The Experts below are selected from a list of 115320 Experts worldwide ranked by ideXlab platform
Kare Hapgood - One of the best experts on this subject based on the ideXlab platform.
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Drug Distribution in wet granulation foam versus spray
Drug Development and Industrial Pharmacy, 2013Co-Authors: Thanh Hai Nguye, Kare HapgoodAbstract:Foam granulation technology is a new wet granulation approach for pharmaceutical formulations. This study evaluates the performance of foam and spray granulation in achieving uniform Drug Distribution using a model formulation. To observe wetting and nuclei formation, single drop/foam penetration experiments were performed on a static powder bed comprised of varying compositions of hydrophilic/hydrophobic glass ballotini, and hydrophilic lactose/hydrophobic salicylic acid respectively. High shear granulation experiments were performed in a 5L mixer using varying compositions of hydrophilic lactose and hydrophobic salicylic acid. Four percent hydroxylpropyl methylcellulose (HPMC) solution was delivered at 90 g/min as either a foam (92% FQ) or an atomized spray whilst recording impeller power consumption. After drying, the granule size Distribution was measured and the granule composition was estimated using gravimetric filtration in methanol. Foam penetration was less dependent on the powder hydrophobicity compared to drop penetration. For glass ballotini powder mixtures, foam induced nucleation created nuclei with relatively uniform structure and size regardless of the powder hydrophobicity. For salicylic acid and lactose mixtures, increasing the proportion of salicylic acid reduced the nuclei granule size for both foam and drop binder addition. The granule Drug Distribution was not significantly affected by the binder addition method. Processing conditions, including liquid binder amount, impeller speed, wet massing, and the wettability properties of the formulation were the dominant factors for delivering homogeneous granules. The study reveals that foam and spray granulation involve different nucleation mechanisms - spray tends to incur early liquid penetration whereas foam granulation operates well in mechanical dispersion.
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effect of formulation hydrophobicity on Drug Distribution in wet granulation
Chemical Engineering Journal, 2010Co-Authors: Thanh Hai Nguye, Wei She, Kare HapgoodAbstract:Abstract Wet granulation is a process of enhancing the powder properties by producing larger particles from the agglomeration of agitated fine particles with liquid. The production of enlarged “granules” is often carried out in high-shear granulators, an equipment item prevalent in the pharmaceutical and food industries. In the pharmaceutical industry, good wettability between the liquid binder and the powder components in the formulation are relied upon to produce strong granules with a narrow size Distribution. The wettability of hydrophobic Drugs in the formulation is often improved by the use of surfactants; but this may not always be possible. Previous work on heterogeneous-wetting granulation [1] , [2] , [3] has found that as the formulation hydrophobicity increases, the average granule size decreases. The decreasing proportion of hydrophilic component available for granulation may influence the decreasing average granule size, however an explanation for this has not been clearly proposed. The observation and reasoning behind the granulation behaviour for heterogeneous-wetting powders forms the basis of this paper. Granulation experiments were carried out on varying degrees of formulation hydrophobicity and the granulation batch is sieved into different size fractions for sieve fraction assay analysis to determine the average granule composition and the Drug Distribution throughout the granulation batch. The sieve fraction assay analysis revealed that the Drug Distribution in the granular batch is strongly dependent upon the formulation wettability. This was seen for batches with water as the granulating fluid where the Drug Distribution was uneven and resulted in some sieve fractions being enriched or deficient of Drug content. When the wettability of the formulation was improved a more uniform Distribution of Drug was achieved across all sieve fractions and formulation hydrophobicity. The average granule size decreased as the formulation hydrophobicity increased, supporting previous works, and this is due to the decreasing liquid bridge strength between the particles.
Thanh Hai Nguye - One of the best experts on this subject based on the ideXlab platform.
