gene sequencing analyses to detect changes in gut microbiota. Results showed that the prepared alginate aerogel has an average BET-specific surface area of around 540 m2/g, with a pore volume of 7.4 cc/g, and pore width of 30-50 nm. The in vivo study revealed that the levels of the studied kidney and liver enzymes didn't exceed the highest level of the normal range. The study of gut microbiota showed different patterns; certain groups of bacteria, such as Clostridia and Bacteriodia, increased during the aerogels regime and continued to increase after the aerogel was stopped. While other groups such as Erysipelotrichia, and Candidatus saccharibacteria increased during aerogels treatment, and then decreased again after one month. Members of the Bacilli class showed a unique trend, that is, after being the most abundant group (63%) at time 0, their relative abundance decreased dramatically until it reached < 5%; which was the case even after stopping the aerogel treatment.

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 CO2 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 0.0087 and 0.0634 g/cm3 as well as high surface areas between 354 and 759 m2/g. The obtained microspheres showed aerodynamic diameter below 5 µm making them suitable for pulmonary drug delivery. An in vitro drug release study with the model drug sodium naproxen was conducted and a non-Fickian drug release mechanism was observed, with no significant difference between the release profiles of alginate and alginate-hyaluronic acid microspheres. During the emulsion gelation step, the feasibility of using the capillary number to estimate the largest stable droplet size in the emulsions was also studied and it was found that using this number, the droplet size in the emulsions may well be predicted.

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. In order to find optimal tablet performance, different lignin formulations were assessed, and the concentrations were given by extreme vertices mixture design (13 formulations). The blends were composed of AS Lignin, Microcrystalline Cellulose, and Lactose monohydrate and the optimized blend was found to be 14.53 w/w% of disintegrant, 26.57 w/w% of binder and 58.9 w/w% of AS lignin. This proportion was further used to evaluate the performance of lignin-based tablets in drug release, using Ibuprofen as a drug model (50 w/w% and 70 w/w%) and for comparison of direct compression with wet granulation. Direct compressed tablets resulted in higher drug dissolution rates when compared with wet granulation, nevertheless; both tableting techniques showed promising results for lignin. More than 5 formulations tested in this work are compliant with International Pharmacopoeia regulations for solid dosage pharmaceutical forms, thus AS Lignin shows potential to be used as an excipient in pharmaceutical formulations. INDUSTRIAL RELEVANCE: Industrially, AS Lignin appears as promising excipient in the pharmaceutical technologies as well as boost in the biorefining technologies in the following years. Lignin produced is free of sulfur, can be labelled as clean and environmentally-friendly and in this study, was proven this non-cytotoxic AS lignin can be used for excipients and drug carriers. The findings in this paper showed the use of product formulation for life science purposes, thus stressing one of possibilities for lignin valorization in biorefineries.

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. It was demonstrated that intermolecular interactions between Eudragit® NM-L55 and pullulan did not exist. An increasing fraction of up to 30% pullulan in the Eudragit® NM-L55 blend film led to films with rising tensile strength, increasing Young's modulus, and decreasing elongation at break. With increasing fraction of pullulan in the blend films, the thermal stability thereof decreased up to around 400°C. Because of the high hydrophilicity of pullulan, the water vapor permeance increased with increasing fraction of pullulan in the blend films. The addition of pullulan influenced the swelling behavior of the blend films at pH 1.2 and 6.8. The higher the fraction of pullulan in the blend films the earlier the films eroded. These results demonstrate that the polysaccharide pullulan had a major impact on the Eudragit® NM-L55 blend film. It turned out that a fraction of up to 20% pullulan in the synthetic blend film is appropriate to be applied as a coating material. Thus, suitable film properties may be obtained by adjusting the fraction of pullulan in the Eudragit® NM-L55 blend film.

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. In the present study, a novel lower punch vibration technique was used to decrease the capping or lamination tendency of different powder formulations. Different microcrystalline cellulose types, as well as an API (acetaminophen), were selected as model powders. The powders were investigated regarding their powder flow, density, particle morphology, and surface area. Moreover, the manufactured tablets were characterized regarding their tablet weight, tensile strength, and capping or lamination indices. It was shown that the capping or lamination tendency was strongly affected by the physical powder properties, the formulation composition, and the adjusted turret speed. In addition, the application of externally applied lower punch vibration led to a pronounced decrease of the capping or lamination tendency and improved mechanical stability of the manufactured tablets.

