A sensitive and reliable method for the detection of lipid peroxidation in biological tissues
- Anoopkumar-Dukie, Shailendra, Walker, Roderick B, Daya, Santylal
- Authors: Anoopkumar-Dukie, Shailendra , Walker, Roderick B , Daya, Santylal
- Date: 2001
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184325 , vital:44208 , xlink:href="https://doi.org/10.1211/0022357011775299"
- Description: A simple, accurate and cost effective method has been designed for the determination of lipid peroxidation in biological tissue samples. The method was a modification and improvement on existing methods available for lipid peroxidation determination. Solid-phase extraction was used to separate the thiobarbituric acid–malondialdehyde complex from thiobarbituric acidreactive substances and HPLC was performed using a C18 (Waters Spherisorb, 5 µm, 250¬4.6 mm i.d.) column to achieve isolation of the complex. The procedure was validated with respect to linearity of calibration (0.998), precision, sensitivity and limits of quantitation (1 nmol mL−1) and detection (0.5 nmol mL−1). Resorcinol was used as an external standard. The method was tested by inducing free radical generation with a known free radical generator, quinolinic acid, in rat brain homogenate. The results showed that the method presented allowed detection of lipid peroxidation products at concentrations in the nanomolar (nM) range compared with the micromolar (µM) range detected by other methods, thus rendering it suitable for use with biological samples. In addition, the modified method allowed for detection of the purified lipid peroxidation products, thus eliminating the possibility of simultaneous detection of impurities that absorb at the same wavelength.
- Full Text:
- Date Issued: 2001
- Authors: Anoopkumar-Dukie, Shailendra , Walker, Roderick B , Daya, Santylal
- Date: 2001
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184325 , vital:44208 , xlink:href="https://doi.org/10.1211/0022357011775299"
- Description: A simple, accurate and cost effective method has been designed for the determination of lipid peroxidation in biological tissue samples. The method was a modification and improvement on existing methods available for lipid peroxidation determination. Solid-phase extraction was used to separate the thiobarbituric acid–malondialdehyde complex from thiobarbituric acidreactive substances and HPLC was performed using a C18 (Waters Spherisorb, 5 µm, 250¬4.6 mm i.d.) column to achieve isolation of the complex. The procedure was validated with respect to linearity of calibration (0.998), precision, sensitivity and limits of quantitation (1 nmol mL−1) and detection (0.5 nmol mL−1). Resorcinol was used as an external standard. The method was tested by inducing free radical generation with a known free radical generator, quinolinic acid, in rat brain homogenate. The results showed that the method presented allowed detection of lipid peroxidation products at concentrations in the nanomolar (nM) range compared with the micromolar (µM) range detected by other methods, thus rendering it suitable for use with biological samples. In addition, the modified method allowed for detection of the purified lipid peroxidation products, thus eliminating the possibility of simultaneous detection of impurities that absorb at the same wavelength.
- Full Text:
- Date Issued: 2001
Melatonin alters the photodegradation of paracetamol
- Anoopkumar-Dukie, Shailendra, Glass, Beverley D, Walker, Roderick B, Daya, Santylal
- Authors: Anoopkumar-Dukie, Shailendra , Glass, Beverley D , Walker, Roderick B , Daya, Santylal
- Date: 2000
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184357 , vital:44211 , xlink:href="https://doi.org/10.1211/146080800128735755"
- Description: The effects of melatonin, a known free-radical scavenger, on paracetamol in the presence of UV irradiation was studied by use of HPLC. The experiments were performed in air and nitrogen. The results show that the rate of photodegradation of melatonin is faster in air than in nitrogen whereas that of paracetamol is similar in air and nitrogen. When the two drugs were combined, melatonin retarded the degradation of paracetamol for up to 6h in the presence of nitrogen. However, in the presence of air melatonin rapidly enhances the photodegradation of paracetamol. This study shows that a combination of melatonin and paracetamol in the presence of air and UV irradiation can lead to rapid inactivation of both agents, thus raising important concerns about the possible use of melatonin as sunscreen
- Full Text:
- Date Issued: 2000
- Authors: Anoopkumar-Dukie, Shailendra , Glass, Beverley D , Walker, Roderick B , Daya, Santylal
- Date: 2000
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184357 , vital:44211 , xlink:href="https://doi.org/10.1211/146080800128735755"
- Description: The effects of melatonin, a known free-radical scavenger, on paracetamol in the presence of UV irradiation was studied by use of HPLC. The experiments were performed in air and nitrogen. The results show that the rate of photodegradation of melatonin is faster in air than in nitrogen whereas that of paracetamol is similar in air and nitrogen. When the two drugs were combined, melatonin retarded the degradation of paracetamol for up to 6h in the presence of nitrogen. However, in the presence of air melatonin rapidly enhances the photodegradation of paracetamol. This study shows that a combination of melatonin and paracetamol in the presence of air and UV irradiation can lead to rapid inactivation of both agents, thus raising important concerns about the possible use of melatonin as sunscreen
- Full Text:
- Date Issued: 2000
Synthesis and characterization of ZnO nanoparticle synthesized by a microwave-assisted combustion method and catalytic activity for the removal of ortho-nitrophenol
- Assi, Navid, Mohammadi, Ali, Sadr Manuchehri, Q, Walker, Roderick B
- Authors: Assi, Navid , Mohammadi, Ali , Sadr Manuchehri, Q , Walker, Roderick B
- Date: 2015
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183850 , vital:44075 , xlink:href="https://doi.org/10.1080/19443994.2014.891083"
- Description: ZnO nanoparticles were manufactured using microwave-assisted combustion. The structural and morphological properties of the nanoparticles were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy, and Fourier transform infrared spectroscopy. Photocatalytic degradation of ortho-nitrophenol (O-NP) in aqueous solution using the synthesized nanoparticles was performed under UV–C irradiation and is reported for the first time. The effect of the initial O-NP concentration, amount of photocatalyst, pH, and salt was investigated during photodegradation. Analysis of the degraded samples using HPLC with UV detection revealed that photocatalysis in the presence of ZnO nanoparticles removed 98% of the O-NP in 5 h. In addition, the photocatalytic degradation kinetics of O-NP were studied, and the results suggest that the data are best fitted to pseudo-first-order kinetic and Langmuir–Hinshelwood models.
