No description available.

Magister Pharmaceuticae - MPharm / Background/Introduction: Atopic dermatitis (AD) is one of the most prevalent diseases worldwide. It is a rapidly growing field of study with several research avenues to explore its pathophysiology and to find innovative treatment and management regimens. Clinically, it is classified as a non-contagious, intensely pruritic, inflammatory, chronic skin disorder mediated by abnormalities associated with atopy. Symptoms include inflammation, redness, pain and a negative impact on the patient‘s overall quality of life. Chronic itching often leads to the formation of lichenified skin, which may increase the thickness of the epidermis and exacerbate the barrier function of the skin. AD is treated with topical corticosteroids which help to decrease inflammation. However, lichification of the skin may decrease the efficacy of topical dosage forms. Nanomedicine is a rapidly developing field where advances have been made using ethosomes for topical delivery. As such, corticosteroid loaded ethosomal formulations containing hydrocortiosone acetate (HCA) and betamethasone valerate (BMV) were developed and characterised to develop novel tools for topical drug delivery. Aim: This study aimed at developing corticosteroid loaded ethosomes as a pre-formulation component for inclusion in a topical dosage form. To date, no ethosmal formulation with HCA and BMV has been investigated for topical drug delivery. Method: Ethosomes were synthesised using the hot method and the cold method, a modified version of a double emulsion (o/w/o), solvent evaporation technique, as developed by Touitou et al, 2007.1 Ethosomes were prepared using fixed concentrations of either BMV or HCA (10 mg/ml), ethanol (30% v/v) and purified water (70% v/v) and were comminuted using bath sonication or mini-extrusion. Centrifugation and centrifugal drying were used to purify and isolate the ethosomes for solid state characterisation. The morphology was determined using Scanning electron microscopy (SEM). Ethosomes were characterised using: dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), hot stage microscopy (HSM), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The encapsulation efficiency (EE) and drug loading (DL) were determined using validated HPLC methods. Finally, the drug release was determined using Franz diffusion cells and mathematical models were fitted to the % cumulative release data to determine the release kinetics. Results: Ethosomes were assessed according to the following criteria for topical drug delivery which were determined using dynamic light scattering (DLS): Hydrodynamic diameter (HdD), ~ 200 nm, polydispersity index (PdI) < 0.5 and zeta potential (ζp) ± 30 mV. The optimum formulations contained phosphatidylcholine (PC) 50 mg/ml. Extrusion was found to be the best method for particle reduction based on the reproducibility of the results. The HdD was 163.8±31.99 and 147.7±19.91 for BMV loaded ethosomes and HCA loaded ethosomes respectively and both formulations had an acceptable PdI of 0.049 and 0.111, respectively. SEM analyses indicated that the ethosomes had a spherical shape. Encapsulation of the APIs was verified by the thermoanalyses and possible intermolecular interactions were identified using FTIR. BMV loaded and HCA loaded ethosomes had a respective EE of 74.57 % and 37.30 %, and a DL of 14.91 % and 7.46 %, respectively. The release kinetics best fit the Peppas-Sahlin model indicative of an anomalous non-Fickian diffusion coupled with polymer relaxation and zero order release. Conclusions: BMV and HCA loaded ethosomes for topical drug delivery were successfully synthesised and characterised. These novel nanoparticles have provided an array of avenues for further investigation and application in the topical delivery of corticosteroids

No description available.

Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2008.

