The aim of this study was to determine the relationship between the breaking force of lactose, gl... more The aim of this study was to determine the relationship between the breaking force of lactose, glucose and mannitol tablets and the pore structure characterised by numeric porosity parameters: total pore volume, total pore surface area, mean pore diameter, median pore diameter and volume-size distribution of pores, obtained by mercury porosimetry. A clear overall relationship was found between breaking force of tablets and the median of the cumulative pore volume-pore diameter curve and pore volume-size distribution. The dependence of the breaking force on total surface area of pores was less evident. Fragmentation of granules contributes to the creation of large intergranular and intragranular pores, and further fragmentation and plastic deformation of the primary particles contributes to their reduction in number and size. According to pore volume-size distributions, the decrease in the volume of large pores and the shift of the maximum for volume-size distribution towards smaller pore diameter were related to the increased breaking force of tablets.
The effect of compression force, compression speed and the amount of granulation liquid on the po... more The effect of compression force, compression speed and the amount of granulation liquid on the porosity parameters determined from lactose, glucose and mannitol tablets by high-pressure mercury porosimetry was investigated. Compression force affected all parameters measured, except the total pore surface area of lactose tablets. The changes in tablet microstructure with increasing compression force were particularly well detected from the pore volume size distributions of tablets. Compression speed affected the total pore volume of lactose tablets, both mean and median pore diameters of lactose tablets and mannitol tablets compressed from granules produced with a low amount of liquid, and the median pore diameter of glucose tablets. The compression speed dependence of these parameters was a sign of the time-dependent deformation of materials during compression. The amount of granulation liquid affected the total pore surface area of lactose and mannitol tablets. With a high amount of liquid, the surface area of pores was greater. The mean pore size of all tablets and the median pore diameter of mannitol tablets were smaller when a high amount of granulation liquid was used. Even when compressed with a high force, the pore volume size distributions of mannitol tablets with a low amount of granulation liquid were broader and the maxima were at larger pore diameters. It was concluded that each porosity parameter measured characterised the pore structure of compressed tablets from a different aspect. Thus, the use of all porosity parameters proved to be useful.
Journal of parenteral science and technology: a publication of the Parenteral Drug Association
The effect of sterilization on the number of particles released from five different types of rubb... more The effect of sterilization on the number of particles released from five different types of rubber stoppers, as well as on their surface roughness and elemental composition before and after sterilization is described. The stoppers were immersed in 200 ml of 0.9% sodium chloride solution in conical flasks. The number of particles released into the sodium chloride solution was measured by Coulter Counter. The surface roughness and the elemental composition of the stoppers were determined by SEM/EDX. All measurements were made both before and after sterilization at 121 degrees C to F0 15 mins. The number of particles released from a stopper during sterilization varies considerably between different stoppers and even between different batches of the same stopper. The only non-siliconized stopper in this study performed well. The absence of surface siliconization may have contributed to this performance. The scanning electron micrographs revealed well the differences in the surface roughness of the stoppers. The sterilization generally increases the surface roughness of the samples. The x-ray microanalysis revealed that the elemental composition of the stoppers may vary not only between different types of stoppers but also between different batches of the same stopper.
The effect of the amount of granulation liquid, compression speed and maximum compression force o... more The effect of the amount of granulation liquid, compression speed and maximum compression force on then 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 compressibility than glucose granules. Mannitol granules produced the hardest tablets and lactose and glucose the weakest. The change in the amount of granulation liquid caused changes both in the granule porosity and in the amount of binder; this was attributed to differences in tablet strength. All parameters studied were relatively insensitive to changing speeds of compression in the range used, except for the breaking force of mannitol tablets, which was greatest with the lowest speed of compression. All granule masses showed a relatively good continuous flow suitable for table production. Tablets compressed from lactose granules had the best uniformity of weight of the tablets studied.
