An investigation into the possible neuroprotective or neurotoxic properties of metrifonate
- Authors: Ramsunder, Adrusha
- Date: 2005 , 2013-06-11
- Subjects: Nervous system -- Degeneration -- Treatment , Neurotoxic agents , Alzheimer's disease -- Treatment , Metrifonate
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3833 , http://hdl.handle.net/10962/d1007560 , Nervous system -- Degeneration -- Treatment , Neurotoxic agents , Alzheimer's disease -- Treatment , Metrifonate
- Description: Alzheimer's disease is a progressive neurodegenerative disorder, in which there is a marked decline in neurotransmitters, especially those of the cholinergic pathways. One of the approaches to the symptomatic treatment of Alzheimer's disease is the inhibition of the breakdown of the neurotransmitter acetylcholine, using an acetylcholinesterase inhibitor. One such drug tested, is the organophosphate, metrifonate. Any drug used for the treatment of neurodegenerative disorders should preferably not induce further neurological damage. Thus, in the present study, we investigated whether or not metrifonate is neuroprotective. The in vivo and in vitro effect of this drug on free radicals generation shows that metrifonate increases the level ofthese reactive species. Lipid peroxidation induced using quinolinic acid (QA) and iron (II) and show that metrifonate increased the peroxidative damage induced by using quinolinic acid. Metrifonate is also able to induce lipid peroxidation both in vivo and in vitro. This was reduced in vitro in the presence of melatonin. Using iron (II), in vi/ro, there was no significant difference in the level of lipid peroxidation in the presence of this drug. An investigation of the activity of the mitochondrial electron transport chain and complex I of the electron transport chain in the presence of metrifonate revealed that metrifonate reduces the activity of the electron transport chain at the level of complex I. The activity of the mitochondrial electron transport chain was restored in the presence of melatonin. Pineal organ culture showed that metrifonate does not increase melatonin production. Histological and apoptosis studies show that tissue necrosis and apoptosis respectively, occur in the presence of this agent, which is reduced in the presence of melatonin. Metal binding studies were performed USing ultraviolet spectroscopy, and electrochemical analysis to examine the interaction of metrifonate with iron (II) and iron (III). No shift in the peak was observed in the ultraviolet spectrum when iron (ll) was added to metrifonate. Electrochemical studies show that there may be a very weak or no ligand formed between the metal and drug. This study shows that while drugs such as metrifonate may be beneficial in restoring cognitive function in Alzheimer's disease, it could also have the potential to enhance neurodegeneration, thus worsening the condition, in the long term. , KMBT_363 , Adobe Acrobat 9.54 Paper Capture Plug-in
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- Date Issued: 2005
Development and assessment of medicines information for antiretroviral therapy in Sub-Saharan Africa
- Authors: Mwingira, Betty
- Date: 2005
- Subjects: AIDS (Disease) -- Africa, Sub-Saharan , AIDS (Disease) -- Treatment -- Africa, Sub-Saharan , AIDS (Disease) -- Juvenile literature -- Africa, Sub-Saharan , HIV infections -- Treatment -- Africa, Sub-Saharan , HIV infections -- Africa, Sub-Saharan , Antiretroviral agents -- Africa, Sub-Saharan , HIV-positive persons -- Care -- Africa, Sub-Saharan , Hiv-positive persons -- Medical care -- Africa, Sub-Saharan , AIDS (Disease) -- Study and teaching -- Africa, Sub-Saharan
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3779 , http://hdl.handle.net/10962/d1003257 , AIDS (Disease) -- Africa, Sub-Saharan , AIDS (Disease) -- Treatment -- Africa, Sub-Saharan , AIDS (Disease) -- Juvenile literature -- Africa, Sub-Saharan , HIV infections -- Treatment -- Africa, Sub-Saharan , HIV infections -- Africa, Sub-Saharan , Antiretroviral agents -- Africa, Sub-Saharan , HIV-positive persons -- Care -- Africa, Sub-Saharan , Hiv-positive persons -- Medical care -- Africa, Sub-Saharan , AIDS (Disease) -- Study and teaching -- Africa, Sub-Saharan
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- Date Issued: 2005
A study of plocamium corallorhiza secondary metabolites and their biological activity
