There is an urgent need for the analysis of melamine in the global pharmaceutical supply chain to... more There is an urgent need for the analysis of melamine in the global pharmaceutical supply chain to detect economically motivated adulteration or unintentional contamination using a simple, nondestructive analytical technique that confirms the extent of adulteration in a shorter time period. In this work, different analytical techniques (thermal analysis, X-ray diffraction, Fourier transform infrared (FT-IR), FT-Raman, and near-infrared (NIR) spectroscopy) were evaluated for their ability to detect a range of melamine levels in gelatin. While FT-IR and FT-Raman provided qualitative assessment of melamine contamination or adulteration, powder X-ray diffraction and NIR were able to detect and quantify the presence of melamine at levels as low as 1.0% w/w. Multivariate analysis of the NIR data yielded the most accurate model when three principal components were used. Data were pretreated using standard normal variate transformation to remove multiplicative interferences of scatter and particle size. The model had a root-mean-square error of calibration of 2.4 (R 2 = 0.99) and root-mean square error of prediction of 2.5 (R 2 = 0.96). The value of the paired t test for actual and predicted samples (1%-50% w/w) was 0.448 (p < 0.05), further indicating the robustness of the model.
Drug development and industrial pharmacy, Jan 7, 2014
The purpose of this research was to develop an orally disintegrating tablet (ODT) dosage form con... more The purpose of this research was to develop an orally disintegrating tablet (ODT) dosage form containing taste-masked beads of clindamycin HCl. Several formulation strategies were evaluated and a taste-masked ODT of clindamycin HCl was prepared without the use of a waxy cushioning agent. Clindamycin HCl (ca. 46% w/w) was coated onto microcrystalline cellulose beads (Cellets® 200) followed by the addition of a taste-masking layer of amino methacrylate copolymer, NF (Eudragit EPO® (EPO)) coating suspension. The efficiency of both the drug coating process and the taste-masking polymer coating process, as well as the taste masking ODTs was determined using potency and drug release analysis. Magnesium stearate was found to be advantageous over talc in improving the efficiency of the EPO coating suspension. A response surface methodology using a Box-Behnken design for the tablets revealed compression force and levels of both disintegrant and talc to be the main factors influencing the ODT...
Drug Development and Industrial Pharmacy, May 19, 2009
Background: The mechanical properties of extrusion-spheronized beads as part of multiparticulate ... more Background: The mechanical properties of extrusion-spheronized beads as part of multiparticulate systems has not been adequately studied. Aim: The purpose was to study the mechanical properties of such drug beads and blends of drug beads and glycerol monostearate (GMS)-placebo beads. Method: Heckel analysis (mean yield pressure, P y), strain rate sensitivity (SRS), elastic recovery (ER), and total work of compression (TWC) studies were conducted using a Presster TM linear rotary tablet machine simulator operating at several combinations of speed and force. Results: The GMS-placebo beads exhibited the lowest P y values (9.1 ± 1.6 MPa) and TWC (1.9 ± 0.3 J) overall and these values steadily increased with increases in both applied speed and force. Although the placebo beads had the lowest ER values of 3.8 ± 0.7%, these beads showed significant time-dependent deformation behavior based on their SRS value of 70.2%. Heckel analysis showed that uncoated theophylline beads containing 58% ethylcellulose were more compressible than control beads containing 58% dicalcium phosphate dihydrate, the latter having the highest overall P y of 79.3 ± 3.8 MPa for the low speed/low force condition. Heckel plots also showed that 50:50 ratios of blends containing drug beads coated with either Surelease® or Eudragit® NE30D behaved similarly under increasing force and speed. Surelease®-coated cimetidine beads gave the highest P y , TWC, and ER values and these values were higher than Eudragit® NE30D-coated beads. The 50:50 blend ratios containing coated cimetidine beads showed higher P y , TWC, and ER values than the 60:40 ratios. Conclusion: Variation in the compressibility of different beads and blends can be attributed to excipients used in their formulation as well as to the drug bead-to-placebo bead ratio.
