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Knowledge and practices of patent medicine vendors in the use of artemisinin based combination therapy in the treatment of malaria in an urban community in Lagos.Momodu, Rametu Omamegbe. January 2008 (has links)
<p>Malaria is a health, social and economic burden in Nigeria and consistently ranks amongst the four most common causes of childhood deaths. Treatment of malaria is usually started at home / care is only sought from the health facility when the treatment is ineffective (McCombie, 1996). Patent medicine vendors (PMVs) have been identified as a widely patronized source for drugs used in the home treatment of malaria (Breiger et al, 2001 / Goodman, et al, 2007 / Salako et al, 2001). Inadequate or poor knowledge and practices in the use of anti-malaria drugs (AMDs) increases morbidity and mortality, undermines therapeutic efficacy, and promotes the emergence and spread of drugresistant malaria. Aim: The aim of the study was to describe and quantify the knowledge and self-reported practices of PMVs in the use of antimalarials, particularly artemisinin-based combination therapies (ACTs), in a poor urban community in Lagos state, Nigeria.</p>
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Knowledge and practices of patent medicine vendors in the use of artemisinin based combination therapy in the treatment of malaria in an urban community in Lagos.Momodu, Rametu Omamegbe. January 2008 (has links)
<p>Malaria is a health, social and economic burden in Nigeria and consistently ranks amongst the four most common causes of childhood deaths. Treatment of malaria is usually started at home / care is only sought from the health facility when the treatment is ineffective (McCombie, 1996). Patent medicine vendors (PMVs) have been identified as a widely patronized source for drugs used in the home treatment of malaria (Breiger et al, 2001 / Goodman, et al, 2007 / Salako et al, 2001). Inadequate or poor knowledge and practices in the use of anti-malaria drugs (AMDs) increases morbidity and mortality, undermines therapeutic efficacy, and promotes the emergence and spread of drugresistant malaria. Aim: The aim of the study was to describe and quantify the knowledge and self-reported practices of PMVs in the use of antimalarials, particularly artemisinin-based combination therapies (ACTs), in a poor urban community in Lagos state, Nigeria.</p>
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Knowledge and practices of patent medicine vendors in the use of artemisinin based combination therapy in the treatment of malaria in an urban community in LagosMomodu, Rametu Omamegbe January 2008 (has links)
Magister Public Health - MPH / Malaria is a health, social and economic burden in Nigeria and consistently ranks amongst the four most common causes of childhood deaths. Treatment of malaria is usually started at home; care is only sought from the health facility when the treatment is ineffective (McCombie, 1996). Patent medicine vendors (PMVs) have been identified as a widely patronized source for drugs used in the home treatment of malaria (Breiger et al, 2001; Goodman, et al, 2007; Salako et al, 2001). Inadequate or poor knowledge and practices in the use of anti-malaria drugs (AMDs) increases morbidity and mortality, undermines therapeutic efficacy, and promotes the emergence and spread of drugresistant malaria. Aim: The aim of the study was to describe and quantify the knowledge and self-reported practices of PMVs in the use of antimalarials, particularly artemisinin-based combination therapies (ACTs), in a poor urban community in Lagos state, Nigeria. / South Africa
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Development and evaluation of a solid oral dosage form for an artesunate and mefloquine drug combination / Abel Hermanus van der WattVan der Watt, Abel Hermanus January 2014 (has links)
Malaria affects about forty percent of the world’s population. Annually more than 1.5 million fatalities due to malaria occur and parasite resistance to existing antimalarial drugs such as mefloquine has already reached disturbingly high levels in South-East Asia and on the African continent. Consequently, there is a dire need for new drugs or formulations in the prophylaxis and treatment of malaria. Artesunate, an artemisinin derivative, represents a new category of antimalarials that is effective against drug-resistant Plasmodium falciparum strains and is of significance in the current antimalarial campaign. As formulating an ACT double fixed-dose combination is technically difficult, it is essential that fixed-dose combinations are shown to have satisfactory ingredient compatibility, stability, and dissolution rates similar to the separate oral dosage forms.
