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.
| Identifer | oai:union.ndltd.org:NWUBOLOKA1/oai:dspace.nwu.ac.za:10394/1668 |
| Date | January 2007 |
| Creators | Botes, Adèle |
| Publisher | North-West University |
| Source Sets | North-West University |
| Detected Language | English |
| Type | Thesis |
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