Kyriakos Kachrimanis - Academia.edu (original) (raw)

Papers by Kyriakos Kachrimanis

Research paper thumbnail of Compatibility study between trandolapril and natural excipients used in solid dosage forms

Journal of Thermal Analysis and Calorimetry, 2013

Research paper thumbnail of Controlled release of 5-fluorouracil from microporous zeolites

Nanomedicine Nanotechnology Biology and Medicine, 2014

Zeolite particles with different pore diameter and particle size were loaded with the model antic... more Zeolite particles with different pore diameter and particle size were loaded with the model anticancer drug 5-fluorouracil. The loaded zeolites were characterized by means of SEM, XRD, DSC, XPS, N2 physisorption and FT-IR. Higher loading of 5-FU was observed for NaX-FAU than BEA. Release studies were carried out in HCl 0.1N. Release of 5-FU from NaX-FAU showed exponential-type behaviour with the drug fully released within 10 min. In the case of BEA, the kinetics of 5-FU shows a multi-step profile with prolonged release over time. Molecular dynamics simulations showed that diffusion of the drug molecule through the BEA framework is lower than for NaX-FAU due to increased van der Waals interaction between the drug and the framework. The effect of zeolitic particles on the viability of Caco-2 monolayers showed that the NaX-FAU particles cause a reduction of cell viability in a more pronounced way compared with the BEA particles. This article describes zeolite-based nanoparticles in generating time-controlled release of 5-FU from zeolite preparations for anti-cancer therapy.

Research paper thumbnail of Image analysis by pulse coupled neural networks (PCNN)-a novel approach in granule size characterization

Journal of Pharmacy and Pharmacology, 2007

Research paper thumbnail of Influence of hydrophilic polymers on the complexation of carbamazepine with hydroxypropyl-β-cyclodextrin

European Journal of Pharmaceutical Sciences, 2015

In this study binary carbamazepine-hydroxypropyl-β-cyclodextrin, as well as ternary carbamazepine... more In this study binary carbamazepine-hydroxypropyl-β-cyclodextrin, as well as ternary carbamazepine-hydroxypropyl-β-cyclodextrin-hydrophilic polymer systems were used to improve dissolution rate of carbamazepine. It has been shown that addition of hydrophilic polymers (Soluplus(®) and two types of hydroxypropyl methylcellulose-Metolose(®) 90SH-100 and Metolose(®) 65SH-1500) significantly increased solubilization capacity of hydroxypropyl-β-cyclodextrin for carbamazepine. Evaluation of carbamazepine-hydroxypropyl-β-cyclodextrin-hydrophilic polymer interactions using molecular modeling techniques showed interactions between carbamazepine, which dissociates from inclusion complexes and hydroxypropyl methylcellulose that can prevent crystallization of dissolved carbamazepine. These results can contribute to better understanding of drug-cyclodextrin-hydrophilic polymer interactions which are still not well understood. After evaluation of carbamazepine solubilization with hydroxypropyl-β-cyclodextrin and hydrophilic polymers, both binary carbamazepine-hydroxypropyl-β-cyclodextrin and ternary carbamazepine-hydroxypropyl-β-cyclodextrin-hydrophilic polymer systems were prepared by spray drying. The results of solid state characterization methods showed amorphous nature of carbamazepine in all spray dried systems, which together with the results of molecular modeling techniques indicates inclusion complex formation. Carbamazepine dissolution rate was significantly improved from spray dried formulations compared to pure drug. Binary carbamazepine-hydroxypropyl-β-cyclodextrin and ternary carbamazepine-hydroxypropyl-β-cyclodextrin-Soluplus(®) systems exhibited the fastest carbamazepine release, wherein the entire amount of carbamazepine was released during first 5 min.

Research paper thumbnail of Modeling the drugs' passive transfer in the body based on their chromatographic behavior

Journal of pharmaceutical and biomedical analysis, 2014

One of the most challenging aims in modern analytical chemistry and pharmaceutical analysis is to... more One of the most challenging aims in modern analytical chemistry and pharmaceutical analysis is to create models for drugs' behavior based on simulation experiments. Since drugs' effects are closely related to their molecular properties, numerous characteristics of drugs are used in order to acquire a model of passive absorption and transfer in the human body. Importantly, such direction in innovative bioanalytical methodologies is also of stressful need in the area of personalized medicine to implement nanotechnological and genomics advancements. Simulation experiments were carried out by examining and interpreting the chromatographic behavior of 113 analytes/drugs (400 observations) in RP-HPLC. The dataset employed for this purpose included 73 descriptors which are referring to the physicochemical properties of the mobile phase mixture in different proportions, the physicochemical properties of the analytes and the structural characteristics of their molecules. A series of ...

