Jouko Yliruusi

University of Helsinki | HY · Division of Pharmaceutical Technology

The solubility and dissolution rates of chemical compounds are crucial properties in several fields of industry and research. However, accurate, rapid and green methods for their measurement, which only consume micrograms of compound, are lacking. Here, the unique approach of non-specific, image-based single particle analysis (SPA) for solubility t...

The effect of colloidal silicon dioxide (CSD) on powder flow properties of poor-flowing excipient lactose 200M was investigated. Binary mixtures of different ratios of CSD as glidant were examined using a modern image-based flow measuring technique. Special attention was placed to subtle variations in powder flow from small changes in glidant conce...

p class="ADMETabstracttext">Poor solubility of crystalline drugs can be overcome by amorphization – the production of high-energy disordered solid with improved solubility. However, the improved solubility comes at a cost of reduced stability; amorphous drugs are prone to recrystallization. Because of recrystallization, the initial solubility enhan...

Salt formation is a well-established method to increase the solubility of ionizable drug candidates. However, the possible conversion of salt to its original form of free acid or base – disproportionation – can have a drastic effect on solubility and consequently bioavailability of a drug. Therefore, during the salt selection process, salt dissolut...

Powder flowability plays an important role in die filling during tablet manufacturing. The present study introduces a novel small-scale measuring technique for powder flow. Based on image analysis, the flow was defined depending on the variation of luminous intensity and the movement of powder inside the measurement cuvette. Using quantities around...

Amorphous materials exhibit distinct physicochemical properties compared to their respective crystalline counterparts. One of these properties – the increased solubility of amorphous materials – is exploited in the pharmaceutical industry as a way of increasing bioavailability of poorly water-soluble drugs. Despite the increasing interest in drug a...

Solubility is a physicochemical property highly dependent on the solid-state form of a compound. Thus, alteration of a compound's solid-state form can be undertaken to enhance the solubility of poorly soluble drug compounds. In the Biopharmaceutics Classification System (BCS), drugs are classified based on their aqueous solubility and permeability....

The present study introduces a modified melt-electrospinning (MES) method for fabricating the melt-electrospun fibers (MSFs) of a poorly water-soluble drug and carrier polymer. The MES of poorly water-soluble model drug indomethacin (IND) and hydrophilic carrier polymer, Soluplus® (SOL) were prepared at a 1:3 drug-polymer weight ratio. Water was us...

Raman spectroscopy is widely used for quantitative pharmaceutical analysis, but a common obstacle to its use is sample fluorescence masking the Raman signal. Time-gating provides an instrument-based method for rejecting fluorescence through temporal resolution of the spectral signal, and allows Raman spectra of fluorescent materials to be obtained....

Solid dispersions (SDs) hold a proven potential in formulating poorly water-soluble drugs. The present paper investigates the interfacial phenomena associated with the bulk powder flow, water sorption, wetting and dissolution of the SDs prepared by a modified melt and quench-cooling (QC) method. Poorly water-soluble indomethacin (IND) was QC molten...

The compression physics of powders must be considered when developing a suitable tablet formulation. In the present study, the gravitation-based high-velocity method was utilized to analyze mechanical properties of eight common pharmaceutical excipients: two grades of lactose, anhydrous glucose, anhydrous calcium hydrogen phosphate, three grades of...

The goal of this work was to study the printability of PDMS with a semi-solid extrusion printer in combination with the UV-assisted crosslinking technology using UV-LED light to manufacture drug containing structures. Structures with different pore sizes and different drug loadings were prepared containing prednisolone as a model drug. The work sho...

Introduction: The technological advancements in the pharmaceutical field are constantly improving and provide various possibilities for meeting the needs of personalized drug therapy. The three-dimensional (3D) printing technology has endless potential in the fabrication of patient-specific drug delivery devices (DDD) and dosage forms as the techno...

We introduce a system with a lyophilic matrix to aid dissolution studies of powders and particulate systems. This lyophilic matrix method (LM method) is based on the ability to discriminate between non-dissolved particles and the dissolved species. In the LM method the test substance is embedded in a thin lyophilic core-shell matrix. This permits r...

