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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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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