Research paper thumbnail of Solubility enhancement of desloratadine by solid dispersion in poloxamers

International journal of pharmaceutics, Jan 15, 2012

The present study investigates the possibility of using poloxamers as solubility and dissolution ... more The present study investigates the possibility of using poloxamers as solubility and dissolution rate enhancing agents of the poorly water soluble drug substance desloratadine that can be used for the preparation of immediate release tablet formulation. Two commercially available poloxamer grades (poloxamer P 188 and poloxamer P 407) were selected, and solid dispersions (SDs) containing different weight ratio of poloxamers and desloratadine were prepared by a low temperature melting method. All SDs were subjected to basic physicochemical characterization by thermal and vibrational spectroscopy methods in order to evaluate the efficiency of poloxamers as solubility enhancers. Immediate release tablets were prepared by direct compression of powdered solid dispersions according to a General Factorial Design, in order to evaluate the statistical significance of two formulation (X(1) - type of poloxamer in SD and X(2) - poloxamer ratio in SD) and one process variable (X(3) - compression ...

Research paper thumbnail of Dissolution rate enhancement and physicochemical characterization of carbamazepine-poloxamer solid dispersions

Pharmaceutical Development and Technology, 2015

Research paper thumbnail of Effects of Moisture and Residual Solvent on the Phase Stability of Orthorhombic Paracetamol

Pharmaceutical Research, 2008

At high relative humidity (RH), orthorhombic paracetamol (form II) crystallized from ethanol tran... more At high relative humidity (RH), orthorhombic paracetamol (form II) crystallized from ethanol transforms to monoclinic (form I) faster than such crystallized from the melt. The present study attempts to elucidate the reasons for this difference in stability. The transformation of form II was investigated by powder X-ray diffraction, optical microscopy, gravimetric moisture sorption, thermogravimetry, and vibrational spectroscopy. Solution-grown form II was found to be always contaminated with form I nuclei but still transforms much faster than corresponding physical mixtures of the pure forms in high RH, at a rate that is depending on the RH and the size of the crystals. A 0.1-0.6% w/w mass loss, inversely related to the initial monoclinic content, was observed during transformation of solution-grown form II, and was found to be due to residual ethanol that could not be removed by grinding, indicating incorporation by a solid solution mechanism. Moisture triggers the growth of existing form I nuclei but it exerts a weaker effect on nucleation, and the presence of residual ethanol greatly accelerates the transformation.

Research paper thumbnail of Controlled release of 5-fluorouracil from microporous zeolites

Nanomedicine: Nanotechnology, Biology and Medicine, 2014

Zeolite particles with different pore diameter and particle size were loaded with the model antic... more Zeolite particles with different pore diameter and particle size were loaded with the model anticancer drug 5-fluorouracil. The loaded zeolites were characterized by means of SEM, XRD, DSC, XPS, N2 physisorption and FT-IR. Higher loading of 5-FU was observed for NaX-FAU than BEA. Release studies were carried out in HCl 0.1N. Release of 5-FU from NaX-FAU showed exponential-type behaviour with the drug fully released within 10 min. In the case of BEA, the kinetics of 5-FU shows a multi-step profile with prolonged release over time. Molecular dynamics simulations showed that diffusion of the drug molecule through the BEA framework is lower than for NaX-FAU due to increased van der Waals interaction between the drug and the framework. The effect of zeolitic particles on the viability of Caco-2 monolayers showed that the NaX-FAU particles cause a reduction of cell viability in a more pronounced way compared with the BEA particles. This article describes zeolite-based nanoparticles in generating time-controlled release of 5-FU from zeolite preparations for anti-cancer therapy.