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). The powders were characterized by helium pycnometry, laser diffraction, scanning electron microscopy, and by determination of the powder flow. Furthermore, a novel technique to determine the occurrences of segregation within a tablet after manufacturing was introduced. For this purpose, a powder blend containing one spray-colored type of microcrystalline cellulose (Vivapur® 200) were prepared. RESULTS: It was shown that under application of externally applied lower punch vibration, the powder flow into the die increased and thus the die filling process was significantly improved. Hence, it was possible to manufacture tablets from powders, which are actually unsuitable for direct compression. In addition, the mechanical stability of the produced tablets was distinctly improved by application of lower punch vibration, whereby the occurrence of segregation was comparatively low. CONCLUSION: In summary, lower punch vibration allows a more efficient die filling, whereby the powder flow as well as mechanical stability of the tablets are improved.

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. 3 mg/cm2 of tablet surface seemed to be sufficient if sustained release is not required. Thereby, hot-melt coating did not adversely affect the tablet properties with regard to subsequent processing steps. Compared to the tablet cores it was possible to reduce the moisture uptake by 85% at 75% relative humidity with tablets coated with a combination of Precirol® ATO 5 and Eudragit® L 30D-55. This combination was more efficient than high amounts of Eudragit® L 30D-55. Hot-melt coating proved to be a suitable technique for the application of subcoating material to tablet cores serving as a barrier against water permeation into hygroscopic tablet cores without exceeding the required disintegration times.

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. The powders were characterized by laser diffraction, scanning electron microscopy, helium pycnometry, ring shear testing, gas adsorption, and by determination of the powder flowability. Furthermore, the extent of densification within the die during vibration was visualized by a high-speed camera system and analyzed by an image-analyzing software. It was observed that lower punch vibration was able to densify the powder bed to a sufficient extent and within an adequate time period. Consequently, the presented results revealed that lower punch vibration may be a promising technique to remove entrapped air from powder beds, thus obtaining a denser powder bed within the die, which might potentially improve the tableting process and prevent complications during tablet manufacture.

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.

Objective: 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. Significance: Insights are provided regarding the influence of the paddle wheel geometry on the powder distribution to optimize the die filling process. Materials and methods: Avicel PH 102 served as model powder. A laser triangulator was used to scan the powder surface level within the feed frame and, combined with the determination of the angle position of the paddle wheel, an in-house written software was used to calculate the powder surface profiles and filling levels. Two experimental setups, one based on the filling chamber filled with a defined amount of powder (offline) and one using the filling chamber during tableting (inline) were applied. Results: Both paddle wheel geometries caused a significantly different distribution behavior of the powder within the filling chamber. The tablets obtained with the round rod filling wheel showed significantly higher tablet masses and significantly lower standard deviations. The inflow of powder into the filling chamber appeared to be improved with the round rod filling wheel. Conclusions: Under the applied experimental conditions, the round rod filling wheel showed obvious advantages compared to that with flat rods in terms of the uniformity of tablet masses and the extent of die filling.

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). The film-coated tablets were immersed in 0.1 M HCl for 0, 45, and 120 min and their solid-state properties were analysed by X-ray powder diffractometry (XRPD), differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and Fourier transformed infrared spectroscopy (FTIR). The drug release behaviour from these tablets was investigated at pH 6.8. It was shown that the formulation containing carvedilol with aspartic acid formed a co-amorphous system during immersion, while the formulation containing only carvedilol remained crystalline. FTIR spectroscopy indicated molecular interactions in the co-amorphous carvedilol-aspartic acid system, which explained the single Tg found using DMA (106 ±â€¯4 °C). However, because of a lack of sufficient disintegration, drug release of the immersed co-amorphous formulation was lower than from the untreated tablets (immersed for 0 min) containing only carvedilol or the crystalline physical mixture of carvedilol and aspartic acid. After overcoming the disadvantage of the insufficient disintegration, it may be concluded that in situ co-amorphisation in a film-coated tablet by immersion in 0.1 M HCl appears to be a feasible formulation approach for poorly water-soluble basic drugs.

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. It was assumed that an in situ co-amorphisation may be achieved, if a tablet containing a crystalline acidic API and the basic amino acid arginine, coated with a gastro-resistant but water-permeable coating, is exposed to an acidic medium. To investigate this hypothesis, tablets containing arginine and either indomethacin or furosemide were coated with Eudragit®L. After different time periods of immersion (10, 20, 30, 60, 120 min) in 0.1 MHCl, samples were analysed with respect to their solid state properties by XRPD, FTIR spectroscopy and modulated temperature DSC. In both formulations co-amorphous API-arginine was already detected after 10 min of immersion. The maximum of co-amorphous content was reached after 20 min with both formulations, while longer immersion time periods than 60 min revealed a partial API recrystallisation. In addition, during immersion of the indomethacin-arginine formulation, basic hydrolysis of indomethacin was observed, which could be prevented by addition of citric acid to the tablet formulation. However, this addition also inhibited the co-amorphisation of indomethacin. In this proof-of-principle study it was shown that the concept of in situ co-amorphisation of APIs with arginine might be a feasible formulation approach for those poorly water-soluble drugs, which are not susceptible to basic hydrolysis.