A new dry granulation technique, gas-assisted roller compaction (GARC), was compared with conventional roller compaction (CRC) by manufacturing 34 granulation batches. The process variables studied were roll pressure, roll speed, and sieve size of the conical mill. The main quality attributes measured were granule size and flow characteristics. Wit...

With modern tableting machines large amounts of tablets are produced with high output. Consequently, methods to examine powder compression in a high-velocity setting are in demand. In the present study, a novel gravitation-based method was developed to examine powder compression. A steel bar is dropped on a punch to compress microcrystalline cellul...

The isolation and physical material properties of suberin fatty acids (SFAs) were investigated with special reference to their potential applications as novel pharmaceutical excipients. SFAs were isolated from outer birch bark (OBB) with a new extractive hydrolysis method. The present simplified isolation process resulted in a moderate batch yield...

Amorphous solid dispersions (SDs) are a promising approach to improve the dissolution rate of and oral bioavailability of poorly water-soluble drugs. In some cases multi-phase, instead of single-phase, SD systems with amorphous drug are obtained. While it is widely assumed that one-phase amorphous systems are desirable, two-phase systems may still...

Electrospinning was used as a novel technique for fabricating polymeric nanofibers of a serum cholesterol lowering and poorly water-soluble plant sterol, β-sitosterol. Chitosan was used as a stabilizer/carrier polymer. The mean diameters of nanofibers ranged from 150 nm to 218 nm. β-sitosterol was in an amorphous form and homogeneously dispersed in...

In this paper we present a fast model system for monitoring the recrystallization of quench-cooled amorphous xylitol using Raman spectroscopy and wide-angle X-ray scattering. The use of these two methods enables comparison between surface and bulk crystallization. Non-ordered mesoporous silica micro-particles were added to the system in order to al...

Suberin fatty acids (SFAs) isolated from outer birch bark were investigated as an antimicrobial agent and biomaterial in nanofibrous mats intended for wound treatment. Electrospinning (ES) was used in preparing the composite nonwoven nanomats containing chloramphenicol (CAM; as a primary antimicrobial drug), SFAs, and polyvinylpyrrolidone (as a car...

Intrinsic dissolution rate (IDR) has traditionally been determined from a constant surface area of a substance. Here we present an optofluidic single-particle intrinsic dissolution rate (SIDR) method, by means of which real-time determination of IDR from continuously changing effective surface areas of dissolving individual micro-particles, is poss...

In the present study the mechanical properties of microcrystalline cellulose compacts compressed were studied. The resistance to crushing was tested using diametral compression testing and apparent Young's modulus was determined using consecutive uniaxial compression of the full cross-sectional area of single tablets. As non-elastic deformation dur...

Amorphous solid dispersions (SDs) open up exciting opportunities in formulating poorly water-soluble active pharmaceutical ingredients (APIs). In the present study, novel catalytic pretreated softwood cellulose (CPSC) and polyvinylpyrrolidone (PVP) were investigated as carrier polymers for preparing and stabilizing cryogenic co-ground SDs of poorly...

We showed that the addition of suberin fatty acids (SFAs) even at small concentrations significantly improves the water vapor barrier properties of hydroxypropyl methylcellulose (HPMC) films. SFAs were isolated from the outer birch bark using extractive hydrolysis. The effects of SFAs on the film formation of aqueous HPMC were investigated with fre...

Solubility is the primary physicochemical property determining the absorption and bioavailability of substances. Here we present an optofluidic single-particle technique for micro-scale equilibrium solubility determination, based on on-chip hydrodynamic particle trapping and optical particle size monitoring. The method combines the rapidity, univer...

The conversion of active pharmaceutical ingredient (API) from amorphous to crystalline form is the primary stability issue in formulating amorphous solid dispersions (SDs). The aim of the present study was to carry out qualitative and quantitative analysis of the physical solid-state stability of the SDs of poorly water-soluble piroxicam (PRX) and...

This multiauthor review article aims to bring readers up to date with some of the current trends in the field of process analytical technology (PAT) by summarizing each aspect of the subject (sensor development, PAT based process monitoring and control methods) and presenting applications both in industrial laboratories and in manufacture e.g. at G...

Tablet compression process has been studied over the years from various perspectives. However what exactly happens to material during compression is still unknown. In this study a novel compression die which enables real-time spectroscopic measurements during the compression of material is represented. Both near infrared and Raman spectroscope prob...