Research paper thumbnail of Image analysis by pulse coupled neural networks (PCNN)-a novel approach in granule size characterization

Journal of Pharmacy and Pharmacology, 2007

Research paper thumbnail of Combined effects of wetting, drying, and microcrystalline cellulose type on the mechanical strength and disintegration of pellets

Journal of Pharmaceutical Sciences, 2009

Effects of wetting and drying conditions on micromeritic, mechanical and disintegration propertie... more Effects of wetting and drying conditions on micromeritic, mechanical and disintegration properties of microcrystalline cellulose (MCC) pellets were evaluated. Extrusion/spheronization and three drying methods (fluidized bed, microwaves, and freeze drying) were applied using two wetting liquids (water or water-isopropanol 60:40 w/w) and three MCC types: (standard, silicified, and modified). Additionally, the effects of drying method were compared on highly porous pellets prepared by the incorporation and extraction of pore former (NaCl). It was found that the drying method has the greatest effect on the pellet size and porosity followed by the wetting liquid. The modification of MCC resulted in reduced water retention ability, implying hornification, increased porosity, reduced resistance to deformation and tensile strength of pellets. The disintegration time also decreased markedly due to the modification but only in the low porosity range <37%. Silicification increased greatly the disintegration time of the low porosity pellets (<14%). Combination of water-isopropanol, freeze drying and modified MCC gave the greatest increase in pellet size and porosity. The increase in pellet porosity caused exponential reduction in the resistance to deformation, tensile strength and disintegration time, as expected. Compared to fluidized bed, the freeze drying resulted in 20-30% higher porosity for pellets prepared without pore former and 6% for those with pore former, indicating the possibility of preparing highly porous pellets by employing freeze drying.

Research paper thumbnail of Tensile strength and disintegration of tableted silicified microcrystalline cellulose: Influences of interparticle bonding

Journal of Pharmaceutical Sciences, 2003

Research paper thumbnail of Quantitative analysis of paracetamol polymorphs in powder mixtures by FT-Raman spectroscopy and PLS regression

Journal of Pharmaceutical and Biomedical Analysis, 2007

Research paper thumbnail of Dynamic moisture sorption and desorption of standard and silicified microcrystalline cellulose

European Journal of Pharmaceutics and Biopharmaceutics, 2006

Moisture sorption and desorption isotherms of standard and silicified microcrystalline cellulose ... more Moisture sorption and desorption isotherms of standard and silicified microcrystalline cellulose (MCC and SMCC) were determined using an automatic multi-sample gravimetric analyzer, and compared by fitting different kinetic models, including the excess surface work model (ESW), the BET and GAB model, Young and Nelson model and recently developed parallel exponential kinetics (PEK) model. It was found that silicification affects the moisture sorption and desorption properties of SMCC mainly at high relative humidity (above 50% and 70%, respectively). In general, the differences in the moisture sorption and desorption properties of MCC and SMCC can be elucidated by the different kinetic models. Particularly the PEK model shows that hysteresis is related primarily to a fast sorption process, which corresponds to bound water, and secondarily to a slow process, which corresponds to sorption of free water and that SMCC acquires more water than MCC at RH higher than 50% by the slow (secondary) sorption process. A possible mechanism for this process is presumably the hydrolysis of SiO2 particles and formation of silanol groups that act as a water reservoir, preventing the accumulation of more water in the polymer matrix and thus may be protecting the structure of SMCC from undergoing irreversible structural changes that would impair its performance as an excipient.

Research paper thumbnail of Solid dispersions in the development of a nimodipine floating tablet formulation and optimization by artificial neural networks and genetic programming

European Journal of Pharmaceutics and Biopharmaceutics, 2011

Research paper thumbnail of “Apparent” Young’s elastic modulus and radial recovery for some tableted pharmaceutical excipients

European Journal of Pharmaceutical Sciences, 2004

Research paper thumbnail of Compact size and mechanical strength of pharmaceutical diluents