- Authors: Mkwananzi, Henry Bayanda
- Date: 2005
- Subjects: Natural products -- Therapeutic use , Marine metabolites -- Therapeutic use , Marine pharmacology , Marine algae , Monoterpenes
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3841 , http://hdl.handle.net/10962/d1007666 , Natural products -- Therapeutic use , Marine metabolites -- Therapeutic use , Marine pharmacology , Marine algae , Monoterpenes
- Description: Seaweeds of the genus Plocamium are known to produce a variety of halogenated monoterpenes. In addition to their ecological role as feeding deterrents, biological activities reported for these compounds include antibacterial, antialgal, antifungal and anticancer activities. An investigation of the non-polar extracts of the seaweed Plocamium corallorhiza resulted in the isolation of six known halogenated monoterpene compounds, 4-bromo-5-bromomethyl-1-chlorovinyl-2, 5-dichloro-methylcyclohexane (2.68), 1,4,8-tribromo-3 ,7-dichloro-3, 7-dimethyl-1,5-octadiene (2.67), 8-bromo-1 ,3,4,7-tetrachloro-3, 7-dimethyl-1,5-octadiene (2.66), 4,6-dibromo-1,1-dichloro-3,7-dimethyl-2,7-octadiene (2.64), 4,8-dibromo-1,1,7-trichloro-3,7-dimethyl-2,5-octadiene (2.65) and 3,4 ,6,7-tetrachloro-3, 7-dimethyl-1-octene (2.63) as well as eight new compounds, including five halogenated monoterpene aldehydes. The new compounds were identified by 1D and 2D NMR spectroscopic techniques as: 8-Bromo-6,7-dichloro-3,7-dimethyl-octa-2,4-dienal (2.72), 8-Bromo-1,1,2,7-tetrachloro-3,7-dimethyl-octa-3,5-diene (2.70), 4,8-Dichloro-3,7-dimethyl-octa-2,4,6-trienal (2.74), 4-Bromo-8-chloro-3, 7-di methyl-octa-2, 6-dienal (2 76), 8-Bromo-4-chloro-3, 7-dimethyl-octa-2,4 ,6-trienaI (2.75), 4-Bromo-1,3,6,7-tetrachloro-3 ,7-dimethyl-octa-1,4-diene (2.71), 8-Bromo-1,3,4,7-tetrachloro-3,7-dimethyl-octa-1,5-diene (2.69), 4,6-Dibromo-3,7 -dimethyl-octa-2,7-dienal (2.73). All compounds were screened for antimicrobial activity, brine shrimp lethality and cytotoxicity towards oesophageal cancer cells. Compound 2.68 was toxic to brine shrimp larvae at a concentration of 50 μ/mL. It also showed promising activity towards oesophageal cancer cells with an IC₅₀, of 2 μg/mL.
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- Date Issued: 2005
An investigation into the neuroprotective properties of acetylsalicylic acid and acetaminophen
- Authors: Maharaj, Himant
- Date: 2005
- Subjects: Aspirin Acetaminophen Analgesics Alzheimer's disease -- Treatment Parkinson's disease
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3769 , http://hdl.handle.net/10962/d1003247
- Description: The potent analgesic property of acetylsalicylic acid and acetaminophen makes these the most commonly used analgesics in the world. Easy accessibility and cost effectiveness of these agents are attractive to patients seeking pain relief. However, the abuse of nonnarcotic analgesics such as acetaminophen and acetylsalicylic acid by alcoholics and patients seeking to relieve dysphoric moods is well documented. These agents therefore impact on the brain neurotransmitter levels and therefore all processes involved in the synthesis and metabolism of neurotransmitters may be affected. The use of non-narcotic analgesics has been reported to reduce the incidence of neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). The mode of action by which acetylsalicylic acid and acetaminophen elicit neuroprotection is however unclear as many mechanisms of action have been inconclusively postulated. The first part of this study aims to elucidate the various mechanisms by which acetylsalicylic acid and acetaminophen affect the enzymes responsible for the catabolism of tryptophan, which is a precursor for the mood elevating neurotransmitter serotonin, as well as to investigate whether these agents alter the interplay between serotonin and pineal indole metabolism. The second part of this study focuses on the neuroprotective properties of acetylsalicylic acid and acetaminophen utilizing the neurotoxic metabolite of the kynurenine pathway, quinolinic acid and the potent Parkinsonian neurotoxin, 1-methyl-4-phenylpyridinium (MPP+). The ability of acetylsalicylic acid and acetaminophen to alter TRP metabolism was determined by investigating the effects of these agents on the primary enzymes of the kynurenine pathway i.e. tryptophan 2, 3-dioxygenase and indoleamine 2,3-dioxygenase as well as to investigate whether these agents would have any effects on 3-hydroxyanthranilic acid oxygenase. 