The purpose of this study was to utilize near-infrared spectroscopy and chemical imaging to chara... more The purpose of this study was to utilize near-infrared spectroscopy and chemical imaging to characterize extrusion-spheronized drug beads, lipid-based placebo beads, and modified release tablets prepared from blends of these beads. The tablet drug load (10.5–19.5 mg) of theophylline (2.25 mg increments) and cimetidine (3 mg increments) could easily be differentiated using univariate analyses. To evaluate other tablet attributes (i.e., compression force, crushing force, content uniformity), multivariate analyses were used. Partial least squares (PLS) models were used for prediction and principal component analysis (PCA) was used for classification. The PLS prediction models (R2 > 0.98) for content uniformity of uncoated compacted theophylline and cimetidine beads produced the most robust models. Content uniformity data for tablets with drug content ranging between 10.5 and 19.5 mg showed standard error of calibration (SEC), standard error of cross-validation, and standard error of prediction (SEP) values as 0.31, 0.43, and 0.37 mg, and 0.47, 0.59, and 0.49 mg, for theophylline and cimetidine, respectively, with SEP/SEC ratios less than 1.3. PCA could detect blend segregation during tableting for preparations using different ratios of uncoated cimetidine beads to placebo beads (20:80, 50:50, and 80:20). Using NIR chemical imaging, the 80:20 formulations showed the most pronounced blend segregation during the tableting process. Furthermore, imaging was capable of quantitating the cimetidine bead content among the different blend ratios. Segregation testing (ASTM D6940-04 method) indicated that blends of coated cimetidine beads and placebo beads (50:50 ratio) also tended to segregate.
The user has requested enhancement of the downloaded file. All in-text references underlined in b... more The user has requested enhancement of the downloaded file. All in-text references underlined in blue are linked to publications on ResearchGate, letting you access and read them immediately. Cantor et al. flow better and are usually more compactible than the original powders. Granulation also permits handling of powders without loss of blend quality, since after blending particles are locked in-place within granules in a form of ordered mix.
Background: The mechanical properties of extrusion-spheronized beads as part of multiparticulate ... more Background: The mechanical properties of extrusion-spheronized beads as part of multiparticulate systems has not been adequately studied. Aim: The purpose was to study the mechanical properties of such drug beads and blends of drug beads and glycerol monostearate (GMS)-placebo beads. Method: Heckel analysis (mean yield pressure, P y ), strain rate sensitivity (SRS), elastic recovery (ER), and total work of compression (TWC) studies were conducted using a Presster TM linear rotary tablet machine simulator operating at several combinations of speed and force. Results: The GMS-placebo beads exhibited the lowest P y values (9.1 ± 1.6 MPa) and TWC (1.9 ± 0.3 J) overall and these values steadily increased with increases in both applied speed and force. Although the placebo beads had the lowest ER values of 3.8 ± 0.7%, these beads showed significant time-dependent deformation behavior based on their SRS value of 70.2%. Heckel analysis showed that uncoated theophylline beads containing 58% ethylcellulose were more compressible than control beads containing 58% dicalcium phosphate dihydrate, the latter having the highest overall P y of 79.3 ± 3.8 MPa for the low speed/low force condition. Heckel plots also showed that 50:50 ratios of blends containing drug beads coated with either Surelease® or Eudragit® NE30D behaved similarly under increasing force and speed. Surelease®-coated cimetidine beads gave the highest P y , TWC, and ER values and these values were higher than Eudragit® NE30D-coated beads. The 50:50 blend ratios containing coated cimetidine beads showed higher P y , TWC, and ER values than the 60:40 ratios. Conclusion: Variation in the compressibility of different beads and blends can be attributed to excipients used in their formulation as well as to the drug bead-to-placebo bead ratio.