Since the general deployment of a combination of artesunate and mefloquine in 1994, the cure rate increased again to almost 100% from 1998 onwards, and there has been a sustained decline in the incidence of Plasmodium falciparum malaria in the experimental studies (Nosten et al., 2000:297; WHO, 2010:17). However, the successful formulation of a solid oral dosage form and fixed dosage combination of artesunate and mefloquine remains both a market opportunity and a challenge.
Artesunate and mefloquine both exhibited poor flow properties. Furthermore, different elimination half-lives, treatment dosages as well as solubility properties of artesunate and mefloquine required different formulation approaches. To substantiate the FDA’s pharmaceutical quality by design concept, the double fixed-dose combination of artesunate and mefloquine required strict preliminary formulation considerations regarding compatibility between excipients and between the APIs. Materials and process methods were only considered if theoretically and experimentally proved safe. Infrared absorption spectroscopy (IR) and X-ray powder diffraction (XRPD) data proved compatibility between ingredients and stability during the complete manufacturing process by a peak by peak correlation. Scanning Electron Micrographs (SEM) provided explanations for the inferior flow properties exhibited by the investigated APIs. Particle size analysis and SEM micrographs confirmed that the larger, rounder and more consistently sized particles of the granulated APIs contributed to improved flow under the specified testing conditions.
A compressible mixture containing 615 mg of the APIs in accordance with the WHO recommendation of 25 mg/kg of mefloquine taken in two or three divided dosages, and 4 mg/kg/day for 3 days of artesunate for uncomplicated falciparum malaria was developed. Mini-tablets of artesunate and mefloquine were compressed separately and successfully with the required therapeutic dosages and complied with pharmacopoeial standards. Preformulation studies eventually led to a formula for a double fixed-dose combination and with the specific aim of delaying the release of artesunate due to its short half-life.
A factorial design revealed the predominant factors contributing to the successful wet granulation of artesunate and mefloquine. A fractional factorial design identified the optimum factors and factor levels. The application of the granulation fluid (20% w/w) proved to be sufficient by a spraying method for both artesunate and mefloquine. A compatible acrylic polymer and coating agent for artesunate, Eudragit® L100 was employed to delay the release of approximately half of the artesunate dose from the double fixed-dose combination tablet until a pH of 6.8.
A compressible mixture was identified and formulated to contain 200 mg of artesunate and 415 mg of mefloquine per tablet. The physical properties of the tablets complied with BP standards.
An HPLC method from available literature was adapted and validated for analytical procedures. Dissolution studies according to a USP method were conducted to verify and quantify the release of the APIs in the double fixed-dose combination. The initial dissolution rate (DRi) of artesunate and mefloquine in the acidic dissolution medium was rapid as required. The enteric coated fraction of the artesunate exhibited no release in an acidic environment after 2 hours, but rapid release in a medium with a pH of 6.8. The structure of the granulated particles of mefloquine may have contributed to its first order release profile in the dissolution mediums. A linear correlation was present between the rate of mefloquine release and the percentage of mefloquine dissolved (R2 = 0.9484). Additionally, a linear relationship was found between the logarithm of the percentage mefloquine remaining against time (R2 = 0.9908). First order drug release is the dominant release profile found in the pharmaceutical industry today and is coherent with the kinetics of release obtained for mefloquine.
A concept pre-clinical phase, double fixed-dose combination solid oral dosage form for artesunate and mefloquine was developed. The double fixed-dose combination was designed in accordance with the WHO’s recommendation for an oral dosage regimen of artesunate and mefloquine for the treatment of uncomplicated falciparum malaria. The specifications of the double fixed-dose combination were developed in close accordance with the FDA’s quality by design concept and WHO recommendations. An HPLC analytical procedure was developed to verify the presence of artesunate and mefloquine. The dissolution profiles of artesunate and mefloquine were investigated during the dissolution studies. / PhD (Pharmaceutics), North-West University, Potchefstroom Campus, 2014
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Development and evaluation of a solid oral dosage form for an artesunate and mefloquine drug combination / Abel Hermanus van der WattVan der Watt, Abel Hermanus January 2014 (has links)
Malaria affects about forty percent of the world’s population. Annually more than 1.5 million fatalities due to malaria occur and parasite resistance to existing antimalarial drugs such as mefloquine has already reached disturbingly high levels in South-East Asia and on the African continent. Consequently, there is a dire need for new drugs or formulations in the prophylaxis and treatment of malaria. Artesunate, an artemisinin derivative, represents a new category of antimalarials that is effective against drug-resistant Plasmodium falciparum strains and is of significance in the current antimalarial campaign. As formulating an ACT double fixed-dose combination is technically difficult, it is essential that fixed-dose combinations are shown to have satisfactory ingredient compatibility, stability, and dissolution rates similar to the separate oral dosage forms.
