Inhibitory activities of selected south west Nigerian medicinal plants against mycobacterium tuberculosis.

INTRODUCTION: Tuberculosis (TB), an infectious disease prevalent in the tropics especially in Africa and Asia is one of the highest causes of morbidity and mortality and a global concern. With increasing resistance of the pathogen, to existing antituberculosis drugs and the synergy between TB infection and acquired immune deficiency syndrome (AIDS), the need for development of new drugs to cope with the infection is urgent. OBJECTIVE: Extracts from 16 plants identified and selected from the ethnomedicine of the Ijebus in Southwestern Nigeria as remedies for tuberculosis were evaluated for activity against Mycobacterium tuberculosis, in vitro. METHODOLOGY: Plant extracts were screened against clinical isolate of Mycobacterium tuberculosis using agar plate method on Middlebrook 7H11 medium and observed for 12 weeks. RESULTS: The crude aqueous methanol extracts. showed varying degrees of activity at concentrations of 0.025 - 100 mg/mL. Ocimum grattisimum (leaf) demonstrated the highest activity with minimum inhibitory concentration (MIC) of 0.025 mg/mL. Two standard anti-tuberculosis drugs; rifampicin and isoniazid, included in the assay had MIC values of 0.01 mg/mL and 0.0005 mg/mL, respectively. CONCLUSION: The results of the study confirm the ethnopharmacological uses of some of the plants for TB indicating their potential as sources for the discovery of anti-tuberculosis drugs.

Effects of material properties and speed of compression on microbial survival and tensile strength in diclofenac tablet formulations.

A work has been done to study the effects of material properties and compression speed on microbial survival and tensile strength in diclofenac tablet formulations. Tablets were produced from three formulations containing diclofenac and different excipients (DC, DL and DDCP). Two types of machines (Hydraulic hand press and single punch press), which compress the tablets at different speeds, were used. The compression properties of the tablets were analyzed using Heckel and Kawakita equations. A 3-dimensional plot was produced to determine the relationship between the tensile strength, compression speed and percentage survival of Bacillus subtilis in the diclofenac tablets. The mode of consolidation of diclofenac was found to depends on the excipient used in the formulation. DC deformed mainly by plastic flow with the lowest Py and Pk values. DL deformed plastically at the initial stage, followed by fragmentation at the later stage of compression, whereas DDCP deformed mainly by fragmentation with the highest Py and Pk values. The ranking of the percentage survival of B. subtilis in the formulations was DDCP > DL > DC, whereas the ranking of the tensile strength of the tablets was DDCP > DL > DC. Tablets produced on a hydraulic hand press with a lower compression speed had a lower percentage survival of microbial contaminants than those produced on a single punch press, which compressed the tablets at a much higher speed. The mode of consolidation of the materials and the speed at which tablet compression is carried out have effects on both the tensile strength of the tablets and the extent of destruction of microbial contaminants in diclofenac tablet formulations.

Physical and release properties of metronidazole suppositories

Purpose: A study was made of the effects of some bases and adjuvants on the physical and release properties of metronidazole suppositories with a view to providing more information for the optimization of the rectal formulation of metronidazole. Method: Suppositories (1g) containing 200mg of metronidazole each were prepared in witepsol (H15 and E75) and polyethylene glycol (PEG 2850 and 4650) bases; using different concentrations of Tween 80; sodium salicylate and methylcellulose as adjuvants. The setting time; solidification point and melting range of the suppositories were determined; along with their crushing strength; disintegration time and the time for 80of metronidazole to be released from the suppositories (t80). Results: The ranking of setting time for the suppositories was witepsol H15 PEG 2850 witepsol E75 PEG 4650; while the ranking of solidification point; melting range; crushing strength; disintegration time and the time for 80of metronidazole to be released from the suppositories (t80) was the reverse of that for setting time. Optimal concentrations of Tween 80 and sodium salicylate were observed for the suppository formulations. Using Kitazawa plots; all formulations showed two dissolution rate constants; k1 and k2 intersecting at time t1; with formulations containing 5 to 20w/w of methylcellulose exhibiting a third dissolution rate constant; k3 intersecting with k2 at time t2. Conclusion: The physical and release properties of metronidazole sup-positories are influenced considerably by the bases and adjuvants employed. Tween 80 and sodium salicylate can probably be used to formulate only immediate-release supposi- tories while methylcellulose can be useful for sustained-release metronidazole suppositories. Some insight into these inferences can be obtained from parameters derived from Kitazawa plots

