Enhancement of Biological and Pharmacological Properties of an Encapsulated Polyphenol: Curcumin
- Witika, Bwalya A, Makoni, Pedzisai A, Matafwali, Scott K, Mweetwa, Larry L, Shandele, Ginnethon C, Walker, Roderick B
- Authors: Witika, Bwalya A , Makoni, Pedzisai A , Matafwali, Scott K , Mweetwa, Larry L , Shandele, Ginnethon C , Walker, Roderick B
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183161 , vital:43917 , xlink:href="https://doi.org/10.3390/molecules26144244"
- Description: There is a dearth of natural remedies available for the treatment of an increasing number of diseases facing mankind. Natural products may provide an opportunity to produce formulations and therapeutic solutions to address this shortage. Curcumin (CUR), diferuloylmethane; I,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione is the major pigment in turmeric powder which has been reported to exhibit a number of health benefits including, antibacterial, antiviral, anti-cancer, anti-inflammatory and anti-oxidant properties. In this review, the authors attempt to highlight the biological and pharmacological properties of CUR in addition to emphasizing aspects relating to the biosynthesis, encapsulation and therapeutic effects of the compound. The information contained in this review was generated by considering published information in which evidence of enhanced biological and pharmacological properties of nano-encapsulated CUR was reported. CUR has contributed to a significant improvement in melanoma, breast, lung, gastro-intestinal, and genito-urinary cancer therapy. We highlight the impact of nano-encapsulated CUR for efficient inhibition of cell proliferation, even at low concentrations compared to the free CUR when considering anti-proliferation. Furthermore nano-encapsulated CUR exhibited bioactive properties, exerted cytotoxic and anti-oxidant effects by acting on endogenous and cholinergic anti-oxidant systems. CUR was reported to block Hepatitis C virus (HCV) entry into hepatic cells, inhibit MRSA proliferation, enhance wound healing and reduce bacterial load. Nano-encapsulated CUR has also shown bioactive properties when acting on antioxidant systems (endogenous and cholinergic). Future research is necessary and must focus on investigation of encapsulated CUR nano-particles in different models of human pathology.
- Full Text:
- Date Issued: 2021
- Authors: Witika, Bwalya A , Makoni, Pedzisai A , Matafwali, Scott K , Mweetwa, Larry L , Shandele, Ginnethon C , Walker, Roderick B
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183161 , vital:43917 , xlink:href="https://doi.org/10.3390/molecules26144244"
- Description: There is a dearth of natural remedies available for the treatment of an increasing number of diseases facing mankind. Natural products may provide an opportunity to produce formulations and therapeutic solutions to address this shortage. Curcumin (CUR), diferuloylmethane; I,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione is the major pigment in turmeric powder which has been reported to exhibit a number of health benefits including, antibacterial, antiviral, anti-cancer, anti-inflammatory and anti-oxidant properties. In this review, the authors attempt to highlight the biological and pharmacological properties of CUR in addition to emphasizing aspects relating to the biosynthesis, encapsulation and therapeutic effects of the compound. The information contained in this review was generated by considering published information in which evidence of enhanced biological and pharmacological properties of nano-encapsulated CUR was reported. CUR has contributed to a significant improvement in melanoma, breast, lung, gastro-intestinal, and genito-urinary cancer therapy. We highlight the impact of nano-encapsulated CUR for efficient inhibition of cell proliferation, even at low concentrations compared to the free CUR when considering anti-proliferation. Furthermore nano-encapsulated CUR exhibited bioactive properties, exerted cytotoxic and anti-oxidant effects by acting on endogenous and cholinergic anti-oxidant systems. CUR was reported to block Hepatitis C virus (HCV) entry into hepatic cells, inhibit MRSA proliferation, enhance wound healing and reduce bacterial load. Nano-encapsulated CUR has also shown bioactive properties when acting on antioxidant systems (endogenous and cholinergic). Future research is necessary and must focus on investigation of encapsulated CUR nano-particles in different models of human pathology.