European Journal of Pharmaceutical Sciences, 2005

The effects of compact size and powder particle size on the axial compressive (sigma(C)) and diam... more The effects of compact size and powder particle size on the axial compressive (sigma(C)) and diametral tensile (sigma(T)) strength were evaluated, for three compressed pharmaceutical diluents (microcrystalline cellulose, MCC, calcium hydrogen phosphate dihydrate, CHPD, and pregelatinized starch, PGS) differing in deformational behaviour during compaction and testing. Cylindrical specimens of similar aspect ratio ( approximately 1) but different diameter (13, 10 and 5mm) and total porosity (0.35-0.05) were employed and the extrapolated and interpolated strength values, at zero and 0.15 porosity (sigma(C0) or sigma(T0) and sigma(C0.15) or sigma(T0.15)), were predicted by applying an exponential relation. The ratio of sigma(C0.15)/sigma(T0.15) was correlated to the corresponding percent radial elastic recovery (%RR). It was found that the changes of compressive and tensile strength with compact size were not characteristic and general. Specimen's size affected both extrapolated and interpolated values of sigma(C) and sigma(T) most significantly in the case of MCC, for which sigma(T) increased while sigma(C) decreased, as the compact size became smaller. Less significant was the effect of compact size on the interpolated value of compressive strength (sigma(C)) and the extrapolated value of tensile strength (sigma(T)) for PGS. For CHPD, no significant and characteristic effect of compact size was observed. Particle size significantly affected the interpolated values of sigma(T) for MCC and both sigma(C) and sigma(T) for CHPD; they all increased with decreasing particle size. The sigma(C0.15)/sigma(T0.15) ratio was affected significantly by the compact size only in the case of MCC and seems to be an indication of material elasto-plasticity, since PGS has by far the highest ratio, followed by MCC and CHPD. A correlation between sigma(C0.15)/sigma(T0.15) and %RR was established as was its dependence upon deformational behaviour.

Research paper thumbnail of Physicochemical characterization of nimodipine–polyethylene glycol solid dispersion systems

Drug Development and Industrial Pharmacy, 2013

This study investigates the solid-solid interactions between nimodipine (NIM) and polyethylene gl... more This study investigates the solid-solid interactions between nimodipine (NIM) and polyethylene glycol (PEG) of different mean molecular weights (PEG 2000, 4000 and 6000), in solid dispersion systems, applying differential scanning calorimetry (DSC), Fourier-Transform infrared spectroscopy, powder X-ray diffraction (PXRD), hot stage microscopy (HSM) and theoretical modeling by the Flory-Huggins (FH) solution theory. Phase diagrams constructed with the aid of DSC and FH solution theory showed sensitivity on the estimated values of the FH interaction parameter (χ). When χ is considered a constant number (χ = α, α ≠ 0), formation of a eutectic mixture is predicted in the 70-80% w/w PEG concentration region, while when χ was considered as a function of concentration and temperature (χ = f(φ,Τ)), the model predicts the formation of monotectic systems. Construction of more precise phase diagrams by HSM to the aid of Kofler's "contact preparation" method confirmed the monotectic nature of the examined systems. Studies on NIM's re-crystallization process in the solid dispersions revealed a strong dependence of the crystallization rate, as well as the resulting crystal form, on the mean molecular weight and concentration of PEG: NIM crystallization rates decrease as PEG's MW increases, while NIM mod II crystals predominate in dispersions prepared at temperatures above NIM's liquidus and growth of NIM mod I prevailing in PEG-rich samples.

Research paper thumbnail of The influence of spiral jet-milling on the physicochemical properties of carbamazepine form III crystals: Quality by design approach

Chemical Engineering Research and Design, 2014

Research paper thumbnail of Release of ibuprofen from spherical crystal agglomerates prepared using the solvent-change technique in the presence of Eudragit polymers and from corresponding compacts

Cited By (since 1996):5, Export Date: 6 June 2013, Source: Scopus, Language of Original Document:... more Cited By (since 1996):5, Export Date: 6 June 2013, Source: Scopus, Language of Original Document: English, Correspondence Address: Malamataris, S.; Dept. of Pharmaceutical Technology, School of Pharmacy, University of Thessaloniki, Thessaloniki 54006, Greece, References: Inseln, P.P.A., Analgesic-antipyretics and anti-inflammatory agents (1990), pp. 665-666. , Goodman and Gilman's The Pharmacological Basis of Therapeutics, A.G. Gilman, T.W. Rall, A.S. Nies and P. Taylor Eds., 8th ed., Pergamon Press, New YorkKawashima, Y., Niwa, T., Handa, T., Takeuchi, H., Iwamoto, T., Itoh, Y., Preparation of prolonged-release spherical micro-matrix of ibuprofen with acrylic polymer by the emulsion-solvent diffusion method for improving bioavailability (1989) Chem. Pharm. Bull., 37 (2), pp. 425-429;