Compression, mechanical and release properties of chloroquine phosphate tablets containing corn and trifoliate yam starches as binders

PURPOSE : A study was made of the binding properties of trifoliate yam starch; obtained from Dioscorea dumetorum (Pax); in chloroquine phosphate tablet formulations in comparison with official corn starch. METHOD: Compressional properties were analyzed using density measurements and compression equations of Heckel and Kawakita. The mechanical properties of the tablets were assessed using the crushing strength and friability of the tablets; while drug release properties of the tablets were assessed using disintegration and dissolution times. RESULTS : Tablet formulations containing trifoliate yam starch exhibited faster onset and higher amount of plastic deformation during compression than those containing corn starch. The crushing strength; disintegration and dissolution times of the tablets increased with binder concentration while friability values decreased. Trifoliate yam starch produced tablets with stronger mechanical properties and longer disintegration and dissolution times than those containing corn starch. CONCLUSION : Trifoliate yam starch would be a better alternative to corn starch in producing uncoated tablets for which high bond strength is essential

Efficacy of herbal remedies used by herbalists in Oyo State Nigeria for treatment of Plasmodium falciparum infections--a survey and an observation.

In the course of evaluating the contribution of phytomedicine to possible drug discovery of antimalarial drugs, an ethnomedical survey of specialized children traditional clinics was done. In the observational multi center study, efficacy of eight different herbal remedies, each consisting of 3-8 ingredients and administered by herbalists were investigated in clients enrolled in the six traditional clinics in Oyo (urban center) and Otu (rural center) of Oyo State, Nigeria. The clients, aged between six months and fifteen years with clinical symptoms of malaria were enrolled in the clinics of the herbalists, as their usual practice. Oral informed consents were obtained from their parents or guardians. Microscopic diagnosis of malaria infection was used to evaluate parasitaemia and validate efficacy of herbal remedies. Results of the analysis showed that, of the 163 clients of the herbalists, only 62 (30 from Oyo, 32 from Otu) had microscopically confirmed P. falciparum infection. Only results from 54 clients (29/30 (Oyo) and 25/32 (Otu) with P. falciparum infection could be evaluated. Plasmodium falciparum infection in 88% (23/29) of clients from Oyo responded to treatment with the herbal remedies while cure rate in clients from Otu was 42% (13/25). Parasite densities ranged from 171 to 53,613 parasites/microl blood and 87 to 36,209 parasites/microl blood in patients from Oyo and Otu respectively. The herbalists administered the remedies and Gossypium arboreum, Anarcadium occidentalis, Citrus medica, Phyllanthus amarus and Lippia multiflora were the main ingredients in the efficacious remedies. The herbalists gave detailed descriptions of each of the 8 herbal remedies proffered. The results confirm the efficacy of two of the eight herbal remedies, thereby validating the role of ethnomedicine as a possible source for the discovery of new chemotherapeutic agents in the treatment of P. falciparum malaria.

Evaluation of valuation of toxicity profile of an alkaloidal fraction of the stem bark of Picralima nitida (fam. Apocynacaes).

Dermal and acute toxicity evaluation of the basic alkaloidal fraction of the stem bark of Picralima nitida, which has been shown to have pronounced activity against causative organisms of dermatomycosis in man, was carried out in animals. Acute intraperitoneal toxicity tests showed a dose-dependent toxicity. There was inflammation and necrosis of liver hepatocytes accompanied by reduction in neutrophilic count and a corresponding increase in lymphocytic count. There was no sign of reddening or irritation when applied into the eye conjunctiva. Dermal tests also showed that the fraction caused no sensitization, inflammation or death in the animal models used.

