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
Detection of pharmaceutical residues in surface waters of the Eastern Cape Province:
- Vumazonke, Sesethu, Khamanga, Sandile M, Ngqwala, Nosiphiwe P
- Authors: Vumazonke, Sesethu , Khamanga, Sandile M , Ngqwala, Nosiphiwe P
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/149693 , vital:38875 , https://doi.org/10.3390/ijerph17114067
- Description: Pharmaceuticals are emerging contaminants in the aquatic environments. Their presence poses toxicological effects in humans and animals even at trace concentrations. This study investigated the presence of antibiotics, anti-epilepsy and anti-inflammatory drugs in river water of selected rivers in the Eastern Cape Province in South Africa. Enzyme-linked immunosorbent assay was used for screening of sulfamethoxazole and fluoroquinolones antibiotics. The samples were collected in upper-stream, middle-stream and lower-stream regions of the rivers and effluent of selected wastewater treatment plants. Pre-concentration of the samples was conducted using lyophilisation and extraction was conducted using solid phase extraction (SPE) on Waters Oasis hydrophilic-lipophilic-balanced cartridge.
- Full Text:
- Date Issued: 2020
- Authors: Vumazonke, Sesethu , Khamanga, Sandile M , Ngqwala, Nosiphiwe P
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/149693 , vital:38875 , https://doi.org/10.3390/ijerph17114067
- Description: Pharmaceuticals are emerging contaminants in the aquatic environments. Their presence poses toxicological effects in humans and animals even at trace concentrations. This study investigated the presence of antibiotics, anti-epilepsy and anti-inflammatory drugs in river water of selected rivers in the Eastern Cape Province in South Africa. Enzyme-linked immunosorbent assay was used for screening of sulfamethoxazole and fluoroquinolones antibiotics. The samples were collected in upper-stream, middle-stream and lower-stream regions of the rivers and effluent of selected wastewater treatment plants. Pre-concentration of the samples was conducted using lyophilisation and extraction was conducted using solid phase extraction (SPE) on Waters Oasis hydrophilic-lipophilic-balanced cartridge.
- 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
Formulation optimization of smart thermosetting lamotrigine loaded hydrogels using response surface methodology, box benhken design and artificial neural networks
- Melamane, Siyabonga, Walker, Roderick B, Khamanga, Sandile M
- Authors: Melamane, Siyabonga , Walker, Roderick B , Khamanga, Sandile M
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183265 , vital:43936 , xlink:href="https://doi.org/10.1080/03639045.2020.1791163"
- Description: The aim of this research was to develop lamotrigine containing thermosetting hydrogel for intranasal administration to manage and treat generalized epilepsy. Thermosetting hydrogels were prepared using different ratios of poloxamer 407 (L127), poloxamer 188 (L68) and CarbopolVR 974 P NF (C974) using the cold production process. The in situ thermosetting hydrogel was optimized using Box Behken design. Co-solvency approach was used to increase the solubility of lamotrigine by dissolving it in propylene glycol and polyethylene glycol 400 (0.2: 0.8) and the resultant solution was incorporated in the hydrogel to manufacture an LTG hydrogel. The presence of a higher amount of L127 resulted in higher viscosity at 22 0C and 34 0C and decreased the overall release of LTG. An increase in the amount of C974 resulted in a decrease in the pH of the hydrogel. The results show that formulations F10, F12, F13, F14, F15, F16 and F17 exhibited acceptable thermosetting behavior, pH and released adequate Lamotrigine above the minimum effective concentration to treat generalized epilepsy. The optimized formulation exhibited acceptable thermosetting behavior, pH and lamotrigine release but formed a stiff gel at 22 0C. The average LTG content of the optimized hydrogel was 5.00 ± 0.0225mg/ml with % recovery of 99.17%. The amount of LTG released at 12 h from the optimized hydrogel was 3.21 ± 0.0155mg and will be therapeutically effective in the brain after absorption via the olfactory region in the nasal cavity.