Research paper thumbnail of Compatibility study between trandolapril and natural excipients used in solid dosage forms

Journal of Thermal Analysis and Calorimetry, 2013

Research paper thumbnail of Controlled release of 5-fluorouracil from microporous zeolites

Nanomedicine Nanotechnology Biology and Medicine, 2014

Zeolite particles with different pore diameter and particle size were loaded with the model antic... more Zeolite particles with different pore diameter and particle size were loaded with the model anticancer drug 5-fluorouracil. The loaded zeolites were characterized by means of SEM, XRD, DSC, XPS, N2 physisorption and FT-IR. Higher loading of 5-FU was observed for NaX-FAU than BEA. Release studies were carried out in HCl 0.1N. Release of 5-FU from NaX-FAU showed exponential-type behaviour with the drug fully released within 10 min. In the case of BEA, the kinetics of 5-FU shows a multi-step profile with prolonged release over time. Molecular dynamics simulations showed that diffusion of the drug molecule through the BEA framework is lower than for NaX-FAU due to increased van der Waals interaction between the drug and the framework. The effect of zeolitic particles on the viability of Caco-2 monolayers showed that the NaX-FAU particles cause a reduction of cell viability in a more pronounced way compared with the BEA particles. This article describes zeolite-based nanoparticles in generating time-controlled release of 5-FU from zeolite preparations for anti-cancer therapy.

Research paper thumbnail of Image analysis by pulse coupled neural networks (PCNN)-a novel approach in granule size characterization

Journal of Pharmacy and Pharmacology, 2007

Research paper thumbnail of Influence of hydrophilic polymers on the complexation of carbamazepine with hydroxypropyl-β-cyclodextrin

European Journal of Pharmaceutical Sciences, 2015

In this study binary carbamazepine-hydroxypropyl-β-cyclodextrin, as well as ternary carbamazepine... more In this study binary carbamazepine-hydroxypropyl-β-cyclodextrin, as well as ternary carbamazepine-hydroxypropyl-β-cyclodextrin-hydrophilic polymer systems were used to improve dissolution rate of carbamazepine. It has been shown that addition of hydrophilic polymers (Soluplus(®) and two types of hydroxypropyl methylcellulose-Metolose(®) 90SH-100 and Metolose(®) 65SH-1500) significantly increased solubilization capacity of hydroxypropyl-β-cyclodextrin for carbamazepine. Evaluation of carbamazepine-hydroxypropyl-β-cyclodextrin-hydrophilic polymer interactions using molecular modeling techniques showed interactions between carbamazepine, which dissociates from inclusion complexes and hydroxypropyl methylcellulose that can prevent crystallization of dissolved carbamazepine. These results can contribute to better understanding of drug-cyclodextrin-hydrophilic polymer interactions which are still not well understood. After evaluation of carbamazepine solubilization with hydroxypropyl-β-cyclodextrin and hydrophilic polymers, both binary carbamazepine-hydroxypropyl-β-cyclodextrin and ternary carbamazepine-hydroxypropyl-β-cyclodextrin-hydrophilic polymer systems were prepared by spray drying. The results of solid state characterization methods showed amorphous nature of carbamazepine in all spray dried systems, which together with the results of molecular modeling techniques indicates inclusion complex formation. Carbamazepine dissolution rate was significantly improved from spray dried formulations compared to pure drug. Binary carbamazepine-hydroxypropyl-β-cyclodextrin and ternary carbamazepine-hydroxypropyl-β-cyclodextrin-Soluplus(®) systems exhibited the fastest carbamazepine release, wherein the entire amount of carbamazepine was released during first 5 min.

Research paper thumbnail of Modeling the drugs' passive transfer in the body based on their chromatographic behavior

Journal of pharmaceutical and biomedical analysis, 2014

One of the most challenging aims in modern analytical chemistry and pharmaceutical analysis is to... more One of the most challenging aims in modern analytical chemistry and pharmaceutical analysis is to create models for drugs' behavior based on simulation experiments. Since drugs' effects are closely related to their molecular properties, numerous characteristics of drugs are used in order to acquire a model of passive absorption and transfer in the human body. Importantly, such direction in innovative bioanalytical methodologies is also of stressful need in the area of personalized medicine to implement nanotechnological and genomics advancements. Simulation experiments were carried out by examining and interpreting the chromatographic behavior of 113 analytes/drugs (400 observations) in RP-HPLC. The dataset employed for this purpose included 73 descriptors which are referring to the physicochemical properties of the mobile phase mixture in different proportions, the physicochemical properties of the analytes and the structural characteristics of their molecules. A series of ...