The aim of this in vitro study was to investigate the feasibility of the transdermal delivery of isoniazid (INH) and rifampicin (RMP) by means of the novel PheroidTM technology system. 'The application of the latter is being investigated in combination with various actives such as peptides (insulin, human growth hormone), anti-malarial drugs (chloroquine), anti-fungals (ketoconazole), local anaesthetics (lidocaine, prilocaine) as well as tuberculostatics (ethambutol, pyrazinamide etc.) via different administration routes at the North- West University. PheroidTM, a stable skin-friendly carrier, comprises of a submicron (200 nm - 2 m) emulsion type formulation for which previous studies have confirmed the ability to penetrate keratinised tissue, skin, intestinal linings, the vascular system, fungi, bacteria and even parasites. Studies involving an oral PheroidTM formulation containing the current approved regime of four anti-tuberculosis drugs showed improved efficacy results whilst an in vitro analysis of bacterial growth indicated a reduction in drug resistance in multidrug resistant tuberculosis (MDR-TB) strains. Therefore we thought it prudent to ascertain whether or not the PheroidTM system would be able to improve the transdermal delivery of a combination of INH and RMP as a possible treatment against cutaneous tuberculosis (tuberculosis involving the skin). The latter refers to pathological lesions of the skin caused by any one of the following: Mycobacterium tuberculosis, Mycobacterium bovis or the bacilli Calmette- Guerin (BCG) vaccine. Demonstration of M. tuberculosis within the infected tissues by traditional acid-fast bacilli (AFB) staining, culture or polymerase chain reaction (PCR) confirms the diagnosis. CTB lesions are associated with various degrees of one or more of the following ulceration, plaque formation, hyperkeratosis or the presence of necrotic matter. Seeing as C-TB is mostly associated with systemic involvement, current treatment comprises of the standard three/four drug regimens used for pulmonary 'TB in general. Cases of CTB usually show improvement within 1 month of therapy with anti-TB drugs, but complete resolution is only attained after 4 - 6 months. 'The major drawback to current therapy is that patients not only remain a source of infection (viable organisms can still be demonstrated in the lesions), but they also suffer from constant embarrassment due to the disfiguring nature of CTB until these lesions have healed completely. No evidence of an already existing topical formulation of this kind could be found. Therefore in vitro permeation studies were conducted using vertical Franz diffusion cells and female abdominal skin as permeation membrane over a period of 12 hours. Concentrations of 5 mg/ml and 10 mg/ml for isoniazid( INH) and rifampicin (RMP) respectively, were applied to the donor phase suspended in either phosphate buffered saline (PBS) or entrapped in PheroidTM. Permeation studies were conducted at pH 5.5. In vitro penetration of INH and RMP were assayed directly by HPLC. Particle size distribution for rifampicin and entrapment of actives within the PheroidTM carrier system was determined by polarized light and laser scanning microscopy (CLSM) respectively and revealed definite entrapment. Permeation profiles obtained for INH in PheroidTM indicated a biphasic character, whilst that obtained for RMP in PheroidTM showed a triphasic character. The PheroidTM delivery system proved more efficacious for delivery of both anti-tubercular drugs and resulted in greater percentage yield as well as flux values than that for a PBS solution. Furthermore, the PheroidTM formulation was able to deliver, the entrapped INH and RMP in concentrations sufficient to exceed their respective minimum inhibitory concentrations (MIC). / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2008.