Despite a global interest in companion animal pharmaceuticals, feline peroral medication is still... more Despite a global interest in companion animal pharmaceuticals, feline peroral medication is still lacking in palatable and voluntarily acceptable drugs of suitable size and attractive taste. As a consequence, treating cats with canine or human medicinal products has weakened patient compliance and treatment commitment resulting in many pet cats going untreated. In the future, the companion animal pharmaceutical business is expected to focus particularly on cats and the development of palatable feline medication. Based on this, the overall aim of this study was to facilitate voluntary drug administration to felines. Specifically the aim was to develop sophisticated and tailor-made feline medicinal products, in the form of mini-tablets, focusing on flavors palatable to felines. Rapid preformulation compatibility and stability screening tests of synthetic flavors were carried out using readily available oral solid form excipients. On the basis that felines are carnivorous, L-methionine...
ABSTRACT Purpose This study identifies key determinants of new product launch success, examines t... more ABSTRACT Purpose This study identifies key determinants of new product launch success, examines their role and impact on launch performance and links them to the different stages of product life cycle in the pharmaceutical new product launch context. Methods Survey data from pharmaceutical industry was analysed with multivariate data analysis using latent variable regression modelling followed by the calculation of selectivity ratios to reveal the most informative determinants. Results The results distinguish between the determinants driving financial new product launch success and those driving customer acceptance. Whereas financial success is driven by strategic choices and tactical decisions, the relationship approach is vital in fostering customer acceptance at different phases of the innovation diffusion. Product advantage and relationship marketing activities contribute to achieving key opinion leaders’ acceptance in the early phase, while the accumulated market-based assets largely determine acceptance of a majority of other target customers in the later phase. Furthermore, launch performance is enhanced by a relationship-oriented company culture. Conclusions The study emphasises the significance of relational aspects in new product launches and provides both important theoretical insights and managerial implications for commercialising new pharmaceutical products.
The present study shows that roller compaction (RC) can successfully be used as a granulation met... more The present study shows that roller compaction (RC) can successfully be used as a granulation method to prepare hydroxypropyl methylcellulose (HPMC)-based extended release matrix tablets containing a high drug load, both for materials deforming mainly by fragmentation (paracetamol) as for those having mainly plastic deformation (ibuprofen). The combined effect of RC process variables and composition on the manufacturability of HPMC tablets was investigated. Standard wet granulation grade HPMC was compared with a larger particle size direct compressible HPMC grade. Higher roll pressure was found to result in larger paracetamol granules and narrower granule particle size distributions, especially for formulations containing smaller size HPMC. However, for ibuprofen, no clear effect of roll pressure was observed. High roll pressure also resulted in denser ribbon and less bypass fines during RC. Loss of compactibility was observed for granules compared to powder blends, which was found ...
Both clodronate and bioactive glass are mostly used alone as treatment in various bone diseases b... more Both clodronate and bioactive glass are mostly used alone as treatment in various bone diseases but, they are also known to have beneficial effects in dental application. The same processes that lead to loss of bone can also result in alveolar bone loss. The object of this study was to define the optimal combination of clodronate and bioactive glass (BAG) to be used locally in dentistry. The evaluation was based on measurements and solid state properties obtained with pH, scanning electron microscopy (SEM), differential scanning calorimetric (DSC), X-ray powder diffraction (XRPD), Fourier transform infrared spectroscopy (FTIR) and Focused-ion beam (FIB) and energy dispersive X-ray spectroscopic (EDS) mapping. The results indicate that if too much calcium clodronate precipitation is formed, the activity of BAG is affected negatively. As there is more reaction surface to form calcium clodronate, similar to the amount of clodronate present, this reduces the bioactivity of BAG. Therefore, in dental treatment the most suitable BAG and clodronate combination product would have apatite (HA, hydroxyapatite) formation ability and amount of clodronate enough to enhance the bioactivity of BAG allowing HA formation. Based on combinations investigated, the one with 200 mg clodronate and 1 g BAG with particle size 0.5-0.8 mm was chosen to be the most promising for local dental application.
