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Development and formulation of an intranasal dosage form for cyclizine hydrochloride / Ntseliseng Selloane BohlokoBohloko, Ntseliseng Selloane January 2004 (has links)
A comprehensive review of the nasal route of administration, in particular the nasal drug
delivery system has been presented. The physicochemical properties, mode of action and
pharmacology of H1-receptor antagonists, in particular cyclizine HCl, have been
highlighted. The techniques for the assessment of toxicity (in-vitro ciliary beat frequency
(CBF) studies for human nasal explants and morphology studies of the rat nasal mucosa),
synthesis of cyclizine lactate, solubility studies of both cyclizine HCI and cyclizine
lactate, viscosity determination of the gel formulated and assessment of the deposition
and distribution of the hydroxypropylmethyl cellulose (HPMC) dispersions within the
human nasal cavity model were conducted.
In this study, preliminary studies on the toxicity of the various formulation components
(excipients and active ingredient) were carried out. Results from these studies indicated
that for both the excipients and the drug, pH significantly affects the ciliary motility
hence all ciliary beat frequency determinations were conducted at nasal pH. Furthermore,
effects of the various concentrations (0.0625%(w/v), 0.125%(w/v), 0.25%(w/v),
0.5%(w/v) and l%(w/v)) of the excipients on ciliary motility were investigated.
Transmission electron microscopy (TEM) studies proved useful in evaluating the
integrity and changes in the surface morphology of the rat nasal mucosa post treatment
with the various excipients (carboxymethyl cellulose, hydroxypropylmethyl cellulose,
trimethyl chitosan 36.3% DQ, Carbopol P934 and polysorbate-80) at varying
concentrations.
Of the excipients investigated, hydroxypropylmethyl cellulose (HPMC) showed ciliofriendliness
since there was no apparent ultra structural damage, although a slight
decrease in ciliary beat frequency (CBF) was observed at the highest viscosity. Moreover,
hydroxypropylmethyl cellulose (HPMC) is said to be a bioadhesive excipient, which
would therefore confer its bioadhesive properties to the intranasal preparation to enhance
the retention time between the absorbing mucosa and the drug and hence increase nasal
drug absorption. This excipient was therefore selected as the ideal for use in the
formulation of the intranasal preparation.
The aqueous solubility of a drug plays an important role in nasal administration since it is
required that the drug component be applied in a limited volume of about 200pl. To
enhance the aqueous solubility of the sparingly water-soluble cyclizine HCl, a lactate salt
was synthesised and characterised. This compound was found to be highly soluble in
water. The intranasal preparation was therefore manufactured using the lactate form of
cyclizine.
A single blind study was conducted to determine and compare the pharmacokinetic
parameters for both Valoid oral tablets containing 100mg cyclizine HCl (reference
drug) and cyclizine lactate intranasal preparation 125mglml (study drug). The results
obtained indicated a significant improvement in the bioavailability of cyclizine. For oral
administration Cmax = 200.79ng/ml at tmax = 5.57h and for the intranasal preparation Cmax = 5354.22ng/ml at tmax = 1.59h.
A 19.2-fold increase in drug bioavailability was observed after intranasal administration
(AUCin = 122860.70ng/ml/h) compared with oral administration (AUCpo =
5943.48ng/ml/h). This enhanced bioavailability through nasal administration indicated
that enhanced nasal drug absorption and hence increased bioavailability not only depends
on the favourable anatomical and physiological characteristics of the nasal mucosa but
possibly on the inherent physico-chemical characteristics of the drug molecule and the
formulation components. Thus chemical modification of the sparingly water-soluble
cyclizine HCl to the highly water-soluble cyclizine lactate facilitated the dissolution of
more solute in a limited volume of solvent. This new feature therefore may have
impacted positively to the transport of cyclizine across the nasal mucosa. Furthermore,
the hydroxypropylmethyl cellulose (HPMC), component of the formulation, could have
conferred its mucoadhesive properties to the preparation. Perhaps it increased the
retention time of the dosage form within the nasal passages through bond formation with
the nasal mucosa thereby increasing the contact time between the absorbing mucosa and
the dosage form. This interaction between the mucoadhesive and the nasal mucosa may
have resulted in the modification of tissue permeability (possibly transient opening of the
tight junctions) and eventual increase in the drug penetration/absorption. / Thesis (Ph.D. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2004.
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Influence of Digestion Model, Product Type, and Enrichment Level on in vitro Bioavailability of Lutein from High Lutein Functional Bakery ProductsRead, Andrew 23 January 2012 (has links)
Lutein is a lipid soluble plant pigment with recognized health benefits, although intake levels by the general population and bioavailability are generally low. These factors have led to interest in producing high lutein functional foods, including baked products. Cookies, muffins, and flatbreads, were produced at three enrichment levels (equivalent to 0.5, 1.0, and 2.0 mg per serving) and then subjected to an in vitro simulation of human gastric and duodenal digestion coupled with Caco-2 monolayers. Lutein transfer to the aqueous phase during digestion (i.e. bioaccessibility) and monolayer absorption were determined as estimates of potential bioavailability. The higher fat products (muffins and cookies) resulted in higher overall bioaccessibility (p<0.05) and absorption at most levels of enrichment. Digestive conditions representative of the fed and fasted state were compared, with the fed model resulting in much higher estimates of bioavailability. Lutein concentration in the aqueous was the most important factor in determining subsequent monolayer absorption.