Evaluation of the effects of khaya gum on the mechanical and release properties of paracetamol tablets.

A study of the comparative effects of khaya gum and two standard binding agents-polyvinylpyrrolidone (PVP) and gelatin--on crushing strength and friability, and the disintegration and dissolution characteristics of paracetamol tablets was made. The crushing strength-friability ratio (CSFR), the disintegration times, D, and the dissolution times t50, t90, and t1 (derived from the equation of Noyes and Whitney), all increased with an increase in binder concentration; however, the dissolution rate constants, k1 and k2, decreased. The ranking for the values of CSFR for tablets containing the different binders was PVP > gelatin > khaya gum. The ranking for D and the dissolution times was gelatin > khaya gum > PVP, whereas the ranking for the dissolution rate constants was PVP > khaya gum > gelatin. There were significant linear correlations between CSFR, D, t50, t90, and t1 for the tablets. There were also significant correlations between k1 and D, t50, t90, and t1, and between k2 and t90. The results suggest that khaya gum could be useful as an alternative binding agent to produce tablets with particular mechanical strength and drug release profiles.

Cultural categorization of febrile illnesses in correlation with herbal remedies used for treatment in Southwestern Nigeria.

The ethnographic study was conducted in two communities in Oyo State in Southwestern Nigeria. The study sites consisted of a rural and an urban local government area located in the tropical rain forest zone of Nigeria. The study was designed to obtain information on febrile illnesses and herbal remedies for treatment with the aim of identifying potential antimalarial drugs. The study revealed that fever is a general term for describing illnesses associated with elevated body temperature. The indigenous Yoruba ethnic population has categorized fever based on symptoms and causes. The present communication is the result of focus group discussion and semi-structured questionnaire administered to traditional healers, herb sellers, elders and mothers. This was on types of fevers, symptoms and causes of febrile illnesses. The investigation also included use of traditional herbs in the prevention and treatment of the illnesses in the two communities.A total of 514 respondents were interviewed. This was made up of 266 (51.8%) from Atiba local government area (LGA), an urban centre while 248 (48.2%) respondents were interviewed from Itesiwaju LGA, a rural community. The LGAs are located in Oyo State of Nigeria. The respondents proffered 12 types of febrile illnesses in a multiple response answering system in Yoruba language. The most common ones (direct translation into English) were: yellow fever (39.1%), typhoid (34.8%), ordinary (28.8%), rainy season (20.8%) and headache (10.5%) fevers, respectively. Perceived causes of each of the febrile illnesses included stress, mosquito bites, unclean water, rains and over exposure to the sun. Methods of fever prevention were mainly with the use of herbal decoctions, powdered herbs, orthodox medications and maintenance of proper hygiene. Of a total of 112 different herbal remedies used in the treatment of the febrile illnesses compiled from the study, 25 recipes are presented. Recipes consisted of 2-7 ingredients. Oral decoctions (84%), oral powders (63%), use as soaps and creams (40%) in a multiple response system, were the most prevalent routes of administration of prepared herbs used in the treatment of the fevers. Boiling in water or alcohol was the most common method used in the preparation of the remedies. The four most frequently mentioned (multiple response system) plants in the Southwest ethnobotany for fevers were Azadirachta indica (87.5%), Mangifera indica (75.0%), Morinda lucida (68.8%) and Citrus medica (68.8%).

Formulation effects on the mechanical and release properties of metronidazole suppositories.