Cytokines are messenger proteins that regulate the proliferation and differentiation of cells and... more Cytokines are messenger proteins that regulate the proliferation and differentiation of cells and control immune responses. Interferons, interleukins, and growth factors have applications in cancer, autoimmune, and viral disease treatment. The cytokines are susceptible to chemical and physical instability. This article reviews the structure and stability issues of clinically used cytokines, as well as formulation strategies for improved stability. Some general aspects for identifying most probable stability concerns, selecting excipients, and developing stable cytokine formulations are presented. The vast group of cytokines offers possibilities for new biopharmaceuticals. The formulation approaches of the current cytokine products could facilitate development of new biopharmaceuticals. C
Bone tissue engineering is a rapidly growing area of research involving the use of bioactive glas... more Bone tissue engineering is a rapidly growing area of research involving the use of bioactive glass (BG) alone and in combination with different materials. The objective of this study was to investigate the interaction of BG with clodronate. Characterisation of the interaction between BG and clodronate was undertaken using; scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), Fourier transform Raman spectroscopy and Fourier transform infrared spectroscopy (FTIR). The interaction was examined in vitro with respect to the ion exchange and surface modification on the surface of the bioactive glass in the combination product. The results showed clear ion exchange enhancement by clodronate. Additionally, this ion exchange was more extensive and long lasting in the combination product than in BG alone. Clodronate promotes the activity of the BG and a calcium clodronate precipitation is formed. It can be assumed that this solid combination could be used in clinical applications. Therefore, it can be concluded that clodronate makes a beneficial environment for BG and could enhance also the apatite formation of BG.
Purpose The purpose of this study is to show how disaccharides differ in their ability to protect... more Purpose The purpose of this study is to show how disaccharides differ in their ability to protect lyophilized βgalactosidase from enzymatic activity loss and secondary structure changes during storage. Methods β-galactosidase was lyophilized with trehalose, sucrose, cellobiose or melibiose at 2:1, 20:1 and 40:1 excipient/ protein weight ratios, and stored up to 90 days at 45°C. Protein enzymatic activity was studied using o-nitrophenyl-β-D-galactopyranoside cleavage test, and its secondary structure in lyophilizates analyzed using Fourier transform infrared spectroscopy. The crystallization tendencies, glass transition temperatures and water contents of lyophilizates were evaluated using x-ray powder diffractometry, differential scanning calorimetry and thermogravimetry, respectively. Results The enzymatic activity of β-galactosidase decreased more slowly in lyophilizates containing trehalose or melibiose at 2:1 excipient/protein weight ratio when compared to those containing sucrose or cellobiose. Similar behavior was observed when analyzing the protein's secondary structure in lyophilizates. In 20:1 and 40:1 excipient/protein weight ratio lyophilizates the decrease of enzymatic activity was less dependent on the excipient, but activity was always amongst the highest in melibiose lyophilizates. Conclusions Melibiose was shown to be effective in protecting lyophilized β-galactosidase during storage. The protein secondary structure was shown to change at comparable rate in lyophilizates as its enzymatic activity after rehydration.
The aim of the present study was to prepare controlled-release tablets of poorly-soluble drug, fe... more The aim of the present study was to prepare controlled-release tablets of poorly-soluble drug, felodipine, and various erodable lipophilic excipients. Spray chilling was used to formulate the drug and the excipients into solid dispersion microparticles, which were then compressed. The microparticles were characterised by Fourier transform infrared spectroscopy, hot-stage microscopy, scanning electron microscopy, and image analysis. The amine and the carbonyl groups of felodipine formed hydrogen bonds with the carriers. The shape of the particles was spherical with the median particle diameter ranging from 25 to 35 mm. Surprisingly, the degree of crystallinity in felodipine and the ease of tablet disintegration played a more significant role on the felodipine dissolution rate than the matrix lipophilicity. Felodipine release rate was slowest from the least lipophilic tablets. #
The rheological properties of silicified microcrystalline cellulose (Prosolv 50) were compared wi... more The rheological properties of silicified microcrystalline cellulose (Prosolv 50) were compared with those of standard grades of microcrystalline cellulose (Emcocel 50 and Avicel PH 101). Cellulose samples were analyzed using nitrogen adsorption together with particle size, flowability, density and swelling volume studies. The rheological behaviour of the wet powder masses was studied as a function of mixing time using a mixer torque rheometer (MTR). Silicified microcrystalline cellulose exhibited improved flow characteristics and increased specific surface area compared to standard microcrystalline cellulose grades. Although the silicification process affected the swelling properties and, furthermore, the mixing kinetics of microcrystalline cellulose, the source of the microcrystalline cellulose had a stronger influence than silicification on the liquid requirement at peak torque.