Overall, the cookie was the most effective product for bioaccessibility, and enriching them to the highest level would result in the greatest delivery of bioavailable lutein to the body. / Agriculture and Agri-Food Canada
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Field Trial of Dolomitic Limestone as an In Situ Soil Remediation Technique to Reduce Nickel Toxicity in Soybean and OatCioccio, Stephen Christopher 14 September 2012 (has links)
As more contaminated sites are being discovered, new in situ remediation techniques need to be developed. Chemically treating soil with lime to increase soil pH is a method that may decrease the bioavailability of the contaminant. To test the usefulness of rendering metal-contaminated soils alkaline with dolomitic lime, to improve crop performance, field trials at a site in Port Colborne, ON, with soil nickel concentration (as high as 5000 mg/kg) from refinery emissions were completed. Oat and soybean yield, as well as plant uptake and bioavailabilty of nickel in soil were evaluated. Liming Ni-contaminated soils decreased soybean foliar Ni concentrations from 36.68 µg/g in unlimed fields to 19.98 µg/g in 50 t/ha limed fields in the 2007 growing season; yield of both oat and soybean in unlimed soils was the same (p>0.05) as at a reference site, suggesting that for these soils, remediation is not necessary for yield.
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Diesel exhaust and wood smoke : mechanisms, inflammation and interventionMuala, Ala January 2014 (has links)
Background Particulate matter (PM) air pollution is associated with increased respiratory and cardiovascular morbidity and mortality. Diesel engine exhaust (DE) and wood combustion are major contributors to ambient air pollution and adverse health effects. The aim of this thesis was to investigate the fate of inhaled combustion-derived PM, the subsequent effects on pulmonary inflammation and symptomatology and to explore the potential for particle filters to improve public health. Additionally, it aimed at increasing the understanding of the pathophysiological mechanisms underlying the adverse vascular effects of PM inhalation in man. Methods In study I, lung deposition of wood smoke-derived particulates from incomplete combustion was determined in healthy and COPD subjects. In study II, airway inflammation was assessed in healthy subjects exposed to wood smoke and filtered air. In study III, vehicle cabin air inlet filters were evaluated regarding filtering capacity for DE and whether they affected the toxicological potential of the filtered PM. Healthy subjects were then exposed to filtered air and unfiltered DE, as well as DE filtered through two selected filters. In study IV, healthy subjects were exposed to filtered air and DE. Nitric oxide bioavailability was assessed by plethysmography in the presence of an NO clamp (NO synthase inhibitor NG-monomethyl locally and systemically administered) with measurements of arterial stiffness, cardiac output and blood pressure (BP). Results Study I: The total PM number deposition fraction of the wood smoke was 0.32 and 0.35 for healthy and COPD subjects respectively. Study II: Inhalation of wood smoke caused CD3+ and mast cell infiltration in the bronchial submucosa along with CD8+ cell recruitment to the epithelium. In bronchial wash, inflammatory cells, myeloperoxidase and matrix metalloproteinase 9 levels decreased. Study III: An efficient cabin air filter with an active charcoal component was most favourable in in-vitro tests and reduced symptoms in the human exposure study. Study IV: Local NO synthase inhibition caused similar vasoconstriction after exposure to DE and filtered air, along with an increase in plasma nitrate concentrations, suggesting an increase in the basal NO release due to oxidative stress. Systemic NO synthase inhibition increased arterial stiffness and blood pressure after DE exposure along with an increase in systemic vascular resistance and reduced cardiac output, implying that the increased basal NO release could not compensate for the reduced NO bioavailability in the conduit vessels. Conclusion Wood smoke particles from incomplete combustion tend to have a greater airway deposition than particles from better combustion. The airway inflammatory responses to the former particles differ from what have been shown for other PM pollutants, which may be of importance for subsequent health effects. The vasomotor dysfunction shown after DE exposure may largely be explained by reduced NO bioavailability. A vehicle cabin air inlet particle filter with active charcoal was effective to reduce DE exposure and subsequent symptoms. This may conceptually be of benefit when it comes to decreasing engine exhaust-related adverse health effects.
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Development and formulation of an intranasal dosage form for cyclizine hydrochloride / Ntseliseng Selloane BohlokoBohloko, Ntseliseng Selloane January 2004 (has links)
A comprehensive review of the nasal route of administration, in particular the nasal drug
delivery system has been presented. The physicochemical properties, mode of action and
pharmacology of H1-receptor antagonists, in particular cyclizine HCl, have been
highlighted. The techniques for the assessment of toxicity (in-vitro ciliary beat frequency
(CBF) studies for human nasal explants and morphology studies of the rat nasal mucosa),
synthesis of cyclizine lactate, solubility studies of both cyclizine HCI and cyclizine
lactate, viscosity determination of the gel formulated and assessment of the deposition
and distribution of the hydroxypropylmethyl cellulose (HPMC) dispersions within the
human nasal cavity model were conducted.