The purpose was to investigate the effectiveness of an ethylcellulose (EC) bead matrix and differ... more The purpose was to investigate the effectiveness of an ethylcellulose (EC) bead matrix and different film-coating polymers in delaying drug release from compacted multiparticulate systems. Formulations containing theophylline or cimetidine granulated with Eudragit ® RS 30D were developed and beads were produced by extrusion-spheronization. Drug beads were coated using 15% wt/wt Surelease ® or Eudragit ® NE 30D and were evaluated for true density, particle size, and sphericity. Lipid-based placebo beads and drug beads were blended together and compacted on an instrumented Stokes B2 rotary tablet press. Although placebo beads were significantly less spherical, their true density of 1.21 g/cm 3 and size of 855 mm were quite close to Surelease ® -coated drug beads. Curing improved the crushing strength and friability values for theophylline tablets containing Surelease ® -coated beads; 5.7 ± 1.0 kP and 0.26 ± 0.07%, respectively. Dissolution profiles showed that the EC matrix only provided 3 h of drug release. Although tablets containing Surelease ® -coated theophylline beads released drug fastest overall (t 44.2% = 8 h), profiles showed that coating damage was still minimal. Size and density differences indicated a minimal segregation potential during tableting for blends containing Surelease ® -coated drug beads. Although modified release profiles >8 h were achievable in tablets for both drugs using either coating polymer, Surelease ® -coated theophylline beads released drug fastest overall. This is likely because of the increased solubility of theophylline and the intrinsic properties of the Surelease ® films. Furthermore, the lipid-based placebos served as effective cushioning agents by protecting coating integrity of drug beads under a number of different conditions while tableting.
The aim of this study is to determine the change of some physical properties (oven-dry density, w... more The aim of this study is to determine the change of some physical properties (oven-dry density, weight loss, swelling and anti-swelling efficiency) and mechanical properties (compression strength parallel to grain, bending strength, modulus of elasticity in bending, janka-hardness (cross-section, radial, tangential), impact bending strength and tension strength perpendicular to grain) of wild cherry woods after heat treatment under different durations. Specimens are exposed to temperature levels of 212 °C for time spans of 1,5 and 2,5 h. Based on the findings in this study, the results showed that oven-dry density, swelling, compression strength parallel to grain, bending strength, modulus of elasticity in bending, janka-hardness (Cross-section, Radial, Tangential), impact bending strength and tension strength perpendicular to grain values decreased with increasing treatment time.
The purpose was to investigate the effectiveness of an ethylcellulose (EC) bead matrix and differ... more The purpose was to investigate the effectiveness of an ethylcellulose (EC) bead matrix and different film-coating polymers in delaying drug release from compacted multiparticulate systems. Formulations containing theophylline or cimetidine granulated with Eudragit ® RS 30D were developed and beads were produced by extrusion-spheronization. Drug beads were coated using 15% wt/wt Surelease ® or Eudragit ® NE 30D and were evaluated for true density, particle size, and sphericity. Lipid-based placebo beads and drug beads were blended together and compacted on an instrumented Stokes B2 rotary tablet press. Although placebo beads were significantly less spherical, their true density of 1.21 g/cm 3 and size of 855 mm were quite close to Surelease ® -coated drug beads. Curing improved the crushing strength and friability values for theophylline tablets containing Surelease ® -coated beads; 5.7 ± 1.0 kP and 0.26 ± 0.07%, respectively. Dissolution profiles showed that the EC matrix only provided 3 h of drug release. Although tablets containing Surelease ® -coated theophylline beads released drug fastest overall (t 44.2% = 8 h), profiles showed that coating damage was still minimal. Size and density differences indicated a minimal segregation potential during tableting for blends containing Surelease ® -coated drug beads. Although modified release profiles >8 h were achievable in tablets for both drugs using either coating polymer, Surelease ® -coated theophylline beads released drug fastest overall. This is likely because of the increased solubility of theophylline and the intrinsic properties of the Surelease ® films. Furthermore, the lipid-based placebos served as effective cushioning agents by protecting coating integrity of drug beads under a number of different conditions while tableting.