Formation of solid solution particles in the Solution Enhanced Dispersion by Supercritical fluids... more Formation of solid solution particles in the Solution Enhanced Dispersion by Supercritical fluids (SEDS) process from a model drug and two different types of carriers, mannitol and Eudragit † E100 was evaluated. The crystal properties of samples and molecular interactions were investigated with DSC and FTIR, respectively. The effect of cocrystallisation of drug and mannitol on dissolution rate was studied. Even if a true one-phase solid dispersion was not obtained, the crystal structure of both drug and mannitol was mutually affected by the presence of the other. The drug was not in highly crystalline form in the co-precipitates. The interactions between the drug and mannitol could also be identified as hydrogen bonding between the amine or hydroxyl groups of the drug and the hydroxyl groups of mannitol. These interactions and changes in the crystal structure are probably directly related to the increase in the dissolution rate observed. A true solid solution was obtained when the drug was co-processed with Eudragit † E100. A clear interaction between the acid hydroxyl group of the drug and the basic carbonyl group on the Eudragit † E100 was observed. SEDS was shown to be an effective process for forming intimate blends and solid solutions for the drug and two different types of carriers. #
In this research, the tableting properties of ␣-melibiose monohydrate were studied. Melibiose is ... more In this research, the tableting properties of ␣-melibiose monohydrate were studied. Melibiose is a disaccharide which bears structural resemblance to lactose, because they both consist of galactose and glucose monosaccharide subunits. Compactibility and deformation behavior of two melibiose batches from different suppliers were studied and compared with ␣-lactose monohydrate and some other typical tableting excipients. Differences in the deformation behavior were determined comparing the shape of the Heckel plots, the yield pressure values and the strain rate sensitivity (SRS) indexes. In addition, the effect of moisture on the tabletability was studied. According to the yield pressures and SRS indexes melibiose was concluded to be fragmenting, even at higher degree than lactose monohydrate. However, the overall deformation behavior of melibiose was found to be similar to that of lactose monohydrate. Increase in moisture content resulted in higher tensile strengths of tablets for both melibiose batches, but it seemed to have more effect on compactibility of the other batch. In conclusion, melibiose has potential to be used as an excipient in tablet formulations.
The aim of this study was to determine the relationship between the breaking force of lactose, gl... more The aim of this study was to determine the relationship between the breaking force of lactose, glucose and mannitol tablets and the pore structure characterised by numeric porosity parameters: total pore volume, total pore surface area, mean pore diameter, median pore diameter and volume-size distribution of pores, obtained by mercury porosimetry. A clear overall relationship was found between breaking force of tablets and the median of the cumulative pore volume-pore diameter curve and pore volume-size distribution. The dependence of the breaking force on total surface area of pores was less evident. Fragmentation of granules contributes to the creation of large intergranular and intragranular pores, and further fragmentation and plastic deformation of the primary particles contributes to their reduction in number and size. According to pore volume-size distributions, the decrease in the volume of large pores and the shift of the maximum for volume-size distribution towards smaller pore diameter were related to the increased breaking force of tablets.
The effect of compression force, compression speed and the amount of granulation liquid on the po... more The effect of compression force, compression speed and the amount of granulation liquid on the porosity parameters determined from lactose, glucose and mannitol tablets by high-pressure mercury porosimetry was investigated. Compression force affected all parameters measured, except the total pore surface area of lactose tablets. The changes in tablet microstructure with increasing compression force were particularly well detected from the pore volume size distributions of tablets. Compression speed affected the total pore volume of lactose tablets, both mean and median pore diameters of lactose tablets and mannitol tablets compressed from granules produced with a low amount of liquid, and the median pore diameter of glucose tablets. The compression speed dependence of these parameters was a sign of the time-dependent deformation of materials during compression. The amount of granulation liquid affected the total pore surface area of lactose and mannitol tablets. With a high amount of liquid, the surface area of pores was greater. The mean pore size of all tablets and the median pore diameter of mannitol tablets were smaller when a high amount of granulation liquid was used. Even when compressed with a high force, the pore volume size distributions of mannitol tablets with a low amount of granulation liquid were broader and the maxima were at larger pore diameters. It was concluded that each porosity parameter measured characterised the pore structure of compressed tablets from a different aspect. Thus, the use of all porosity parameters proved to be useful.