- Full Text:
- Date Issued: 2015
- Authors: Assi, Navid , Mohammadi, Ali , Sadr Manuchehri, Q , Walker, Roderick B
- Date: 2015
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183850 , vital:44075 , xlink:href="https://doi.org/10.1080/19443994.2014.891083"
- Description: ZnO nanoparticles were manufactured using microwave-assisted combustion. The structural and morphological properties of the nanoparticles were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy, and Fourier transform infrared spectroscopy. Photocatalytic degradation of ortho-nitrophenol (O-NP) in aqueous solution using the synthesized nanoparticles was performed under UV–C irradiation and is reported for the first time. The effect of the initial O-NP concentration, amount of photocatalyst, pH, and salt was investigated during photodegradation. Analysis of the degraded samples using HPLC with UV detection revealed that photocatalysis in the presence of ZnO nanoparticles removed 98% of the O-NP in 5 h. In addition, the photocatalytic degradation kinetics of O-NP were studied, and the results suggest that the data are best fitted to pseudo-first-order kinetic and Langmuir–Hinshelwood models.
- Full Text:
- Date Issued: 2015
Simultaneous liposomal encapsulation of antibiotics and proteins: co-loading and characterization of rifampicin and Human Serum Albumin in soy-liposomes
- Bapolisi, Alain M, Nkanga, Christian I, Walker, Roderick B, Krause, Rui W M
- Authors: Bapolisi, Alain M , Nkanga, Christian I , Walker, Roderick B , Krause, Rui W M
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148617 , vital:38755 , https://doi.org/10.1016/j.jddst.2020.101751
- Description: The recurrent development of resistance to antimicrobial agents threatens the ability for successful treatment of infectious diseases. Hydrophobic antibiotics such as rifampicin (Rif) are particularly affected due to poor bioavailability. On the other hand, proteins play important roles in drug delivery and release. Further, the combination of antimicrobials with therapeutic proteins and their encapsulation in liposomes seems a promising approach for improvement of antimicrobial efficacy. This study aimed to encapsulate Rif simultaneously with a large protein, Human Serum Albumin (HSA) in liposomes made from an inexpensive crude soy lecithin (CSL).
- Full Text:
- Date Issued: 2020
- Authors: Bapolisi, Alain M , Nkanga, Christian I , Walker, Roderick B , Krause, Rui W M
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148617 , vital:38755 , https://doi.org/10.1016/j.jddst.2020.101751
- Description: The recurrent development of resistance to antimicrobial agents threatens the ability for successful treatment of infectious diseases. Hydrophobic antibiotics such as rifampicin (Rif) are particularly affected due to poor bioavailability. On the other hand, proteins play important roles in drug delivery and release. Further, the combination of antimicrobials with therapeutic proteins and their encapsulation in liposomes seems a promising approach for improvement of antimicrobial efficacy. This study aimed to encapsulate Rif simultaneously with a large protein, Human Serum Albumin (HSA) in liposomes made from an inexpensive crude soy lecithin (CSL).
- Full Text:
- Date Issued: 2020
DSC screening of potential prochlorperazine-excipient interactions in preformulation studies
- Brown, Michael E, Antunes, Edith M, Glass, Beverley M, Lebete, Mosimotsana L, Walker, Roderick B
- Authors: Brown, Michael E , Antunes, Edith M , Glass, Beverley M , Lebete, Mosimotsana L , Walker, Roderick B
- Date: 1999
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184367 , vital:44212 , xlink:href="https://doi.org/10.1023/A:1010150305542"
- Description: Differential scanning calorimetry was used to examine the thermal behaviour of mixtures of the drug prochlorperazine with standard excipients, to assess potential interactions, and of mixtures with cyclodextrins, to investigate inclusion complexation which could increase the photostability of the drug. For most of the excipients (magnesium stearate, stearic acid, Explotab®, Ac-Di-Sol®, Encompress® and Ludipress®, lactose and Starch 1500) disappearance or broadening of the melting endotherm of the drug indicated interactions. Lubritab® was the only 'inert' excipient tested. Mixtures of prochlorperazine and the cyclodextrins gave incomplete inclusion complexation as shown by only partial disappearance of the melting endotherm of the drug.
- Full Text: false
- Date Issued: 1999
- Authors: Brown, Michael E , Antunes, Edith M , Glass, Beverley M , Lebete, Mosimotsana L , Walker, Roderick B
- Date: 1999
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184367 , vital:44212 , xlink:href="https://doi.org/10.1023/A:1010150305542"
- Description: Differential scanning calorimetry was used to examine the thermal behaviour of mixtures of the drug prochlorperazine with standard excipients, to assess potential interactions, and of mixtures with cyclodextrins, to investigate inclusion complexation which could increase the photostability of the drug. For most of the excipients (magnesium stearate, stearic acid, Explotab®, Ac-Di-Sol®, Encompress® and Ludipress®, lactose and Starch 1500) disappearance or broadening of the melting endotherm of the drug indicated interactions. Lubritab® was the only 'inert' excipient tested. Mixtures of prochlorperazine and the cyclodextrins gave incomplete inclusion complexation as shown by only partial disappearance of the melting endotherm of the drug.