A study of the effects of Tween 20 and Tween 80 non-ionic surfactants, and witepsol H15 and polyethylene glycol (PEG) 2850 bases, on the mechanical and release properties of metronidazole suppositories was made. Mechanical strength was assessed by breaking strength values F. The values of F increased with increase in concentration of surfactant. The values of F for formulations containing Tween 20 were higher than those obtained for formulations containing Tween 80. Witepsol bases gave higher values of F than corresponding PEG bases. Release characteristics were assessed by the time for 80% drug release (t80), values of dissolution rate constants, k1 and k2 and the time of intersection, t1. The values of t80 decreased while those of k1 and k2 increased with increase in surfactant concentration. The values of t80 were lower, while those of k1 and k2 were higher, for formulations containing Tween 20 than for those formulations containing Tween 80. Witepsol bases gave lower t80 values and higher k1 and k2 values than their corresponding PEG bases. The concentration of surfactant, C, had the largest individual effect on the mechanical and release parameters while the nature of surfactant, S, had the lowest. The ranking for the individual effects of the variables on F and k1 was C > N >> S, on t80 and k2 was C >> N approximately = S, was on t1 was C = N = S. The interactions between S and C were largest for F, t80 and k2, and lowest for k1 and t1. The ranking of the interaction effects of the variables on F and k2 was S-C > N-C > N-S, on t80 was S-C > N-S approximately = N-C, on k1 was N-C > N-S > S-C, and on t1 was N-S = N-C > S-C. The results suggest that the individual and interaction effects of formulation variables would provide useful guides in optimizing metronidazole suppository formulations.

Effects of Interacting Variables on the Tensile Strength and the Release Properties of Paracetamol Tablets

"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 percent and 4 percentw/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 less than N less than C for T and C > N less than D for the disintegration and dissolution parameters while the ranking for the interaction effects was N -D > N -C less than C - D for T and t[50]; N -C > N - D C -D for DT and C -D less than N -C > N -D for t[90]. 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."

Comparative Analysis of Eight Brands of Sulfadoxine-Pyrimethamine Tablets

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 greater than 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

Compressional characteristics of native and pregelatinized forms of sorghum, plantain, and corn starches and the mechanical properties of their tablets.

A study was made of the compressional characteristics of native and pregelatinized forms of sorghum, plantain, and corn starches and the mechanical properties of their tablets. Compressional characteristics were analyzed using density measurements and the Heckel and Kawakita plots. Pregelatinized starches exhibited more densification than native starches during die filling and at low pressures. The ranking for the mean yield pressure (Py) values for the starches was plantain < corn < sorghum, with the pregelatinized starches having lower values than the native starches. The ranking for the values of another pressure term, Pk--an inverse measure of plasticity, was corn < plantain < sorghum, but with the native starches having the lower values. For the tablets, the ranking for values of tensile strength (T) was corn > plantain > sorghum, while the ranking for the brittle fracture index (BFI) was plantain > corn > sorghum. Tablets made from pregelatinized starches had lower T and BFI values than those made from native starches. The results suggest that pregelatinization of the starches facilitated faster onset of plastic deformation but reduced the amount of plastic deformation which occurred during the compression process.

Characterization of khaya gum as a binder in a paracetamol tablet formulation.

The influence of khaya gum, a binding agent obtained from Khaya grandifolia (Meliaceae family), on the bulk, compressional, and tabletting characteristics of a paracetamol tablet formulation was studied in comparison with the effects of two standard binders: polyvinylpyrrolidone (PVP; molecular weight 40,000) and gelatin. The relative ability of khaya gum to destroy any residual microbial contamination in the binder or in the formulation during tabletting was also studied using Bacillus subtilis spores as a model. Formulations containing khaya gum exhibited more densification than formulations containing PVP and gelatin during die filling, but less densification due to rearrangement at low pressures. The mean yield pressure of the formulation particles obtained from Heckel plots, and another pressure term, also inversely related to plasticity, obtained from Kawakita plots, showed dependence on the nature and concentration of the binder, with formulations containing khaya gum exhibiting the lowest and highest values respectively. The values of the pressure terms suggest that the yield pressure relates to the onset of plastic deformation during compression, while the Kawakita pressure relates to the total amount of plastic deformation occurring during the compression process. Tablets made from formulations containing khaya gum had the lowest tensile strength values but also the lowest tendency to laminate or cap, as indicated by their lowest brittleness. All the tablets had friability values < 1% at higher concentrations of the three binders. In addition, khaya gum demonstrated a comparable ability to destroy microorganisms in the formulation during tabletting as the two binders. The characterization of the formulations suggests that khaya gum can be developed into a commercial binding agent for particular tablets.