Journal of parenteral science and technology: a publication of the Parenteral Drug Association
The effect of sterilization on the number of particles released from five different types of rubb... more The effect of sterilization on the number of particles released from five different types of rubber stoppers, as well as on their surface roughness and elemental composition before and after sterilization is described. The stoppers were immersed in 200 ml of 0.9% sodium chloride solution in conical flasks. The number of particles released into the sodium chloride solution was measured by Coulter Counter. The surface roughness and the elemental composition of the stoppers were determined by SEM/EDX. All measurements were made both before and after sterilization at 121 degrees C to F0 15 mins. The number of particles released from a stopper during sterilization varies considerably between different stoppers and even between different batches of the same stopper. The only non-siliconized stopper in this study performed well. The absence of surface siliconization may have contributed to this performance. The scanning electron micrographs revealed well the differences in the surface roughness of the stoppers. The sterilization generally increases the surface roughness of the samples. The x-ray microanalysis revealed that the elemental composition of the stoppers may vary not only between different types of stoppers but also between different batches of the same stopper.
The effect of the amount of granulation liquid, compression speed and maximum compression force o... more The effect of the amount of granulation liquid, compression speed and maximum compression force on then 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 compressibility than glucose granules. Mannitol granules produced the hardest tablets and lactose and glucose the weakest. The change in the amount of granulation liquid caused changes both in the granule porosity and in the amount of binder; this was attributed to differences in tablet strength. All parameters studied were relatively insensitive to changing speeds of compression in the range used, except for the breaking force of mannitol tablets, which was greatest with the lowest speed of compression. All granule masses showed a relatively good continuous flow suitable for table production. Tablets compressed from lactose granules had the best uniformity of weight of the tablets studied.
Despite a global interest in companion animal pharmaceuticals, feline peroral medication is still... more Despite a global interest in companion animal pharmaceuticals, feline peroral medication is still lacking in palatable and voluntarily acceptable drugs of suitable size and attractive taste. As a consequence, treating cats with canine or human medicinal products has weakened patient compliance and treatment commitment resulting in many pet cats going untreated. In the future, the companion animal pharmaceutical business is expected to focus particularly on cats and the development of palatable feline medication. Based on this, the overall aim of this study was to facilitate voluntary drug administration to felines. Specifically the aim was to develop sophisticated and tailor-made feline medicinal products, in the form of mini-tablets, focusing on flavors palatable to felines. Rapid preformulation compatibility and stability screening tests of synthetic flavors were carried out using readily available oral solid form excipients. On the basis that felines are carnivorous, L-methionine...
ABSTRACT Purpose This study identifies key determinants of new product launch success, examines t... more ABSTRACT Purpose This study identifies key determinants of new product launch success, examines their role and impact on launch performance and links them to the different stages of product life cycle in the pharmaceutical new product launch context. Methods Survey data from pharmaceutical industry was analysed with multivariate data analysis using latent variable regression modelling followed by the calculation of selectivity ratios to reveal the most informative determinants. Results The results distinguish between the determinants driving financial new product launch success and those driving customer acceptance. Whereas financial success is driven by strategic choices and tactical decisions, the relationship approach is vital in fostering customer acceptance at different phases of the innovation diffusion. Product advantage and relationship marketing activities contribute to achieving key opinion leaders’ acceptance in the early phase, while the accumulated market-based assets largely determine acceptance of a majority of other target customers in the later phase. Furthermore, launch performance is enhanced by a relationship-oriented company culture. Conclusions The study emphasises the significance of relational aspects in new product launches and provides both important theoretical insights and managerial implications for commercialising new pharmaceutical products.
The present study shows that roller compaction (RC) can successfully be used as a granulation met... more The present study shows that roller compaction (RC) can successfully be used as a granulation method to prepare hydroxypropyl methylcellulose (HPMC)-based extended release matrix tablets containing a high drug load, both for materials deforming mainly by fragmentation (paracetamol) as for those having mainly plastic deformation (ibuprofen). The combined effect of RC process variables and composition on the manufacturability of HPMC tablets was investigated. Standard wet granulation grade HPMC was compared with a larger particle size direct compressible HPMC grade. Higher roll pressure was found to result in larger paracetamol granules and narrower granule particle size distributions, especially for formulations containing smaller size HPMC. However, for ibuprofen, no clear effect of roll pressure was observed. High roll pressure also resulted in denser ribbon and less bypass fines during RC. Loss of compactibility was observed for granules compared to powder blends, which was found ...