- Full Text: false
- Date Issued: 1999
Swelling, erosion and drug release characteristics of salbutamol sulfate from hydroxypropyl methylcellulose-based matrix tablets
- Chaibva, Faith A, Khamanga, Sandile M, Walker, Roderick B
- Authors: Chaibva, Faith A , Khamanga, Sandile M , Walker, Roderick B
- Date: 2010
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184139 , vital:44177 , xlink:href="https://doi.org/10.3109/03639045.2010.488648"
- Description: Background: Hydrophilic matrix formulations are important and simple technologies that are used to manufacture sustained release dosage forms. Method: Hydroxypropyl methylcellulose-based matrix tablets, with and without additives, were manufactured to investigate the rate of hydration, rate of erosion, and rate and mechanism of drug release. Scanning electron microscopy was used to assess changes in the microstructure of the tablets during drug release testing and whether these changes could be related to the rate of drug release from the formulations. Results: The results revealed that the rate of hydration and erosion was dependent on the polymer combination(s) used, which in turn affected the rate and mechanism of drug release from these formulations. It was also apparent that changes in the microstructure of matrix tablets could be related to the different rates of drug release that were observed from the test formulations. Conclusion: The use of scanning electron microscopy provides useful information to further understand drug release mechanisms from matrix tablets.
- Full Text:
- Date Issued: 2010
- Authors: Chaibva, Faith A , Khamanga, Sandile M , Walker, Roderick B
- Date: 2010
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184139 , vital:44177 , xlink:href="https://doi.org/10.3109/03639045.2010.488648"
- Description: Background: Hydrophilic matrix formulations are important and simple technologies that are used to manufacture sustained release dosage forms. Method: Hydroxypropyl methylcellulose-based matrix tablets, with and without additives, were manufactured to investigate the rate of hydration, rate of erosion, and rate and mechanism of drug release. Scanning electron microscopy was used to assess changes in the microstructure of the tablets during drug release testing and whether these changes could be related to the rate of drug release from the formulations. Results: The results revealed that the rate of hydration and erosion was dependent on the polymer combination(s) used, which in turn affected the rate and mechanism of drug release from these formulations. It was also apparent that changes in the microstructure of matrix tablets could be related to the different rates of drug release that were observed from the test formulations. Conclusion: The use of scanning electron microscopy provides useful information to further understand drug release mechanisms from matrix tablets.
- Full Text:
- Date Issued: 2010
Formulation and Characterisation of a Combination Captopril and Hydrochlorothiazide Microparticulate Dosage Form
- Chikukwa, Mellisa T R, Walker, Roderick B, Khamanga, Sandile M
- Authors: Chikukwa, Mellisa T R , Walker, Roderick B , Khamanga, Sandile M
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183200 , vital:43926 , xlink:href="https://doi.org/10.3390/pharmaceutics12080712"
- Description: Cardiovascular diseases such as hypertension and cardiac failure in South African children and adolescents are effectively managed long term, using a combination treatment of captopril and hydrochlorothiazide. The majority of commercially available pharmaceutical products are designed for adult patients and require extemporaneous manipulation, prior to administration to paediatric patients. There is a need to develop an age appropriate microparticulate dosing technology that is easy to swallow, dose and alter doses whilst overcoming the pharmacokinetic challenges of short half-life and biphasic pharmacokinetic disposition exhibited by hydrochlorothiazide and captopril. An emulsion solvent evaporation approach using different combinations of polymers was used to manufacture captopril and hydrochlorothiazide microparticles. Design of experiments was used to develop and analyse experimental data, and identifyoptimum formulation and process conditions for the preparation of the microparticles. Characterisation studies to establish encapsulation efficiency, in vitro release, shape, size and morphology of the microparticles were undertaken. The microparticles produced were in the micrometre size range, with an encapsulation efficiency >75% for both hydrochlorothiazide and captopril. The microparticulate technology is able to offer potential resolution to the half-life mediated dosing frequency of captopril as sustained release of the molecule was observed over a 12-h period. The release of hydrochlorothiazide of >80% suggests an improvement in solubility limited dissolution.
- Full Text:
- Date Issued: 2020
- Authors: Chikukwa, Mellisa T R , Walker, Roderick B , Khamanga, Sandile M
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183200 , vital:43926 , xlink:href="https://doi.org/10.3390/pharmaceutics12080712"
- Description: Cardiovascular diseases such as hypertension and cardiac failure in South African children and adolescents are effectively managed long term, using a combination treatment of captopril and hydrochlorothiazide. The majority of commercially available pharmaceutical products are designed for adult patients and require extemporaneous manipulation, prior to administration to paediatric patients. There is a need to develop an age appropriate microparticulate dosing technology that is easy to swallow, dose and alter doses whilst overcoming the pharmacokinetic challenges of short half-life and biphasic pharmacokinetic disposition exhibited by hydrochlorothiazide and captopril. An emulsion solvent evaporation approach using different combinations of polymers was used to manufacture captopril and hydrochlorothiazide microparticles. Design of experiments was used to develop and analyse experimental data, and identifyoptimum formulation and process conditions for the preparation of the microparticles. Characterisation studies to establish encapsulation efficiency, in vitro release, shape, size and morphology of the microparticles were undertaken. The microparticles produced were in the micrometre size range, with an encapsulation efficiency >75% for both hydrochlorothiazide and captopril. The microparticulate technology is able to offer potential resolution to the half-life mediated dosing frequency of captopril as sustained release of the molecule was observed over a 12-h period. The release of hydrochlorothiazide of >80% suggests an improvement in solubility limited dissolution.
