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Effect of compression force, humidity and disintegrant concentration on the disintegration and dissolution of directly compressed furosemide tablets using croscarmellose sodium as disintegrant
Andries F. Marais1, Mingna Song2 and Melgardt M. de Villiers2*
1School of Pharmacy, Potchefstroom University for Christian Higher Education, Potchefstroom 2520, South Africa and 2School of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71209, USA.
Tropical Journal of Pharmaceutical Research 2003; 2(1): 125-35
Abstract
Purpose: The effect of compression force, relative humidity and disintegrant concentration on furosemide dissolution in directly compressed furosemide/Avicel®-tablets was studied.
Methods: Mixtures of furosemide (12.5% w/w), Ac-Di-Sol® (0, 0.625% to 10% w/w) and Avicel® PH200 (qs to 100% w/w) were prepared in a Turbula® mixer at 69 rpm for 10 min. Tablets were stored for 6 months under conditions similar to the four climatic zones recognized by ICH. Tablet hardness, disintegration time and dissolution were measured.
Results: At the same compression force, disintegration time decreased as the disintegrant concentration increased above 0.625% w/w but an increase in compression force resulted in increased tablet crushing strength and apparent density, both of which prolonged the disintegration time. This effect was less significant when the disintegrant concentration was above 1.25%. However, storage under high relative humidity conditions (mediterranean or subtropical, hot and humid climate) caused softening of tablets leading to the spontaneous disintegration of tablets containing high concentrations of Ac-Di-Sol®.
Conclusion: Fast disintegration of tablets within 1-2 min is a prerequisite for improving the dissolution of furosemide. This was attributed to an increase in the speed at which the maximum surface area of the sparingly water-soluble drug is exposed to the dissolution medium. Ac-Di-Sol® was an efficient disintegrant for furosomide tablets at low concentrations of 1.25% - 10% because it rapidly released the hydrophobic drug particles from tablets. However, tablets containing 10 % disintegrant must be protected from atmospheric moisture because storage at 60-70 % relative humidity led to softening of tablets.
Keywords: Disintegration; Furosemide dissolution; Tablets; Compression Force; Relative Humidity; Croscarmellose sodium
*To whom correspondence should be addressed: E-mail: [email protected] Fax: +1 318 342-3255
Modelling of drug release from ensembles of aspirin microcapsules of certain particle size distribution
Florence E Eichie* and Roland S Okor
Department of Pharmaceutics, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
Tropical Journal of Pharmaceutical Research 2003; 2(1): 137-145
Abstract
Purpose: In order to determine the drug release profile of an ensemble of aspirin crystals or microcapsules from its particle distribution a mathematical model that considered the individual release characteristics of the component single particles was developed. The model assumed that under sink conditions the release from individual (component) particles would be independent of each other and hence simply additive.
Method: The release parameters, mt = the amount of drug released in time t, m¥ = the maximum release and t¥ = the time to attain it were determined for each single particle by simulation using previously derived mathematical models. To obtain the cumulative release curve for the ensemble the individual releases were summed up at each time scale and for the various time intervals. Values of m¥ and t¥ for the ensemble were obtained from the simulated cumulative curves. The release profiles of the ensembles were also determined experimentally and their m¥ and t¥ values deduced from the release curves.
Results: The observed cumulative curves of the ensembles compared favourably with the simulated data. The % difference in the observed and the simulated m¥ and t¥ values of the ensembles was within ± 20%, which indicated that the modelling was valid.
Conclusion: The study showed that the release profile of an ensemble can be determined from its particle distribution which has application in controlled release studies.
Key words: Aspirin microcapsules, drug release simulation, multiparticulate systems
*To whom correspondence should be addressed: E-mail: [email protected]
Effects of interacting variables on the tensile strength and the release properties of paracetamol tablets
Oluwatoyin A Odeku* and Oludele A Itiola
Department of Pharmaceutics & Industrial Pharmacy, University of Ibadan, Ibadan, Nigeria
Tropical Journal of Pharmaceutical Research 2003; 2(1): 147-153
Abstract
Purpose: The individual and interaction effects of nature of binder (N), concentration of binder (C) and the relative density (D) on the tensile strength and release properties of paracetamol tablets have been studied using a 23 factorial experimental design.
Methodology: Khaya gum, which represented the “low” level, and polyvinylpyrrolidone (PVP), which represented the “high” level, was used as binding agent at concentrations of 0.5% and 4%w/w in a paracetamol tablet formulation. The tensile strength, which is a measure of the bond strength of tablets, and the release properties of the tablets- measured by the disintegration and the dissolution times, were used as assessment parameters.
Results: Changing the concentration of binder and the relative density of the tablets from “low” to “high” led to an increase in the tensile strength and the disintegration and dissolution times of the tablets. The ranking of the individual coefficient values for the formulations was D > N > C for T and C >> N > D for the disintegration and dissolution parameters while the ranking for the interaction effects was N - D >> N - C > C – D for T and t50, N - C >> N – D> C - D for DT and C - D > N - C >> N - D for t90.