- Full Text:
- Date Issued: 2021
Nano Co-Crystal Embedded Stimuli-Responsive Hydrogels: A Potential Approach to Treat HIV/AIDS
- Witika, Bwalya A, Stander, Jessé-Clint, Smith, Vincent J, Walker, Roderick B
- Authors: Witika, Bwalya A , Stander, Jessé-Clint , Smith, Vincent J , Walker, Roderick B
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183137 , vital:43915 , xlink:href="https://doi.org/10.3390/pharmaceutics13020127"
- Description: Currently, the human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS) can only be treated successfully, using combination antiretroviral (ARV) therapy. Lamivudine (3TC) and zidovudine (AZT), two compounds used for the treatment of HIV and prevention of disease progression to AIDS are used in such combinations. Successful therapy with 3TC and AZT requires frequent dosing that may lead to reduced adherence, resistance and consequently treatment failure. Improved toxicity profiles of 3TC and AZT were observed when combined as a nano co-crystal (NCC). The use of stimuli-responsive delivery systems provides an opportunity to overcome the challenge of frequent dosing, by controlling and/or sustaining delivery of drugs. Preliminary studies undertaken to identify a suitable composition for a stimulus-responsive in situ forming hydrogel carrier for 3TC-AZT NCC were conducted, and the gelation and erosion time were determined. A 25% w/w Pluronic® F-127 thermoresponsive hydrogel was identified as a suitable carrier as it exhibited a gelation time of 5 min and an erosion time of 7 days. NCC-loaded hydrogels were evaluated using in vitro dissolution and cytotoxicity assays. In vitro dissolution undertaken using membrane-less diffusion over 168 h revealed that 3TC and AZT release from NCC-loaded hydrogels was complete and followed zero-order kinetic processes, whereas those loaded with the micro co-crystal and physical mixture were incomplete and best described using the Korsmeyer–Peppas kinetic model. The release of AZT and 3TC from the physical mixture and MCC-loaded gel exhibited a value for n of 0.595 for AZT release from the physical mixture and 0.540 for the MCC technology, whereas the release exponent for 3TC was 0.513 for the physical mixture and 0.557 for the MCC technology indicating that diffusion and erosion controlled 3TC and AZT release. In vitro cytotoxicity assay data revealed that the addition of NCC to the thermoresponsive hydrogel resulted in an improved cell viability of 88.0% ± 5.0% when compared to the cell viability of the NCC of 76.9% ± 5.0%. The results suggest that the use of a thermoresponsive nanosuspension may have the potential to be delivered as an intramuscular injection that can subsequently increase bioavailability and permit dose reduction and/or permit use of a longer dosing frequency.
- Full Text:
- Date Issued: 2021
- Authors: Witika, Bwalya A , Stander, Jessé-Clint , Smith, Vincent J , Walker, Roderick B
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183137 , vital:43915 , xlink:href="https://doi.org/10.3390/pharmaceutics13020127"
- Description: Currently, the human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS) can only be treated successfully, using combination antiretroviral (ARV) therapy. Lamivudine (3TC) and zidovudine (AZT), two compounds used for the treatment of HIV and prevention of disease progression to AIDS are used in such combinations. Successful therapy with 3TC and AZT requires frequent dosing that may lead to reduced adherence, resistance and consequently treatment failure. Improved toxicity profiles of 3TC and AZT were observed when combined as a nano co-crystal (NCC). The use of stimuli-responsive delivery systems provides an opportunity to overcome the challenge of frequent dosing, by controlling and/or sustaining delivery of drugs. Preliminary studies undertaken to identify a suitable composition for a stimulus-responsive in situ forming hydrogel carrier for 3TC-AZT NCC were conducted, and the gelation and erosion time were determined. A 25% w/w Pluronic® F-127 thermoresponsive hydrogel was identified as a suitable carrier as it exhibited a gelation time of 5 min and an erosion time of 7 days. NCC-loaded hydrogels were evaluated using in vitro dissolution and cytotoxicity assays. In vitro dissolution undertaken using membrane-less diffusion over 168 h revealed that 3TC and AZT release from NCC-loaded hydrogels was complete and followed zero-order kinetic processes, whereas those loaded with the micro co-crystal and physical mixture were incomplete and best described using the Korsmeyer–Peppas kinetic model. The release of AZT and 3TC from the physical mixture and MCC-loaded gel exhibited a value for n of 0.595 for AZT release from the physical mixture and 0.540 for the MCC technology, whereas the release exponent for 3TC was 0.513 for the physical mixture and 0.557 for the MCC technology indicating that diffusion and erosion controlled 3TC and AZT release. In vitro cytotoxicity assay data revealed that the addition of NCC to the thermoresponsive hydrogel resulted in an improved cell viability of 88.0% ± 5.0% when compared to the cell viability of the NCC of 76.9% ± 5.0%. The results suggest that the use of a thermoresponsive nanosuspension may have the potential to be delivered as an intramuscular injection that can subsequently increase bioavailability and permit dose reduction and/or permit use of a longer dosing frequency.