There is an urgent need for the analysis of melamine in the global pharmaceutical supply chain to... more There is an urgent need for the analysis of melamine in the global pharmaceutical supply chain to detect economically motivated adulteration or unintentional contamination using a simple, nondestructive analytical technique that confirms the extent of adulteration in a shorter time period. In this work, different analytical techniques (thermal analysis, X-ray diffraction, Fourier transform infrared (FT-IR), FT-Raman, and near-infrared (NIR) spectroscopy) were evaluated for their ability to detect a range of melamine levels in gelatin. While FT-IR and FT-Raman provided qualitative assessment of melamine contamination or adulteration, powder X-ray diffraction and NIR were able to detect and quantify the presence of melamine at levels as low as 1.0% w/w. Multivariate analysis of the NIR data yielded the most accurate model when three principal components were used. Data were pretreated using standard normal variate transformation to remove multiplicative interferences of scatter and particle size. The model had a root-mean-square error of calibration of 2.4 (R 2 = 0.99) and root-mean square error of prediction of 2.5 (R 2 = 0.96). The value of the paired t test for actual and predicted samples (1%-50% w/w) was 0.448 (p < 0.05), further indicating the robustness of the model.
Drug development and industrial pharmacy, Jan 7, 2014
The purpose of this research was to develop an orally disintegrating tablet (ODT) dosage form con... more The purpose of this research was to develop an orally disintegrating tablet (ODT) dosage form containing taste-masked beads of clindamycin HCl. Several formulation strategies were evaluated and a taste-masked ODT of clindamycin HCl was prepared without the use of a waxy cushioning agent. Clindamycin HCl (ca. 46% w/w) was coated onto microcrystalline cellulose beads (Cellets® 200) followed by the addition of a taste-masking layer of amino methacrylate copolymer, NF (Eudragit EPO® (EPO)) coating suspension. The efficiency of both the drug coating process and the taste-masking polymer coating process, as well as the taste masking ODTs was determined using potency and drug release analysis. Magnesium stearate was found to be advantageous over talc in improving the efficiency of the EPO coating suspension. A response surface methodology using a Box-Behnken design for the tablets revealed compression force and levels of both disintegrant and talc to be the main factors influencing the ODT...
Drug Development and Industrial Pharmacy, May 19, 2009
Background: The mechanical properties of extrusion-spheronized beads as part of multiparticulate ... more Background: The mechanical properties of extrusion-spheronized beads as part of multiparticulate systems has not been adequately studied. Aim: The purpose was to study the mechanical properties of such drug beads and blends of drug beads and glycerol monostearate (GMS)-placebo beads. Method: Heckel analysis (mean yield pressure, P y), strain rate sensitivity (SRS), elastic recovery (ER), and total work of compression (TWC) studies were conducted using a Presster TM linear rotary tablet machine simulator operating at several combinations of speed and force. Results: The GMS-placebo beads exhibited the lowest P y values (9.1 ± 1.6 MPa) and TWC (1.9 ± 0.3 J) overall and these values steadily increased with increases in both applied speed and force. Although the placebo beads had the lowest ER values of 3.8 ± 0.7%, these beads showed significant time-dependent deformation behavior based on their SRS value of 70.2%. Heckel analysis showed that uncoated theophylline beads containing 58% ethylcellulose were more compressible than control beads containing 58% dicalcium phosphate dihydrate, the latter having the highest overall P y of 79.3 ± 3.8 MPa for the low speed/low force condition. Heckel plots also showed that 50:50 ratios of blends containing drug beads coated with either Surelease® or Eudragit® NE30D behaved similarly under increasing force and speed. Surelease®-coated cimetidine beads gave the highest P y , TWC, and ER values and these values were higher than Eudragit® NE30D-coated beads. The 50:50 blend ratios containing coated cimetidine beads showed higher P y , TWC, and ER values than the 60:40 ratios. Conclusion: Variation in the compressibility of different beads and blends can be attributed to excipients used in their formulation as well as to the drug bead-to-placebo bead ratio.