Research paper thumbnail of Solubility enhancement of desloratadine by solid dispersion in poloxamers

International journal of pharmaceutics, Jan 15, 2012

The present study investigates the possibility of using poloxamers as solubility and dissolution ... more The present study investigates the possibility of using poloxamers as solubility and dissolution rate enhancing agents of the poorly water soluble drug substance desloratadine that can be used for the preparation of immediate release tablet formulation. Two commercially available poloxamer grades (poloxamer P 188 and poloxamer P 407) were selected, and solid dispersions (SDs) containing different weight ratio of poloxamers and desloratadine were prepared by a low temperature melting method. All SDs were subjected to basic physicochemical characterization by thermal and vibrational spectroscopy methods in order to evaluate the efficiency of poloxamers as solubility enhancers. Immediate release tablets were prepared by direct compression of powdered solid dispersions according to a General Factorial Design, in order to evaluate the statistical significance of two formulation (X(1) - type of poloxamer in SD and X(2) - poloxamer ratio in SD) and one process variable (X(3) - compression ...

Research paper thumbnail of Dissolution rate enhancement and physicochemical characterization of carbamazepine-poloxamer solid dispersions

Pharmaceutical Development and Technology, 2015

Research paper thumbnail of Effects of Moisture and Residual Solvent on the Phase Stability of Orthorhombic Paracetamol

Pharmaceutical Research, 2008

At high relative humidity (RH), orthorhombic paracetamol (form II) crystallized from ethanol tran... more At high relative humidity (RH), orthorhombic paracetamol (form II) crystallized from ethanol transforms to monoclinic (form I) faster than such crystallized from the melt. The present study attempts to elucidate the reasons for this difference in stability. The transformation of form II was investigated by powder X-ray diffraction, optical microscopy, gravimetric moisture sorption, thermogravimetry, and vibrational spectroscopy. Solution-grown form II was found to be always contaminated with form I nuclei but still transforms much faster than corresponding physical mixtures of the pure forms in high RH, at a rate that is depending on the RH and the size of the crystals. A 0.1-0.6% w/w mass loss, inversely related to the initial monoclinic content, was observed during transformation of solution-grown form II, and was found to be due to residual ethanol that could not be removed by grinding, indicating incorporation by a solid solution mechanism. Moisture triggers the growth of existing form I nuclei but it exerts a weaker effect on nucleation, and the presence of residual ethanol greatly accelerates the transformation.

Research paper thumbnail of Controlled release of 5-fluorouracil from microporous zeolites

Nanomedicine: Nanotechnology, Biology and Medicine, 2014

Zeolite particles with different pore diameter and particle size were loaded with the model antic... more Zeolite particles with different pore diameter and particle size were loaded with the model anticancer drug 5-fluorouracil. The loaded zeolites were characterized by means of SEM, XRD, DSC, XPS, N2 physisorption and FT-IR. Higher loading of 5-FU was observed for NaX-FAU than BEA. Release studies were carried out in HCl 0.1N. Release of 5-FU from NaX-FAU showed exponential-type behaviour with the drug fully released within 10 min. In the case of BEA, the kinetics of 5-FU shows a multi-step profile with prolonged release over time. Molecular dynamics simulations showed that diffusion of the drug molecule through the BEA framework is lower than for NaX-FAU due to increased van der Waals interaction between the drug and the framework. The effect of zeolitic particles on the viability of Caco-2 monolayers showed that the NaX-FAU particles cause a reduction of cell viability in a more pronounced way compared with the BEA particles. This article describes zeolite-based nanoparticles in generating time-controlled release of 5-FU from zeolite preparations for anti-cancer therapy.

