Drug transport mechanisms from carbopol/eudragit verapamil sustained-release tablets
- Khamanga, Sandile M, Walker, Roderick B
- Authors: Khamanga, Sandile M , Walker, Roderick B
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184801 , vital:44273 , xlink:href="https://doi.org/10.14227/dt180311p30"
- Description: The objectives of this study were to compare dissolution profiles of a verapamil (VRP) formulation manufactured inhouse and Isoptin SR using USP Apparatus 2 and 3 and to elucidate drug release kinetics of these dosage forms. Eudragit NE 30D (ethyl acrylate–methyl methacrylate copolymer in a 2:1 ratio) aqueous dispersion was used as a granulating binder for the manufacture of VRP mini-matrix sustained-release tablets. The wet granulation process was performed to prepare free-flowing granules that were blended with Carbopol. The tablets were manufactured using a single-punch press by compression of the granules with magnesium stearate as a lubricant. Drug release was determined in phosphate buffer solution using USP Apparatus 2 and 3. Dissolution data were fitted to zero- and first-order models; in addition, the kinetic data were determined by evaluation of Higuchi release kinetics. The mechanism of drug release was established using the Korsmeyer–Peppas model. In general, all tablets showed high mechanical resistance with less than 1% friability. There was no significant difference between the dissolution profiles of the formulation manufactured in-house and the commercially available product. The release mechanism of the formulated and marketed products was controlled by anomalous non-Fickian diffusion. VRP release was prolonged for 12 h indicating the usefulness of the formulation as a twice-daily dosage form. The mechanism of drug release for the dosage forms was unaffected by the choice of apparatus.
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- Authors: Khamanga, Sandile M , Walker, Roderick B
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184801 , vital:44273 , xlink:href="https://doi.org/10.14227/dt180311p30"
- Description: The objectives of this study were to compare dissolution profiles of a verapamil (VRP) formulation manufactured inhouse and Isoptin SR using USP Apparatus 2 and 3 and to elucidate drug release kinetics of these dosage forms. Eudragit NE 30D (ethyl acrylate–methyl methacrylate copolymer in a 2:1 ratio) aqueous dispersion was used as a granulating binder for the manufacture of VRP mini-matrix sustained-release tablets. The wet granulation process was performed to prepare free-flowing granules that were blended with Carbopol. The tablets were manufactured using a single-punch press by compression of the granules with magnesium stearate as a lubricant. Drug release was determined in phosphate buffer solution using USP Apparatus 2 and 3. Dissolution data were fitted to zero- and first-order models; in addition, the kinetic data were determined by evaluation of Higuchi release kinetics. The mechanism of drug release was established using the Korsmeyer–Peppas model. In general, all tablets showed high mechanical resistance with less than 1% friability. There was no significant difference between the dissolution profiles of the formulation manufactured in-house and the commercially available product. The release mechanism of the formulated and marketed products was controlled by anomalous non-Fickian diffusion. VRP release was prolonged for 12 h indicating the usefulness of the formulation as a twice-daily dosage form. The mechanism of drug release for the dosage forms was unaffected by the choice of apparatus.