In this study, preliminary studies on the toxicity of the various formulation components
(excipients and active ingredient) were carried out. Results from these studies indicated
that for both the excipients and the drug, pH significantly affects the ciliary motility
hence all ciliary beat frequency determinations were conducted at nasal pH. Furthermore,
effects of the various concentrations (0.0625%(w/v), 0.125%(w/v), 0.25%(w/v),
0.5%(w/v) and l%(w/v)) of the excipients on ciliary motility were investigated.
Transmission electron microscopy (TEM) studies proved useful in evaluating the
integrity and changes in the surface morphology of the rat nasal mucosa post treatment
with the various excipients (carboxymethyl cellulose, hydroxypropylmethyl cellulose,
trimethyl chitosan 36.3% DQ, Carbopol P934 and polysorbate-80) at varying
concentrations.
Of the excipients investigated, hydroxypropylmethyl cellulose (HPMC) showed ciliofriendliness
since there was no apparent ultra structural damage, although a slight
decrease in ciliary beat frequency (CBF) was observed at the highest viscosity. Moreover,
hydroxypropylmethyl cellulose (HPMC) is said to be a bioadhesive excipient, which
would therefore confer its bioadhesive properties to the intranasal preparation to enhance
the retention time between the absorbing mucosa and the drug and hence increase nasal
drug absorption. This excipient was therefore selected as the ideal for use in the
formulation of the intranasal preparation.
The aqueous solubility of a drug plays an important role in nasal administration since it is
required that the drug component be applied in a limited volume of about 200pl. To
enhance the aqueous solubility of the sparingly water-soluble cyclizine HCl, a lactate salt
was synthesised and characterised. This compound was found to be highly soluble in
water. The intranasal preparation was therefore manufactured using the lactate form of
cyclizine.
A single blind study was conducted to determine and compare the pharmacokinetic
parameters for both Valoid oral tablets containing 100mg cyclizine HCl (reference
drug) and cyclizine lactate intranasal preparation 125mglml (study drug). The results
obtained indicated a significant improvement in the bioavailability of cyclizine. For oral
administration Cmax = 200.79ng/ml at tmax = 5.57h and for the intranasal preparation Cmax = 5354.22ng/ml at tmax = 1.59h.
A 19.2-fold increase in drug bioavailability was observed after intranasal administration
(AUCin = 122860.70ng/ml/h) compared with oral administration (AUCpo =
5943.48ng/ml/h). This enhanced bioavailability through nasal administration indicated
that enhanced nasal drug absorption and hence increased bioavailability not only depends
on the favourable anatomical and physiological characteristics of the nasal mucosa but
possibly on the inherent physico-chemical characteristics of the drug molecule and the
formulation components. Thus chemical modification of the sparingly water-soluble
cyclizine HCl to the highly water-soluble cyclizine lactate facilitated the dissolution of
more solute in a limited volume of solvent. This new feature therefore may have
impacted positively to the transport of cyclizine across the nasal mucosa. Furthermore,
the hydroxypropylmethyl cellulose (HPMC), component of the formulation, could have
conferred its mucoadhesive properties to the preparation. Perhaps it increased the
retention time of the dosage form within the nasal passages through bond formation with
the nasal mucosa thereby increasing the contact time between the absorbing mucosa and
the dosage form. This interaction between the mucoadhesive and the nasal mucosa may
have resulted in the modification of tissue permeability (possibly transient opening of the
tight junctions) and eventual increase in the drug penetration/absorption. / Thesis (Ph.D. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2004.
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106 |
Use of in silico predictors, solubility and permeability to select bioavailability and bioequivalence markers in herbal supplementsPade, Devendra Shrikant, January 1900 (has links)
Thesis (Ph. D.)--University of Texas at Austin, 2007. / Vita. Includes bibliographical references.
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107 |
Effects of sorption and desorption on bioavailbility of atrazine in soils amended with crop residue derived charLoganathan, Vijay Anand. Clement, Prabhakar. Feng, Yucheng. January 2006 (has links) (PDF)
Thesis(M.S.)--Auburn University, 2006. / Abstract. Includes bibliographic references.
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108 |
Interactions between pesticides and microorganisms in freshwater sediments : toxic effects and implications for bioavailability /Widenfalk, Anneli, January 2005 (has links) (PDF)
Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniversitet, 2005. / Härtill 4 uppsatser.
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109 |
Soy isoflavone bioavailability effects of probiotic and prebiotic consumption and oil supplementation /Larkin, Theresa Anne. January 2005 (has links)
Thesis (Ph.D.)--University of Wollongong, 2005. / Typescript. Includes bibliographical references: leaf 279-310.
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110 |
Development of an integrative sampler for bioavailable metals in water /Brumbaugh, William G. January 1997 (has links)
Thesis (Ph. D.)--University of Missouri-Columbia, 1997. / Typescript. Vita. Includes bibliographical references (leaves 173-179). Also available on the Internet.
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