Both clodronate and bioactive glass are mostly used alone as treatment in various bone diseases b... more Both clodronate and bioactive glass are mostly used alone as treatment in various bone diseases but, they are also known to have beneficial effects in dental application. The same processes that lead to loss of bone can also result in alveolar bone loss. The object of this study was to define the optimal combination of clodronate and bioactive glass (BAG) to be used locally in dentistry. The evaluation was based on measurements and solid state properties obtained with pH, scanning electron microscopy (SEM), differential scanning calorimetric (DSC), X-ray powder diffraction (XRPD), Fourier transform infrared spectroscopy (FTIR) and Focused-ion beam (FIB) and energy dispersive X-ray spectroscopic (EDS) mapping. The results indicate that if too much calcium clodronate precipitation is formed, the activity of BAG is affected negatively. As there is more reaction surface to form calcium clodronate, similar to the amount of clodronate present, this reduces the bioactivity of BAG. Therefore, in dental treatment the most suitable BAG and clodronate combination product would have apatite (HA, hydroxyapatite) formation ability and amount of clodronate enough to enhance the bioactivity of BAG allowing HA formation. Based on combinations investigated, the one with 200 mg clodronate and 1 g BAG with particle size 0.5-0.8 mm was chosen to be the most promising for local dental application.
Cytokines are messenger proteins that regulate the proliferation and differentiation of cells and... more Cytokines are messenger proteins that regulate the proliferation and differentiation of cells and control immune responses. Interferons, interleukins, and growth factors have applications in cancer, autoimmune, and viral disease treatment. The cytokines are susceptible to chemical and physical instability. This article reviews the structure and stability issues of clinically used cytokines, as well as formulation strategies for improved stability. Some general aspects for identifying most probable stability concerns, selecting excipients, and developing stable cytokine formulations are presented. The vast group of cytokines offers possibilities for new biopharmaceuticals. The formulation approaches of the current cytokine products could facilitate development of new biopharmaceuticals. C
Bone tissue engineering is a rapidly growing area of research involving the use of bioactive glas... more Bone tissue engineering is a rapidly growing area of research involving the use of bioactive glass (BG) alone and in combination with different materials. The objective of this study was to investigate the interaction of BG with clodronate. Characterisation of the interaction between BG and clodronate was undertaken using; scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), Fourier transform Raman spectroscopy and Fourier transform infrared spectroscopy (FTIR). The interaction was examined in vitro with respect to the ion exchange and surface modification on the surface of the bioactive glass in the combination product. The results showed clear ion exchange enhancement by clodronate. Additionally, this ion exchange was more extensive and long lasting in the combination product than in BG alone. Clodronate promotes the activity of the BG and a calcium clodronate precipitation is formed. It can be assumed that this solid combination could be used in clinical applications. Therefore, it can be concluded that clodronate makes a beneficial environment for BG and could enhance also the apatite formation of BG.
Purpose The purpose of this study is to show how disaccharides differ in their ability to protect... more Purpose The purpose of this study is to show how disaccharides differ in their ability to protect lyophilized βgalactosidase from enzymatic activity loss and secondary structure changes during storage. Methods β-galactosidase was lyophilized with trehalose, sucrose, cellobiose or melibiose at 2:1, 20:1 and 40:1 excipient/ protein weight ratios, and stored up to 90 days at 45°C. Protein enzymatic activity was studied using o-nitrophenyl-β-D-galactopyranoside cleavage test, and its secondary structure in lyophilizates analyzed using Fourier transform infrared spectroscopy. The crystallization tendencies, glass transition temperatures and water contents of lyophilizates were evaluated using x-ray powder diffractometry, differential scanning calorimetry and thermogravimetry, respectively. Results The enzymatic activity of β-galactosidase decreased more slowly in lyophilizates containing trehalose or melibiose at 2:1 excipient/protein weight ratio when compared to those containing sucrose or cellobiose. Similar behavior was observed when analyzing the protein's secondary structure in lyophilizates. In 20:1 and 40:1 excipient/protein weight ratio lyophilizates the decrease of enzymatic activity was less dependent on the excipient, but activity was always amongst the highest in melibiose lyophilizates. Conclusions Melibiose was shown to be effective in protecting lyophilized β-galactosidase during storage. The protein secondary structure was shown to change at comparable rate in lyophilizates as its enzymatic activity after rehydration.