Conclusion: The results suggest that khaya gum could be useful as an alternative binding agent to produce tablets with particular tensile strength and drug release profiles and there was considerable interaction between the variables employed on the tablet properties.
Keywords: Binding agent, khaya gum, release properties, paracetamol tablets, tensile strength
*To whom correspondence should be addressed: E-mail: [email protected] Tel: 234 208 106 403
Adsorptive property of kaolin in some drug formulations
Anthony O Onyekweli1*, Cyril O Usifoh2, Lucky O Okunrobo2 and Jessica D Zuofa1
1Department of Pharmaceutics and Pharmaceutical Technology, and 2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Benin, Benin-City, Nigeria
Tropical Journal of Pharmaceutical Research 2003; 2(1): 155-159
Abstract
Purpose: Kaolin is a known adsorbent, has lubricant property in powders and is therefore proposed as a lubricant in tablet formulations. This study was carried out to evaluate whether kaolin can adsorb some active drugs when mixed with them in tablet formulations even at very low concentrations.
Method: Chloroquine and chlorpheniramine tablets were formulated with powder mixtures containing various concentrations of kaolin. The effect of kaolin on the physical properties of the tablets were examined and compared with those of standard lubricants like magnesium stearate and talc. Chloroquine and chlorpheniramine tablets and powders of amoxicillin/clavulanic acid oral powder and ampicillin/cloxacillin injection were also mixed with and without various concentrations of kaolin in water. Chemical assay of the drugs in the solutions were determined over time.
Results: Kaolin significantly reduced the amount of each of the drugs in the solutions containing kaolin.
Conclusion: Kaolin reduces the amount of some drugs when incorporated in drug formulations. Therefore, its inclusion in such drug formulations should not be encouraged.
Keywords: Adsorption, ampicillin/cloxacillin, amoxicillin/clavulanic acid, chloroquine, chlorpheniramine, drug formulation, kaolin.
*To whom correspondence should be addressed: E-mail: [email protected]
Comparative analysis of eight brands of sulfadoxine-pyrimethamine tablets
Michael A Odeniyi1, Olajire A Adegoke2, Remilekun B Adereti1, Oluwatoyin A Odeku1* and Oludele A Itiola1
1 Department of Pharmaceutics and Industrial Pharmacy, and 2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria
Tropical Journal of Pharmaceutical Research 2003; 2(1): 161-167
Abstract
Purpose: The aim of the present study is to investigate the physicochemical equivalence of eight brands of tablets containing sulfadoxine-pyrimethamine (antimalarial drug combination) sourced from different retail Pharmacy outlets in the Nigerian market.
Method: The quality and physicochemical equivalence of eight different brands of sulfadoxine-pyrimethamine combination tablets were assessed. The assessment included the evaluation of uniformity of weight, friability, crushing strength, disintegration and dissolution tests as well as chemical assay of the tablets.
Results: All the eight brands of the tablets passed the British Pharmacopoeia (BP) standards for uniformity of weight, disintegration and crushing strength. Three of the eight brands failed the friability test. One of the brands did not comply with the standard assay of content of active ingredients while another brand did not comply with the USP specifications for dissolution test for sulfadoxine-pyrimethamine tablets. There were no significant differences in the amounts of pyrimethamine and sulfadoxine released from the different brands (P>0.05).
Conclusion: Only three brands (registered by NAFDAC) out of the eight brands of sulfadoxine-pyrimethamine tablets that were analysed passed all the BP quality specifications and were physically and chemically equivalent. This study highlights the need for constant market monitoring of new products to ascertain their equivalency to the innovator product.
Keywords: Chemical equivalence, comparative study, pyrimethamine-sulfadoxine tablets
*To whom correspondence should be addressed: E-mail: [email protected] or [email protected]
Chloroquine reduces urinary excretion of cloxacillin when it is administered concurrently with ampicillin-cloxacillin combination
Chinedum P. BabalolaF, Titilayo T. Fashedemi and Ajibola A. Olaniyi
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ibadan, Nigeria
Tropical Journal of Pharmaceutical Research 2003; 2(1): 169-173
Abstract
Purpose: To investigate a possible effect of chloroquine on urinary excretion of cloxacillin when chloroquine is administered concurrently with ampicillin-cloxacillin combination.
Methods: Eight healthy adult volunteers received single oral doses of Ampiclox® (ampicillin-cloxacillin combination) alone and in combination with chloroquine in a cross-over study design with one week washout period between the drug administrations. Total urine voided was collected from each volunteer at predetermined time intervals for a period of 9 hr. The urine was analyzed for cloxacillin by a reversed-phase HPLC method.