Research paper thumbnail of Image analysis by pulse coupled neural networks (PCNN)-a novel approach in granule size characterization

Journal of Pharmacy and Pharmacology, 2007

Research paper thumbnail of Combined effects of wetting, drying, and microcrystalline cellulose type on the mechanical strength and disintegration of pellets

Journal of Pharmaceutical Sciences, 2009

Effects of wetting and drying conditions on micromeritic, mechanical and disintegration propertie... more Effects of wetting and drying conditions on micromeritic, mechanical and disintegration properties of microcrystalline cellulose (MCC) pellets were evaluated. Extrusion/spheronization and three drying methods (fluidized bed, microwaves, and freeze drying) were applied using two wetting liquids (water or water-isopropanol 60:40 w/w) and three MCC types: (standard, silicified, and modified). Additionally, the effects of drying method were compared on highly porous pellets prepared by the incorporation and extraction of pore former (NaCl). It was found that the drying method has the greatest effect on the pellet size and porosity followed by the wetting liquid. The modification of MCC resulted in reduced water retention ability, implying hornification, increased porosity, reduced resistance to deformation and tensile strength of pellets. The disintegration time also decreased markedly due to the modification but only in the low porosity range <37%. Silicification increased greatly the disintegration time of the low porosity pellets (<14%). Combination of water-isopropanol, freeze drying and modified MCC gave the greatest increase in pellet size and porosity. The increase in pellet porosity caused exponential reduction in the resistance to deformation, tensile strength and disintegration time, as expected. Compared to fluidized bed, the freeze drying resulted in 20-30% higher porosity for pellets prepared without pore former and 6% for those with pore former, indicating the possibility of preparing highly porous pellets by employing freeze drying.

Research paper thumbnail of Tensile strength and disintegration of tableted silicified microcrystalline cellulose: Influences of interparticle bonding

Journal of Pharmaceutical Sciences, 2003

Research paper thumbnail of Quantitative analysis of paracetamol polymorphs in powder mixtures by FT-Raman spectroscopy and PLS regression

Journal of Pharmaceutical and Biomedical Analysis, 2007

Research paper thumbnail of Dynamic moisture sorption and desorption of standard and silicified microcrystalline cellulose

European Journal of Pharmaceutics and Biopharmaceutics, 2006

Moisture sorption and desorption isotherms of standard and silicified microcrystalline cellulose ... more Moisture sorption and desorption isotherms of standard and silicified microcrystalline cellulose (MCC and SMCC) were determined using an automatic multi-sample gravimetric analyzer, and compared by fitting different kinetic models, including the excess surface work model (ESW), the BET and GAB model, Young and Nelson model and recently developed parallel exponential kinetics (PEK) model. It was found that silicification affects the moisture sorption and desorption properties of SMCC mainly at high relative humidity (above 50% and 70%, respectively). In general, the differences in the moisture sorption and desorption properties of MCC and SMCC can be elucidated by the different kinetic models. Particularly the PEK model shows that hysteresis is related primarily to a fast sorption process, which corresponds to bound water, and secondarily to a slow process, which corresponds to sorption of free water and that SMCC acquires more water than MCC at RH higher than 50% by the slow (secondary) sorption process. A possible mechanism for this process is presumably the hydrolysis of SiO2 particles and formation of silanol groups that act as a water reservoir, preventing the accumulation of more water in the polymer matrix and thus may be protecting the structure of SMCC from undergoing irreversible structural changes that would impair its performance as an excipient.

Research paper thumbnail of Solid dispersions in the development of a nimodipine floating tablet formulation and optimization by artificial neural networks and genetic programming

European Journal of Pharmaceutics and Biopharmaceutics, 2011

Research paper thumbnail of “Apparent” Young’s elastic modulus and radial recovery for some tableted pharmaceutical excipients

European Journal of Pharmaceutical Sciences, 2004

Research paper thumbnail of Compact size and mechanical strength of pharmaceutical diluents