The aim of this in vitro study was to investigate the feasibility of the transdermal delivery of isoniazid (INH) and rifampicin (RMP) by means of the novel PheroidTM technology system. 'The application of the latter is being investigated in combination with various actives such as peptides (insulin, human growth hormone), anti-malarial drugs (chloroquine), anti-fungals (ketoconazole), local anaesthetics (lidocaine, prilocaine) as well as tuberculostatics (ethambutol, pyrazinamide etc.) via different administration routes at the North- West University. PheroidTM, a stable skin-friendly carrier, comprises of a submicron (200 nm - 2 m) emulsion type formulation for which previous studies have confirmed the ability to penetrate keratinised tissue, skin, intestinal linings, the vascular system, fungi, bacteria and even parasites. Studies involving an oral PheroidTM formulation containing the current approved regime of four anti-tuberculosis drugs showed improved efficacy results whilst an in vitro analysis of bacterial growth indicated a reduction in drug resistance in multidrug resistant tuberculosis (MDR-TB) strains. Therefore we thought it prudent to ascertain whether or not the PheroidTM system would be able to improve the transdermal delivery of a combination of INH and RMP as a possible treatment against cutaneous tuberculosis (tuberculosis involving the skin). The latter refers to pathological lesions of the skin caused by any one of the following: Mycobacterium tuberculosis, Mycobacterium bovis or the bacilli Calmette- Guerin (BCG) vaccine. Demonstration of M. tuberculosis within the infected tissues by traditional acid-fast bacilli (AFB) staining, culture or polymerase chain reaction (PCR) confirms the diagnosis. CTB lesions are associated with various degrees of one or more of the following ulceration, plaque formation, hyperkeratosis or the presence of necrotic matter. Seeing as C-TB is mostly associated with systemic involvement, current treatment comprises of the standard three/four drug regimens used for pulmonary 'TB in general. Cases of CTB usually show improvement within 1 month of therapy with anti-TB drugs, but complete resolution is only attained after 4 - 6 months. 'The major drawback to current therapy is that patients not only remain a source of infection (viable organisms can still be demonstrated in the lesions), but they also suffer from constant embarrassment due to the disfiguring nature of CTB until these lesions have healed completely. No evidence of an already existing topical formulation of this kind could be found. Therefore in vitro permeation studies were conducted using vertical Franz diffusion cells and female abdominal skin as permeation membrane over a period of 12 hours. Concentrations of 5 mg/ml and 10 mg/ml for isoniazid( INH) and rifampicin (RMP) respectively, were applied to the donor phase suspended in either phosphate buffered saline (PBS) or entrapped in PheroidTM. Permeation studies were conducted at pH 5.5. In vitro penetration of INH and RMP were assayed directly by HPLC. Particle size distribution for rifampicin and entrapment of actives within the PheroidTM carrier system was determined by polarized light and laser scanning microscopy (CLSM) respectively and revealed definite entrapment. Permeation profiles obtained for INH in PheroidTM indicated a biphasic character, whilst that obtained for RMP in PheroidTM showed a triphasic character. The PheroidTM delivery system proved more efficacious for delivery of both anti-tubercular drugs and resulted in greater percentage yield as well as flux values than that for a PBS solution. Furthermore, the PheroidTM formulation was able to deliver, the entrapped INH and RMP in concentrations sufficient to exceed their respective minimum inhibitory concentrations (MIC). / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2008.

Pharmaceutical companies and FDA (Federal Drug Administration) rules rely heavily on crystalline active pharmaceutical ingredients delivered as tablets and powders in the form of neutral compounds, salts and solvates of neutral compounds and salts. About half of all drugs sold in the market are in the form of salts which are held together by ionic bonds along with some other forces. Recently, Ionic liquids (ILs) an interesting class of chemical compounds have offered potential opportunity for exploration as novel drug ionic liquid salts, particularly in the field of transdermal/topical drug delivery. Due to the multifunctional nature of these salts they could allow generation of new pathway to manipulate the transport and deposition behaviour of the drug molecule. It is this modular approach of IL that forms the basis of the research presented here, in which pharmaceutically acceptable compounds are combined with selected drugs with known problems. IL salts were generated by combining at least one drug molecule with FDA approved compounds and were assessed for physicochemical properties, skin deposition and permeation studies. Skin deposition data suggested that these systems exhibit high skin retention, which was found to correlate with the molecular weight. On the other hand, permeation data displayed an inverse relationship between flux values and molecular weight of the permeant. Similar work was extended with ILs with mixed anions containing two drugs. The benzalkonium-sulfacetamide ILs were investigated for synergism and the biological studies data display no synergistic effect. It was also illustrated that in-situ IL based ibuprofen hydrogels systems could be manipulated via IL approach for topical application. These findings suggest the potential applicability of IL based formulations for topical delivery of drugs.