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Background: Active pharmaceutical ingredient (API) content is a critical quality attribute (CQA) of amorphous solid dispersions (ASDs) prepared by spraying a solution of APIs and polymers onto the excipients in fluid bed granulator. This study presents four methods for quantifying API content during ASD preparation. Methods: Raman and three near-in...

The mathematical models available in DDSolver were applied to experimental dissolution data obtained by analysing carvedilol release from hypromellose (HPMC)-based matrix tablets. Different carvedilol release profiles were generated by varying a comprehensive selection of fillers and carvedilol release modifiers in the formulation. Model fitting wa...

Solid dosage forms based on hypromellose (HPMC) with prolonged/extended drug release are very important from the research and industrial viewpoint. In the present research, the influence of selected excipients on carvedilol release performance from HPMC-based matrix tablets was studied. A comprehensive group of selected excipients was used within t...

Liquid atomization plays an important role in the manufacturing of the pharmaceutical products. It is used in all production steps where liquid is applied. In some productions steps precise control over spraying parameters is essential. These steps include fluid bed granulation, film coating of tablets and pellet coating. Precise atomization of liq...

The importance of roller compaction is recently increasing. This study evaluates the combined effects of formulation factors, process parameters, and selected quality attributes on drug release from roller-compacted hypromellose-based matrix tablets containing carvedilol as a model drug. The influence of selected factors was statistically assessed...

This study investigates the use of the spatial filtering technique (SFT¹) to monitor the particle size distribution (PSD²) of granules obtained by roller compaction. In the first part of the study, the influence of the selected process and formulation parameters on the PSD² of granules is monitored at-line using SFT¹. The correlation between the PS...

In this study, various formulations of solidified carvedilol-loaded SMEDDS with high SMEDDS loading (up to 67% w/w) were produced with the spray drying process using various porous silica-based carriers. The process yield was improved with higher atomization gas flow rate during the spray drying process and with prolonged mixing time of dispersion...

The freeze-drying process is an expensive, time-consuming and rather complex process. Therefore, process analytical technology (PAT) tools have been introduced to develop an optimized process and control critical process parameters, which affect the final product quality. The aim of the present work was to study the applicability of at-line near-in...

This study explores the use of a statistical model to build a design space for freeze-drying two formulations with ibuprofen. A 2 × 3 factorial experimental design was used to evaluate independent variables (filling volume and annealing time) and responses as residual moisture content, specific surface area and reconstitution time. A statistical mo...

Solidification of self-microemulsifying drug delivery systems (SMEDDS) is a rising experimental field with important potential for pharmaceutical industry, however fluid-bed granulation with SMEDDS is yet an unexplored solidification technique. The aim of the study was to solidify carvedilol-loaded SMEDDS utilizing fluid bed granulation process and...

Self-(micro)emulsifying drug delivery systems (S(M)EDDS) have emerged as effective vehicles for enhancing bioavailability of poorly water soluble drugs, however solidification of the systems represents a major challenge. Objective of this study was development of carvedilol loaded liquid SMEDDS and transformation into solid pellets employing fluid-...

Ibuprofen, a weakly acidic non-steroidal anti-inflammatory drug having poor aqueous solubility, is a challenging drug for the development of pharmaceutical formulations, resulting in numerous research attempts focusing on improvement of its solubility and consequently bioavailability. Most studies have been done for solid dosage forms, with very li...

Process analytical technology (PAT) has become an important factor in design, analysis and control of complex technological processes. In the present study, pellet coating process was monitored using four different PAT approaches, i.e. near-infrared (NIR) spectroscopy, Raman spectroscopy, in-line image analysis, and spatial filtering technique (SFT...

Wet granulation is mostly used process for manufacturing matrix tablets. Compared to the direct compression method, it allows for a better flow and compressibility properties of compression mixtures. Granulation, including process parameters and tableting, can influence critical quality attributes (CQAs) of hydrophilic matrix tablets. One of the mo...