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. The extracts were analyzed for their physical properties and stored at accelerated conditions. Sennoside degradation was monitored by HPLC analysis. RESULTS: An increase of the atomizing gas pressure had the most pronounced influence on the decrease of moisture content and particle size. An increase of the inlet temperature led to a decrease of moisture content and particle density, as well as an increase of smooth particle amount. An increase in the pump feed rate, increased the moisture content and resulted in stable hollow spheres. The different conditions also led to smooth or wrinkled particle surfaces, and to golfball, donut, and shard particle shapes. The chemical stability of the sennosides differed from each other after storage. Stability-reducing factors were the moisture content of the samples and their hygroscopicities, as well as different particle morphologies. These factors were influenced by the inlet temperature of the spray-drying process. High inlet temperatures led to a positive influence on dryness and particle morphology and therefore on the stability of the sennosides. CONCLUSIONS: Variation of the process conditions affected the resulting particle properties and their storage stability of Sennae fructus extract.

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. the previously observed co-amorphisation of indomethacin and arginine upon storage of tablets containing both components in an initially crystalline form at room temperature (RT) and 75% relative humidity (RH). Therefore, the aim of the present study was to further investigate this unintended co-amorphisation by storing plain crystalline γ-indomethacin and arginine as well as physical mixtures of both components at RT and three different RH levels (28, 58, and 75% RH). After storage for up to 101 days, their properties were analysed by X-ray powder diffraction, infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, and HPLC. Results showed that the solid state of plain γ-indomethacin did not change during storage at all three storage conditions. In contrast, arginine was found to form a dihydrate upon storage at RT/58% RH and RT/75% RH. The physical mixtures, stored at RT/28% RH and RT/58% RH, remained crystalline and were chemically stable, while the formation of a co-amorphous salt between indomethacin and arginine as well as basic hydrolysis of indomethacin started already 1 day after exposure to RT/75% RH. Moreover, formation of a crystalline salt of indomethacin and arginine upon storage at RT/75% RH was observed. As neither of these instabilities occurred, if indomethacin was stored separately, the simultaneous effects of arginine and moisture on the solid state properties and chemical stability of indomethacin should be taken into account, if selecting arginine as excipient.

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. To understand this phenomenon, key properties of the punches were investigated. The AFM adhesive forces of both APIs to the differently coated punches as well as the surface free energies and the surface texture of these punches were determined. Separately evaluating these properties revealed only a partial correlation with the sticking observed during tableting. Consistent results with the tableting data could only be achieved if evaluating the surface texture in context with the chemical composition of the respective punch surfaces. It was concluded that each punch tip coating represents an entirely different system, which were described in detail as a result of the performed investigations. Particularly, chromium nitride-coated punches resulted in excellent anti-sticking performances because of a low chemical interaction with the APIs combined with a smooth and homogeneous surface texture.

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. It was shown that Ibuprofen DC 85 W showed a good tableting behavior with regard to both responses. The tablet disintegration was considerably affected by the maximum compaction force applied, but was also slightly affected by preceding compaction events. The tablet crushing strength was mainly affected by the maximum applied compaction force independent of the order of these forces. The sticking tendency of Ibuprofen DC 85 W was compared with that two other ibuprofen powder formulations in long-term tableting runs. Compared to the other two formulations, sticking was considerably lower with Ibuprofen DC 85 W. The sticking tendency was not influenced by the addition of an intermediate compaction force, but was remarkably reduced by the choice of the punch tip coating.

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. The terahertz pulse beam propagates through the tablets and is back-reflected at the interface between the MCC matrix and the coated pellets within the tablet causing a peak in the terahertz waveform. Cross-section images of the tablets were extracted at different depths and parallel to the tablet faces from 3D terahertz data to visualise the surface-near structure of the MUPS tablets. The images of the surface-near structure of the MUPS tablets were compared to X-ray microtomography images at the same depths. The surface-near structure could be clearly resolved by TPI at depths between 24 and 152µm below the tablet surface. An increasing amount of pellets within the MUPS tablets appears to slightly decrease the detectability of the pellets within the tablets by TPI. TPI was shown to be a non-destructive method for the detection of pellets within the tablets and could resolve structures thicker than 30µm. In conclusion, a proof-of-concept was provided for TPI as a method of quality control for MUPS tablets.

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. Standardized 3D surface texture parameters were analyzed by principal component analysis (PCA) to characterized differently surface-modified punches, punches with different wear status and the sticking pattern on the punch surfaces. It could be shown that the presented technique was precise enough to differentiate between differently coated and texturized punches, to evaluate the abrasive wear status of the investigated punches, and to visualize and assess punch tip sticking behavior. In conclusion, this novel technique may serve as a valuable tool for systematic punch surface characterization, wear status check-up and optimization of the punch surface quality e.g. for improvement of the anti-sticking behavior.