3-Hydroxyanthranilic acid oxygenase is the enzyme responsible for the synthesis of quinolinic acid. Acetylsalicylic acid and acetaminophen alter tryptophan metabolism by inhibiting tryptophan 2, 3-dioxygenase and indoleamine 2,3-dioxygenase thus increasing the availability of tryptophan for the production of serotonin. Acetylsalicylic acid and acetaminophen also inhibit 3-hydroxyanthranilic acid oxygenase thus implying that these agents could reduce quinolinic acid production. Acetaminophen administration in rats induces a rise in serotonin and norepinephrine in the forebrain. Acetylsalicylic acid curtails the acetaminophen-induced rise in brain norepinephrine levels as well as enhances serotonin metabolism, indicating that analgesic preparations containing both agents would be advantageous, as this would prevent acetaminophen-induced mood elevation. The results from the pineal indole metabolism study show that acetylsalicylic acid enhances pineal metabolism of serotonin whereas acetaminophen induces an increase in melatonin levels in the pineal gland. Neuronal damage due to oxidative stress has been implicated in several neurodegenerative disorders such as AD and PD. The second part of the study aims to elucidate and characterize the mechanism by which acetylsalicylic acid and acetaminophen afford neuroprotection. The hippocampus is an important region of the brain responsible for memory. Agents such as quinolinic acid that are known to induce stress in this area have detrimental effects and could lead to various types of dementia. The striatum is also a vulnerable region to oxidative stress and hence (MPP+), which is toxic for this particular region of the brain, was also used as a neurotoxin. The results show that ASA and acetaminophen alone and in combination, are potent superoxide anion scavengers. In addition, the results imply that these agents offer protection against oxidative stress and lipid peroxidation induced by several neurotoxins in rat brain particularly, the hippocampus and striatum. Histological studies, using Nissl staining and Acid fuchsin, show that acetylsalicylic acid and acetaminophen are able to protect hippocampal neurons against quinolinic acidinduced necrotic cell death. Immunohistochemical investigations show that QA induces apoptotic cell death in the hippocampus, which is inhibited by ASA and acetaminophen. In addition, ASA and acetaminophen inhibited MPP+ induced apoptotic cell death in the rat striatum. The study also sought to elucidate possible mechanisms by which ASA and acetaminophen exert neuroprotective effects in the presence of MPP+ as these agents are shown to prevent the MPP+-induced reduction in dopamine levels. The results show that acetylsalicylic acid and acetaminophen inhibit the action of this neurotoxin on the mitochondrial electron transport chain, a common source of free radicals in the cell. In addition, these agents were shown to block the neurotoxic effects of MPP+ on the enzymatic defence system of the brain i.e. superoxide dismutase, glutathione peroxidase and catalase. The reduction in glutathione levels induced by MPP+ is significantly inhibited by acetylsalicylic acid and acetaminophen. The results imply that these agents are capable of not only scavenging free radicals but also enhance the cell defence mechanism against toxicity in the presence of MPP+. These agents also block the MPP+-induced inhibition of dopamine uptake into the cell. This would therefore reduce auto-oxidation of dopamine thus implying another mechanism by which these agents exert a neuroprotective role in MPP+-induced neurotoxicity. The discovery of neuroprotective properties of acetylsalicylic acid and acetaminophen is important considering the high usage of these agents and the increased incidence in neurological disorders. The findings of this thesis point to the need for clinical studies to be conducted as the results show acetylsalicylic acid and acetaminophen to have a definite role to play as antioxidants. This study therefore provides novel information regarding the neuroprotective effects of these agents and favours the use of these agents in the treatment of neurodegenerative disorders, such as AD and PD, in which oxidative stress is implicated.