Over the last two decades, regulatory agencies have demanded better understanding of pharmaceutical products and processes by implementing new technological approaches, such as process analytical technology (PAT). Process analysers present a key PAT tool, which enables effective process monitoring, and thus improved process control of medicinal pro...

Self-emulsifying drug delivery systems (SEDDS) are lipid formulations that improve solubility and oral bioavailability of the incorporated drug with poor biopharmaceutical properties. As liquids they are traditionally filled into soft or hard capsules. Transformation of SEDDS into solid dosage form has been extensively investigated in the recent ye...

Although process analytical technology (PAT) guidance has been introduced to the pharmaceutical industry just a decade ago, this innovative approach has already become an important part of efficient pharmaceutical development, manufacturing, and quality assurance. PAT tools are especially important in technologically complex operations which requir...

Poor flowability and compressibility of many excipients and active ingredients used in the pharmaceutical industry are important obstacles for using direct compression in manufacturing of tablets. Their rheological and mechanical properties must therefore be improved by pre-processing with an appropriate particle engineering processes, including ag...

Matrix tablets are one of the most commonly used controlled release dosage forms, in which the matrix is formed from one or a combination of different biocompatible polymers. Many release mechanisms of the drug from such system can be obtained, depending on a polymer type and physico-chemical characteristics of a drug. Natural polymers offer new te...

Simvastatin crystals, having same crystal structure but different types of habits and hence different intrinsic dissolution rate, were prepared by recrystallization from solvents selected according to their polarity index. Scanning electron microscopy, laser diffraction, image analysis, X-ray powder diffractometry, Fourier transform infrared spectr...

In order to achieve better in-vivo performance of the final dosage form comprising a poorly soluble drug the physicochemical properties of the active pharmaceutical ingredient can be altered not only by changing the solid state form but also through the conversion of their crystal habits. To elucidate this approach in the case of simvastatin, the d...

Polymethacrylate polymers are commonly used for the coating of prolonged-release pellets. Due to environmental and other concerns, aqueous latex dispersions are preferred over organic solutions. When using aqueous dispersions, a curing step is needed to ensure complete film formation. The aim of the present work was to investigate the impact of the...

The purpose of this study was to compare different solidification techniques (i.e. adsorption technique,spray-drying process, high-shear granulation, fluid-bed granulation) for preparing solid SMEDDS powders by using solid carriers identified as appropriate and to produce a single (tablets) or multiunit (minitablets) solid dosage form based on prep...

Special populations including paediatric and elderly patients often need advanced approaches in treatment, such as one-a-day dosing, which is achieved with modified release formulations or alternative routes of applications such as nasogastric route. Pellets are a dosage form that is frequently used in such formulations. The aim of the present work...

The purpose of this study was to prepare solid SMEDDS (sSMEDDS) particles produced by spray-drying using maltodextrin (MD), hypromellose (HPMC), and a combination of the two as a solid carrier. Naproxen (NPX) as the model drug was dissolved (at 6% concentration) or partially suspended (at 18% concentration) in a liquid SMEDDS composed of Miglyol(®)...

Context: Comparative evaluation of liquid and solid self-microemulsifying drug delivery systems (SMEDDS) as promising approaches for solubility enhancement. Objective: The aim of this work was to develop, characterize, and evaluate a solid SMEDDS prepared via spray-drying of a liquid SMEDDS based on Gelucire® 44/14 to improve the solubility and...

The influence of different additives on the mechanical properties of hydroxypropyl methylcellulose (HPMC) free films was studied using tensile testing. Free films were prepared using the cast method and sliced into bands, and their tensile strength and maximal elongation at break was measured. The results showed that the addition of PEG 400 and pol...

The purpose of this research was to predict the in vivo dissolution of lansoprazole from enteric coated pellets in the fasted state using a biorelevant flow-through dissolution method with low flow rates and volumes close to those in vivo. Additionally, a novel rotating stirring element, composed from magnet inserted in a silicone tube, was used to...