This paper introduces and discusses a photometric surface imaging approach for on-line monitoring of fluid bed granulation. Five granule batches consisting of paracetamol and varying amounts of lactose and microcrystalline cellulose were manufactured with an instrumented fluid bed granulator. Photometric images and NIR spectra were continuously cap...

Novel, simple and cost effective methods are needed to replace advanced chemical analytical techniques, in small-scale dissolution studies. Optical microscopy of individual particles could provide such a method. The aim of the present work was to investigate and verify the applicability of optical microscopy as an analytical technique for drug diss...

In this paper, linkages between tablet surface roughness, tablet compression forces, material properties, and the tensile strength of tablets were studied. Pure sodium halides (NaF, NaBr, NaCl, and NaI) were chosen as model substances because of their simple and similar structure. Based on the data available in the literature and our own measuremen...

Plasticizer is an essential adjuvant in food and pharmaceutical film coatings affecting the appearance, mechanical and permeation properties of the final coat. In the present study, film formation and plasticization of native whey proteins (potential future “green” coating agents for pharmaceuticals and food products), were studied with free isolat...

The cocrystal formation potential of itraconazole, a potent antifungal drug, with C2−C10 aliphatic dicarboxylic acids has been investigated. Using two experimental screening techniques (solvent-assisted grinding and evaporation-based crystallization), the cocrystals of itraconazole with C2−C7 dicarboxylic acids have been successfully synthesized an...

Tablet compression of softwood cellulose and lignin prepared by a new catalytic oxidation and acid precipitation method were investigated and compared with the established pharmaceutical direct compression excipients. Catalytic pretreated softwood cellulose (CPSC) and lignin (CPSL) were isolated from pine wood (Pinus sylvestris). The compaction stu...

Magnesium stearate (MS) is the most commonly used lubricant in pharmaceutical industry. During blending, MS particles form a thin layer on the surfaces of the excipient and drug particles prohibiting the bonding from forming between the particles. This hydrophobic layer decreases the tensile strength of tablets and prevents water from penetrating i...

Particle size, packing density and blend composition of glass ballotini, microcrystalline cellulose pellets and theophylline granules were studied by diffuse light transmission. Diffuse visible light was directed to the sample and the intensity of the light transmitted to the opposite side of the sample was measured through a diffusing lens using a...

Solid-state and powder properties of softwood lignin and cellulose prepared by a new catalytic oxidation and acid precipitation method were characterized and compared with the commercial softwood and hardwood lignin and cellulose products. Catalytic pre-treated softwood lignin (CPSL) and cellulose (CPSC) were isolated from pine wood (Pinus sylvestr...

Coenzyme Q10 (CoQ10) is a natural antioxidant of the oil-soluble benzoquinone group that is involved in electron transport in mitochondria. CoQ10 possesses a broad spectrum of pharmacological activity. However, its insolubility in water and low bioavailability upon peroral administration are significant disadvantages. The present work was aimed at...

Cocrystallization and salt formation have been shown to entail substantial promise in tailoring the physicochemical properties of drug compounds, in particular, their dissolution and hygroscopicity. In this work, we report on the preparation and comparative evaluation of a new cocrystal of itraconazole and malonic acid and two new hydrochloric salt...

To date, little is known on applicability of different types of pharmaceutical dosage forms in an automated high-speed multi-dose dispensing process. The purpose of the present study was to identify and further investigate various process-induced and/or product-related limitations associated with multi-dose dispensing process. The rates of product...

Extrusion-spheronization (ES) is a frequently used agglomeration process in the pharmaceutical industry to manufacture spherical solid units or pellets with a narrow size and shape distribution. In this study, photometric stereo imaging was applied in real-time during the final steps of the ES process, being spheronization and drying. In addition t...

Direct compression of chitin was studied with special reference to the effects of moisture content on tablet formation and properties. Two cellulosic direct compression materials, microcrystalline cellulose (MCC) and spray-dried lactose-cellulose (SDLC, (Cellactose®) were used as reference materials. The compaction studies were carried out using an...