- Full Text:
- Date Issued: 2020
Assessment of taste masking of captopril by ion-exchange resins using electronic gustatory system
- Chikukwa, Mellisa T R, Wesoly, Malgorzata, Korzeniowska, Aleksandra B, Ciosek-Skibinska, Patrycja, Walker, Roderick B, Khamanga, Sandile M M
- Authors: Chikukwa, Mellisa T R , Wesoly, Malgorzata , Korzeniowska, Aleksandra B , Ciosek-Skibinska, Patrycja , Walker, Roderick B , Khamanga, Sandile M M
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184710 , vital:44265 , xlink:href="https://doi.org/10.1080/10837450.2019.1687520"
- Description: The objective of the study was to mask the unpleasant taste of captopril (CPT). Taste masking was achieved by complexation of CPT with a basic ion exchange resin, Dowex® 66, using the batch method. Dowex® 66 was used for the adsorption of CPT, and physical and chemical parameters of the CPT resinates complex were evaluated. A central composite design was used to generate the experiments for the manufacture of resinates using different process and formulation variables. In vitro dissolution studies were performed for 2 h in 0.01N HCl (pH 1.6) using USP Apparatus I. The compatibility of CPT and the resin was evaluated by Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD). The resinates were evaluated for micromeritic properties and further characterised using FTIR, DSC, and PXRD. Response surface methodology was used to determine the significance of input variables on the CPT content and release. The CPT resin ratio was found to have a significant impact on content of the resinates and on CPT release. The formulations were also studied for taste masking ability by means of an electronic gustatory system – electronic tongue.
- Full Text:
- Date Issued: 2020
- Authors: Chikukwa, Mellisa T R , Wesoly, Malgorzata , Korzeniowska, Aleksandra B , Ciosek-Skibinska, Patrycja , Walker, Roderick B , Khamanga, Sandile M M
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184710 , vital:44265 , xlink:href="https://doi.org/10.1080/10837450.2019.1687520"
- Description: The objective of the study was to mask the unpleasant taste of captopril (CPT). Taste masking was achieved by complexation of CPT with a basic ion exchange resin, Dowex® 66, using the batch method. Dowex® 66 was used for the adsorption of CPT, and physical and chemical parameters of the CPT resinates complex were evaluated. A central composite design was used to generate the experiments for the manufacture of resinates using different process and formulation variables. In vitro dissolution studies were performed for 2 h in 0.01N HCl (pH 1.6) using USP Apparatus I. The compatibility of CPT and the resin was evaluated by Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD). The resinates were evaluated for micromeritic properties and further characterised using FTIR, DSC, and PXRD. Response surface methodology was used to determine the significance of input variables on the CPT content and release. The CPT resin ratio was found to have a significant impact on content of the resinates and on CPT release. The formulations were also studied for taste masking ability by means of an electronic gustatory system – electronic tongue.
- Full Text:
- Date Issued: 2020
The effect of variations in pH and temperature on stability of melatonin in aqueous solution
- Daya, Santylal, Walker, Roderick B, Glass, Beverley D, Anoopkumar-Dukie, Shailendra
- Authors: Daya, Santylal , Walker, Roderick B , Glass, Beverley D , Anoopkumar-Dukie, Shailendra
- Date: 2001
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184314 , vital:44207 , xlink:href="https://doi.org/10.1034/j.1600-079x.2001.310209.x"
- Description: Melatonin (N-acetyl-5-methoxytryptamine) has a diverse range of functions, including the control of neuroendocrine events. A number of studies have shown that melatonin may be of potential benefit for the treatment of insomnia, as well as neurodegenerative disorders. At present, there are numerous dosage forms of melatonin, with the oral route of administration being most popular. Presently, there is little information on the stability of melatonin over a pH range. With the changes in pH in the gastro-intestinal tract, as well as in different experimental conditions, information on the stability of melatonin would be important. We used a high-performance liquid chromatography method to determine the stability of melatonin solutions over a pH range (1.2–12) at room temperature and at 37°C over a period of 21 days. The results show that no melatonin degradation occurred in the first 2 days. From days 3 to 21, there was a gradual decline in melatonin at all pHs, with the decline not exceeding 30%. No decline in melatonin levels occurred in the first 2 days at 37°C. From days 3 to 21, melatonin levels declined gradually, with the decline not exceeding 29%.
- Full Text:
- Date Issued: 2001
- Authors: Daya, Santylal , Walker, Roderick B , Glass, Beverley D , Anoopkumar-Dukie, Shailendra
- Date: 2001
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184314 , vital:44207 , xlink:href="https://doi.org/10.1034/j.1600-079x.2001.310209.x"
- Description: Melatonin (N-acetyl-5-methoxytryptamine) has a diverse range of functions, including the control of neuroendocrine events. A number of studies have shown that melatonin may be of potential benefit for the treatment of insomnia, as well as neurodegenerative disorders. At present, there are numerous dosage forms of melatonin, with the oral route of administration being most popular. Presently, there is little information on the stability of melatonin over a pH range. With the changes in pH in the gastro-intestinal tract, as well as in different experimental conditions, information on the stability of melatonin would be important. We used a high-performance liquid chromatography method to determine the stability of melatonin solutions over a pH range (1.2–12) at room temperature and at 37°C over a period of 21 days. The results show that no melatonin degradation occurred in the first 2 days. From days 3 to 21, there was a gradual decline in melatonin at all pHs, with the decline not exceeding 30%. No decline in melatonin levels occurred in the first 2 days at 37°C. From days 3 to 21, melatonin levels declined gradually, with the decline not exceeding 29%.
- Full Text:
- Date Issued: 2001
Cyanide-induced free radical production and lipid peroxidation in rat brain homogenate is reduced by aspirin
- Daya, Santylal, Walker, Roderick B, Anoopkumar-Dukie, Shailendra
- Authors: Daya, Santylal , Walker, Roderick B , Anoopkumar-Dukie, Shailendra
- Date: 2000
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184346 , vital:44210 , xlink:href="https://doi.org/10.1007/BF02674529"
- Description: The neuroprotective properties of aspirin were investigated using cyanide-induced neurotoxicity as model. Cyanide, a known neurotoxic agent significantly increased lipid peroxidation and superoxide anion levels in rat brain homogenate in a concentration-dependent manner (0.25–1.0 mM). When homogenate, containing 1.0 mM KCN was cotreated with aspirin (1.0 mM) there was a significant decrease in lipid peroxidation. Aspirin (0.5 mM and 1.0 mM) also significantly reduced KCN-induced superoxide anion generation. The results of the present report therefore indicate a neuroprotective role for aspirin.