Abstract Low oral bioavailability as a consequence of low water solubility of drugs is a growing challenge to the development of new pharmaceutical products. One of the most popular approaches of oral bioavailability and solubility enhancement is the utilization of lipid-based drug delivery systems. Their use in product development is growing due t...

The main purpose of this study was to investigate the influence of different additives on the physical properties of polymer coating dispersions (surface tension, wettability, and viscosity) as well as the adhesion of the final coating onto tablet cores composed of microcrystalline cellulose (MCC), lactose (Tablettose 80), croscarmellose sodium (Ac...

This chapter describes a study of the influence of particle size and the settings of tableting parameters on tablet capping tendency. Artificial neural network (ANN) and fuzzy models were used for modelling the effect of particle size and tableting machine settings on the capping coefficient. The basic principles of the tableting process are descri...

Objective: The aim of this work was to study the granule growth kinetics during in situ fluid bed melt granulation process using real-time particle size measurement techniques. In addition, the usefulness of these techniques during scale-up of melt granulation was evaluated. Materials and methods: Focused beam reflectance measurement (FBRM) and...

The objective of this work was to investigate the influence of selected individual variables (binder content, inlet air temperature, and product endpoint temperature) of in situ fluid bed melt granulation on the granule particle size distribution and percentage of dissolved carvedilol using a three-factor, five-level circumscribed central composite...

This study investigates the effect of particle size on the compression characteristics of wet- (fluid-bed granulation - FBG) and dry-granulated (slugging - DGS) tableting mixtures. Particle-size distribution, flowability, compressibility, using the Heckel and Walker model, compactibility and elastic recovery as well as friability and disintegration...

The absorption and bioavailability of drugs can be substantially affected by the transit of dosage forms through the gastrointestinal (GI) tract. Gastric emptying is one of the most critical parameters contributing to this inter- and intra-individual GI transit variability. It is especially important for the delayed release dosage forms whose relea...

The purpose of this study was to prepare and characterize granulated carvedilol by melt-in and spray-on melt granulation in a fluid bed and a high shear granulator. Granulates having comparable particle size distribution and good flow properties were obtained with proper adjustment of process parameters for each binder (poloxamer 188, polyethylene...

The key physicochemical properties of functional excipients should be identified, and the influence of their variability on the properties of the final dosage form should be evaluated during the development phase. Excipients produced by different manufacturers and/or by different manufacturing processes should have comparable properties. Hydroxypro...

Spherical crystallization of drugs Spherical crystallization of drugs is the process of obtaining larger particles by agglomeration during crystallization. The most common techniques used to obtain such particles are spherical agglomeration and quasi-emulsion solvent diffusion. Ammonia diffusion systems and crystallo-co-agglomeration are extensions...

The importance of functionality-related characteristics (FRC) of hydroxypropyl methylcellulose (HPMC) described in the pharmacopeia monograph can be evaluated only for selected formulation or technological process. The aim of our work was to investigate the influence of apparent viscosity as one of the FRC for two batches of the same HPMC grade on...

A delivery system which provides bimodal pH dependent release of poorly water soluble carvedilol in gastric and intestinal environment was designed. Preparation of solid dispersion with porous silica ensured a significantly higher dissolution rate of carvedilol in acidic and alkaline media in comparison to pure drug, while granulation of that solid...

The purpose of this study was to investigate the influence of various powder agglomeration processes on tableting mixture flow and compaction properties. Four different granulation methods of the same model placebo formulation were tested at a semi-industrial scale and their properties were compared to those of the directly compressed mixture. The...

Solid dispersion particles of carvedilol (CAR) were prepared with porous silica (Sylysia 350) by the solvent evaporation method in a vacuum evaporator to ensure an effective pore-filling procedure. Two sets were prepared, each with various amounts of CAR in solid dispersions, and with the pore-filling process differing each time. Set A was prepared...

