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Desenvolvimento e caracterização físico-química de complexos de inclusão de amilose com diferentes moléculas hóspedesRibeiro, Andresa da Costa January 2016 (has links)
A amilose, na presença de agentes complexantes adequados, tende a formar complexos de inclusão. Os mesmos são carregadores promissores, já que os ligantes aprisionados podem ser libertados posteriormente, o que conduz a muitas aplicações. Porém, a utilização da amilose nativa (AM) na formação dos complexos é limitada devido a sua baixa solubilidade em água. Sendo assim, estudos envolvendo a modificação desta molécula tornam-se promissores. O objetivo da presente tese foi preparar complexos de inclusão a partir da amilose nativa (AM) e modificada (AMA) usando como ligantes Rifampicina (RIF), Rodamina B (RB) e o Azul de Bromotimol (AB). Primeiramente, dentre os métodos existentes para modificação, escolheu-se a acetilação. O grau de acetilação foi investigado e a estrutura da amilose foi caracterizada por meio de FTIR, MEV, TGA e DSC. Quando comparada à AM, AMA apresentou maior solubilidade em água. A presença das bandas de absorção no FTIR à 1727, 1240 e 1122 cm-1, confirmaram a acetilação. Os resultados de MEV sugeriram que a superfície lisa da AM foi transformada em uma superfície mais áspera em AMA e as análises de TGA e DSC mostraram uma estrutura instável para a mesma. Após esta etapa os complexos foram produzidos e a influência da temperatura e dos ligantes foi avaliada através da caracterização físico-química. UV-vis, DLS, PZ e MEV foram as técnicas usadas neste processo. As análises de UV confirmaram a formação dos complexos e aqueles desenvolvidos na temperatura de 65°C foram mais eficientes. Dentre estes destacam-se aqueles complexos preparados com RIF. O diâmetro hidrodinâmico médio (dh) dos complexos medidos por DLS variou entre 70 e 100 nm, indicando que os mesmos podem ser utilizados em sistema de liberação controlada. Comparando o dh da AM e AMA, observou-se que os tamanhos são maiores após a complexação, o que pode indicar que para AMA ou a interação forma complexos mais compactos, ou os ligantes não interagiram com a AMA. Análise de PZ mostrou que os complexos AM-RB e AM-AB apresentam alta estabilidade (PZ < -30 mV) e que os demais complexos apresentam valores de PZ próximos da neutralidade, o que pode melhorar a adsorção dos mesmos em sistemas biológicos. Os complexos AMA-RB e AMA-AB não formaram complexos no estado sólido e os demais formaram uma estrutura amorfa após precipitação. Em conclusão, este estudo levou ao desenvolvimento de um método eficaz para a preparação de complexos de inclusão de amilose. / In the presence of suitable complexing agents, amylose tends to form inclusion complexes. This polymer is considered a promisor carrier since the ligands confined in its chains can be released later, leading to various applications. However, the use of native amylose (AM) in complexes formation is restricted due to its low water solubility. Therefore, studies regarding amylose modification become promising. The aim of this thesis was preparing inclusion complexes made of native (AM) and modified (AMA) amylose using rifampicin (RIF), rhodamine B (RB), and bromothymol blue (AB) as ligands. At first, acetylation was the chosen modification among the modified methods described in the literature. The acetylation degree was investigated and the modified macromolecule was characterized using FTIR, SEM, TGA, and DSC analysis. Compared with AM, AMA presented increased water solubility. The presence of absorption bands at 1727, 1240, and 1121 cm-1 confirmed the acetylation. SEM images suggested that the smooth surface of AM was turned into a rougher surface in AMA, while TGA and DSC results showed a less stable structure for AMA. After this step, the complexes were prepared and the influence of the temperature and ligand type was evaluated through physicochemical characterization. UV-Vis, DLS, PZ, and SEM were the techniques used in this process. UV-Vis analysis confirmed complexes formation, revealing that the ones prepared at 65°C were more efficient. Among those, complexes prepared with RIF stand out. The average hydrodynamic diameter (dh) of the complexes measured by DLS ranged from 70 to 100 nm, indicating that these complexes can be used in controlled release systems. Comparing the dh of AM and AMA, it was observed that the sizes were larger after complexation, which may indicate more compact complexes or no interaction between AMA and ligands. ZP results showed that AM-RB and AM-AB complexes presented high stability (PZ < -30 mV), while the others presented PZ values near neutrality, which can increase their adsorption in biological systems. AMA-RB and AMA-AB did not form complexes in solid state, while the others formed an amorphous structure after precipitation. In conclusion, this study leaded to an effective method development for the amylose inclusion complexes preparation.
