Browsing by Author "Ngilirabanga, Jean Baptiste"

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    Mechanochemical synthesis and physicochemical characterization of isoniazid and pyrazinamide co-crystals with Glutaric acid
    (Frontiers Media S.A., 2020) Ngilirabanga, Jean Baptiste; Aucamp, Marique Elizabeth; Samsodien, Halima
    The present work reports two novel pharmaceutical co-crystals; 2:1 isoniazid-glutaric acid (INHGA) and 2:1 pyrazinamide-glutaric acid (PGA). Isoniazid and pyrazinamide are key first-line drugs used for the treatment of tuberculosis. The co-crystals were produced via solid-state and solvent assisted grinding methods. Thermal characteristics of the samples were obtained using the differential scanning calorimetry, hot stage microscopy, and thermogravimetric analyses. The morphology of the powder samples by scanning electron microscopy, structural analysis by Fourier transform infrared spectroscopy and powder X-rays diffraction ensured co-crystal formation. Thermal analyses confirmed the co-crystals with new melting transitions ranging between their respective starting materials. Unique morphologies of the co-crystal particles were clear in SEM micrographs. The formation of intermolecular interactions with the co-crystal former was confirmed by the FT-IR spectral band shifting and was supported by distinct PXRD patterns of co-crystals thereby authenticating the successful co-crystal formation. In vitro solubility evaluation of the synthesized co-crystals by HPLC suggested a remarkable increase in solubility of both INH and PZA in their respective co-crystals.
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    Selected antiretroviral and anti-tuberculosis drug combinations by non-covalent bonding
    (University of Western Cape, 2021) Ngilirabanga, Jean Baptiste; Samsodien, Halima
    Treatment of the human immunodeficiency virus (HIV) and tuberculosis (TB) infections have become very complicated due to the advent of drug resistance. Drug combinations offer an alternative approach to reducing the emergence of drug resistance. Pharmaceutical co-crystals have provided the pharmaceutical industry with the ability to optimise the physicochemical properties of active pharmaceutical ingredients (APIs) while preserving the biological activity. Pharmaceutical co-crystals are formed between APIs and suitable co-formers that are biologically safe or even a second or third API.
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    A supramolecular derivatised study of BIS(Adamantan-1- Aminium) carbonate
    (University of the Western Cape, 2014) Ngilirabanga, Jean Baptiste; Samsodien, Halima; Joubert, Jacques
    In this study, new solid supramolecular derivatised forms of bis(adamantine-1-aminium) carbonate (ADTCO3) were prepared. ADTCO3 is a derivative of amantadine used for Parkinson’s disease and has antiviral properties against influenza-A, dengue fever and pharmacological activity towards Parkinson’s disease. The new forms prepared were polymorphic and co-crystal forms of ADTCO3. Polymorphism is a phenomenon where the ability of a substance to exist in two or more crystalline forms occurs when crystallised under different conditions and co-crystallization is the process of formation of multicomponent crystals of a drug substance. New solid forms often display different mechanical, physicochemical and thermal properties that can remarkably influence the bioavailability, hygroscopicity and stability of active pharmaceutical ingredients (APIs). For the formation of polymorphs of ADTCO3, techniques such as dry grinding, solvent-drop grinding, co-precipitation, sublimation and vapour diffusion were applied. For the development of co-crystals and/or complex formation, ADTCO3 was treated in combination with ten selected co-formers viz; benzoic acid, 4-hydroxybenzoic acid, cinnamic acid, 4-hydroxycinnamic acid, succinic acid, tartaric acid, salicylic acid, L-glutamic acid, citric acid monohydrate and L-glutaric acid using similar techniques as applied in the polymorphism study. The first four co-formers were selected for their potential biological activity and the latter six were selected for their generally regarded as safe (GRAS) status. All products were isolated and characterized using different analytical techniques to assess the thermal behaviour of the products by hot stage microscopy (HSM), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). FTIR spectroscopy and proton-nuclear magnetic resonance (1HNMR) were used to identify and determine the purity of the parent compounds and the modified forms. X-ray powder diffraction was used to determine the formation of a new phase and single crystal X-ray diffraction was applied at the initial stages to identify ADTCO3 by its unit cell parameters. Furthermore, the Cambridge Structural Database (CSD) and other resources were used to generate information on the molecular structures of all elucidated parent compounds, their polymorphs and reported co-crystals. Four different polymorphic forms of ADTCO3 were identified (viz. ADTCO3 Forms I to IV) and sixteen co-crystals (viz. ADTCO3BA1 to ADTCO3BA5, ADTCO3HBA, ADTCO3CIN, ADTCO3HCIN, ADTCO3SUC, ADTCO3LTTA, ADTCO3SA, ADTCO3CA, ADTCO3GLA, ADTCO3GA) were synthesised. Of the sixteen co-crystals 5 were identified as ADTCO3BA “salt” co-crystal polymorphic forms and 2 as ADTCO3SUC co-crystal polymorphic forms. Two solvated “salt” co-crystal forms were also identified, namely; ADTCO3GLA and ADTCO3LTTA. ADTCO3GLA had a mass loss of 10.3% (n = 2.4) and ADTCO3LTTA had a mass loss of 5.25% (n = 0.86). Finally, the rest of the co-crystals ADTCO3HBA, ADTCO3CIN, ADTCO3HCIN, ADTCO3SA, ADTCO3CA and ADTCO3GA all crystallised as “salt” co-crystals.