- Full Text:
- Date Issued: 2021
Top-Down Synthesis of a Lamivudine-Zidovudine Nano Co-Crystal
- Witika, Bwalya A, Smith, Vincent J, Walker, Roderick B
- Authors: Witika, Bwalya A , Smith, Vincent J , Walker, Roderick B
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183172 , vital:43918 , xlink:href="https://doi.org/10.3390/cryst11010033"
- Description: Lamivudine (3TC) and zidovudine (AZT) are antiretroviral agents used to manage HIV/AIDS infection. A wet media milling top-down approach was used to develop and produce nano co-crystals of 3TC and AZT. Micro co-crystals were prepared by solvent evaporation and subsequently milled in the presence of two surfactants, viz., sodium lauryl sulfate (SLS) and α-tocopheryl polyethylene glycol succinate 1000 (TPGS 1000). Optimisation was undertaken using design of experiments (DoE) and response surface methodology (RSM) to establish and identify parameters that may affect the manufacturing of nano co-crystals. The impact of SLS and TPGS 1000 concentration, milling time, and number of units of milling medium on the manufacturing of nano co-crystals, was investigated. The critical quality attributes (CQA) monitored were particle size (PS), Zeta potential (ZP), and polydispersity index (PDI). Powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, transmission electron microscopy, energy dispersive X-ray spectroscopy scanning electron microscopy, and cytotoxicity assays were used for additional characterization of the optimised nano co-crystal. The mean PS, PDI, and ZP of the optimised top-down nanocrystal were 271.0 ± 92.0 nm, 0.467 ± 0.073, and −41.9 ± 3.94 mV, respectively. In conclusion, a simple, inexpensive, rapid, and precise method of nano co-crystal manufacturing was developed, validated, and optimised using DoE and RSM, and the final product exhibited the target CQA.
- Full Text:
- Date Issued: 2021
- Authors: Witika, Bwalya A , Smith, Vincent J , Walker, Roderick B
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183172 , vital:43918 , xlink:href="https://doi.org/10.3390/cryst11010033"
- Description: Lamivudine (3TC) and zidovudine (AZT) are antiretroviral agents used to manage HIV/AIDS infection. A wet media milling top-down approach was used to develop and produce nano co-crystals of 3TC and AZT. Micro co-crystals were prepared by solvent evaporation and subsequently milled in the presence of two surfactants, viz., sodium lauryl sulfate (SLS) and α-tocopheryl polyethylene glycol succinate 1000 (TPGS 1000). Optimisation was undertaken using design of experiments (DoE) and response surface methodology (RSM) to establish and identify parameters that may affect the manufacturing of nano co-crystals. The impact of SLS and TPGS 1000 concentration, milling time, and number of units of milling medium on the manufacturing of nano co-crystals, was investigated. The critical quality attributes (CQA) monitored were particle size (PS), Zeta potential (ZP), and polydispersity index (PDI). Powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, transmission electron microscopy, energy dispersive X-ray spectroscopy scanning electron microscopy, and cytotoxicity assays were used for additional characterization of the optimised nano co-crystal. The mean PS, PDI, and ZP of the optimised top-down nanocrystal were 271.0 ± 92.0 nm, 0.467 ± 0.073, and −41.9 ± 3.94 mV, respectively. In conclusion, a simple, inexpensive, rapid, and precise method of nano co-crystal manufacturing was developed, validated, and optimised using DoE and RSM, and the final product exhibited the target CQA.
- Full Text:
- Date Issued: 2021
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
A comparative study of the effect of different stabilizers on the critical quality attributes of self-assembling nano co-crystals
- Witika, Bwalya A, Smith, Vincent J, Walker, Roderick B
- Authors: Witika, Bwalya A , Smith, Vincent J , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183224 , vital:43931 , xlink:href=" https://doi.org/10.3390/pharmaceutics12020182"
- Description: Lamivudine (3TC) and zidovudine (AZT) are antiviral agents used orally to manage HIV/AIDS infection. A pseudo one-solvent bottom-up approach was used to develop and produce nano co-crystals of 3TC and AZT. Equimolar amounts of 3TC dissolved in de-ionized water and AZT in methanol were rapidly injected into a pre-cooled vessel and sonicated at 4 °C. The resultant suspensions were characterized using a Zetasizer. The particle size, polydispersity index and Zeta potential were elucidated. Further characterization was undertaken using powder X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and energy dispersive X-ray spectroscopy scanning electron microscopy. Different surfactants were assessed for their ability to stabilize the nano co-crystals and for their ability to produce nano co-crystals with specific and desirable critical quality attributes (CQA) including particle size (PS) less than 1000 nm, polydispersity index (PDI) less than 0.500 and Zeta potential (ZP) less than −30 mV. All surfactants produced co-crystals in the nanometer range. The PDI and PS are concentration-dependent for all nano co-crystals manufactured while only ZP was within specification when sodium dodecyl sulfate was used in the process.