Since the general deployment of a combination of artesunate and mefloquine in 1994, the cure rate increased again to almost 100% from 1998 onwards, and there has been a sustained decline in the incidence of Plasmodium falciparum malaria in the experimental studies (Nosten et al., 2000:297; WHO, 2010:17). However, the successful formulation of a solid oral dosage form and fixed dosage combination of artesunate and mefloquine remains both a market opportunity and a challenge.
Artesunate and mefloquine both exhibited poor flow properties. Furthermore, different elimination half-lives, treatment dosages as well as solubility properties of artesunate and mefloquine required different formulation approaches. To substantiate the FDA’s pharmaceutical quality by design concept, the double fixed-dose combination of artesunate and mefloquine required strict preliminary formulation considerations regarding compatibility between excipients and between the APIs. Materials and process methods were only considered if theoretically and experimentally proved safe. Infrared absorption spectroscopy (IR) and X-ray powder diffraction (XRPD) data proved compatibility between ingredients and stability during the complete manufacturing process by a peak by peak correlation. Scanning Electron Micrographs (SEM) provided explanations for the inferior flow properties exhibited by the investigated APIs. Particle size analysis and SEM micrographs confirmed that the larger, rounder and more consistently sized particles of the granulated APIs contributed to improved flow under the specified testing conditions.
A compressible mixture containing 615 mg of the APIs in accordance with the WHO recommendation of 25 mg/kg of mefloquine taken in two or three divided dosages, and 4 mg/kg/day for 3 days of artesunate for uncomplicated falciparum malaria was developed. Mini-tablets of artesunate and mefloquine were compressed separately and successfully with the required therapeutic dosages and complied with pharmacopoeial standards. Preformulation studies eventually led to a formula for a double fixed-dose combination and with the specific aim of delaying the release of artesunate due to its short half-life.
A factorial design revealed the predominant factors contributing to the successful wet granulation of artesunate and mefloquine. A fractional factorial design identified the optimum factors and factor levels. The application of the granulation fluid (20% w/w) proved to be sufficient by a spraying method for both artesunate and mefloquine. A compatible acrylic polymer and coating agent for artesunate, Eudragit® L100 was employed to delay the release of approximately half of the artesunate dose from the double fixed-dose combination tablet until a pH of 6.8.
A compressible mixture was identified and formulated to contain 200 mg of artesunate and 415 mg of mefloquine per tablet. The physical properties of the tablets complied with BP standards.
An HPLC method from available literature was adapted and validated for analytical procedures. Dissolution studies according to a USP method were conducted to verify and quantify the release of the APIs in the double fixed-dose combination. The initial dissolution rate (DRi) of artesunate and mefloquine in the acidic dissolution medium was rapid as required. The enteric coated fraction of the artesunate exhibited no release in an acidic environment after 2 hours, but rapid release in a medium with a pH of 6.8. The structure of the granulated particles of mefloquine may have contributed to its first order release profile in the dissolution mediums. A linear correlation was present between the rate of mefloquine release and the percentage of mefloquine dissolved (R2 = 0.9484). Additionally, a linear relationship was found between the logarithm of the percentage mefloquine remaining against time (R2 = 0.9908). First order drug release is the dominant release profile found in the pharmaceutical industry today and is coherent with the kinetics of release obtained for mefloquine.