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- Date Issued: 2005
Formulation and assessment of verapamil sustained release tablets
- Authors: Khamanga, Sandile Maswazi Malungelo
- Date: 2005
- Subjects: Verapamil , Tablets (Medicine) , Drugs -- Administration , Cardiovascular agents , Calcium -- Antagonists , Drugs -- Controlled release
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3869 , http://hdl.handle.net/10962/d1018236
- Description: The oral route of drug administration is most extensively used due to the obvious ease of administration. Verapamil hydrochloride is a WHO listed phenylalkylarnine, L-type calcium channel antagonist that is mainly indicated for cardiovascular disorders such as angina pectoris, supraventricular tachycardia and hypertension. Due to its relatively short half-life of approximately 4.0 hours, the formulation of a sustained-release dosage form is useful to improve patient compliance and to achieve predictable and optimized therapeutic plasma concentrations. Direct compression and wet granulation were initially used as methods for tablet manufacture. The direct compression method of manufacture produced tablets that exhibited formulation and manufacturing difficulties. Mini-tablets containing veraparnil hydrochloride were then prepared by wet granulation using Surelease® E-7-19010.and Eudragit® NE 30D as the granulating agents after which the granules were incorporated with an hydrophilic matrix material, Carbopol® 974P NF. Granule and powder blends were evaluated using the angle of repose, loose and tapped bulk density, Can's compressibility index, Hausner's ratio and drug content. Granules with good flow properties and satisfactory compressibility were used for further studies. Tablets were subjected to thickness, diameter and weight variation tests, crushing strength, tensile strength, friability and content uniformity studies. Tablets that showed acceptable pharmaco-technical properties were selected for further analysis. Drug content uniformity and dissolution release rates were determined using a validated isocratic HPLC method. Initially, USP apparatus 1 and 3 dissolution apparatus were used to determine in-vitro drug release rates from the formulations over a 22-hour period. USP apparatus 3 was finally selected as it offers the advantages of mimicking, in part, the changes in the physicochemical environment experienced by products in the gastro-intestinal tract. Differences in release rates between the test formulations and a commercially available product, Isoptin® SR were observed at different pH's using USP apparatus 1. The release of veraparnil hydrochloride from matrix tablets was pH dependent and was markedly reduced at higher pH values. This may be due, in part, to the poor solubility of veraparnil hydrochloride at these pH values and also the possible interaction of verapamil hydrochloride with anionic polymers used in these formulations. Swelling and erosion behaviour of the tablets were evaluated and differences in behaviour were observed which may be attributed to the physico-chemical characteristics of the polymers used in this study. In-vitro dissolution profiles were characterized by the difference (j1) and similarity factor (j2) and also by a new similarity factor, Sct. In addition, the mechanism of drug release from these dosage forms was mainly evaluated using the Korsmeyer-Peppas model and the kinetics of drug release assessed using other models, including Zero order, First order, Higuchi, HixsonCrowell, Weibull and the Baker-Lonsdale model. Dissolution kinetics were best described by application of the Weibull model, and the Korsmeyer-Peppas model. The release exponent, n, confirmed that drug release from these dosage forms was due to the mixed effects of diffusion and swelling and therefore, anomalous release kinetics are predominant. In conclusion, two test batches were found to be comparable to the reference product Isoptin® SR with respect to their in-vitro release profiles.
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- Date Issued: 2005
An investigation into the antidepressant activity of hypericum perforatum
- Authors: Stephens, Linda Lee
- Date: 2005
- Subjects: Hypericum perforatum -- Physiological effect Hypericum perforatum -- Therapeutic use Antidepressants
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3793 , http://hdl.handle.net/10962/d1003271