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Evaluation of the in vitro differential protein adsorption patterns of didanosine-loaded nanostructured lipid carriers (NLCs) for potential targeting to the brain
- Kasongo, Kasongo W, Jansch, Mirko, Müller, Rainer H, Walker, Roderick B
- Authors: Kasongo, Kasongo W , Jansch, Mirko , Müller, Rainer H , Walker, Roderick B
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184035 , vital:44160 , xlink:href="https://doi.org/10.3109/08982104.2010.539186"
- Description: The preferential in vitro adsorption of apolipoprotein E (Apo E) onto the surface of colloidal drug carriers may be used as a strategy to evaluate the in vivo potential for such systems to transport drugs to the brain. The aim of this research was to investigate the in vitro protein adsorption patterns of didanosine-loaded nanostructured lipid carriers (DDI-NLCs), using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), in order to establish the potential for NLCs to deliver DDI to the brain. NLC formulations were manufactured using high-pressure homogenization using a lipid matrix consisting of a mixture of Precirol® ATO 5 and Transcutol® HP. The 2-D PAGE analysis revealed that NLCs in formulations stabilized using Solutol® HS 15 alone or with a ternary surfactant system consisting of Solutol® HS 15, Tween® 80, and Lutrol® F68, preferentially adsorbed proteins, such as Apo E. Particles stabilized with Tween® 80 and Lutrol® F68 did not adsorb Apo E in these studies, which could be related to the relatively large particle size and hence small surface area observed for these NLCs. These findings have revealed that DDI-loaded NLCs may have the potential to deliver DDI to the brain in vivo and, in addition, to Tween® 80, which has already been shown to have the ability to facilitate the targeting of colloidal drug delivery systems to the brain. Solutol® HS 15–stabilized nanoparticles may also achieve a similar purpose.
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- Authors: Kasongo, Kasongo W , Jansch, Mirko , Müller, Rainer H , Walker, Roderick B
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184035 , vital:44160 , xlink:href="https://doi.org/10.3109/08982104.2010.539186"
- Description: The preferential in vitro adsorption of apolipoprotein E (Apo E) onto the surface of colloidal drug carriers may be used as a strategy to evaluate the in vivo potential for such systems to transport drugs to the brain. The aim of this research was to investigate the in vitro protein adsorption patterns of didanosine-loaded nanostructured lipid carriers (DDI-NLCs), using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), in order to establish the potential for NLCs to deliver DDI to the brain. NLC formulations were manufactured using high-pressure homogenization using a lipid matrix consisting of a mixture of Precirol® ATO 5 and Transcutol® HP. The 2-D PAGE analysis revealed that NLCs in formulations stabilized using Solutol® HS 15 alone or with a ternary surfactant system consisting of Solutol® HS 15, Tween® 80, and Lutrol® F68, preferentially adsorbed proteins, such as Apo E. Particles stabilized with Tween® 80 and Lutrol® F68 did not adsorb Apo E in these studies, which could be related to the relatively large particle size and hence small surface area observed for these NLCs. These findings have revealed that DDI-loaded NLCs may have the potential to deliver DDI to the brain in vivo and, in addition, to Tween® 80, which has already been shown to have the ability to facilitate the targeting of colloidal drug delivery systems to the brain. Solutol® HS 15–stabilized nanoparticles may also achieve a similar purpose.
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Evaluation of the kinetics and mechanism of drug release from Econazole nitrate nanosponge loaded Carbapol Hydrogel
- Sharma, Renuka, Walker, Roderick B, Pathak, Kamla
- Authors: Sharma, Renuka , Walker, Roderick B , Pathak, Kamla
- Date: 2011
- Language: English
- Type: text , Article
- Identifier: vital:6437 , http://hdl.handle.net/10962/d1006614
- Description: The objective of this study was to investigate the mechanism of release of econazole nitrate (EN) nanosponges loaded hydrogel and to compare it with EN hydrogel so as to develop an extended release topical drug delivery system of EN. Nanosponges of EN were prepared using ethyl cellulose and PVA by emulsion solvent evaporation method. On the basis of pharmacotechnical evaluation nanosponges with least particle size of 230.1 nm and good rheological properties were formulated as hydrogel (F1 – F7). In vitro drug release data of EN nanosponges loaded hydrogels in phosphate buffer pH 6.8 and 7.4 when analysed by GraphPad Prism software version 4.0 San Diego, USA best fitted the Makoid-2 Banakar model (R value greater than 0.98). The Korsmeyer-Peppas release exponent (n) ranged between 0.331 – 0.418, which confirmed diffusion as the principle mechanism of drug release. The release mechanism was further confirmed by calculating the ratio of exponents A/B ratio derived from the Kopcha model.