- Full Text:
- Date Issued: 2000
- Authors: Daya, Santylal , Walker, Roderick B , Anoopkumar-Dukie, Shailendra
- Date: 2000
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184346 , vital:44210 , xlink:href="https://doi.org/10.1007/BF02674529"
- Description: The neuroprotective properties of aspirin were investigated using cyanide-induced neurotoxicity as model. Cyanide, a known neurotoxic agent significantly increased lipid peroxidation and superoxide anion levels in rat brain homogenate in a concentration-dependent manner (0.25–1.0 mM). When homogenate, containing 1.0 mM KCN was cotreated with aspirin (1.0 mM) there was a significant decrease in lipid peroxidation. Aspirin (0.5 mM and 1.0 mM) also significantly reduced KCN-induced superoxide anion generation. The results of the present report therefore indicate a neuroprotective role for aspirin.
- Full Text:
- Date Issued: 2000
Ultrasound-Triggered Release of 5-Fluorouracil from Soy Lecithin Echogenic Liposomes
- Ezekiel, Charles I, Bapolisi, Alain M, Walker, Roderick B, Krause, Rui W M
- Authors: Ezekiel, Charles I , Bapolisi, Alain M , Walker, Roderick B , Krause, Rui W M
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183115 , vital:43913 , xlink:href="https://doi.org/10.3390/pharmaceutics13060821"
- Description: Colorectal cancer is the third most diagnosed cancer and the second leading cause of death. The use of 5-fluorouracil (5-FU) has been the major chemotherapeutic treatment for colorectal cancer patients. However, the efficacy of 5-FU is limited by drug resistance, and bone marrow toxicity through high-level expression of thymidylate synthase, justifying the need for improvement of the therapeutic index. In this study, the effects of ultrasound on echogenic 5-FU encapsulated crude soy liposomes were investigated for their potential to address these challenges. Liposomes were prepared by thin-film hydration using crude soy lecithin and cholesterol. Argon gas was entrapped in the liposomes for sonosensitivity (that is, responsiveness to ultrasound). The nanoparticles were characterized for particle size and morphology. The physicochemical properties were also evaluated using differential scanning calorimetry, Fourier transform infrared and X-ray diffraction. The release profile of 5-FU was assessed with and without 20 kHz low-frequency ultrasound waves at various amplitudes and exposure times. The result reveal that 5-FU-loaded liposomes were spherical with an encapsulation efficiency of approximately 60%. Approximately 65% of 5-FU was released at the highest amplitude and exposure time was investigated. The results are encouraging for the stimulated and controlled release of 5-FU for the management of colorectal cancer.
- Full Text:
- Date Issued: 2021
- Authors: Ezekiel, Charles I , Bapolisi, Alain M , Walker, Roderick B , Krause, Rui W M
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183115 , vital:43913 , xlink:href="https://doi.org/10.3390/pharmaceutics13060821"
- Description: Colorectal cancer is the third most diagnosed cancer and the second leading cause of death. The use of 5-fluorouracil (5-FU) has been the major chemotherapeutic treatment for colorectal cancer patients. However, the efficacy of 5-FU is limited by drug resistance, and bone marrow toxicity through high-level expression of thymidylate synthase, justifying the need for improvement of the therapeutic index. In this study, the effects of ultrasound on echogenic 5-FU encapsulated crude soy liposomes were investigated for their potential to address these challenges. Liposomes were prepared by thin-film hydration using crude soy lecithin and cholesterol. Argon gas was entrapped in the liposomes for sonosensitivity (that is, responsiveness to ultrasound). The nanoparticles were characterized for particle size and morphology. The physicochemical properties were also evaluated using differential scanning calorimetry, Fourier transform infrared and X-ray diffraction. The release profile of 5-FU was assessed with and without 20 kHz low-frequency ultrasound waves at various amplitudes and exposure times. The result reveal that 5-FU-loaded liposomes were spherical with an encapsulation efficiency of approximately 60%. Approximately 65% of 5-FU was released at the highest amplitude and exposure time was investigated. The results are encouraging for the stimulated and controlled release of 5-FU for the management of colorectal cancer.
- Full Text:
- Date Issued: 2021
Forced degradation studies of clobetasol 17‐propionate in methanol, propylene glycol, as bulk drug and cream formulations by RP‐HPLC
- Fauzee, Ayesha F, Walker, Roderick B
- Authors: Fauzee, Ayesha F , Walker, Roderick B
- Date: 2013
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184005 , vital:44154 , xlink:href="https://doi.org/10.1002/jssc.201200969"
- Description: A rapid, simple, stability-indicating forced degradation study of clobetasol 17-propionate was conducted using RP-HPLC. The method was used to analyze clobetasol 17-propionate in methanol, propylene glycol, and a cream formulation. Isocratic elution of clobetasol and its degradation products was achieved using a Nova-Pak® 4 μm C18 150 mm × 3.9 mm id cartridge column and a mobile phase of methanol: water (68:32 v/v) at a flow rate of 0.9 mL min−1. Quantitation was achieved with UV detection at 239 nm. Nondegraded clobetasol was eluted at a retention time of 6.0 min. Clobetasol 17-propionate was subjected to different stress conditions viz., acidic, basic, heat, oxidation, light, and neutral hydrolysis. The greatest degradation occurred under strong base and oxidative conditions. Strong base-degraded clobetasol produced additional peaks at retention times of 1.8, 4.0, 5.0, and 8.0 min and clobetasol oxidation degradation peaks eluted at 2.2 and 24 min. Complete validation was performed for linearity, accuracy, and precision over the concentration range 0.15–15 μg mL−1. All data were analyzed statistically and this RP-HPLC method proved to be accurate, precise, linear, and stability indicating for the quantitation of clobetasol 17-propionate in methanol, propylene glycol, and cream formulations.