Impregnation of porous SiO(2) (Sylysia) with carvedilol from acetone solution was used to improve dissolution of this poorly water-soluble drug. Solvent evaporation in a vacuum evaporator and adsorption from acetone solution were the methods used to load various amounts of carvedilol into the Sylysia pores. The impregnated carriers were characteriz...

The use of polymeric polyelectrolytes as matrix-forming agents is far from optimally or fully understood. Polyelectrolyte carrageenan (CARR) matrices loaded with oppositely charged active substance doxazosin mesylate (DM) were investigated according to their water-uptake/erosion properties, in situ complexation ability of CARR with DM, and the poss...

When ionic polymers (polyelectrolytes) are used as excipients in pharmaceutical formulations, the properties of oppositely charged drugs may be strongly affected by the charge-charge interactions or complex formation. Usually these effects are considered as a negative event resulting in a drug-excipient incompatibility. Sometimes ionic interactions...

Physico-chemical properties of active substances such as solubility, dissolution rate, chemical stability, pharmaceutical processibility, etc. can be improved by salt formation of active substances. Characterization of physical properties of such salts is important for selection of an optimal salt having required biopharmaceutical properties, stabi...

The present study showed, that the crystal structures of R-isomer and the polymorphic form 1 of clopidrogrel hydrogensulphate S-isomer are very similar.

A quality-by-design (QbD) principle, including process analytical technology, is becoming the principal idea in drug development and manufacturing. The implementation of QbD into product development and manufacturing requires larger resources, both human and financial, however, large-scale production can be established in a more cost-effective mann...

Active pharmaceutical ingredients (API) are found in different solid state forms, which differ in their physicochemical and pharmacological properties. Properties of API on molecular scale has been traditionally limited to salt formation, isolation of different polymorphs, pseudopolymorphs or amorphous form, but in the last few years formation of p...

In pharmaceutical production we often deal with poorly flowable and poorly compressible formulations containing higher proportion of fine particles or the active substance. Such mixtures are usually necessary to be pre-processed with the appropriate agglomeration method. Basic knowledge of porosity and the primary mechanism of volume reduction or t...

The effects of process conditions and binder content on the process yield and pellet characteristics of two formulations prepared by melt pelletization in a laboratory-type high shear mixer were investigated. The formulations were prepared using Gelucire 50/13 and Lutrol F68 as meltable binders. The factors under investigation were impeller speed,...

The pharmaceutical industry is increasingly aware of the advantages of implementing a quality-by-design (QbD) principle, including process analytical technology, in drug development and manufacturing. Although the implementation of QbD into product development and manufacturing inevitably requires larger resources, both human and financial, large-s...

Our aim was to investigate the texture of hydrated biopolymer matrices that are now being considered in the design of pharmaceutical controlled-release dosage forms, in order to determine their influence on the release of an active compound. Prolonged release of pentoxifylline, a highly soluble drug, is needed for once-daily administration to achie...

The developement of new pharmaceutical excipients is proceeding simultaneously with developement of new active pharmaceutical ingredients. The purpose of the developement of new pharmaceutical excipients is to achieve desirable properties in dosage forms like controlled release, improved bioavailabilty, enhanced stability etc. An example of new exc...

The effect of dry granulation (roller compaction and slugging) on compactibility and tablet capping tendency in a formulation with macrolide antibiotic and microcrystalline cellulose (MCC) was investigated. Direct tableting of this formulation revealed a pronounced capping tendency. Both dry granulated systems exhibit better compactibility and sign...

The aim of this study was to evaluate melt pelletization in a high shear mixer as a method for the production of immediate release spherical agglomerates containing lansoprazole (CAS 103577-45-3), thereby increasing the dissolution rate of this poorly soluble model drug. The pellets were prepared in a laboratory-scale high-shear mixer, using two ty...

Different crystal forms and amorphous form of donepezil hydrochloride were prepared and characterized, using various analytical techniques. Hydrate form I is stable only at lower relative humidity (RH), while at higher RH it sorbes additional water. Forms II, III and V were identified as polymorphs, whereas form III is thermodynamically stable. For...