Powder mixing is being modeled using a simulation based on Newtonian mechanics. Variables under consideration include particle friction and the amplitude, frequency, and direction of shaking. Trajectories for each particle were recorded, and a mixing degree was calculated for each simulation, for which the average energy transferred into the powder...

The effects of spray-drying process and acidic solvent system on physicochemical properties of chitosan salts were investigated. Chitosan used in spray dryings was obtained by deacetylation of chitin from lobster (Panulirus argus) origin. The chitosan acid salts were prepared in a laboratory-scale spray drier, and organic acetic acid, lactic acid,...

This study presents a new approach to model powder compression during tableting. The purpose of this study is to introduce a new discrete element simulation model for particle-particle bond formation during tablet compression. This model served as the basis for calculating tablet strength distribution during a compression cycle. Simulated results w...

The need for effective solid-form screening approaches, especially designed for the early discovery phases, is well recognized within the pharmaceutical industry. Here we report on the early polymorphism and solvatomorphism evaluation of a new drug candidate for selective α2C-adrenoceptor antagonists ORM10921·HCl. The approach we use is based on th...

The effect of the amount of granulation liquid, compression speed and maximum compression force on the compressibility and compactibility of lactose, glucose and mannitol granules was studied. The porosity based on the geometrical shape and the uniformity of weight of tablets was also studied. Lactose and mannitol granules showed a greater compress...

The present study introduces a new three-dimensional (3D) surface image analysis technique in which white light illumination from different incident angles is used to create 3D surfaces with a photometric approach. The three-dimensional features of the surface images created are then used in the characterization of particle size distributions of gr...

A correlation between absorbance value in the near infrared (NIR) range and granule particle size may allow measurement of particle growth during granulation. The effect of various grades of microcrystalline cellulose on NIR reflectance spectroscopic measurement was studied.Three grades with different median particle sizes and a mixture of these we...

The aim of this study was to evaluate how different granule size distributions affect the tablet compression process. The emphasis was on developing new analytic methods for compression data for entire batch. In all, 18 batches of granules containing theophylline and lactose were tabletted, using an instrumented eccentric tabletting machine. During...

Powder flow is influenced by environmental factors, such as moisture and static electricity, as well as powder related factors, such as morphology, size, size distribution, density, and surface area. Pharmaceutical solids may be exposed to water during storage in an atmosphere containing water vapor, or in a dosage form consisting of materials (e.g...

An ultrasound-assisted powder-coating technique was used to produce a homogeneous powder formulation of a low-dose active pharmaceutical ingredient (API). The powdered particles of microcrystalline cellulose (MCC; Avicel® PH-200) were coated with a 4% m/V aqueous solution of riboflavin sodium phosphate, producing a uniform drug layer on the particl...

We nano-coated powdered lactose particles with the enzyme beta-galactosidase using an ultrasound-assisted technique. Atomization of the enzyme solution did not change its activity. The amount of surface-attached beta-galactosidase was measured through its enzymatic reaction product D-galactose using a standardized method. A near-linear increase was...

Drying is one of the standard unit operations in the pharmaceutical industry and it is important to become aware of the circumstances that dominate during the process. The purpose of this study was to test microcapsulated thermochromic pigments as heat indicators in a fluid bed drying process. The indicator powders were manually granulated with alp...

The droplet size affects the final product in fluid-bed granulation and coating. In the present study, spray characteristics of aqueous granulation liquid (purified water) were determined in situ in a fluid-bed granulator. Droplets were produced by a pneumatic nozzle. Diode laser stroboscopy (DLS) was used for droplet detection and particle trackin...

A "simplex-centroid mixture design" was used to study the direct-compression properties of binary and ternary mixtures of chitin and two cellulosic direct-compression diluents. Native milled and fractioned (125-250 microm) crustacean chitin of lobster origin was blended with microcrystalline cellulose, MCC (Avicel PH 102) and spray-dried lactose-ce...

In powder technology, it is often important to directly measure real powder flow rate from a small amount of powder. For example, in pharmaceutical industry, a frequent problem is to determine powder flow properties of new active pharmaceutical ingredient (API) in an early stage of the development when the amount of API is limited. The purpose of t...