- Description: Hypericum perforatum is a herbal medicine that has been used for centuries for the treatment of depression. Many studies have been conducted in the Northern hemisphere on the efficacy of the HP extracts produced there. These studies include clinical trials and pharmacological investigations using a standardised HP extract or a fraction of the HP extract containing certain compounds, such as hypericin, pseudohypericin, hyperforin and several of the flavonoids thought to be responsible for the antidepressant activity. The mechanism of action of HP and its constituents is still not completely clear and it is speculated that the antidepressant activity is the result of several of the compounds acting synergistically. HP is indigenous to and also cultivated in the Western Cape of South Africa. Extracts from these plants are sold in the local health shops and there are no previous studies evaluating the efficacy of these products. The aim of this thesis is to investigate the antidepressant activity of one of these products and two of its constituents, quercetin and caffeic acid, to gain further insight into their mode of antidepressant action and to compare these results with similar studies which used a standardised extract produced in the northern hemisphere. The first study investigated the effect of HP, quercetin and caffeic acid on pineal metabolism. Changes in the synthesis of melatonin produced by the pineal gland have been implicated in depression. The results showed an increase in the level of melatonin produced in the animals treated with quercetin, which suggests that this compound may mediate antidepressant activity through such a mechanism. There are no previous reports on the in vivo effects of HP or any of its constituents on pineal metabolism. The second study investigated the effect of HP, quercetin and caffeic acid on the activity of the liver enzyme, tryptophan-2,3-dioxygenase (TDO). Inhibition of this enzyme has been shown to increase plasma levels of tryptophan, a precursor of serotonin and thereby result in increased serotonin levels in the brain. Low levels of serotonin in the brain have been implicated in depression. This study revealed significant inhibition of TDO by caffeic acid and this suggests that this constituent of HP could be contributing to its antidepressant activity through such a mechanism. There are no previous reports investigating the in vivo effect of HP or any of its constituents on TDO activity. Modulation of the levels of indoleamines, serotonin (5-HT) and dopamine (DA) as well as the metabolites, 3,4 dihydroxyphenyl acetic acid (DOPAC), 5-hydroxyindole acetic acid (5-HIAA) and homovallinic acid (HVA) in the brain have been implicated in the neuropharmacology of depression. Different studies using enzyme-linked immunosorbant assay (ELISA), high performance liquid chromatography with electrochemical detection (HPLC-ECD) and liquid chromatography-mass spectrometry (LC-MS) were used to determine changes in the levels of these indoleamines brought about after treatment with HP caffeic acid and quercetin. The results of the ELISA study showed significant increases in 5-HT levels in the brains of the animals treated with caffeic acid and quercetin. The results of the HPLC-ECD studies also revealed significant increases in 5-HT levels and a decrease in the turnover of 5-HT in the animals treated with quercetin. A significant increase in DA levels in the animals treated with quercetin was shown in both the HPLC-ECD and LC-MS studies. There was also an increase in DA turnover in the animals treated with HP shown in the HPLC-ECD and LC-MS studies. These results suggest that HP and its constituents, quercetin and caffeic acid mediate their antidepressant effects through serotonergic and dopaminergic neurotransmission. Adaptive changes in the density of b-adrenergic (b-AR), 5-HT2 and N-methyl-D-aspartate (NMDA) receptors have been implicated in depression. Several studies, investigating the effect of treatment with HP and quercetin on these different receptor densities, were undertaken using radioactive binding assays. Treatment with HP resulted in significant down regulation of b-AR and NMDA receptor densities and up-regulation of 5HT2 receptors. The effects on the b-AR and 5-HT2 receptors are similar to the results reported using HP in the Northern hemisphere, but the effect on the NMDA receptors is novel providing insight into the mode of action of HP. Apoptosis of neuronal cells has been implicated in neuro-degenerative and depressive disorders. Detection of apoptosis, using fluorescent microscopy observed through the labelling of DNA strand breaks, showed a decrease in the amount of apoptosis in the animals treated with HP and quercetin. This adds further support for the use of HP as an antidepressant and these results are similar to results reported from the Northern hemisphere. The results of all these studies suggest that the quality of the locally produced tincture is similar in efficacy to that of the standardised product of the Northern hemisphere.