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Nanoemulsão catiônica contendo rifampicina para o tratamento da tuberculose ocular: preparação e caracterização físico-química e microbiológica / Rifampicin cationic nanoemulsion for treatment of ocular tuberculosis: preparation, physical-chemical and microbiological characterizationHenostroza, Mirla Anali Bazan 22 May 2018 (has links)
A tuberculose ocular afeta 1 a 2% dos pacientes com diagnóstico de tuberculose sistêmica. O tratamento convencional consiste na administração oral dos agentes antituberculosos. Devido às barreiras oculares, o tratamento tópico requer dose elevada e repetidas administrações para atingir efeito terapêutico no olho. Assim, a toxicidade, nos tratamentos convencionais, pode ser relevante. Considerando tais limitações, o desenvolvimento de preparações que permitam a obtenção de produtos com maior eficácia e segurança é de fundamental importância. Nesse sentido, o presente trabalho teve como objetivos o desenvolvimento, a caracterização físico-química e microbiológica de nanoemulsão contendo rifampicina (NR) revestidas empregando cloreto de quitosana (NR-Quit) e sulfato de polimixina B (NR-Poli) com potencial aplicação para o tratamento da tuberculose ocular por via tópica. A NR foi preparada empregando método por homogeneização a alta pressão e apresentou diâmetro hidrodinâmico médio (DHM), índice de polidispersão (IP), potencial zeta (PZ) e pH entre 131,0 e 137,3 nm, entre 0,19 e 0,24, entre -31,0 e -35,4 mV e entre 5,10 e 5,26, respectivamente. A eficiência de encapsulação da rifampicina, determinada por espectrofotometria UV-vis, foi de 82,5 % m/v. Para obtenção de NR-Quit e NR-Poli foi empregado planejamento fatorial completo. Foi observada alteração do PZ de NR após adição de cloreto de quitosana de -35,4 para +51,3 mV. No caso da adição de sulfato de polimixina B o PZ foi alterado de -35,4 para +5,5 mV. Nesse sentido, a abordagem metodológica elucidou que a concentração do cloreto de quitosana e sulfato de polimixina B influenciou significativamente no potencial zeta da NR-Quit e da NR-Poli. Além disso, foi observada a relação linear entre a concentração dos agentes catiônicos empregados e o potencial zeta da NR-Quit e NR-Poli. Essas preparações, no estudo de estabilidade, mostraram aspecto visual, DHM, IP e PZ inalterados por período maior que 90 dias. Também, os valores de pH, viscosidade e osmolalidade foram ajustados entre 4,07 e 4,55, 1,03 e 1,08 cP, 209,7 e 213,4 mOsm/Kg, respectivamente. A atividade antimicrobiana realizada frente ao Mycobacterium tuberculosis H37Rv da NR, NR-Quit, NR-Poli e solução padrão de rifampicina, determinada pela concentração mínima inibitória (CMI), revelou CMI igual 0,125 µg/mL para todas as preparações. Tal resultado demonstrou que os processos de obtenção da nanoemulsão e do revestimento não alteraram a eficácia antimicrobiana da rifampicina. O presente trabalho permitiu o desenvolvimento de preparações inovadoras para o tratamento da tuberculose ocular, por via tópica, com potencial maior eficácia e segurança. / Ocular tuberculosis affects 1 to 2% of the patients diagnosed with systemic tuberculosis. The conventional treatment is the oral administration of the anti-tuberculosis agents. Due to eye barriers, topical treatment requires high dose and repeated administrations to achieve a therapeutic effect on the eye. Thus, toxicity is a major concern in these conventional treatments. Considering these limitations, development of preparations that enable products with higher efficacy and safety is of fundamental importance. In this sense, the present work aimed preparation, physicochemical properties evaluation and microbiological characterization of the rifampicin nanoemulsion (RN) coated using chitosan chloride (RN-Chit) and polymyxin B sulfate (RN-Poly) with potential application for topical treatment of ocular tuberculosis. The RN was prepared by high-pressure homogenization and present droplet mean size (DMS), polydispersity index (PdI), zeta potential and pH between 131.0 and 137.3 nm, between 0.19 and 0.24, between -31.0 and -35.4 mV and between 5.10 and 5.26, respectively. The encapsulation efficiency of rifampicin determined of using spectrophotometric UV-vis method was 82.5% w/v. For preparations RN-Chit and RN-Poly factorial experimental design was employed. The change in the zeta potential of RN-Chit was observed after the addition of chitosan chloride, from -35.4 to +51.3 mV. In the other case, an addition of polymyxin B sulfate changed the PZ from -35.4 to +5.5 mV. Therefore, the methodological approach elucidated that the concentration of chitosan chloride and polymyxin B sulfate significantly influenced the zeta potential of RN-Chit and RN-Poly. Furthermore, the linear relationship between the concentration of cationic agents employed and the zeta potential of RN-Chit and RN-Poly was observed. These preparations, in the stability study, showed visual appearance, DMS, PdI and PZ unchanged for a period greater than 90 days. Additionally, pH, viscosity and osmolality values were adjusted between 4.07 and 4.55, 1.03 and 1.08 cP, 209.7 and 213.4 mOsm/kg, respectively. The antimicrobial activity against Mycobacterium tuberculosis H37Rv of RN, RN-Chit, RN-Poly and the standard solution of rifampicin, determined by the minimum inhibitory concentration (MIC), showed MIC of 0.125 µg/mL for all preparations. This result demonstrated that the processes of nanoemulsion preparation and coating did not affect the antimicrobial efficacy of rifampicin. The present work allowed the development of innovative preparations for the treatment of topical ocular tuberculosis with potential high efficacy and safety.