The flow behaviour of binary mixtures of paracetamol and different grades of microcrystalline celluloses (Avicel PH101, PH102 and PH200) was studied using a new testing method. The effect ® of physical characteristics of the powder including tribocharging and the addition of lubricant on the flow properties of the different mixtures was investigate...

We have developed a new method to determine the degree of mixing for a given system. The method assumes knowledge of the locations of all or some studied particles both before and after mixing. The method is scalable and gives comparable results for systems with varying shapes and sizes of the mixing space. It can also be used to determine the mixi...

In the present study, thin-coating as a potential method for improving flow properties of cohesive ibuprofen powder was introduced. Briefly, the technique was based on the successive deposition of ultrasound-assisted fine polymer mist onto the surface of the powdered active pharmaceutical ingredient (API), producing individual particles with a hydr...

In this study, a new concept for particle size prediction during the fluid bed granulation is presented. Using the process measurements data obtained from a design of experimental study, predictive partial least squares models were developed for spraying and drying phases. Measured and calculated process parameters from an instrumented fluid bed gr...

Scratch resistance (SR) of externally plasticized hydroxypropyl methylcellulose (HPMC) films intended for tablet film coatings was studied. Special attention was paid to effects of short-term aging and ultraviolet (UV) treatment on the SR properties of these films. Controlled scratching of the films was performed with a Lloyd LRX materials tester f...

Nanosizing is an advanced formulation approach to address the issues of poor aqueous solubility of active pharmaceutical ingredients. Here we present a procedure to prepare a nanoparticulate formulation with the objective to enhance dissolution kinetics of taxifolin dihydrate, a naturally occurring flavonoid with antioxidant, anti-inflammatory, and...

The primary aim of the study was to investigate the effects of pulsed liquid feed on granule size. The secondary aim was to increase knowledge of this technique in granule size targeting. Pulsed liquid feed refers to the pump changing between on- and off-positions in sequences, called duty cycles. One duty cycle consists of one on- and off-period....

Sugar end-capped poly-D,L-lactide (SPDLA) polymers were investigated as a potential release controlling excipient in oral sustained release matrix tablets. The SPDLA polymers were obtained by a catalytic ring-opening polymerization technique using methyl alpha-D-gluco-pyranoside as a multifunctional initiator in the polymerization. Polymers of diff...

Different process phenomena and process failure modes could be monitored using the in-line particle size data measured by spatial filtering technique (SFT). In addition to the real-time granule growth monitoring, other events, such as the blocking of filter bags and the distributor plate, could be observed. SFT was used off-line, at-line and in-lin...

Crystal morphology engineering of a macrolide antibiotic, erythromycin A dihydrate, was investigated as a tool for tailoring tabletting performance of pharmaceutical solids. Crystal habit modification was induced by using a common pharmaceutical excipient, hydroxypropyl cellulose, as an additive during crystallization from solution. Observed morpho...

The goal of the present study was to design a new technique to modify particle surface properties and, through that, to improve flowability of poorly flowing drug thiamine hydrochloride and pharmaceutical sugar lactose monohydrate of two different grades. The powdered particles were supplied by a vibratory feeder and exposed to an instantaneous eff...

Amorphous drugs have a higher kinetic solubility and dissolution rate than their crystalline counterparts. However, this advantage is lost if the amorphous form converts to the stable crystalline form during the dissolution as the dissolution rate will gradually change to that of the crystalline form. The purpose of this study was to use in situ Ra...

The purpose of this study was to determine the variation in the granule size distribution in a die of an eccentric tableting machine. Theophylline anhydrate and alpha-lactose monohydrate were granulated with an aqueous solution of polyvinylpyrrolidone, using an instrumented fluid bed granulator. The granules were tabletted, using an instrumented ec...

The surfaces of ibuprofen particles (d(50) 42 microm) were modified by coating the particles with diluted aqueous hydroxypropyl methylcellulose (HPMC) solution in an instrumentated top-spray fluid bed granulator. The objective was to evaluate whether an extremely thin polymer coating could be an alternative to granulation in enhancing powder flow a...

The purpose of this research was to create a calibration model based on near-infrared (NIR) spectroscopy data obtained during a small-scale coating process to predict in-line the coating layer thickness of tablets coated in a side-vented drum coater. The developed setup for the small-scale coating process consisted of a rotating plate with 20 table...