- Full Text:
- Date Issued: 2020
- Authors: Witika, Bwalya A , Smith, Vincent J , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183224 , vital:43931 , xlink:href=" https://doi.org/10.3390/pharmaceutics12020182"
- Description: Lamivudine (3TC) and zidovudine (AZT) are antiviral agents used orally to manage HIV/AIDS infection. A pseudo one-solvent bottom-up approach was used to develop and produce nano co-crystals of 3TC and AZT. Equimolar amounts of 3TC dissolved in de-ionized water and AZT in methanol were rapidly injected into a pre-cooled vessel and sonicated at 4 °C. The resultant suspensions were characterized using a Zetasizer. The particle size, polydispersity index and Zeta potential were elucidated. Further characterization was undertaken using powder X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and energy dispersive X-ray spectroscopy scanning electron microscopy. Different surfactants were assessed for their ability to stabilize the nano co-crystals and for their ability to produce nano co-crystals with specific and desirable critical quality attributes (CQA) including particle size (PS) less than 1000 nm, polydispersity index (PDI) less than 0.500 and Zeta potential (ZP) less than −30 mV. All surfactants produced co-crystals in the nanometer range. The PDI and PS are concentration-dependent for all nano co-crystals manufactured while only ZP was within specification when sodium dodecyl sulfate was used in the process.
- Full Text:
- Date Issued: 2020
Biocompatibility of biomaterials for nanoencapsulation: Current approaches
- Witika, Bwalya A, Makoni, Pedzisai A, Matafwali, Scott K, Chabalenge, Billy, Mwila, Chiluba, Kalungia, Aubrey C, Nkanga, Christian I, Bapolisi, Alain M, Walker, Roderick B
- Authors: Witika, Bwalya A , Makoni, Pedzisai A , Matafwali, Scott K , Chabalenge, Billy , Mwila, Chiluba , Kalungia, Aubrey C , Nkanga, Christian I , Bapolisi, Alain M , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183289 , vital:43939 , xlink:href="https://doi.org/10.3390/nano10091649"
- Description: Nanoencapsulation is an approach to circumvent shortcomings such as reduced bioavailability, undesirable side effects, frequent dosing and unpleasant organoleptic properties of conventional drug delivery systems. The process of nanoencapsulation involves the use of biomaterials such as surfactants and/or polymers, often in combination with charge inducers and/or ligands for targeting. The biomaterials selected for nanoencapsulation processes must be as biocompatible as possible. The type(s) of biomaterials used for different nanoencapsulation approaches are highlighted and their use and applicability with regard to haemo- and, histocompatibility, cytotoxicity, genotoxicity and carcinogenesis are discussed.
- Full Text:
- Date Issued: 2020
- Authors: Witika, Bwalya A , Makoni, Pedzisai A , Matafwali, Scott K , Chabalenge, Billy , Mwila, Chiluba , Kalungia, Aubrey C , Nkanga, Christian I , Bapolisi, Alain M , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183289 , vital:43939 , xlink:href="https://doi.org/10.3390/nano10091649"
- Description: Nanoencapsulation is an approach to circumvent shortcomings such as reduced bioavailability, undesirable side effects, frequent dosing and unpleasant organoleptic properties of conventional drug delivery systems. The process of nanoencapsulation involves the use of biomaterials such as surfactants and/or polymers, often in combination with charge inducers and/or ligands for targeting. The biomaterials selected for nanoencapsulation processes must be as biocompatible as possible. The type(s) of biomaterials used for different nanoencapsulation approaches are highlighted and their use and applicability with regard to haemo- and, histocompatibility, cytotoxicity, genotoxicity and carcinogenesis are discussed.
- Full Text:
- Date Issued: 2020
Design, Optimization, Manufacture and Characterization of Efavirenz-Loaded Flaxseed Oil Nanoemulsions
- Mazonde, Priveledge, Khamanga, Sandile M, Walker, Roderick B
- Authors: Mazonde, Priveledge , Khamanga, Sandile M , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183183 , vital:43919 , xlink:href="https://doi.org/10.3390/pharmaceutics12090797"
- Description: The formation, manufacture and characterization of low energy water-in-oil (w/o) nanoemulsions prepared using cold pressed flaxseed oil containing efavirenz was investigated. Pseudo-ternary phase diagrams were constructed to identify the nanoemulsion region(s). Other potential lipid-based drug delivery phases containing flaxseed oil with 1:1 m/m surfactant mixture of Tween® 80, Span® 20 and different amounts of ethanol were tested to characterize the impact of surfactant mixture on emulsion formation. Flaxseed oil was used as the oil phase as efavirenz exhibited high solubility in the vehicle when compared to other vegetable oils tested. Optimization of surfactant mixtures was undertaken using design of experiments, specifically a D-optimal design with the flaxseed oil content set at 10% m/m. Two solutions from the desired optimization function were produced based on desirability and five nanoemulsion formulations were produced and characterized in terms of in vitro release of efavirenz, physical and chemical stability. Metastable nanoemulsions containing 10% m/m flaxseed oil were successfully manufactured and significant isotropic gel (semisolid) and o/w emulsions were observed during phase behavior studies. Droplet sizes ranged between 156 and 225 nm, zeta potential between −24 and −41 mV and all formulations were found to be monodisperse with polydispersity indices ≤ 0.487.