A concept pre-clinical phase, double fixed-dose combination solid oral dosage form for artesunate and mefloquine was developed. The double fixed-dose combination was designed in accordance with the WHO’s recommendation for an oral dosage regimen of artesunate and mefloquine for the treatment of uncomplicated falciparum malaria. The specifications of the double fixed-dose combination were developed in close accordance with the FDA’s quality by design concept and WHO recommendations. An HPLC analytical procedure was developed to verify the presence of artesunate and mefloquine. The dissolution profiles of artesunate and mefloquine were investigated during the dissolution studies. / PhD (Pharmaceutics), North-West University, Potchefstroom Campus, 2014
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Development and evaluation of an oral fixed–dose triple combination dosage form for artesunate, dapsone and proguanil / van der Merwe, A.J.Van der Merwe, Adriana Johanna January 2011 (has links)
Malaria is a life–threatening disease caused by Plasmodium spp and causes over one million
deaths annually. The complex life cycle of the malaria parasite offers several points of attack
for the antimalarial drugs. The rapid spread of resistance against antimalarial drugs, especially
chloroquine and pyrimethamine–sulphadoxine, emphasises the need for new alternatives or
modification of existing drugs. Artemisinin–based combination therapies (ACT’s) with different
targets prevent or delay the development of drug resistance and therefore have been adopted
as first–line therapy by all endemic countries. Proguanil–dapsone, an antifolate combination is
more active than pyrimethamine–sulphadoxine and is being considered as an alternative to
pyrimethamine–sulphadoxine. Artesunate–proguanil–dapsone is a new ACT that has wellmatched
pharmacokinetics and is relatively rapidly eliminated; therefore there is a reduced risk
of exposure to any single compound and potentially a decreasing risk of resistance. A few
studies have been done on a triple fixed–dose combination therapy for malaria treatment and
such a combination for artesunate, proguanil and dapsone are not currently investigated,
manufactured or distributed. The aim of this study was to develop a triple fixed–dose
combination for artesunate, proguanil and dapsone.
The formulation was developed in three phases; basic formulation development, employing
factorial design to obtain two possible optimised formulations and evaluating the optimised
formulations. During the formulation development the most suitable manufacturing procedure
and excipients were selected. A full 24 factorial design (four factors at two levels) was used to
obtain the optimised formulations. As end–points to identify the optimised formulations, weight
variation, friability, crushing strength and disintegration of the tablets, were used. Statistical
analysis (one way ANOVA) was used to identify optimal formulations. To identify any
interaction between the active pharmaceutical ingredients (API’s) and the API’s and excipients,
differential scanning calorimetry was done. Flow properties of the powder mixtures (of the
optimised formulations) were characterised by means of angle of repose; critical orifice diameter
(COD); bulk density and tapped density; and flow rate. Tablets of the two optimised powder
formulations were compressed. The tablets were evaluated and characterised in terms of
weight variation, friability, crushing strength, disintegration and dissolution behaviour. Initial
formulation development indicated that wet granulation was the most suitable manufacturing method. The results from the factorial design indicated that different amounts (% w/w) of the
lubricant and binder as well as two different fillers influenced the weight variation, crushing
strength and disintegration statistically significant. Two formulations containing two different
fillers (microcrystalline cellulose or Avicel® PH 101, and lactose or Granulac® 200) were found to
be within specifications and ideal for manufacturing.
Tablets prepared from the FA formulation (formulation containing Avicel® PH 101) complied with
the standards and guidelines for weight variation, friability, crushing strength and disintegration
as set by the British Pharmacopoeia (BP). Tablets had an average crushing strength of 121.56
± 0.022 N. Tablets disintegrated within 52.00 seconds and a maximum weight loss of 0.68%
occurred during the friability test. Weight variation of the tablets prepared from the FG
formulation (formulation containing Granulac® 200) complied with the standards. Average
crushing strength was 91.99 ± 6.008 N and the tablets disintegrated within 140.00 seconds.
Percentage friability (1.024%) did not comply with the guideline of a percentage friability of less
than 1%, however, no cracked or broken tablets were seen.