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Drug Distribution in wet granulation foam versus spray
Drug Development and Industrial Pharmacy, 2013Co-Authors: Thanh Hai Nguye, Kare HapgoodAbstract:Foam granulation technology is a new wet granulation approach for pharmaceutical formulations. This study evaluates the performance of foam and spray granulation in achieving uniform Drug Distribution using a model formulation. To observe wetting and nuclei formation, single drop/foam penetration experiments were performed on a static powder bed comprised of varying compositions of hydrophilic/hydrophobic glass ballotini, and hydrophilic lactose/hydrophobic salicylic acid respectively. High shear granulation experiments were performed in a 5L mixer using varying compositions of hydrophilic lactose and hydrophobic salicylic acid. Four percent hydroxylpropyl methylcellulose (HPMC) solution was delivered at 90 g/min as either a foam (92% FQ) or an atomized spray whilst recording impeller power consumption. After drying, the granule size Distribution was measured and the granule composition was estimated using gravimetric filtration in methanol. Foam penetration was less dependent on the powder hydrophobicity compared to drop penetration. For glass ballotini powder mixtures, foam induced nucleation created nuclei with relatively uniform structure and size regardless of the powder hydrophobicity. For salicylic acid and lactose mixtures, increasing the proportion of salicylic acid reduced the nuclei granule size for both foam and drop binder addition. The granule Drug Distribution was not significantly affected by the binder addition method. Processing conditions, including liquid binder amount, impeller speed, wet massing, and the wettability properties of the formulation were the dominant factors for delivering homogeneous granules. The study reveals that foam and spray granulation involve different nucleation mechanisms - spray tends to incur early liquid penetration whereas foam granulation operates well in mechanical dispersion.
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effect of formulation hydrophobicity on Drug Distribution in wet granulation
Chemical Engineering Journal, 2010Co-Authors: Thanh Hai Nguye, Wei She, Kare HapgoodAbstract:Abstract Wet granulation is a process of enhancing the powder properties by producing larger particles from the agglomeration of agitated fine particles with liquid. The production of enlarged “granules” is often carried out in high-shear granulators, an equipment item prevalent in the pharmaceutical and food industries. In the pharmaceutical industry, good wettability between the liquid binder and the powder components in the formulation are relied upon to produce strong granules with a narrow size Distribution. The wettability of hydrophobic Drugs in the formulation is often improved by the use of surfactants; but this may not always be possible. Previous work on heterogeneous-wetting granulation [1] , [2] , [3] has found that as the formulation hydrophobicity increases, the average granule size decreases. The decreasing proportion of hydrophilic component available for granulation may influence the decreasing average granule size, however an explanation for this has not been clearly proposed. The observation and reasoning behind the granulation behaviour for heterogeneous-wetting powders forms the basis of this paper. Granulation experiments were carried out on varying degrees of formulation hydrophobicity and the granulation batch is sieved into different size fractions for sieve fraction assay analysis to determine the average granule composition and the Drug Distribution throughout the granulation batch. The sieve fraction assay analysis revealed that the Drug Distribution in the granular batch is strongly dependent upon the formulation wettability. This was seen for batches with water as the granulating fluid where the Drug Distribution was uneven and resulted in some sieve fractions being enriched or deficient of Drug content. When the wettability of the formulation was improved a more uniform Distribution of Drug was achieved across all sieve fractions and formulation hydrophobicity. The average granule size decreased as the formulation hydrophobicity increased, supporting previous works, and this is due to the decreasing liquid bridge strength between the particles.
Veria Khosrawipour - One of the best experts on this subject based on the ideXlab platform.
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exploring the spatial Drug Distribution pattern of pressurized intraperitoneal aerosol chemotherapy pipac
Annals of Surgical Oncology, 2016Co-Authors: Veria Khosrawipour, Tanja Khosrawipour, David Diazcarballo, Eckart Forster, Jurgen Zieren, Urs GigerpabstAbstract:Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel approach to delivering intraperitoneal chemotherapy (IPC) as a pressurized aerosol. One of the assumed advantages is the homogeneous Drug Distribution in the intraperitoneal cavity compared with conventional liquid in situ chemotherapy. However, to date, the spatial Drug Distribution pattern of PIPAC has not been investigated in detail. Doxorubicin was aerosolized in an ex vivo PIPAC model containing native fresh tissue samples of swine peritoneum at a pressure of 12 mmHg CO2 at 36 °C. In the center of the top cover of the PIPAC chamber, a PIPAC micropump was installed. Tissue specimens were placed as follows: (A) bottom of the plastic box, (B) margin of the aerosol jet covered with a bilaterally open tunnel, (C) side wall, and (D) top cover, respectively. In-tissue doxorubicin penetration was measured using fluorescence microscopy on frozen thin sections. The depth of doxorubicin penetration was found to be significantly higher in tissues directly exposed to the aerosol jet (A: 215 ± 79 µm) compared with the side wall (C: 77 ± 18 µm; p < 0.01) and the top of the box (D: 65 ± 17 µm; p < 0.01). The poorest penetration was observed for peritoneal tissue covered under a bilaterally open plastic tunnel (B: 34 ± 19 µm; p < 0.001). The study data suggest that the spatial Drug Distribution pattern of ex vivo PIPAC is heterogeneous.
