Muco-adhesive clarithromycin-loaded nanostructured lipid carriers for ocular delivery: Formulation, characterization, cytotoxicity and stability
- Makoni, Pedzisai A, Khamanga, Sandile M, Walker, Roderick B
- Authors: Makoni, Pedzisai A , Khamanga, Sandile M , Walker, Roderick B
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183150 , vital:43916 , xlink:href="https://doi.org/10.1016/j.jddst.2020.102171"
- Description: Topical ophthalmic formulations are the preferred approach to treat the anterior segment of the eye as it is a non-invasive therapeutic approach. The ocular bioavailability of drugs is generally limited, due to the presence of impervious anatomical barriers and low residence time and contact with the target tissue. Optimization of clarithromycin-loaded nanostructured lipid carriers using Design of Experiments was undertaken. Manufacture of nanostructured lipid carriers was achieved using hot emulsification ultrasonication. Formulation and process parameters were successfully identified following screening and subsequently optimized using Tween® 20, as a stabilizer. Muco-adhesive properties that could potentially increase ocular residence time, in vitro clarithromycin release and cytotoxicity against HeLa cells were evaluated. Short term stability studies of the optimized lipidic formulations was assessed at 4 °C and 22 °C. The optimized formulation exhibited muco-adhesive properties under stationary conditions assessed using Laser Doppler Anemometry, sustained release of API over 24 h under in vitro conditions. In vitro cytotoxicity studies revealed that the NLC were less cytotoxic to HeLa cells in comparison to pure API. The results suggest that the optimized carriers may have the potential to enhance precorneal retention, increase ocular availability and permit dose reduction or permit use of a longer dosing frequency.
- Full Text:
- Date Issued: 2021
- Authors: Makoni, Pedzisai A , Khamanga, Sandile M , Walker, Roderick B
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183150 , vital:43916 , xlink:href="https://doi.org/10.1016/j.jddst.2020.102171"
- Description: Topical ophthalmic formulations are the preferred approach to treat the anterior segment of the eye as it is a non-invasive therapeutic approach. The ocular bioavailability of drugs is generally limited, due to the presence of impervious anatomical barriers and low residence time and contact with the target tissue. Optimization of clarithromycin-loaded nanostructured lipid carriers using Design of Experiments was undertaken. Manufacture of nanostructured lipid carriers was achieved using hot emulsification ultrasonication. Formulation and process parameters were successfully identified following screening and subsequently optimized using Tween® 20, as a stabilizer. Muco-adhesive properties that could potentially increase ocular residence time, in vitro clarithromycin release and cytotoxicity against HeLa cells were evaluated. Short term stability studies of the optimized lipidic formulations was assessed at 4 °C and 22 °C. The optimized formulation exhibited muco-adhesive properties under stationary conditions assessed using Laser Doppler Anemometry, sustained release of API over 24 h under in vitro conditions. In vitro cytotoxicity studies revealed that the NLC were less cytotoxic to HeLa cells in comparison to pure API. The results suggest that the optimized carriers may have the potential to enhance precorneal retention, increase ocular availability and permit dose reduction or permit use of a longer dosing frequency.
- Full Text:
- Date Issued: 2021
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 response surface methodology in the evaluation of captopril microparticles manufactured using an oil in oil solvent evaporation technique
- Khamanga, Sandile M, Walker, Roderick B
- Authors: Khamanga, Sandile M , Walker, Roderick B
- Date: 2012
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184221 , vital:44191 , xlink:href="https://doi.org/10.3109/02652048.2011.629744"
- Description: Captopril (CPT) microparticles were manufactured by solvent evaporation using acetone (dispersion phase) and liquid paraffin (manufacturing phase) with Eudragit® and Methocel® as coat materials. Design of experiments and response surface methodology (RSM) approaches were used to optimize the process. The microparticles were characterized based on the percent of drug released and yield, microcapsule size, entrapment efficiency and Hausner ratio. Differential scanning calorimetry (DSC), Infrared (IR) spectroscopy, scanning electron microscopy (SEM) and in vitro dissolution studies were conducted. The microcapsules were spherical, free-flowing and IR and DSC thermograms revealed that CPT was stable. The percent drug released was investigated with respect to Eudragit® RS and Methocel® K100M, Methocel® K15M concentrations and homogenizing speed. The optimal conditions for microencapsulation were 1.12 g Eudragit® RS, 0.67 g Methocel® K100M and 0.39 g Methocel® K15M at a homogenizing speed of 1643 rpm and 89% CPT was released. The value of RSM-mediated microencapsulation of CPT was elucidated.
- Full Text:
- Date Issued: 2012
- Authors: Khamanga, Sandile M , Walker, Roderick B
- Date: 2012
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184221 , vital:44191 , xlink:href="https://doi.org/10.3109/02652048.2011.629744"
- Description: Captopril (CPT) microparticles were manufactured by solvent evaporation using acetone (dispersion phase) and liquid paraffin (manufacturing phase) with Eudragit® and Methocel® as coat materials. Design of experiments and response surface methodology (RSM) approaches were used to optimize the process. The microparticles were characterized based on the percent of drug released and yield, microcapsule size, entrapment efficiency and Hausner ratio. Differential scanning calorimetry (DSC), Infrared (IR) spectroscopy, scanning electron microscopy (SEM) and in vitro dissolution studies were conducted. The microcapsules were spherical, free-flowing and IR and DSC thermograms revealed that CPT was stable. The percent drug released was investigated with respect to Eudragit® RS and Methocel® K100M, Methocel® K15M concentrations and homogenizing speed. The optimal conditions for microencapsulation were 1.12 g Eudragit® RS, 0.67 g Methocel® K100M and 0.39 g Methocel® K15M at a homogenizing speed of 1643 rpm and 89% CPT was released. The value of RSM-mediated microencapsulation of CPT was elucidated.
- Full Text:
- Date Issued: 2012
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
- «
- ‹
- 1
- ›
- »