Dissolution showed that 98, 93 and 94% of artesunate, proguanil and dapsone were
respectively released (of the label value) within 15 minutes for the FA formulations. Release of
artesunate, proguanil and dapsone for the FG formulation was 62, 85 and 92% for the same
time period. The release of the three API’s (the FG formulation) increased to 78, 89 and 92%, respectively, after 45 minutes. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2012.
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Development and evaluation of an oral fixed–dose triple combination dosage form for artesunate, dapsone and proguanil / van der Merwe, A.J.Van der Merwe, Adriana Johanna January 2011 (has links)
Malaria is a life–threatening disease caused by Plasmodium spp and causes over one million
deaths annually. The complex life cycle of the malaria parasite offers several points of attack
for the antimalarial drugs. The rapid spread of resistance against antimalarial drugs, especially
chloroquine and pyrimethamine–sulphadoxine, emphasises the need for new alternatives or
modification of existing drugs. Artemisinin–based combination therapies (ACT’s) with different
targets prevent or delay the development of drug resistance and therefore have been adopted
as first–line therapy by all endemic countries. Proguanil–dapsone, an antifolate combination is
more active than pyrimethamine–sulphadoxine and is being considered as an alternative to
pyrimethamine–sulphadoxine. Artesunate–proguanil–dapsone is a new ACT that has wellmatched
pharmacokinetics and is relatively rapidly eliminated; therefore there is a reduced risk
of exposure to any single compound and potentially a decreasing risk of resistance. A few
studies have been done on a triple fixed–dose combination therapy for malaria treatment and
such a combination for artesunate, proguanil and dapsone are not currently investigated,
manufactured or distributed. The aim of this study was to develop a triple fixed–dose
combination for artesunate, proguanil and dapsone.
The formulation was developed in three phases; basic formulation development, employing
factorial design to obtain two possible optimised formulations and evaluating the optimised
formulations. During the formulation development the most suitable manufacturing procedure
and excipients were selected. A full 24 factorial design (four factors at two levels) was used to
obtain the optimised formulations. As end–points to identify the optimised formulations, weight
variation, friability, crushing strength and disintegration of the tablets, were used. Statistical
analysis (one way ANOVA) was used to identify optimal formulations. To identify any
interaction between the active pharmaceutical ingredients (API’s) and the API’s and excipients,
differential scanning calorimetry was done. Flow properties of the powder mixtures (of the
optimised formulations) were characterised by means of angle of repose; critical orifice diameter
(COD); bulk density and tapped density; and flow rate. Tablets of the two optimised powder
formulations were compressed. The tablets were evaluated and characterised in terms of
weight variation, friability, crushing strength, disintegration and dissolution behaviour. Initial
formulation development indicated that wet granulation was the most suitable manufacturing method. The results from the factorial design indicated that different amounts (% w/w) of the
lubricant and binder as well as two different fillers influenced the weight variation, crushing
strength and disintegration statistically significant. Two formulations containing two different
fillers (microcrystalline cellulose or Avicel® PH 101, and lactose or Granulac® 200) were found to
be within specifications and ideal for manufacturing.
Tablets prepared from the FA formulation (formulation containing Avicel® PH 101) complied with
the standards and guidelines for weight variation, friability, crushing strength and disintegration
as set by the British Pharmacopoeia (BP). Tablets had an average crushing strength of 121.56
± 0.022 N. Tablets disintegrated within 52.00 seconds and a maximum weight loss of 0.68%
occurred during the friability test. Weight variation of the tablets prepared from the FG
formulation (formulation containing Granulac® 200) complied with the standards. Average
crushing strength was 91.99 ± 6.008 N and the tablets disintegrated within 140.00 seconds.
Percentage friability (1.024%) did not comply with the guideline of a percentage friability of less
than 1%, however, no cracked or broken tablets were seen.
Dissolution showed that 98, 93 and 94% of artesunate, proguanil and dapsone were
respectively released (of the label value) within 15 minutes for the FA formulations. Release of
artesunate, proguanil and dapsone for the FG formulation was 62, 85 and 92% for the same
time period. The release of the three API’s (the FG formulation) increased to 78, 89 and 92%, respectively, after 45 minutes. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2012.
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