- Full Text:
- Date Issued: 2013
- Authors: Fauzee, Ayesha F , Walker, Roderick B
- Date: 2013
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184005 , vital:44154 , xlink:href="https://doi.org/10.1002/jssc.201200969"
- Description: A rapid, simple, stability-indicating forced degradation study of clobetasol 17-propionate was conducted using RP-HPLC. The method was used to analyze clobetasol 17-propionate in methanol, propylene glycol, and a cream formulation. Isocratic elution of clobetasol and its degradation products was achieved using a Nova-Pak® 4 μm C18 150 mm × 3.9 mm id cartridge column and a mobile phase of methanol: water (68:32 v/v) at a flow rate of 0.9 mL min−1. Quantitation was achieved with UV detection at 239 nm. Nondegraded clobetasol was eluted at a retention time of 6.0 min. Clobetasol 17-propionate was subjected to different stress conditions viz., acidic, basic, heat, oxidation, light, and neutral hydrolysis. The greatest degradation occurred under strong base and oxidative conditions. Strong base-degraded clobetasol produced additional peaks at retention times of 1.8, 4.0, 5.0, and 8.0 min and clobetasol oxidation degradation peaks eluted at 2.2 and 24 min. Complete validation was performed for linearity, accuracy, and precision over the concentration range 0.15–15 μg mL−1. All data were analyzed statistically and this RP-HPLC method proved to be accurate, precise, linear, and stability indicating for the quantitation of clobetasol 17-propionate in methanol, propylene glycol, and cream formulations.
- Full Text:
- Date Issued: 2013
The impact of formulation variables on the optimization of pilot scale clobetasol 17-propionate creams
- Fauzee, Ayesha F B, Walker, Roderick B
- Authors: Fauzee, Ayesha F B , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183275 , vital:43937 , xlink:href="https://doi.org/10.1080/23311916.2020.1804713"
- Description: The impact of formulation variables on the optimization of pilot scale clobetasol 17-propionate (CP) cream formulations was investigated using a Central Composite Design of Experiments. Thirty batches of cream were manufactured and the formulation variables assessed were % v/v propylene glycol, % w/w Gelot® 64, cetostearyl alcohol and glyceryl monostearate content. The responses monitored included viscosity, spreadability, pH, CP content, extrudability, electrical conductivity, and % CP released at 72 hours. The responses were compared to those of a reference product, Dermovate® cream. ANOVA analysis revealed that viscosity, spreadability, and % CP released at 72 hours were significant formulation responses (p more than 0.05). Cetostearyl alcohol had the greatest impact on quality of pilot scale products. An increase in cetostearyl alcohol resulted in an increase in viscosity, a decrease in spreadability, and a decrease in % CP released at 72 hours. The optimized pilot scale CP formulation contained 46% v/v propylene glycol, 8.6% w/w cetostearyl alcohol, 10.5% w/w glyceryl monostearate, and 3.8% w/w Gelot® 64. The resultant viscosity, spreadability, pH, CP content, extrudability, electrical conductivity, and % CP released were 44633cP, 24.91cm2, 101.23 %, 76.98 g/cm2, 198.23 µS/cm, and 50.23%. The addition of cetostearyl alcohol and Gelot® 64 is critical for establishing a soft formulation that leads to the formation of a mixed crystal bilayer network of high viscosity. The formation of a separate crystalline lipophilic network usually occurs in semi-solid formulations that contain high concentrations of emulsifier, leading to an increase in shear stress and greater physicochemical stability of the formulation. The use of experimental design approaches to formulation development activities, permit evaluation of multiple factors simultaneously, reducing the time and costs associated with product development activities, whilst identifying a composition design space and ensuring stable and effective dosage forms are produced.
- Full Text:
- Date Issued: 2020
- Authors: Fauzee, Ayesha F B , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183275 , vital:43937 , xlink:href="https://doi.org/10.1080/23311916.2020.1804713"
- Description: The impact of formulation variables on the optimization of pilot scale clobetasol 17-propionate (CP) cream formulations was investigated using a Central Composite Design of Experiments. Thirty batches of cream were manufactured and the formulation variables assessed were % v/v propylene glycol, % w/w Gelot® 64, cetostearyl alcohol and glyceryl monostearate content. The responses monitored included viscosity, spreadability, pH, CP content, extrudability, electrical conductivity, and % CP released at 72 hours. The responses were compared to those of a reference product, Dermovate® cream. ANOVA analysis revealed that viscosity, spreadability, and % CP released at 72 hours were significant formulation responses (p more than 0.05). Cetostearyl alcohol had the greatest impact on quality of pilot scale products. An increase in cetostearyl alcohol resulted in an increase in viscosity, a decrease in spreadability, and a decrease in % CP released at 72 hours. The optimized pilot scale CP formulation contained 46% v/v propylene glycol, 8.6% w/w cetostearyl alcohol, 10.5% w/w glyceryl monostearate, and 3.8% w/w Gelot® 64. The resultant viscosity, spreadability, pH, CP content, extrudability, electrical conductivity, and % CP released were 44633cP, 24.91cm2, 101.23 %, 76.98 g/cm2, 198.23 µS/cm, and 50.23%. The addition of cetostearyl alcohol and Gelot® 64 is critical for establishing a soft formulation that leads to the formation of a mixed crystal bilayer network of high viscosity. The formation of a separate crystalline lipophilic network usually occurs in semi-solid formulations that contain high concentrations of emulsifier, leading to an increase in shear stress and greater physicochemical stability of the formulation. The use of experimental design approaches to formulation development activities, permit evaluation of multiple factors simultaneously, reducing the time and costs associated with product development activities, whilst identifying a composition design space and ensuring stable and effective dosage forms are produced.