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- Authors: Sharma, Renuka , Walker, Roderick B , Pathak, Kamla
- Date: 2011
- Language: English
- Type: text , Article
- Identifier: vital:6437 , http://hdl.handle.net/10962/d1006614
- Description: The objective of this study was to investigate the mechanism of release of econazole nitrate (EN) nanosponges loaded hydrogel and to compare it with EN hydrogel so as to develop an extended release topical drug delivery system of EN. Nanosponges of EN were prepared using ethyl cellulose and PVA by emulsion solvent evaporation method. On the basis of pharmacotechnical evaluation nanosponges with least particle size of 230.1 nm and good rheological properties were formulated as hydrogel (F1 – F7). In vitro drug release data of EN nanosponges loaded hydrogels in phosphate buffer pH 6.8 and 7.4 when analysed by GraphPad Prism software version 4.0 San Diego, USA best fitted the Makoid-2 Banakar model (R value greater than 0.98). The Korsmeyer-Peppas release exponent (n) ranged between 0.331 – 0.418, which confirmed diffusion as the principle mechanism of drug release. The release mechanism was further confirmed by calculating the ratio of exponents A/B ratio derived from the Kopcha model.
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Formulation development and in vitro evaluation of didanosine-loaded nanostructured lipid carriers for the potential treatment of AIDS dementia complex
- Wa Kasongo, Kasongo, Shegokar, Ranjita, Müller, Rainer H, Walker, Roderick B
- Authors: Wa Kasongo, Kasongo , Shegokar, Ranjita , Müller, Rainer H , Walker, Roderick B
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184210 , vital:44190 , xlink:href="https://doi.org/10.3109/03639045.2010.516264"
- Description: The purpose of this article was to investigate the feasibility of incorporating didanosine (DDI) into nanostructured lipid carriers (NLC) for potential treatment of AIDS dementia complex. Aqueous DDI-free and DDI-loaded NLC were manufactured using hot high-pressure homogenization. The lipid matrix contained a mixture of Precirol ® ATO 5 and Transcutol ® HP. Photon correlation spectroscopy revealed that the mean particle size for all formulations was below 250 nm with narrow polydispersity indices. In addition, the d99% values for all formulations determined using laser diffractometry were below 400 nm with the span values ranging from 0.84 to 1.0. The zeta potential values ranged from −18.4 to −11.4 mV and the encapsulation efficiency of NLC for DDI ranged from 33.02% to 78.34%. These parameters remained relatively constant for all formulations tested following storage for 2 months at 25°C indicating that all the formulations were relatively stable. Differential scanning calorimetry revealed a decrease in the degree of crystallinity of NLC in all formulations developed relative to the bulk lipid material. In addition, wide-angle X-ray scattering showed that NLC in all formulations tested existed in a single β-modification form and that DDI that had been incorporated into the NLC appeared to be molecularly dispersed in the lipid matrices. Images of the NLC formulations obtained using transmission electron microscopy revealed that all formulations contained a mixture of spherical and nonspherical particles irrespective of the amount of DDI that was added during the manufacture of the formulations.
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- Authors: Wa Kasongo, Kasongo , Shegokar, Ranjita , Müller, Rainer H , Walker, Roderick B
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184210 , vital:44190 , xlink:href="https://doi.org/10.3109/03639045.2010.516264"
- Description: The purpose of this article was to investigate the feasibility of incorporating didanosine (DDI) into nanostructured lipid carriers (NLC) for potential treatment of AIDS dementia complex. Aqueous DDI-free and DDI-loaded NLC were manufactured using hot high-pressure homogenization. The lipid matrix contained a mixture of Precirol ® ATO 5 and Transcutol ® HP. Photon correlation spectroscopy revealed that the mean particle size for all formulations was below 250 nm with narrow polydispersity indices. In addition, the d99% values for all formulations determined using laser diffractometry were below 400 nm with the span values ranging from 0.84 to 1.0. The zeta potential values ranged from −18.4 to −11.4 mV and the encapsulation efficiency of NLC for DDI ranged from 33.02% to 78.34%. These parameters remained relatively constant for all formulations tested following storage for 2 months at 25°C indicating that all the formulations were relatively stable. Differential scanning calorimetry revealed a decrease in the degree of crystallinity of NLC in all formulations developed relative to the bulk lipid material. In addition, wide-angle X-ray scattering showed that NLC in all formulations tested existed in a single β-modification form and that DDI that had been incorporated into the NLC appeared to be molecularly dispersed in the lipid matrices. Images of the NLC formulations obtained using transmission electron microscopy revealed that all formulations contained a mixture of spherical and nonspherical particles irrespective of the amount of DDI that was added during the manufacture of the formulations.