Export Date: 18 October 2014

The aim of our research was to apply experimental design methodology in the development and optimization of drug release methods. Diclofenac sodium (2-[(2,6-dichlorophenyl)amino]benzeneacetic acid monosodium salt) was selected as a model drug and Naklofen retard prolonged release tablets, containing 100 mg of diclofenac sodium, were chosen as a mod...

Only two crystal forms of pantoprazole sodium, i.e. mono and sesquihydrate, were described in the literature. The objective of the present work was to study the polymorphisms and pseudopolymorphism of pantoprazole sodium and to characterize already known and new crystal forms. Two additional hydrate forms; i.e. form A, form B and amorphous form wer...

Extrusion and spheronization (ES), direct rotor pelletizaton (DRP) and high-shear mixer pelletization (HSMP) are alternative techniques for matrix pellet production in process of wet agglomeration. The ES is the most widely used technique. In this study some of the physico-technological parameters of matrix pellets produced by DRP and HSMP were com...

In the present work different parameters, which influence the release of diclofenac sodium (2-[(2,6-dichlorophenyl)amino]benzeneacetic acid mono sodium salt) from lipophilic matrix prolonged release tablets, were investigated. Solubility characteristics of diclofenac sodium in aqueous media with various ionic strengths, ionic compositions and pH in...

Diclofenac sodium (2-[(2,6-dichlorophenyl)amino]benzeneacetic acid monosodium salt) was investigated as a low-solubility drug and Naklofen® retard prolonged release tablets, containing 100 mg of diclofenac sodium as a prolonged release lipophilic matrix system using factorial design approach. First, the solubility characteristics of diclofenac sodi...

In comparison with crystalline form, amorphous form of drug is thermodynamically less stable and its higher solubility represents the main advantage. Amorphous drugs can be produced by common technological processes including milling, freeze drying, spray drying, melt quenching, formation of solid dispersion, drying the solvated or hydrated crystal...

Lovastatin is a cholesterol-lowering agent, which competitively inhibits the enzyme HMG-CoA reductase. Several HPLC methods for its analysis have been developed but there is no report of its determination using capillary electrophoresis (CE). In this paper, we report the development of a simple CE method for lovastatin determination, which is selec...

The aim of this research was to develop and optimize the drug release determination of iron from iron prolonged release tablets. First, solubility characteristics of ferrous sulfate in different aqueous media with a pH in the range of 1 to 8 were studied. According to the results obtained different physicochemical conditions that influence drug rel...

Piroxicam polymorphism was extensively studied in the past. The objective of the present work was to evaluate polymorphism of piroxicam once again and to characterize the obtained crystal forms. Three polymorphic forms and one monohydrate form were obtained by crystallization from saturated solutions in various solvents. Polarity of solvents and cr...

The objective of the present study was to evaluate three formulation parameters for the application of polymethacrylic films from aqueous dispersions in order to obtain multiparticulate sustained release of diclofenac sodium. Film coating of pellet cores was performed in a laboratory fluid bed apparatus. The chosen independent variables, i.e. the c...

Recent advances in genomics and proteomics have resulted in the number of biologically active peptides and proteins. Their therapeutic use is limited by the lack of convenient methods for their effective delivery. Following oral administration protein drugs are namely rapidly degraded by the proteolytic enzymes and acidic conditions of the gastroin...

Enalaprilat is a typical angiotensin-converting enzyme inhibitor and is very poorly absorbed from the gastrointestinal tract. The aim of this study was to design and characterize poly-(lactide-co-glycolide) (PLGA) and polymethylmethacrylate (PMMA) nanoparticles containing enalaprilat and to evaluate the potential of these colloidal carriers for the...

Seven polymorphic modifications of doxazosin mesylate, designed as forms A, D, E, F, G, H, I, and the amorphous state were studied by thermal methods (TG and DSC), temperature resolved X-ray powder diffractometry, hot stage and scanning electron microscopy and by FT-IR spectroscopy. Amorphous form was obtained either by fast evaporation of the solv...