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Transdermal delivery of isoniazid and rifampicin by pheroid technology / Adèle BotesBotes, Adèle January 2007 (has links)
Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2008.
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Dry powder antibiotics for inhaled anti-tuberculosis therapySon, Yoen Ju 09 February 2011 (has links)
The aim of this research was to develop and fully investigate a novel method of antibiotic drug delivery to the lung that will address problems with current therapeutic regimens for treatment of airway infections. To demonstrate the performance of prepared formulations, the design of suitable characterization methods were also aimed. A novel dissolution method for evaluating the in vitro dissolution behavior of inhalation formulations was developed. The membrane holder was designed to enclose previously air-classified formulations so that they could be uniformly tested in the dissolution apparatus. Dissolution procedures, the apparatus, the dose collection, the medium, and test conditions were developed and the dissolution behaviors of test compounds were evaluated by experimental and mathematical analysis. It was proved that the aerodynamic separation of formulation prior to dissolution assessment have a significant influence on the dissolution profiles. The optimized test method using the membrane holder was applied to evaluate in vitro dissolution profiles of the manufactured formulations of rifampicin (RF). The carrier/excipient-free RF dry powder formulation was investigated. The rifampicin dihydrate (RFDH) powders having MMAD of 2.2 um were prepared using a simple recrystallization process. The RFDH powders have a thin flaky structure, and this unique morphology provides improved aerosolization properties at maximal API loading. The manufactured RFDH formulation showed 80% drug release within 2 hours. To retard the release rate of RF, the prepared RFDH crystals were coated with hydrophobic polymer, PLA or PLGA, using spray-dryer equipped with multi-channel spray nozzles. The multi-channel spray nozzle used in this study has two separate nozzles for aqueous solution and one for gas fluid. The RFDH crystals and the coating solutions were sprayed through the two separate liquid nozzles at the same time. The coated RFDH formulations were prepared using multi-channel spray nozzles. The coated formulations contained at least 50% w/w of RF with no change of their flaky morphology. The initial RF release was lowered by coating; the lowest initial RF release was observed from the coated powders with PLA polymer as 32% among the coated formulations. Overall, the 80% of RF was released within 8 hours. The RFDH and coated RFDH formulations delivered via the pulmonary route would be anticipated to provide higher local (lung) drug concentrations than that of orally delivered powders. Particularly, the coated RFDH powders deposited in the alveolar region may prolong the drug residence time in the site of infections. Additionally, it was proved that the RFDH and coated RFDH formulations provided much better stability than the amorphous RF. / text
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The effect of pharmaceutical excipients on rifampicin release from chitosan beads / Mangaabane Gorden MohlalaMohlala, Mangaabane Gorden January 2004 (has links)
Controlled release systems aim at achieving a predictable and reproducible drug
release over a desired time period. These systems allow reduced dosing frequency,
constant drug levels in the blood, increased patient compliance and decreased adverse
effects. In a recent study, Chitosan beads, containing N-trimethyl Chitosan chloride,
have shown a potential in the delivery of rifampicin. However, because of inadequate
amounts of rifampicin released over 24 hours, incorporation of other pharmaceutical
excipients to increase the swelling behaviour of the beads to improve drug release,
was considered in this study.