European Journal of Pharmaceutical Sciences, 2005

The effects of compact size and powder particle size on the axial compressive (sigma(C)) and diam... more The effects of compact size and powder particle size on the axial compressive (sigma(C)) and diametral tensile (sigma(T)) strength were evaluated, for three compressed pharmaceutical diluents (microcrystalline cellulose, MCC, calcium hydrogen phosphate dihydrate, CHPD, and pregelatinized starch, PGS) differing in deformational behaviour during compaction and testing. Cylindrical specimens of similar aspect ratio ( approximately 1) but different diameter (13, 10 and 5mm) and total porosity (0.35-0.05) were employed and the extrapolated and interpolated strength values, at zero and 0.15 porosity (sigma(C0) or sigma(T0) and sigma(C0.15) or sigma(T0.15)), were predicted by applying an exponential relation. The ratio of sigma(C0.15)/sigma(T0.15) was correlated to the corresponding percent radial elastic recovery (%RR). It was found that the changes of compressive and tensile strength with compact size were not characteristic and general. Specimen's size affected both extrapolated and interpolated values of sigma(C) and sigma(T) most significantly in the case of MCC, for which sigma(T) increased while sigma(C) decreased, as the compact size became smaller. Less significant was the effect of compact size on the interpolated value of compressive strength (sigma(C)) and the extrapolated value of tensile strength (sigma(T)) for PGS. For CHPD, no significant and characteristic effect of compact size was observed. Particle size significantly affected the interpolated values of sigma(T) for MCC and both sigma(C) and sigma(T) for CHPD; they all increased with decreasing particle size. The sigma(C0.15)/sigma(T0.15) ratio was affected significantly by the compact size only in the case of MCC and seems to be an indication of material elasto-plasticity, since PGS has by far the highest ratio, followed by MCC and CHPD. A correlation between sigma(C0.15)/sigma(T0.15) and %RR was established as was its dependence upon deformational behaviour.

Research paper thumbnail of Physicochemical characterization of nimodipine–polyethylene glycol solid dispersion systems

Drug Development and Industrial Pharmacy, 2013

This study investigates the solid-solid interactions between nimodipine (NIM) and polyethylene gl... more This study investigates the solid-solid interactions between nimodipine (NIM) and polyethylene glycol (PEG) of different mean molecular weights (PEG 2000, 4000 and 6000), in solid dispersion systems, applying differential scanning calorimetry (DSC), Fourier-Transform infrared spectroscopy, powder X-ray diffraction (PXRD), hot stage microscopy (HSM) and theoretical modeling by the Flory-Huggins (FH) solution theory. Phase diagrams constructed with the aid of DSC and FH solution theory showed sensitivity on the estimated values of the FH interaction parameter (χ). When χ is considered a constant number (χ = α, α ≠ 0), formation of a eutectic mixture is predicted in the 70-80% w/w PEG concentration region, while when χ was considered as a function of concentration and temperature (χ = f(φ,Τ)), the model predicts the formation of monotectic systems. Construction of more precise phase diagrams by HSM to the aid of Kofler's "contact preparation" method confirmed the monotectic nature of the examined systems. Studies on NIM's re-crystallization process in the solid dispersions revealed a strong dependence of the crystallization rate, as well as the resulting crystal form, on the mean molecular weight and concentration of PEG: NIM crystallization rates decrease as PEG's MW increases, while NIM mod II crystals predominate in dispersions prepared at temperatures above NIM's liquidus and growth of NIM mod I prevailing in PEG-rich samples.

Research paper thumbnail of The influence of spiral jet-milling on the physicochemical properties of carbamazepine form III crystals: Quality by design approach

Chemical Engineering Research and Design, 2014

Research paper thumbnail of Release of ibuprofen from spherical crystal agglomerates prepared using the solvent-change technique in the presence of Eudragit polymers and from corresponding compacts

Cited By (since 1996):5, Export Date: 6 June 2013, Source: Scopus, Language of Original Document:... more Cited By (since 1996):5, Export Date: 6 June 2013, Source: Scopus, Language of Original Document: English, Correspondence Address: Malamataris, S.; Dept. of Pharmaceutical Technology, School of Pharmacy, University of Thessaloniki, Thessaloniki 54006, Greece, References: Inseln, P.P.A., Analgesic-antipyretics and anti-inflammatory agents (1990), pp. 665-666. , Goodman and Gilman's The Pharmacological Basis of Therapeutics, A.G. Gilman, T.W. Rall, A.S. Nies and P. Taylor Eds., 8th ed., Pergamon Press, New YorkKawashima, Y., Niwa, T., Handa, T., Takeuchi, H., Iwamoto, T., Itoh, Y., Preparation of prolonged-release spherical micro-matrix of ibuprofen with acrylic polymer by the emulsion-solvent diffusion method for improving bioavailability (1989) Chem. Pharm. Bull., 37 (2), pp. 425-429;