The purpose of this study was to utilize near-infrared spectroscopy and chemical imaging to chara... more The purpose of this study was to utilize near-infrared spectroscopy and chemical imaging to characterize extrusion-spheronized drug beads, lipid-based placebo beads, and modified release tablets prepared from blends of these beads. The tablet drug load (10.5–19.5 mg) of theophylline (2.25 mg increments) and cimetidine (3 mg increments) could easily be differentiated using univariate analyses. To evaluate other tablet attributes (i.e., compression force, crushing force, content uniformity), multivariate analyses were used. Partial least squares (PLS) models were used for prediction and principal component analysis (PCA) was used for classification. The PLS prediction models (R2 > 0.98) for content uniformity of uncoated compacted theophylline and cimetidine beads produced the most robust models. Content uniformity data for tablets with drug content ranging between 10.5 and 19.5 mg showed standard error of calibration (SEC), standard error of cross-validation, and standard error of prediction (SEP) values as 0.31, 0.43, and 0.37 mg, and 0.47, 0.59, and 0.49 mg, for theophylline and cimetidine, respectively, with SEP/SEC ratios less than 1.3. PCA could detect blend segregation during tableting for preparations using different ratios of uncoated cimetidine beads to placebo beads (20:80, 50:50, and 80:20). Using NIR chemical imaging, the 80:20 formulations showed the most pronounced blend segregation during the tableting process. Furthermore, imaging was capable of quantitating the cimetidine bead content among the different blend ratios. Segregation testing (ASTM D6940-04 method) indicated that blends of coated cimetidine beads and placebo beads (50:50 ratio) also tended to segregate.
The user has requested enhancement of the downloaded file. All in-text references underlined in b... more The user has requested enhancement of the downloaded file. All in-text references underlined in blue are linked to publications on ResearchGate, letting you access and read them immediately. Cantor et al. flow better and are usually more compactible than the original powders. Granulation also permits handling of powders without loss of blend quality, since after blending particles are locked in-place within granules in a form of ordered mix.
Background: The mechanical properties of extrusion-spheronized beads as part of multiparticulate ... more Background: The mechanical properties of extrusion-spheronized beads as part of multiparticulate systems has not been adequately studied. Aim: The purpose was to study the mechanical properties of such drug beads and blends of drug beads and glycerol monostearate (GMS)-placebo beads. Method: Heckel analysis (mean yield pressure, P y ), strain rate sensitivity (SRS), elastic recovery (ER), and total work of compression (TWC) studies were conducted using a Presster TM linear rotary tablet machine simulator operating at several combinations of speed and force. Results: The GMS-placebo beads exhibited the lowest P y values (9.1 ± 1.6 MPa) and TWC (1.9 ± 0.3 J) overall and these values steadily increased with increases in both applied speed and force. Although the placebo beads had the lowest ER values of 3.8 ± 0.7%, these beads showed significant time-dependent deformation behavior based on their SRS value of 70.2%. Heckel analysis showed that uncoated theophylline beads containing 58% ethylcellulose were more compressible than control beads containing 58% dicalcium phosphate dihydrate, the latter having the highest overall P y of 79.3 ± 3.8 MPa for the low speed/low force condition. Heckel plots also showed that 50:50 ratios of blends containing drug beads coated with either Surelease® or Eudragit® NE30D behaved similarly under increasing force and speed. Surelease®-coated cimetidine beads gave the highest P y , TWC, and ER values and these values were higher than Eudragit® NE30D-coated beads. The 50:50 blend ratios containing coated cimetidine beads showed higher P y , TWC, and ER values than the 60:40 ratios. Conclusion: Variation in the compressibility of different beads and blends can be attributed to excipients used in their formulation as well as to the drug bead-to-placebo bead ratio.