Chitosan beads were prepared through ionotropic gelation with tripolyphosphate
(TPP) as a crosslinking agent. To increase the porosity if the Chitosan beads
Explotab®, Ac-Di-Sol® and vitamin C were added individually to Chitosan solutions
at concentrations of 0.1, 0.25 and 0.5 % w/v before adding the mixture to the TPP
solution. Swelling and morphology studies were used in the evaluation of the different
formulations. The swelling and morphology results were then used to select a set of
combination and concentrations of two excipients sand then prepare and characterise
beads containing two combinations. The combination formulations and formulations
containing single excipients were then loaded with rifampicin. Pure chitosan beads
exhibited a higher drug loading capacity (67.49 %) compared to the lowest loading
capacity of 41.61 % exhibited by chitosan beads containing a combination of
Explotab®, Ac-Di-Sol®.For all the other formulations the drug loading capacity
ranged within 48 and 63 %.
These formulations were used for dissolution studies over a period of 6 hours at pH
5.60 and 7.40. The dissolution results showed that no chitosan has dissolved at both
pH values. A significant amount of rifampicin was, however, released from the beads,
especially at pH 7.40. chitosan beads containing vitamin C also exhibited high
rifampicin release (48.34 ± 1.00) %) at pH 5.60 compared to the other formulations
and this makes vitamin C a potential excipient for enhanced drug release over a wide
pH range (both acidic and alkalinic). However, further studies are necessary to
optimise the preparation method to minimise drug loss during loading and to improve
the drug loading capacity of the beads. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.
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The effect of pharmaceutical excipients on rifampicin release from chitosan beads / Mangaabane Gorden MohlalaMohlala, Mangaabane Gorden January 2004 (has links)
Controlled release systems aim at achieving a predictable and reproducible drug
release over a desired time period. These systems allow reduced dosing frequency,
constant drug levels in the blood, increased patient compliance and decreased adverse
effects. In a recent study, Chitosan beads, containing N-trimethyl Chitosan chloride,
have shown a potential in the delivery of rifampicin. However, because of inadequate
amounts of rifampicin released over 24 hours, incorporation of other pharmaceutical
excipients to increase the swelling behaviour of the beads to improve drug release,
was considered in this study.
Chitosan beads were prepared through ionotropic gelation with tripolyphosphate
(TPP) as a crosslinking agent. To increase the porosity if the Chitosan beads
Explotab®, Ac-Di-Sol® and vitamin C were added individually to Chitosan solutions
at concentrations of 0.1, 0.25 and 0.5 % w/v before adding the mixture to the TPP
solution. Swelling and morphology studies were used in the evaluation of the different
formulations. The swelling and morphology results were then used to select a set of
combination and concentrations of two excipients sand then prepare and characterise
beads containing two combinations. The combination formulations and formulations
containing single excipients were then loaded with rifampicin. Pure chitosan beads
exhibited a higher drug loading capacity (67.49 %) compared to the lowest loading
capacity of 41.61 % exhibited by chitosan beads containing a combination of
Explotab®, Ac-Di-Sol®.For all the other formulations the drug loading capacity
ranged within 48 and 63 %.
These formulations were used for dissolution studies over a period of 6 hours at pH
5.60 and 7.40. The dissolution results showed that no chitosan has dissolved at both
pH values. A significant amount of rifampicin was, however, released from the beads,
especially at pH 7.40. chitosan beads containing vitamin C also exhibited high
rifampicin release (48.34 ± 1.00) %) at pH 5.60 compared to the other formulations
and this makes vitamin C a potential excipient for enhanced drug release over a wide
pH range (both acidic and alkalinic). However, further studies are necessary to
optimise the preparation method to minimise drug loss during loading and to improve
the drug loading capacity of the beads. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.
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Transdermal delivery of isoniazid and rifampicin by pheroid technology / Adèle BotesBotes, Adèle January 2007 (has links)
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.
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The impact of PheroidTM technology on the bioavailability and efficacy of anti-tuberculosis drugs in an animal model / L. NieuwoudtNieuwoudt, Liezl-Marié January 2009 (has links)
Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.
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Transdermal delivery of isoniazid and rifampicin by pheroid technology / Adèle BotesBotes, Adèle January 2007 (has links)
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.
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The impact of PheroidTM technology on the bioavailability and efficacy of anti-tuberculosis drugs in an animal model / L. NieuwoudtNieuwoudt, Liezl-Marié January 2009 (has links)
Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.
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