- Full Text:
- Date Issued: 2020
- Authors: Mazonde, Priveledge , Khamanga, Sandile M , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183183 , vital:43919 , xlink:href="https://doi.org/10.3390/pharmaceutics12090797"
- Description: The formation, manufacture and characterization of low energy water-in-oil (w/o) nanoemulsions prepared using cold pressed flaxseed oil containing efavirenz was investigated. Pseudo-ternary phase diagrams were constructed to identify the nanoemulsion region(s). Other potential lipid-based drug delivery phases containing flaxseed oil with 1:1 m/m surfactant mixture of Tween® 80, Span® 20 and different amounts of ethanol were tested to characterize the impact of surfactant mixture on emulsion formation. Flaxseed oil was used as the oil phase as efavirenz exhibited high solubility in the vehicle when compared to other vegetable oils tested. Optimization of surfactant mixtures was undertaken using design of experiments, specifically a D-optimal design with the flaxseed oil content set at 10% m/m. Two solutions from the desired optimization function were produced based on desirability and five nanoemulsion formulations were produced and characterized in terms of in vitro release of efavirenz, physical and chemical stability. Metastable nanoemulsions containing 10% m/m flaxseed oil were successfully manufactured and significant isotropic gel (semisolid) and o/w emulsions were observed during phase behavior studies. Droplet sizes ranged between 156 and 225 nm, zeta potential between −24 and −41 mV and all formulations were found to be monodisperse with polydispersity indices ≤ 0.487.
- Full Text:
- Date Issued: 2020
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
Improved Stability of Rifampicin in the Presence of Gastric-Resistant Isoniazid Microspheres in Acidic Media
- Mwila, Chiluba, Walker, Roderick B
- Authors: Mwila, Chiluba , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183210 , vital:43929 , xlink:href="https://doi.org/10.3390/pharmaceutics12030234"
- Description: The degradation of rifampicin (RIF) in an acidic medium to form 3-formyl rifamycin SV, a poorly absorbed compound, is accelerated in the presence of isoniazid, contributing to the poor bioavailability of rifampicin. This manuscript presents a novel approach in which isoniazid is formulated into gastric-resistant sustained-release microspheres and RIF into microporous floating sustained-release microspheres to reduce the potential for interaction between RIF and isoniazid (INH) in an acidic environment. Hydroxypropyl methylcellulose acetate succinate and Eudragit® L100 polymers were used for the manufacture of isoniazid-loaded gastric-resistant sustained-release microspheres using an o/o solvent emulsification evaporation approach. Microporous floating sustained-release microspheres for the delivery of rifampicin in the stomach were manufactured using emulsification and a diffusion/evaporation process. The design of experiments was used to evaluate the impact of input variables on predefined responses or quality attributes of the microspheres. The percent degradation of rifampicin following 12 h dissolution testing in 0.1 M HCl pH 1.2 in the presence of isoniazid gastric-resistant sustained-release microspheres was only 4.44%. These results indicate that the degradation of rifampicin in the presence of isoniazid in acidic media can be reduced by encapsulation of both active pharmaceutical ingredients to ensure release in different segments of the gastrointestinal tract, potentially improving the bioavailability of rifampicin.
- Full Text:
- Date Issued: 2020
- Authors: Mwila, Chiluba , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183210 , vital:43929 , xlink:href="https://doi.org/10.3390/pharmaceutics12030234"
- Description: The degradation of rifampicin (RIF) in an acidic medium to form 3-formyl rifamycin SV, a poorly absorbed compound, is accelerated in the presence of isoniazid, contributing to the poor bioavailability of rifampicin. This manuscript presents a novel approach in which isoniazid is formulated into gastric-resistant sustained-release microspheres and RIF into microporous floating sustained-release microspheres to reduce the potential for interaction between RIF and isoniazid (INH) in an acidic environment. Hydroxypropyl methylcellulose acetate succinate and Eudragit® L100 polymers were used for the manufacture of isoniazid-loaded gastric-resistant sustained-release microspheres using an o/o solvent emulsification evaporation approach. Microporous floating sustained-release microspheres for the delivery of rifampicin in the stomach were manufactured using emulsification and a diffusion/evaporation process. The design of experiments was used to evaluate the impact of input variables on predefined responses or quality attributes of the microspheres. The percent degradation of rifampicin following 12 h dissolution testing in 0.1 M HCl pH 1.2 in the presence of isoniazid gastric-resistant sustained-release microspheres was only 4.44%. These results indicate that the degradation of rifampicin in the presence of isoniazid in acidic media can be reduced by encapsulation of both active pharmaceutical ingredients to ensure release in different segments of the gastrointestinal tract, potentially improving the bioavailability of rifampicin.