The purpose was to investigate the effectiveness of an ethylcellulose (EC) bead matrix and differ... more The purpose was to investigate the effectiveness of an ethylcellulose (EC) bead matrix and different film-coating polymers in delaying drug release from compacted multiparticulate systems. Formulations containing theophylline or cimetidine granulated with Eudragit ® RS 30D were developed and beads were produced by extrusion-spheronization. Drug beads were coated using 15% wt/wt Surelease ® or Eudragit ® NE 30D and were evaluated for true density, particle size, and sphericity. Lipid-based placebo beads and drug beads were blended together and compacted on an instrumented Stokes B2 rotary tablet press. Although placebo beads were significantly less spherical, their true density of 1.21 g/cm 3 and size of 855 mm were quite close to Surelease ® -coated drug beads. Curing improved the crushing strength and friability values for theophylline tablets containing Surelease ® -coated beads; 5.7 ± 1.0 kP and 0.26 ± 0.07%, respectively. Dissolution profiles showed that the EC matrix only provided 3 h of drug release. Although tablets containing Surelease ® -coated theophylline beads released drug fastest overall (t 44.2% = 8 h), profiles showed that coating damage was still minimal. Size and density differences indicated a minimal segregation potential during tableting for blends containing Surelease ® -coated drug beads. Although modified release profiles >8 h were achievable in tablets for both drugs using either coating polymer, Surelease ® -coated theophylline beads released drug fastest overall. This is likely because of the increased solubility of theophylline and the intrinsic properties of the Surelease ® films. Furthermore, the lipid-based placebos served as effective cushioning agents by protecting coating integrity of drug beads under a number of different conditions while tableting.
The aim of this study is to determine the change of some physical properties (oven-dry density, w... more The aim of this study is to determine the change of some physical properties (oven-dry density, weight loss, swelling and anti-swelling efficiency) and mechanical properties (compression strength parallel to grain, bending strength, modulus of elasticity in bending, janka-hardness (cross-section, radial, tangential), impact bending strength and tension strength perpendicular to grain) of wild cherry woods after heat treatment under different durations. Specimens are exposed to temperature levels of 212 °C for time spans of 1,5 and 2,5 h. Based on the findings in this study, the results showed that oven-dry density, swelling, compression strength parallel to grain, bending strength, modulus of elasticity in bending, janka-hardness (Cross-section, Radial, Tangential), impact bending strength and tension strength perpendicular to grain values decreased with increasing treatment time.
The purpose was to investigate the effectiveness of an ethylcellulose (EC) bead matrix and differ... more The purpose was to investigate the effectiveness of an ethylcellulose (EC) bead matrix and different film-coating polymers in delaying drug release from compacted multiparticulate systems. Formulations containing theophylline or cimetidine granulated with Eudragit ® RS 30D were developed and beads were produced by extrusion-spheronization. Drug beads were coated using 15% wt/wt Surelease ® or Eudragit ® NE 30D and were evaluated for true density, particle size, and sphericity. Lipid-based placebo beads and drug beads were blended together and compacted on an instrumented Stokes B2 rotary tablet press. Although placebo beads were significantly less spherical, their true density of 1.21 g/cm 3 and size of 855 mm were quite close to Surelease ® -coated drug beads. Curing improved the crushing strength and friability values for theophylline tablets containing Surelease ® -coated beads; 5.7 ± 1.0 kP and 0.26 ± 0.07%, respectively. Dissolution profiles showed that the EC matrix only provided 3 h of drug release. Although tablets containing Surelease ® -coated theophylline beads released drug fastest overall (t 44.2% = 8 h), profiles showed that coating damage was still minimal. Size and density differences indicated a minimal segregation potential during tableting for blends containing Surelease ® -coated drug beads. Although modified release profiles >8 h were achievable in tablets for both drugs using either coating polymer, Surelease ® -coated theophylline beads released drug fastest overall. This is likely because of the increased solubility of theophylline and the intrinsic properties of the Surelease ® films. Furthermore, the lipid-based placebos served as effective cushioning agents by protecting coating integrity of drug beads under a number of different conditions while tableting.
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