Results: A significant reduction in the amount of cloxacillin excreted in urine was observed following the co-administration of chloroquine and the ampicillin-cloxacillin combination products. The mean total amount of cloxacillin (Du¥), maximum peak of excretion (Dumax) and % dose excreted after Ampliclox® was administered alone were 84.6 ± 57.0 mg, 49.5 ±41.6 mg and 33.9 ± 22.7% respectively. The corresponding values after co-administration with chloroquine were 30.2 ± 27.2 mg, 13.5 ± 10.4 mg and 12.1 ±10.9%. The respective times of maximum absorption (Tmax) and elimination half-life (t1/2) of cloxacillin were 2.7 ± 0.4 hr and 0.7 ± 0.4 hr after Ampiclox® alone and 1.5 ± 0.8 hr and 0.6 ± 0.5 hr after co-administration of the two drugs. The results showed a significant decrease (p < 0.0001) in the mean total amount as well as % dose of cloxacillin excreted in urine by 64% and a significant reduction (p < 0.05) in the Tmax of excretion by 45%.
Conclusion: There is appreciable reduction in the urinary excretion of cloxacillin when given concurrently with chloroquine. The mode of this interaction and possible therapeutic implication is unknown. However, caution should be exercised when prescribing or administering these two drugs together.
Key words: Drug-drug interaction, bioavailability, chloroquine, cloxacillin
*To whom correspondence should be addressed: E-mail: [email protected]
Prescribing practices in two health care facilities in Warri, Southern Nigeria: A comparative study
Patrick O Erah*, GO Olumide and Augustine O Okhamafe
Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
Tropical Journal of Pharmaceutical Research 2003; 2(1): 175-182
Abstract
Purpose: Inappropriate prescribing has been identified in many health facilities in developing countries. The purpose of this study was to evaluate the prescribing practices in two health care facilities in Warri located in south-south geopolitical region of Nigeria and identify factors influencing the practices.
Method: WHO Prescribing Indicators were applied to evaluate 2000 prescription records, retrospectively, from a private and a public hospital in Warri. Factors influencing the prescribing practices in the facilities were identified through informal interviews of 10 prescribers in the facilities. Using a self-administered questionnaire administered to 40 prescribers in the facilities, we also evaluated the order of importance of the factors affecting drug prescribing.
Results: Average number of drugs per encounter in the health facilities is 3.4 (3.9 in the public hospital and 2.8 in the private hospital). Generic prescribing was generally low (54% in the public hospital and 16% in the private hospital) while the percentage of encounters with antibiotics prescribed was high (75% in the public hospital and 55% in the private hospital). Antimalarials, antihypertensives, antidiarrhoeals and analgesics accounted for 47.4%, 7.5%, 1.0% and 18.2%, respectively. The overuse of drugs and generic prescribing were significantly lower in the private hospital than in the public hospital. Major factors influencing prescribing practices included drug availability, clinician’s level of training, cost of drugs, feedback from patients and socio-economic status of patients.
Conclusion: Polypharmacy, overuse of antibiotics and low rate generic prescribing still occur in the health facilities studied. Drug availability, clinician’s level of training, cost of drugs, feedback from patients and socio-economic status of patients are major factors influencing prescribing in the facilities.
Keywords: Drug prescribing, Indicators, Practices, Southern Nigeria
*To whom correspondence should be addressed: E-mail: [email protected] Tel:: +234 802 336 0318
Control of hyperlipidaemia, hypercholesterolaemia and hyperketonaemia by aqueous extract of Dioscorea dumetorum tuber
Rachel Nimenibo–Uadia
Department of Biochemistry, Faculty of Science, University of Benin, P.M.B. 1154, Benin City, Nigeria
Tropical Journal of Pharmaceutical Research 2003; 2(1): 183-189
Abstract
Dioscorea dumetorum (Pax) used in traditional medicine for the treatment of diabetes mellitus possesses hypoglycaemic effect. The present study investigates the effect of oral administration of the aqueous extract of the tuber on blood lipid and ketone levels in alloxan–induced diabetic rats.
Method: Wistar strain albino rats were made diabetic with the intraperitoneal administration of alloxan monohydrate. Consequently, an aqueous extract of Dioscorea dumetorum tuber was administered orally to the diabetic rats and their plasma and urine glucose, triacylglycerol, cholesterol and β-hydroxybutyrate concentrations were estimated using standard procedures. Results were compared with untreated normal and diabetic control rats. Phytochemical screening of the extract of the tuber was also carried out.
Results: Treatment with the extract significantly (p<0.05) reduced elevated blood levels of triacylglycerol, cholesterol and β–hydroxybutyrate associated with alloxan-induced diabetes mellitus. The aqueous extract tested positive for flavonoids, alkaloids, saponins and cardiac glycosides.
Conclusion: From this study, the tuber has proved not only to be an effective hypoglycaemic agent, but also possesses significant (p<0.05) hypolipidaemic and hypocholesterolaemic properties while also ameliorating ketosis.
Keywords: Alloxan, β-hydroxybutyrate, diabetes, cholesterol, Dioscorea dumetorum, triacylglycerol
Correspondence should be addressed: E-mail: [email protected]