- Full Text:
- Date Issued: 2020
Nano-biomimetic drug delivery vehicles: Potential approaches for COVID-19 treatment
- Witika, Bwalya A, Makoni, Pedzisai A, Mweetwa, Larry L, Ntemi, Pascal V, Chikukwa, Mellisa T R, Matafwali, Scott K, Mwila, Chiluba, Mudenda, Steward, Katandula, Jonathan, Walker, Roderick B
- Authors: Witika, Bwalya A , Makoni, Pedzisai A , Mweetwa, Larry L , Ntemi, Pascal V , Chikukwa, Mellisa T R , Matafwali, Scott K , Mwila, Chiluba , Mudenda, Steward , Katandula, Jonathan , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183440 , vital:43991 , xlink:href="https://doi.org/10.3390/molecules25245952"
- Description: The current COVID-19 pandemic has tested the resolve of the global community with more than 35 million infections worldwide and numbers increasing with no cure or vaccine available to date. Nanomedicines have an advantage of providing enhanced permeability and retention and have been extensively studied as targeted drug delivery strategies for the treatment of different disease. The role of monocytes, erythrocytes, thrombocytes, and macrophages in diseases, including infectious and inflammatory diseases, cancer, and atherosclerosis, are better understood and have resulted in improved strategies for targeting and in some instances mimicking these cell types to improve therapeutic outcomes. Consequently, these primary cell types can be exploited for the purposes of serving as a "Trojan horse" for targeted delivery to identified organs and sites of inflammation. State of the art and potential utilization of nanocarriers such as nanospheres/nanocapsules, nanocrystals, liposomes, solid lipid nanoparticles/nano-structured lipid carriers, dendrimers, and nanosponges for biomimicry and/or targeted delivery of bioactives to cells are reported herein and their potential use in the treatment of COVID-19 infections discussed. Physicochemical properties, viz., hydrophilicity, particle shape, surface charge, composition, concentration, the use of different target-specific ligands on the surface of carriers, and the impact on carrier efficacy and specificity are also discussed.
- Full Text:
- Date Issued: 2020
- Authors: Witika, Bwalya A , Makoni, Pedzisai A , Mweetwa, Larry L , Ntemi, Pascal V , Chikukwa, Mellisa T R , Matafwali, Scott K , Mwila, Chiluba , Mudenda, Steward , Katandula, Jonathan , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183440 , vital:43991 , xlink:href="https://doi.org/10.3390/molecules25245952"
- Description: The current COVID-19 pandemic has tested the resolve of the global community with more than 35 million infections worldwide and numbers increasing with no cure or vaccine available to date. Nanomedicines have an advantage of providing enhanced permeability and retention and have been extensively studied as targeted drug delivery strategies for the treatment of different disease. The role of monocytes, erythrocytes, thrombocytes, and macrophages in diseases, including infectious and inflammatory diseases, cancer, and atherosclerosis, are better understood and have resulted in improved strategies for targeting and in some instances mimicking these cell types to improve therapeutic outcomes. Consequently, these primary cell types can be exploited for the purposes of serving as a "Trojan horse" for targeted delivery to identified organs and sites of inflammation. State of the art and potential utilization of nanocarriers such as nanospheres/nanocapsules, nanocrystals, liposomes, solid lipid nanoparticles/nano-structured lipid carriers, dendrimers, and nanosponges for biomimicry and/or targeted delivery of bioactives to cells are reported herein and their potential use in the treatment of COVID-19 infections discussed. Physicochemical properties, viz., hydrophilicity, particle shape, surface charge, composition, concentration, the use of different target-specific ligands on the surface of carriers, and the impact on carrier efficacy and specificity are also discussed.