- Full Text:
- Date Issued: 2020
The impact of manufacturing variables on in vitro release of clobetasol 17-propionate from pilot scale cream formulations
- Fauzee, Ayesha F B, Khamanga, Sandile M, Walker, Roderick B
- Authors: Fauzee, Ayesha F B , Khamanga, Sandile M , Walker, Roderick B
- Date: 2014
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183872 , vital:44077 , xlink:href="https://doi.org/10.3109/03639045.2013.842579"
- Description: The purpose of the study was to evaluate the effect of different homogenization speeds and times, anchor speeds and cooling times on the viscosity and cumulative % clobetasol 17-propionate released per unit area at 72 h from pilot scale cream formulations. A 24 full factorial central composite design for four independent variables were investigated. Thirty pilot scale batches of cream formulations were manufactured using a Wintech® cream/ointment plant. The viscosity and in vitro release of CP were monitored and compared to an innovator product that is commercially available on the South African market, namely, Dermovate® cream. Contour and three-dimensional response surface plots were produced and the viscosity and cumulative % CP released per unit area at 72 h were found to be primarily dependent on the homogenization and anchor speeds. An increase in the homogenization and anchor speeds appeared to exhibit a synergistic effect on the resultant viscosity of the cream whereas an antagonistic effect was observed for the in vitro release of CP from the experimental cream formulations. The in vitro release profiles were best fitted to a Higuchi model and diffusion proved to be the dominant mechanism of drug release that was confirmed by use of the Korsmeyer–Peppas model. The research was further validated and confirmed by the high prognostic ability of response surface methodology (RSM) with a resultant mean percentage error of (±SD) 0.17 ± 0.093 suggesting that RSM may be an efficient tool for the development and optimization of topical formulations.
- Full Text:
- Date Issued: 2014
- Authors: Fauzee, Ayesha F B , Khamanga, Sandile M , Walker, Roderick B
- Date: 2014
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183872 , vital:44077 , xlink:href="https://doi.org/10.3109/03639045.2013.842579"
- Description: The purpose of the study was to evaluate the effect of different homogenization speeds and times, anchor speeds and cooling times on the viscosity and cumulative % clobetasol 17-propionate released per unit area at 72 h from pilot scale cream formulations. A 24 full factorial central composite design for four independent variables were investigated. Thirty pilot scale batches of cream formulations were manufactured using a Wintech® cream/ointment plant. The viscosity and in vitro release of CP were monitored and compared to an innovator product that is commercially available on the South African market, namely, Dermovate® cream. Contour and three-dimensional response surface plots were produced and the viscosity and cumulative % CP released per unit area at 72 h were found to be primarily dependent on the homogenization and anchor speeds. An increase in the homogenization and anchor speeds appeared to exhibit a synergistic effect on the resultant viscosity of the cream whereas an antagonistic effect was observed for the in vitro release of CP from the experimental cream formulations. The in vitro release profiles were best fitted to a Higuchi model and diffusion proved to be the dominant mechanism of drug release that was confirmed by use of the Korsmeyer–Peppas model. The research was further validated and confirmed by the high prognostic ability of response surface methodology (RSM) with a resultant mean percentage error of (±SD) 0.17 ± 0.093 suggesting that RSM may be an efficient tool for the development and optimization of topical formulations.
- Full Text:
- Date Issued: 2014
Pharmacokinetics of cyclizine following intravenous administration to human volunteers
- Kanfer, Isadore, Walker, Roderick B
- Authors: Kanfer, Isadore , Walker, Roderick B
- Date: 1996
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184389 , vital:44214 , xlink:href="https://doi.org/10.1016/0928-0987(96)00177-7"
- Description: The pharmacokinetics of cyclizine, a piperazine derivative useful in the prevention and treatment of nausea and vomiting, was investigated in six healthy male volunteers following an intravenous bolus dose. The drug is extensively distributed with a mean volume of distribution of 16.50 ± 3.33 l/kg and a mean total clearance of 0.870 ± 0.105 l/h per kg. Urinary excretion data showed that less than one percent of the dose was excreted up to 36 h as unchanged drug in the urine. The extremely low mean renal clearance (0.005 ± 0.002 l/h per kg) for the parent drug comprised only a small proportion of total clearance indicating that urinary excretion of parent drug is not a major route of elimination for cyclizine. The drug appears to exhibit biexponential pharmacokinetics and has a terminal elimination half-life of approximately 13 h.
- Full Text:
- Date Issued: 1996
- Authors: Kanfer, Isadore , Walker, Roderick B
- Date: 1996
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184389 , vital:44214 , xlink:href="https://doi.org/10.1016/0928-0987(96)00177-7"
- Description: The pharmacokinetics of cyclizine, a piperazine derivative useful in the prevention and treatment of nausea and vomiting, was investigated in six healthy male volunteers following an intravenous bolus dose. The drug is extensively distributed with a mean volume of distribution of 16.50 ± 3.33 l/kg and a mean total clearance of 0.870 ± 0.105 l/h per kg. Urinary excretion data showed that less than one percent of the dose was excreted up to 36 h as unchanged drug in the urine. The extremely low mean renal clearance (0.005 ± 0.002 l/h per kg) for the parent drug comprised only a small proportion of total clearance indicating that urinary excretion of parent drug is not a major route of elimination for cyclizine. The drug appears to exhibit biexponential pharmacokinetics and has a terminal elimination half-life of approximately 13 h.