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- Date Issued: 2005
Marine biotechnology : evaluation and development of methods for the discovery of natural products from fungi
- Authors: Pather, Simisha
- Date: 2005 , 2013-06-18
- Subjects: Marine biotechnology , Marine fungi -- South Africa , Natural products -- South Africa , Marine plants -- South Africa , Marine metabolites -- South Africa , Cancer -- Treatment , DNA
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3839 , http://hdl.handle.net/10962/d1007652 , Marine biotechnology , Marine fungi -- South Africa , Natural products -- South Africa , Marine plants -- South Africa , Marine metabolites -- South Africa , Cancer -- Treatment , DNA
- Description: One of the major impediments in the development of marine natural products is the provision of biologically active natural products in sufficient quantity for complete pharmacological evaluation, clinical trials and eventual commercial production. Marine microorganisms show great promise in providing a renewable source of biologically active natural products. The main aim of this study was to develop and evaluate methods for the isolation, identification and cultivation of marine fungi from the South African marine environment for the production of biologically active secondary metabolites. Twenty-four species of fungi were isolated from marine algae collected from the intertidal zone near Port Alfred, South Africa. The fungi were cultivated in small-scale under static and agitated conditions and their crude intra- and extracellular organic extracts were screened by ¹H NMR and a series of bioassays. Using this as a basis, one isolate was selected for further study. By analyses of the lTS1 region of the ribosomal DNA, the fungal isolate was identified as a marine-derived isolate of Eurotium rubrum (Aspergillus ruber). Although E. rubrum has been isolated from the marine environment, no investigations have been undertaken to determine the adaptation of these isolates to the marine environment. In order to optimise productivity, creativity and incubation time, the fungus was cultivated in small-scale using a variety of carbon (glucose, fructose, lactose, sucrose, marmitol and maltose) and nitrogen sources (ammonium tartrate, urea, peptone and yeast extract). An HPLC-DAD method was developed to assess the metabolic creativity and productivity under different fermentation conditions. Distinctive variations in the range and yield of metabolites produced as well as morphology and growth time were observed. The crude extracts from all fermentations were combined and six known compounds were isolated by reversed-phase chromatography and their structures elucidated by spectroscopic techniques. The known compounds were fIavoglaucin, aspergin, isodihydroauroglaucin, isotetrahydroauroglaucin, neoechinuline A and physcion. Neoechinuline A, isodihydroauroglaucin and isotetrahydroauroglaucin showed activity against oesophageal and cervical cancer cell lines.
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- Date Issued: 2005
In vitro release of ketoprofen from proprietary and extemporaneously manufactured gels
- Authors: Tettey-Amlalo, Ralph Nii Okai
- Date: 2005
- Subjects: Transdermal medication , Drug delivery systems , High performance liquid chromatography , Nonsteroidal anti-inflammatory agents , Rheumatoid arthritis -- Treatment
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3797 , http://hdl.handle.net/10962/d1003275 , Transdermal medication , Drug delivery systems , High performance liquid chromatography , Nonsteroidal anti-inflammatory agents , Rheumatoid arthritis -- Treatment
- Description: Ketoprofen is a potent non-steroidal anti-inflammatory drug which is used for the treatment of rheumatoid arthritis. The oral administration of ketoprofen can cause gastric irritation and adverse renal effects. Transdermal delivery of the drug can bypass gastrointestinal disturbances and provide relatively consistent drug concentrations at the site of administration. The release of ketoprofen from proprietary gel products from three different countries was evaluated by comparing the in vitro release profiles. Twenty extemporaneously prepared ketoprofen gel formulations using Carbopol® polymers were manufactured. The effect of polymer, drug concentration, pH and solvent systems on the in vitro release of ketoprofen from these formulations were investigated. The gels were evaluated for drug content and pH. The release of the drug from all the formulations obeyed the Higuchi principle. Two static FDA approved diffusion cells, namely the modified Franz diffusion cell and the European Pharmacopoeia diffusion cell, were compared by measuring the in vitro release rate of ketoprofen from all the gel formulations through a synthetic silicone membrane. High-performance liquid chromatography and ultraviolet spectrophotometric analytical techniques were both used for the analysis of ketoprofen. The validated methods were employed for the determination of ketoprofen in the sample solutions taken from the receptor fluid. Two of the three proprietary products registered under the same manufacturing license exhibited similar results whereas the third product differed significantly. Among the variables investigated, the vehicle pH and solvent composition were found have the most significant effect on the in vitro release of ketoprofen from Carbopol® polymers. The different grades of Carbopol® polymers showed statistically significantly different release kinetics with respect to lag time. When evaluating the proprietary products, both the modified Franz diffusion cell and the European Pharmacopoeia diffusion cell were deemed adequate although higher profiles were generally obtained from the European Pharmacopoeia diffusion cells. Smoother diffusion profiles were obtained from samples analysed by high-performance liquid chromatography than by ultraviolet spectrophotometry in both diffusion cells. Sample solutions taken from Franz diffusion cells and analysed by ultraviolet spectrophotometry also produced smooth diffusion profiles. Erratic and higher diffusion profiles were observed with samples taken from the European Pharmacopoeia diffusion cell and analysed by ultraviolet spectrophotometry. The choice of diffusion cells and analytical procedure in product development must be weighed against the relatively poor reproducibility as observed with the European Pharmacopoeia diffusion cell.
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- Date Issued: 2005