- Full Text:
- Date Issued: 2020
An artificial neural network approach to predict the effects of formulation and process variables on prednisone release from a multipartite system
- Manda, Arthur, Walker, Roderick B, Khamanga, Sandile M
- Authors: Manda, Arthur , Walker, Roderick B , Khamanga, Sandile M
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183237 , vital:43933 , xlink:href="https://doi.org/10.3390/pharmaceutics11030109"
- Description: The impact of formulation and process variables on the in-vitro release of prednisone from a multiple-unit pellet system was investigated. Box-Behnken Response Surface Methodology (RSM) was used to generate multivariate experiments. The extrusion-spheronization method was used to produce pellets and dissolution studies were performed using United States Pharmacopoeia (USP) Apparatus 2 as described in USP XXIV. Analysis of dissolution test samples was performed using a reversed-phase high-performance liquid chromatography (RP-HPLC) method. Four formulation and process variables viz., microcrystalline cellulose concentration, sodium starch glycolate concentration, spheronization time and extrusion speed were investigated and drug release, aspect ratio and yield were monitored for the trained artificial neural networks (ANN). To achieve accurate prediction, data generated from experimentation were used to train a multi-layer perceptron (MLP) using back propagation (BP) and the Broyden-Fletcher-Goldfarb-Shanno (BFGS) 57 training algorithm until a satisfactory value of root mean square error (RMSE) was observed. The study revealed that the in-vitro release profile of prednisone was significantly impacted by microcrystalline cellulose concentration and sodium starch glycolate concentration. Increasing microcrystalline cellulose concentration retarded dissolution rate whereas increasing sodium starch glycolate concentration improved dissolution rate. Spheronization time and extrusion speed had minimal impact on prednisone release but had a significant impact on extrudate and pellet quality. This work demonstrated that RSM can be successfully used concurrently with ANN for dosage form manufacture to permit the exploration of experimental regions that are omitted when using RSM alone.
- Full Text:
- Date Issued: 2019
- Authors: Manda, Arthur , Walker, Roderick B , Khamanga, Sandile M
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183237 , vital:43933 , xlink:href="https://doi.org/10.3390/pharmaceutics11030109"
- Description: The impact of formulation and process variables on the in-vitro release of prednisone from a multiple-unit pellet system was investigated. Box-Behnken Response Surface Methodology (RSM) was used to generate multivariate experiments. The extrusion-spheronization method was used to produce pellets and dissolution studies were performed using United States Pharmacopoeia (USP) Apparatus 2 as described in USP XXIV. Analysis of dissolution test samples was performed using a reversed-phase high-performance liquid chromatography (RP-HPLC) method. Four formulation and process variables viz., microcrystalline cellulose concentration, sodium starch glycolate concentration, spheronization time and extrusion speed were investigated and drug release, aspect ratio and yield were monitored for the trained artificial neural networks (ANN). To achieve accurate prediction, data generated from experimentation were used to train a multi-layer perceptron (MLP) using back propagation (BP) and the Broyden-Fletcher-Goldfarb-Shanno (BFGS) 57 training algorithm until a satisfactory value of root mean square error (RMSE) was observed. The study revealed that the in-vitro release profile of prednisone was significantly impacted by microcrystalline cellulose concentration and sodium starch glycolate concentration. Increasing microcrystalline cellulose concentration retarded dissolution rate whereas increasing sodium starch glycolate concentration improved dissolution rate. Spheronization time and extrusion speed had minimal impact on prednisone release but had a significant impact on extrudate and pellet quality. This work demonstrated that RSM can be successfully used concurrently with ANN for dosage form manufacture to permit the exploration of experimental regions that are omitted when using RSM alone.
- Full Text:
- Date Issued: 2019
Short term stability testing of efavirenz-loaded solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC) dispersions
- Makoni, Pedzisai A, Kasongo, Kasongo W, Walker, Roderick B
- Authors: Makoni, Pedzisai A , Kasongo, Kasongo W , Walker, Roderick B
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183492 , vital:44000 , xlink:href="https://doi.org/10.3390/pharmaceutics11080397"
- Description: The short term stability of efavirenz-loaded solid lipid nanoparticle and nanostructured lipid carrier dispersions was investigated. Hot High Pressure Homogenization with the capability for scale up production was successfully used to manufacture the nanocarriers without the use of toxic organic solvents for the first time. Glyceryl monostearate and Transcutol® HP were used as the solid and liquid lipids. Tween® 80 was used to stabilize the lipid nanocarriers. A Box-Behnken Design was used to identify the optimum operating and production conditions viz., 1100 bar for 3 cycles for the solid lipid nanoparticles and 1500 bar for 5 cycles for nanostructured lipid carriers. The optimized nanocarriers were predicted to exhibit 10% efavirenz loading with 3% and 4% Tween® 80 for solid lipid nanoparticles and nanostructured lipid carriers, respectively. Characterization of the optimized solid lipid nanoparticle and nanostructured lipid carrier formulations in relation to shape, surface morphology, polymorphism, crystallinity and compatibility revealed stable formulations with particle sizes in the nanometer range had been produced. The nanocarriers had excellent efavirenz loading with the encapsulation efficiency >90%. The optimized nanocarriers exhibited biphasic in vitro release patterns with an initial burst release during the initial 0–3 h followed by sustained release over a 24 h period The colloidal systems showed excellent stability in terms of Zeta potential, particle size, polydispersity index and encapsulation efficiency when stored for 8 weeks at 25 °C/60% RH in comparison to when stored at 40 °C/75% RH. The formulations manufactured using the optimized conditions and composition proved to be physically stable as aqueous dispersions.