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Selection and characterization of suitable lipid excipients for use in the manufacture of didanosine-loaded solid lipid nanoparticles and nanostructured lipid carriers
- Kasongo, Kasongo W, Pardeike, Jana, Muller, Rainer H, Walker, Roderick B
- Authors: Kasongo, Kasongo W , Pardeike, Jana , Muller, Rainer H , Walker, Roderick B
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184016 , vital:44156 , xlink:href="https://doi.org/10.1002/jps.22711"
- Description: This research aimed to evaluate the suitability of lipids for the manufacture of solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) loaded with the hydrophilic drug, didanosine (DDI). The crystalline state and polymorphism of lipids with the best‐solubulizing potential for DDI was investigated using differential scanning calorimetry (DSC) and wide‐angle X‐ray scattering (WAXS). DSC and WAXS were also used to determine potential interactions between the bulk lipids and DDI. Precirol® ATO 5 and Transcutol® HP showed the best‐solubilizing potential for DDI. Precirol® ATO 5 exists in the β‐modification before heating; however, a mixture of both α‐ and β‐modifications were detected following heating. Addition of Transcutol® HP to Precirol® ATO 5 changes the polymorphism of the latter from the β‐modification to a form that exhibits coexistence of the α‐ and β‐modifications. DDI exists in a crystalline state when dispersed at 5% (w/w) in Precirol® ATO 5 or in a Precirol® ATO 5/Transcutol® HP mixture. DSC and WAXS profiles of DDI/bulk lipids mixture obtained before and after exposure to heat revealed no interactions between DDI and the lipids. Precirol® ATO 5 and a mixture of Precirol® ATO 5 and Transcutol® HP may be used to manufacture DDI‐loaded SLN and NLC, respectively.
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- Authors: Kasongo, Kasongo W , Pardeike, Jana , Muller, Rainer H , Walker, Roderick B
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184016 , vital:44156 , xlink:href="https://doi.org/10.1002/jps.22711"
- Description: This research aimed to evaluate the suitability of lipids for the manufacture of solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) loaded with the hydrophilic drug, didanosine (DDI). The crystalline state and polymorphism of lipids with the best‐solubulizing potential for DDI was investigated using differential scanning calorimetry (DSC) and wide‐angle X‐ray scattering (WAXS). DSC and WAXS were also used to determine potential interactions between the bulk lipids and DDI. Precirol® ATO 5 and Transcutol® HP showed the best‐solubilizing potential for DDI. Precirol® ATO 5 exists in the β‐modification before heating; however, a mixture of both α‐ and β‐modifications were detected following heating. Addition of Transcutol® HP to Precirol® ATO 5 changes the polymorphism of the latter from the β‐modification to a form that exhibits coexistence of the α‐ and β‐modifications. DDI exists in a crystalline state when dispersed at 5% (w/w) in Precirol® ATO 5 or in a Precirol® ATO 5/Transcutol® HP mixture. DSC and WAXS profiles of DDI/bulk lipids mixture obtained before and after exposure to heat revealed no interactions between DDI and the lipids. Precirol® ATO 5 and a mixture of Precirol® ATO 5 and Transcutol® HP may be used to manufacture DDI‐loaded SLN and NLC, respectively.