The aim of the present study was to prepare controlled-release tablets of poorly-soluble drug, fe... more The aim of the present study was to prepare controlled-release tablets of poorly-soluble drug, felodipine, and various erodable lipophilic excipients. Spray chilling was used to formulate the drug and the excipients into solid dispersion microparticles, which were then compressed. The microparticles were characterised by Fourier transform infrared spectroscopy, hot-stage microscopy, scanning electron microscopy, and image analysis. The amine and the carbonyl groups of felodipine formed hydrogen bonds with the carriers. The shape of the particles was spherical with the median particle diameter ranging from 25 to 35 mm. Surprisingly, the degree of crystallinity in felodipine and the ease of tablet disintegration played a more significant role on the felodipine dissolution rate than the matrix lipophilicity. Felodipine release rate was slowest from the least lipophilic tablets. #
The rheological properties of silicified microcrystalline cellulose (Prosolv 50) were compared wi... more The rheological properties of silicified microcrystalline cellulose (Prosolv 50) were compared with those of standard grades of microcrystalline cellulose (Emcocel 50 and Avicel PH 101). Cellulose samples were analyzed using nitrogen adsorption together with particle size, flowability, density and swelling volume studies. The rheological behaviour of the wet powder masses was studied as a function of mixing time using a mixer torque rheometer (MTR). Silicified microcrystalline cellulose exhibited improved flow characteristics and increased specific surface area compared to standard microcrystalline cellulose grades. Although the silicification process affected the swelling properties and, furthermore, the mixing kinetics of microcrystalline cellulose, the source of the microcrystalline cellulose had a stronger influence than silicification on the liquid requirement at peak torque.
Formation of solid solution particles in the Solution Enhanced Dispersion by Supercritical fluids... more Formation of solid solution particles in the Solution Enhanced Dispersion by Supercritical fluids (SEDS) process from a model drug and two different types of carriers, mannitol and Eudragit † E100 was evaluated. The crystal properties of samples and molecular interactions were investigated with DSC and FTIR, respectively. The effect of cocrystallisation of drug and mannitol on dissolution rate was studied. Even if a true one-phase solid dispersion was not obtained, the crystal structure of both drug and mannitol was mutually affected by the presence of the other. The drug was not in highly crystalline form in the co-precipitates. The interactions between the drug and mannitol could also be identified as hydrogen bonding between the amine or hydroxyl groups of the drug and the hydroxyl groups of mannitol. These interactions and changes in the crystal structure are probably directly related to the increase in the dissolution rate observed. A true solid solution was obtained when the drug was co-processed with Eudragit † E100. A clear interaction between the acid hydroxyl group of the drug and the basic carbonyl group on the Eudragit † E100 was observed. SEDS was shown to be an effective process for forming intimate blends and solid solutions for the drug and two different types of carriers. #
In this research, the tableting properties of ␣-melibiose monohydrate were studied. Melibiose is ... more In this research, the tableting properties of ␣-melibiose monohydrate were studied. Melibiose is a disaccharide which bears structural resemblance to lactose, because they both consist of galactose and glucose monosaccharide subunits. Compactibility and deformation behavior of two melibiose batches from different suppliers were studied and compared with ␣-lactose monohydrate and some other typical tableting excipients. Differences in the deformation behavior were determined comparing the shape of the Heckel plots, the yield pressure values and the strain rate sensitivity (SRS) indexes. In addition, the effect of moisture on the tabletability was studied. According to the yield pressures and SRS indexes melibiose was concluded to be fragmenting, even at higher degree than lactose monohydrate. However, the overall deformation behavior of melibiose was found to be similar to that of lactose monohydrate. Increase in moisture content resulted in higher tensile strengths of tablets for both melibiose batches, but it seemed to have more effect on compactibility of the other batch. In conclusion, melibiose has potential to be used as an excipient in tablet formulations.
Uploads
Papers by Anne Juppo