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Exploring the Spatial Drug Distribution Pattern of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC)
Annals of surgical oncology, 2015Co-Authors: Veria Khosrawipour, Tanja Khosrawipour, Eckart Forster, Jurgen Zieren, David Diaz-carballo, Urs Giger-pabstAbstract:Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel approach to delivering intraperitoneal chemotherapy (IPC) as a pressurized aerosol. One of the assumed advantages is the homogeneous Drug Distribution in the intraperitoneal cavity compared with conventional liquid in situ chemotherapy. However, to date, the spatial Drug Distribution pattern of PIPAC has not been investigated in detail. Doxorubicin was aerosolized in an ex vivo PIPAC model containing native fresh tissue samples of swine peritoneum at a pressure of 12 mmHg CO2 at 36 °C. In the center of the top cover of the PIPAC chamber, a PIPAC micropump was installed. Tissue specimens were placed as follows: (A) bottom of the plastic box, (B) margin of the aerosol jet covered with a bilaterally open tunnel, (C) side wall, and (D) top cover, respectively. In-tissue doxorubicin penetration was measured using fluorescence microscopy on frozen thin sections. The depth of doxorubicin penetration was found to be significantly higher in tissues directly exposed to the aerosol jet (A: 215 ± 79 µm) compared with the side wall (C: 77 ± 18 µm; p
Urs Gigerpabst - One of the best experts on this subject based on the ideXlab platform.
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exploring the spatial Drug Distribution pattern of pressurized intraperitoneal aerosol chemotherapy pipac
Annals of Surgical Oncology, 2016Co-Authors: Veria Khosrawipour, Tanja Khosrawipour, David Diazcarballo, Eckart Forster, Jurgen Zieren, Urs GigerpabstAbstract:Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel approach to delivering intraperitoneal chemotherapy (IPC) as a pressurized aerosol. One of the assumed advantages is the homogeneous Drug Distribution in the intraperitoneal cavity compared with conventional liquid in situ chemotherapy. However, to date, the spatial Drug Distribution pattern of PIPAC has not been investigated in detail. Doxorubicin was aerosolized in an ex vivo PIPAC model containing native fresh tissue samples of swine peritoneum at a pressure of 12 mmHg CO2 at 36 °C. In the center of the top cover of the PIPAC chamber, a PIPAC micropump was installed. Tissue specimens were placed as follows: (A) bottom of the plastic box, (B) margin of the aerosol jet covered with a bilaterally open tunnel, (C) side wall, and (D) top cover, respectively. In-tissue doxorubicin penetration was measured using fluorescence microscopy on frozen thin sections. The depth of doxorubicin penetration was found to be significantly higher in tissues directly exposed to the aerosol jet (A: 215 ± 79 µm) compared with the side wall (C: 77 ± 18 µm; p < 0.01) and the top of the box (D: 65 ± 17 µm; p < 0.01). The poorest penetration was observed for peritoneal tissue covered under a bilaterally open plastic tunnel (B: 34 ± 19 µm; p < 0.001). The study data suggest that the spatial Drug Distribution pattern of ex vivo PIPAC is heterogeneous.
Ken Korzekwa - One of the best experts on this subject based on the ideXlab platform.
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Drug Distribution. Part 1. Models to Predict Membrane Partitioning
Pharmaceutical Research, 2017Co-Authors: Swati Nagar, Ken KorzekwaAbstract:Purpose Tissue partitioning is an important component of Drug Distribution and half-life. Protein binding and lipid partitioning together determine Drug Distribution. Methods Two structure-based models to predict partitioning into microsomal membranes are presented. An orientation-based model was developed using a membrane template and atom-based relative free energy functions to select Drug conformations and orientations for neutral and basic Drugs. Results The resulting model predicts the correct membrane positions for nine compounds tested, and predicts the membrane partitioning for n = 67 Drugs with an average fold-error of 2.4. Next, a more facile descriptor-based model was developed for acids, neutrals and bases. This model considers the partitioning of neutral and ionized species at equilibrium, and can predict membrane partitioning with an average fold-error of 2.0 ( n = 92 Drugs). Conclusions Together these models suggest that Drug orientation is important for membrane partitioning and that membrane partitioning can be well predicted from physicochemical properties.
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Drug Distribution. Part 1. Models to Predict Membrane Partitioning.
Pharmaceutical research, 2016Co-Authors: Swati Nagar, Ken KorzekwaAbstract:Purpose Tissue partitioning is an important component of Drug Distribution and half-life. Protein binding and lipid partitioning together determine Drug Distribution.