Evaluation of the antimicrobial property of the stem bark of Picralima nitida (Apocynaceae).

The basic fraction (BF) of the methanol extract of the stem bark of Picralima nitida (family Apocynaceae) exhibited significant antimicrobial activity against a wide range of Gram-positive bacteria and fungi, but limited activity against Gram-negative bacteria. The BF had a similar minimum inhibitory concentration (MIC) for S. aureus to the control drug ampicillin, and lower MIC values against A. flavus and A. niger than those of tiaconazole. Values of the minimum bactericidal concentration (MBC) of the BF against microorganisms tested were generally much higher than those for the control drugs ampicillin and gentamicin. The results suggest that some constituents of the stem bark could be isolated and developed into effective antimicrobial agents.

Evaluation of the destructive effect of khaya gum on Bacillus subtilis spores during tableting.

The destructive effect of khaya gum used as a binding agent in a paracetamol formulation on Bacillus subtilis spores during tableting has been investigated, in comparison with the effects of two standard binders-polyvinylpyrrolidone and gelatin. The destructive effect of khaya gum was generally similar to those of the standard binders. Significant (p < 0.001 in each case) inverse linear relationships of log % survival of the B. subtilis spores with compression pressure and with concentration of binder, were established. The effect of the binding agent was significantly dependent (p < 0.001 in each case) on both compression pressure and the binder concentration. However, there was no significant interaction (p > 0.05) between the destructive effects of compression pressure and binder concentration. The results suggest that khaya gum and the standard binders would be useful in the destruction of microorganisms during tableting.

Formulation effects on the mechanical properties of metronidazole tablets.

The individual and interaction effects of nature of binder (N), concentration of binder (C) and the physical form of the formulation (P) on the tensile strengths (T--a measure of the bond strength of tablets) and the brittle fracture index values (BFI--a measure of the lamination tendency of tablets) of metronidazole tablets have been studied using a 2(3) factorial experimental design in each case. Changing binder concentration from a 'low' to a 'high' level increased T and reduced the BFI of the tablets. Methylcellulose 20 exhibited stronger binding effect and greater ability to reduce the lamination tendency of the tablets than polyvinylpyrrolidone of molecular weight 44,000. Granular formulations produced tablets with lower T values but also with lower BFI values than tablets produced from powdered formulations. The ranking of these individual effects on tensile strength was P greater than C greater than N while the ranking for the BFI was P greater than N greater than C. For the interaction effects, the ranking for tensile strength was P-N much greater than N-C greater than P-C while the ranking for the BFI was N-C much greater than P-C greater than P-N.

Fundamental properties of metronidazole formulations in relation to tableting.

A study has been made of the effects of polyvinylpyrrolidone, gelatin and methylcellulose binding agents on the fundamental and tableting properties of a metronidazole-lactose-starch formulation. A material constant, alpha, was derived from the measured values of tensile strength of the materials. The values of alpha for the formulations are lower than that for metronidazole and depend on the nature and concentration of binder present. In terms of tableting properties, alpha supplements the information obtained from the ratios of elastic recovery to plastic compression (ER/PC) and from the brittle fracture index values (BFI) of the materials, although its influence appears to be limited at low values of ER/PC.

Studies on metronidazole tablet formulations.

Incorporating polyvinylpyrrolidone, gelatin and methylcellulose binding agents in a metronidazole formulation alters the tensile strength, disintegration and dissolution times of the tablets by reducing their wettability as measured by the adhesion tension of water. Correlations have been established between the disintegration times, D and the dissolution times t50, t90 and t1 (derived from the equation of Noyes & Whitney). A correlation has also been established between the adhesion tension of water on the tablets and the disintegration and dissolution times. These correlations depend on the nature and concentration of binder used.