- Full Text:
- Date Issued: 2019
- Authors: Makoni, Pedzisai A , Kasongo, Kasongo W , Walker, Roderick B
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183492 , vital:44000 , xlink:href="https://doi.org/10.3390/pharmaceutics11080397"
- Description: The short term stability of efavirenz-loaded solid lipid nanoparticle and nanostructured lipid carrier dispersions was investigated. Hot High Pressure Homogenization with the capability for scale up production was successfully used to manufacture the nanocarriers without the use of toxic organic solvents for the first time. Glyceryl monostearate and Transcutol® HP were used as the solid and liquid lipids. Tween® 80 was used to stabilize the lipid nanocarriers. A Box-Behnken Design was used to identify the optimum operating and production conditions viz., 1100 bar for 3 cycles for the solid lipid nanoparticles and 1500 bar for 5 cycles for nanostructured lipid carriers. The optimized nanocarriers were predicted to exhibit 10% efavirenz loading with 3% and 4% Tween® 80 for solid lipid nanoparticles and nanostructured lipid carriers, respectively. Characterization of the optimized solid lipid nanoparticle and nanostructured lipid carrier formulations in relation to shape, surface morphology, polymorphism, crystallinity and compatibility revealed stable formulations with particle sizes in the nanometer range had been produced. The nanocarriers had excellent efavirenz loading with the encapsulation efficiency >90%. The optimized nanocarriers exhibited biphasic in vitro release patterns with an initial burst release during the initial 0–3 h followed by sustained release over a 24 h period The colloidal systems showed excellent stability in terms of Zeta potential, particle size, polydispersity index and encapsulation efficiency when stored for 8 weeks at 25 °C/60% RH in comparison to when stored at 40 °C/75% RH. The formulations manufactured using the optimized conditions and composition proved to be physically stable as aqueous dispersions.
- Full Text:
- Date Issued: 2019
Stability indicating HPLC-ECD method for the analysis of clarithromycin in pharmaceutical dosage forms: Method scaling versus re-validation.
- Makoni, Pedzisai A, Chikukwa, Mellisa T R, Khamanga, Sandile M, Walker, Roderick B
- Authors: Makoni, Pedzisai A , Chikukwa, Mellisa T R , Khamanga, Sandile M , Walker, Roderick B
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183387 , vital:43984 , xlink:href="https://doi.org/10.3390/scipharm87040031"
- Description: An isocratic high-performance liquid chromatographic method using electrochemical detection (HPLC-ECD) for the quantitation of clarithromycin (CLA) was developed using Response Surface Methodology (RSM) based on a Central Composite Design (CCD). The method was validated using International Conference on Harmonization (ICH) guidelines with an analytical run time of 20 min. Method re-validation following a change in analytical column was successful in reducing the analytical run time to 13 min, decreasing solvent consumption thus facilitating environmental and financial sustainability. The applicability of using the United States Pharmacopeia (USP) method scaling approach in place of method re-validation using a column with a different L–designation to the original analytical column, was investigated. The scaled method met all USP system suitability requirements for resolution, tailing factor and % relative standard deviation (RSD). The re-validated and scaled method was successfully used to resolve CLA from manufacturing excipients in commercially available dosage forms. Although USP method scaling is only permitted for columns within the same L-designation, these data suggest that it may also be applicable to columns of different designation.
- Full Text:
- Date Issued: 2019
- Authors: Makoni, Pedzisai A , Chikukwa, Mellisa T R , Khamanga, Sandile M , Walker, Roderick B
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183387 , vital:43984 , xlink:href="https://doi.org/10.3390/scipharm87040031"
- Description: An isocratic high-performance liquid chromatographic method using electrochemical detection (HPLC-ECD) for the quantitation of clarithromycin (CLA) was developed using Response Surface Methodology (RSM) based on a Central Composite Design (CCD). The method was validated using International Conference on Harmonization (ICH) guidelines with an analytical run time of 20 min. Method re-validation following a change in analytical column was successful in reducing the analytical run time to 13 min, decreasing solvent consumption thus facilitating environmental and financial sustainability. The applicability of using the United States Pharmacopeia (USP) method scaling approach in place of method re-validation using a column with a different L–designation to the original analytical column, was investigated. The scaled method met all USP system suitability requirements for resolution, tailing factor and % relative standard deviation (RSD). The re-validated and scaled method was successfully used to resolve CLA from manufacturing excipients in commercially available dosage forms. Although USP method scaling is only permitted for columns within the same L-designation, these data suggest that it may also be applicable to columns of different designation.
- Full Text:
- Date Issued: 2019
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