- Full Text:
- Date Issued: 2020
- Authors: Melamane, Siyabonga , Walker, Roderick B , Khamanga, Sandile M
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183265 , vital:43936 , xlink:href="https://doi.org/10.1080/03639045.2020.1791163"
- Description: The aim of this research was to develop lamotrigine containing thermosetting hydrogel for intranasal administration to manage and treat generalized epilepsy. Thermosetting hydrogels were prepared using different ratios of poloxamer 407 (L127), poloxamer 188 (L68) and CarbopolVR 974 P NF (C974) using the cold production process. The in situ thermosetting hydrogel was optimized using Box Behken design. Co-solvency approach was used to increase the solubility of lamotrigine by dissolving it in propylene glycol and polyethylene glycol 400 (0.2: 0.8) and the resultant solution was incorporated in the hydrogel to manufacture an LTG hydrogel. The presence of a higher amount of L127 resulted in higher viscosity at 22 0C and 34 0C and decreased the overall release of LTG. An increase in the amount of C974 resulted in a decrease in the pH of the hydrogel. The results show that formulations F10, F12, F13, F14, F15, F16 and F17 exhibited acceptable thermosetting behavior, pH and released adequate Lamotrigine above the minimum effective concentration to treat generalized epilepsy. The optimized formulation exhibited acceptable thermosetting behavior, pH and lamotrigine release but formed a stiff gel at 22 0C. The average LTG content of the optimized hydrogel was 5.00 ± 0.0225mg/ml with % recovery of 99.17%. The amount of LTG released at 12 h from the optimized hydrogel was 3.21 ± 0.0155mg and will be therapeutically effective in the brain after absorption via the olfactory region in the nasal cavity.
- Full Text:
- Date Issued: 2020
The use of quantitative analysis and Hansen solubility parameter predictions for the selection of excipients for lipid nanocarriers to be loaded with water soluble and insoluble compounds
- Makoni, Pedzisai A, Ranchhod, Janeeta, Khamanga, Sandile M, Walker, Roderick B
- Authors: Makoni, Pedzisai A , Ranchhod, Janeeta , Khamanga, Sandile M , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183376 , vital:43981 , xlink:href="https://doi.org/10.1016/j.jsps.2020.01.010"
- Description: The aim of these studies was to determine the miscibility of different API with lipid excipients to predict drug loading and encapsulation properties for the production of solid lipid nanoparticles and nanostructured lipid carriers. Five API exhibiting different physicochemical characteristics, viz., clarithromycin, efavirenz, minocycline hydrochloride, mometasone furoate, and didanosine were used and six solid lipids in addition to four liquid lipids were investigated. Determination of solid and liquid lipids with the best solubilization potential for each API were performed using a traditional shake-flask method and/or a modification thereof. Hansen solubility parameters of the API and different solid and liquid lipids were estimated from their chemical structure using Hiroshi Yamamoto’s molecular breaking method of Hansen Solubility Parameters in Practice software. Experimental results were in close agreement with solubility parameter predictions for systems with ΔδT larger than 4.0 MPa1/2. A combination of Hansen solubility parameters with experimental drug-lipid miscibility tests can be successfully applied to predict lipids with the best solubilizing potential for different API prior to manufacture of solid lipid nanoparticles and nanostructured lipid carriers.
- Full Text:
- Date Issued: 2020
- Authors: Makoni, Pedzisai A , Ranchhod, Janeeta , Khamanga, Sandile M , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183376 , vital:43981 , xlink:href="https://doi.org/10.1016/j.jsps.2020.01.010"
- Description: The aim of these studies was to determine the miscibility of different API with lipid excipients to predict drug loading and encapsulation properties for the production of solid lipid nanoparticles and nanostructured lipid carriers. Five API exhibiting different physicochemical characteristics, viz., clarithromycin, efavirenz, minocycline hydrochloride, mometasone furoate, and didanosine were used and six solid lipids in addition to four liquid lipids were investigated. Determination of solid and liquid lipids with the best solubilization potential for each API were performed using a traditional shake-flask method and/or a modification thereof. Hansen solubility parameters of the API and different solid and liquid lipids were estimated from their chemical structure using Hiroshi Yamamoto’s molecular breaking method of Hansen Solubility Parameters in Practice software. Experimental results were in close agreement with solubility parameter predictions for systems with ΔδT larger than 4.0 MPa1/2. A combination of Hansen solubility parameters with experimental drug-lipid miscibility tests can be successfully applied to predict lipids with the best solubilizing potential for different API prior to manufacture of solid lipid nanoparticles and nanostructured lipid carriers.
- 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
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