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The use of experimental design in the development of an HPLC–ECD method for the analysis of captopril
- Khamanga, Sandile M, Walker, Roderick B
- Authors: Khamanga, Sandile M , Walker, Roderick B
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184056 , vital:44163 , xlink:href="https://doi.org/10.1016/j.talanta.2010.11.025"
- Description: An accurate, sensitive and specific high performance liquid chromatography–electrochemical detection (HPLC–ECD) method that was developed and validated for captopril (CPT) is presented. Separation was achieved using a Phenomenex® Luna 5 μm (C18) column and a mobile phase comprised of phosphate buffer (adjusted to pH 3.0): acetonitrile in a ratio of 70:30 (v/v). Detection was accomplished using a full scan multi channel ESA Coulometric detector in the “oxidative-screen” mode with the upstream electrode (E1) set at +600 mV and the downstream (analytical) electrode (E2) set at +950 mV, while the potential of the guard cell was maintained at +1050 mV. The detector gain was set at 300. Experimental design using central composite design (CCD) was used to facilitate method development. Mobile phase pH, molarity and concentration of acetonitrile (ACN) were considered the critical factors to be studied to establish the retention time of CPT and cyclizine (CYC) that was used as the internal standard. Twenty experiments including centre points were undertaken and a quadratic model was derived for the retention time for CPT using the experimental data. The method was validated for linearity, accuracy, precision, limits of quantitation and detection, as per the ICH guidelines. The system was found to produce sharp and well-resolved peaks for CPT and CYC with retention times of 3.08 and 7.56 min, respectively. Linear regression analysis for the calibration curve showed a good linear relationship with a regression coefficient of 0.978 in the concentration range of 2–70 μg/mL. The linear regression equation was y = 0.0131x + 0.0275. The limits of detection (LOQ) and quantitation (LOD) were found to be 2.27 and 0.6 μg/mL, respectively. The method was used to analyze CPT in tablets. The wide range for linearity, accuracy, sensitivity, short retention time and composition of the mobile phase indicated that this method is better for the quantification of CPT than the pharmacopoeial methods.
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- Authors: Khamanga, Sandile M , Walker, Roderick B
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184056 , vital:44163 , xlink:href="https://doi.org/10.1016/j.talanta.2010.11.025"
- Description: An accurate, sensitive and specific high performance liquid chromatography–electrochemical detection (HPLC–ECD) method that was developed and validated for captopril (CPT) is presented. Separation was achieved using a Phenomenex® Luna 5 μm (C18) column and a mobile phase comprised of phosphate buffer (adjusted to pH 3.0): acetonitrile in a ratio of 70:30 (v/v). Detection was accomplished using a full scan multi channel ESA Coulometric detector in the “oxidative-screen” mode with the upstream electrode (E1) set at +600 mV and the downstream (analytical) electrode (E2) set at +950 mV, while the potential of the guard cell was maintained at +1050 mV. The detector gain was set at 300. Experimental design using central composite design (CCD) was used to facilitate method development. Mobile phase pH, molarity and concentration of acetonitrile (ACN) were considered the critical factors to be studied to establish the retention time of CPT and cyclizine (CYC) that was used as the internal standard. Twenty experiments including centre points were undertaken and a quadratic model was derived for the retention time for CPT using the experimental data. The method was validated for linearity, accuracy, precision, limits of quantitation and detection, as per the ICH guidelines. The system was found to produce sharp and well-resolved peaks for CPT and CYC with retention times of 3.08 and 7.56 min, respectively. Linear regression analysis for the calibration curve showed a good linear relationship with a regression coefficient of 0.978 in the concentration range of 2–70 μg/mL. The linear regression equation was y = 0.0131x + 0.0275. The limits of detection (LOQ) and quantitation (LOD) were found to be 2.27 and 0.6 μg/mL, respectively. The method was used to analyze CPT in tablets. The wide range for linearity, accuracy, sensitivity, short retention time and composition of the mobile phase indicated that this method is better for the quantification of CPT than the pharmacopoeial methods.
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