Thermodynamic of pseudopolymorphic (solvate) transitions is very complex. Technological processes should be followed very carefully due to possible phase transitions that can appear during the process. Preparation of solid dosage forms includes many processes where transitions can occur: grinding, mixing, wet granulation, drying, tabletting and dry...

Oxidative instability of the hydroxy methylglutaryl Co-A reductase inhibitor lovastatin in the solid state and stabilization with natural antioxidants (ascorbic acid, rutin, gallic acid, quercetin and caffeic acid) was investigated. Lovastatin in the solid state and binary mixtures with 10% (w/w), 25% (n/n), 12.5% (n/n) and 6.3% (n/n) of each of th...

Floating tablets offer a new possibility of treating the stomach infected with Helicobacter pylori. The objective of this study was to select suitable materials for the formulation of floating tablets with sustained drug release properties. In the preformulation studies, the differences between cellulose polymer (HEC, HPC, HPMC K4M, Avicel) isother...

Some technologically important physicochemical properties of lansoprazole were investigated. This compound is very unstable, especially in aqueous solutions with low pH. It has one acidic and two basic dissociation constants. Lansoprazole has relatively high solubility in solutions with high pH and is well partitioned from aqueous to n-octanol phas...

The present investigation concerns the development of the floating matrix tablets, which after oral administration are designed to prolong the gastric residence time, increase the drug bioavailability and diminish the side effects of irritating drugs. The importance of the composition optimisation, the technological process development for the prep...

For drug substances suitable for oral administration and sustained- release applications, a controlled and delayed gastric emptying of the dosage form would be advantageous. In the formulation of the floating polymer matrix tablets, different decisive physical and technological parameters were studied. Tablets containing hydroxypropyl cellulose HXF...

The application of a two-level back propagation type of neural network has been demonstrated for studying and optimization of diclofenac sodium dissolution from sustained release matrix tablets. The effects of three formulation components (cetyl alcohol, polyvinylpyrrolidone K-30 and magnesium stearate) on the dissolution rate were analyzed using t...

In this work we established that acyclovir exists in hydrated form and that the ratio between acyclovir and water molecules in the crystal structure is 3:2. The anhydrous crystalline form of acyclovir was also prepared. Both crystalline forms were examined by means of thermal analyses, X-ray powder diffraction, infrared spectroscopy, solubility and...

The effects of cetyl alcohol, polyvinylpyrrolidone K-30 and magnesium stearate amount on diclofenac sodium release from sustained release hydrophobic matrix tablets were evaluated using full 23 factorial design. Magnesium stearate has the most significant influence on drug release - it causes a decrease in dissolution rate followed by polyvinylpyrr...

Results of development of pentoxifylline prolonged release matrix tablets are presented in present article. High viscous sodium alginate in combination with three different calcium salts calcium chloride, calcium lactate-gluconate and dibasic calcium phosphate were used as a matrix former. Results of dissolution tests, DSC and FT-IR analysis have s...

Piroxicam is a highly potent anti-inflammatory and analgetically active drug the bioavailability of which is affected by its low solubility and dissolution rate. To modify its dissolution characteristics, solvent deposits of piroxicam and spin-labelled piroxicam (4-hydroxy-2-methyl-N-(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yi)-2 H-1,2-benzothiazine-...

The polymorphism of piroxicam has been discussed by many authors, but it is still uncertain in how many polymorphic and pseudopolymorphic modifications it can exist. The results of DSC and IR analyses confirm that simple crystallization from different solvents yields modifications designated as I and II and monohydrate. Depending on the cooling rat...

The thermal behaviour of piroxicam (white anhydrous form) and its surface deposit (50 wt.%) on amorphous silicon dioxide was studied using TG and DSC techniques. On the basis of isothermal TG, thermal decomposition kinetic data were obtained and reaction mechanisms were established according to Sharp's method. It was found that the thermal decompos...