- Full Text:
- Date Issued: 1996
Analysis of macrolide antibiotics
- Kanfer, Isadore, Skinner, Michael F, Walker, Roderick B
- Authors: Kanfer, Isadore , Skinner, Michael F , Walker, Roderick B
- Date: 1998
- Language: English
- Type: Article , text
- Identifier: vital:7011 , http://hdl.handle.net/10962/d1008394 , http://www.sciencedirect.com/science/article/pii/S0021967398002763
- Description: The following macrolide antibiotics have been covered in this review: erythromycin and its related substances, azithromycin, clarithromycin, dirithromycin, roxithromycin, flurithromycin, josamycin, rokitamycin, kitasamycin, mycinamycin, mirosamycin, oleandomycin, rosaramicin, spiramycin and tylosin. The application of various thin-layer chromatography, paper chromatography, gas chromatography, high-performance liquid chromatography and capillary zone electrophoresis procedures for their analysis are described. These techniques have been applied to the separation and quantitative analysis of the macrolides in fermentation media, purity assessment of raw materials, assay of pharmaceutical dosage forms and the measurement of clinically useful macrolide antibiotics in biological samples such as blood, plasma, serum, urine and tissues. Data relating to the chromatographic behaviour of some macrolide antibiotics as well as the various detection methods used, such as bioautography, UV spectrophotometry, fluorometry, electrochemical detection, chemiluminescence and mass spectrometry techniques are also included.
- Full Text:
- Date Issued: 1998
- Authors: Kanfer, Isadore , Skinner, Michael F , Walker, Roderick B
- Date: 1998
- Language: English
- Type: Article , text
- Identifier: vital:7011 , http://hdl.handle.net/10962/d1008394 , http://www.sciencedirect.com/science/article/pii/S0021967398002763
- Description: The following macrolide antibiotics have been covered in this review: erythromycin and its related substances, azithromycin, clarithromycin, dirithromycin, roxithromycin, flurithromycin, josamycin, rokitamycin, kitasamycin, mycinamycin, mirosamycin, oleandomycin, rosaramicin, spiramycin and tylosin. The application of various thin-layer chromatography, paper chromatography, gas chromatography, high-performance liquid chromatography and capillary zone electrophoresis procedures for their analysis are described. These techniques have been applied to the separation and quantitative analysis of the macrolides in fermentation media, purity assessment of raw materials, assay of pharmaceutical dosage forms and the measurement of clinically useful macrolide antibiotics in biological samples such as blood, plasma, serum, urine and tissues. Data relating to the chromatographic behaviour of some macrolide antibiotics as well as the various detection methods used, such as bioautography, UV spectrophotometry, fluorometry, electrochemical detection, chemiluminescence and mass spectrometry techniques are also included.
- Full Text:
- Date Issued: 1998
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.
- Full Text:
- Date Issued: 2011
- 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.
- Full Text:
- Date Issued: 2011
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.
- Full Text:
- Date Issued: 2011
- 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.
- Full Text:
- Date Issued: 2011
The use of hot and cold high pressure homogenization to enhance the loading capacity and encapsulation efficiency of nanostructured lipid carriers for the hydrophilic antiretroviral drug, didanosine for potential administration to paediatric patients
- Kasongo, Kasongo W, Müller, Rainer H, Walker, Roderick B
- Authors: Kasongo, Kasongo W , Müller, Rainer H , Walker, Roderick B
- Date: 2012
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184087 , vital:44170 , xlink:href="https://doi.org/10.3109/10837450.2010.542163"
- Description: A major obstacle to the application of nanostructured lipid carriers (NLCs) as carriers for hydrophilic drugs is the limited loading capacity (LC) and encapsulation efficiency (EE) of NLCs for these molecules. The purpose of this research was to design and implement a strategy to enhance the LC and EE of NLCs for the hydrophilic drug, didanosine (DDI). DDI was dispersed in Transcutol® HP and the particle size of DDI in the liquid lipid was reduced gradually using hot high pressure homogenization (HPH). The product obtained thereafter was added to Precirol® ATO 5 and the hot mixture was immediately dried using liquid nitrogen. The dried materials were then ground and passed through a 200 μm sieve and the solid lipid particles were dispersed in a surfactant solution and subsequently used to manufacture DDI-loaded NLCs using cold HPH. The LC and EE of NLCs for DDI manufactured using the new strategy were 3.39 ± 0.63% and 51.58 ± 1.31%, respectively, compared to 0.079 ± 0.001% and 32.45 ± 0.08%, respectively, obtained when DDI-loaded NLCs were produced using conventional hot HPH. The enhanced LC and EE for DDI make NLCs a potential technology for the oral administration of DDI to paediatric patients.
- Full Text:
- Date Issued: 2012
- Authors: Kasongo, Kasongo W , Müller, Rainer H , Walker, Roderick B
- Date: 2012
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184087 , vital:44170 , xlink:href="https://doi.org/10.3109/10837450.2010.542163"
- Description: A major obstacle to the application of nanostructured lipid carriers (NLCs) as carriers for hydrophilic drugs is the limited loading capacity (LC) and encapsulation efficiency (EE) of NLCs for these molecules. The purpose of this research was to design and implement a strategy to enhance the LC and EE of NLCs for the hydrophilic drug, didanosine (DDI). DDI was dispersed in Transcutol® HP and the particle size of DDI in the liquid lipid was reduced gradually using hot high pressure homogenization (HPH). The product obtained thereafter was added to Precirol® ATO 5 and the hot mixture was immediately dried using liquid nitrogen. The dried materials were then ground and passed through a 200 μm sieve and the solid lipid particles were dispersed in a surfactant solution and subsequently used to manufacture DDI-loaded NLCs using cold HPH. The LC and EE of NLCs for DDI manufactured using the new strategy were 3.39 ± 0.63% and 51.58 ± 1.31%, respectively, compared to 0.079 ± 0.001% and 32.45 ± 0.08%, respectively, obtained when DDI-loaded NLCs were produced using conventional hot HPH. The enhanced LC and EE for DDI make NLCs a potential technology for the oral administration of DDI to paediatric patients.
- Full Text:
- Date Issued: 2012
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.
- Full Text:
- Date Issued: 2011
- 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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- Date Issued: 2011