Preformulation studies of efavirenz with lipid excipients using thermal and spectroscopic techniques
- Authors: Makoni, Pedzisai A , Kasongo, Kasongo W , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183253 , vital:43934 , xlink:href=" https://doi.org/10.1691/ph.2020.0053"
- Description: Investigation and identification of potential lipids for the manufacture of efavirenz loaded solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) was undertaken. Polymorphic modification and characteristics of the lipids with the best solubilising potential for efavirenz was explored using Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC) and Wide-angle X-ray Scattering (WAXS). Lipid screening revealed that EFV is highly soluble in solid and liquid lipids, with glyceryl monostearate (GM) and Transcutol® HP (THP) exhibiting the best solubilising potential for EFV. GM exists in a stable β-polymorphic modification prior to exposure to heat, but exists in an α-polymorphic modification following exposure to heat. However, it was established that the addition of THP to GM revealed the co-existence of the α- and β'-polymorphic modifications of the lipid. EFV (60% w/w) exists in a crystalline state in a 70:30 mixture of GM and THP. Investigation of binary mixtures of EFV/GM and GM/THP, in addition to eutectic mixtures of EFV, GM and THP using FT-IR, DSC and WAXS revealed no potential interactions between EFV and the lipids selected for the production of the nanocarriers.
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- Date Issued: 2020
Short term stability testing of efavirenz-loaded solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC) dispersions
- 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.
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- Date Issued: 2019
The use of experimental design for the development and validation of an HPLC-ECD method for the quantitation of efavirenz
- Authors: Makoni, Pedzisai A , Khamanga, Sandile M , Kasongo, Kasongo W , Walker, Roderick B
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183556 , vital:44006 , xlink:href="https://doi.org/10.1691/ph.2018.8074"
- Description: A high performance liquid chromatography with electrochemical detection (HPLC-ECD) method for the quantitation of efavirenz (EFV) was developed, since traditional HPLC-UV methods may be inappropriate, given that EFV undergoes photolytic degradation following exposure to UV light. This work describes the use of response surface methodology (RSM) based on a central composite design (CCD) to develop a stability-indicating HPLC method with pulsed ECD in direct current (DC) mode at an applied potential difference and current of +1400 mV and 1.0 μA for the analysis of EFV. Separation of EFV and imipramine was achieved using a Nova-Pak®C18 cartridge column and a mobile phase of phosphate buffer (pH 4.5): acetonitrile (ACN) (55:45 v/v). Mobile phase pH, buffer molarity, ACN concentration and applied potential difference were investigated. The optimized method produced sharp well resolved peaks for imipramine and EFV with retention times of 3.70 and 8.89 minutes. The calibration curve was linear (R2 = 0.9979) over the range 5-70 μg/mL. Repeatability and intermediate precision ranged between 3.37 and 4.34 % RSD and 1.31 and 4.29 % RSD and accuracy between -0.80 and 4.71 % bias. The LOQ and LOD were 5.0 and 1.5 μg/mL. The method was specific for EFV and was used to analyse EFV in commercially available tablets. The HPLC-ECD method is more suitable for quantitative analysis of EFV than HPLC-UV.
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- Date Issued: 2018
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
- 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.
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- Date Issued: 2012
Evaluation of the in vitro differential protein adsorption patterns of didanosine-loaded nanostructured lipid carriers (NLCs) for potential targeting to the brain
- Authors: Kasongo, Kasongo W , Jansch, Mirko , Müller, Rainer H , Walker, Roderick B
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184035 , vital:44160 , xlink:href="https://doi.org/10.3109/08982104.2010.539186"
- Description: The preferential in vitro adsorption of apolipoprotein E (Apo E) onto the surface of colloidal drug carriers may be used as a strategy to evaluate the in vivo potential for such systems to transport drugs to the brain. The aim of this research was to investigate the in vitro protein adsorption patterns of didanosine-loaded nanostructured lipid carriers (DDI-NLCs), using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), in order to establish the potential for NLCs to deliver DDI to the brain. NLC formulations were manufactured using high-pressure homogenization using a lipid matrix consisting of a mixture of Precirol® ATO 5 and Transcutol® HP. The 2-D PAGE analysis revealed that NLCs in formulations stabilized using Solutol® HS 15 alone or with a ternary surfactant system consisting of Solutol® HS 15, Tween® 80, and Lutrol® F68, preferentially adsorbed proteins, such as Apo E. Particles stabilized with Tween® 80 and Lutrol® F68 did not adsorb Apo E in these studies, which could be related to the relatively large particle size and hence small surface area observed for these NLCs. These findings have revealed that DDI-loaded NLCs may have the potential to deliver DDI to the brain in vivo and, in addition, to Tween® 80, which has already been shown to have the ability to facilitate the targeting of colloidal drug delivery systems to the brain. Solutol® HS 15–stabilized nanoparticles may also achieve a similar purpose.
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- Date Issued: 2011
Selection and characterization of suitable lipid excipients for use in the manufacture of didanosine-loaded solid lipid nanoparticles and nanostructured lipid carriers
- Authors: Kasongo, Kasongo W , Pardeike, Jana , Muller, Rainer H , Walker, Roderick B
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184016 , vital:44156 , xlink:href="https://doi.org/10.1002/jps.22711"
- Description: This research aimed to evaluate the suitability of lipids for the manufacture of solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) loaded with the hydrophilic drug, didanosine (DDI). The crystalline state and polymorphism of lipids with the best‐solubulizing potential for DDI was investigated using differential scanning calorimetry (DSC) and wide‐angle X‐ray scattering (WAXS). DSC and WAXS were also used to determine potential interactions between the bulk lipids and DDI. Precirol® ATO 5 and Transcutol® HP showed the best‐solubilizing potential for DDI. Precirol® ATO 5 exists in the β‐modification before heating; however, a mixture of both α‐ and β‐modifications were detected following heating. Addition of Transcutol® HP to Precirol® ATO 5 changes the polymorphism of the latter from the β‐modification to a form that exhibits coexistence of the α‐ and β‐modifications. DDI exists in a crystalline state when dispersed at 5% (w/w) in Precirol® ATO 5 or in a Precirol® ATO 5/Transcutol® HP mixture. DSC and WAXS profiles of DDI/bulk lipids mixture obtained before and after exposure to heat revealed no interactions between DDI and the lipids. Precirol® ATO 5 and a mixture of Precirol® ATO 5 and Transcutol® HP may be used to manufacture DDI‐loaded SLN and NLC, respectively.
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- Date Issued: 2011