PHARMACEUTICAL SCIENCES

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    ALKALOIDS OF THE AFRICAN RAUWOLFIA SPECIES OF THE SUB-SECTION OPHIOXYLANTHUS
    (1978-11) Bamidele, Akinyemi Akinloye
    The a l k a l o i d s of t h e Rauwolfia s p e c i e s have been reviewed and s p e c t r o s c o p i c methods of i d e n t i f i c a t i o n d i s c u s s e d. D e t a i l e d phytochemical i n v e s t i g a t i o n s have "been c a r r i e d out on t h e two s p e c i e s of t h e s e c t i o n Ophioxylanthus of P i c h o n ' s c l a s s i f i c a t i on of t h e genus Rauwolfia. In a l l , n i n e t y a l k a l o i d s were i s o l a t e d and t h e i r s t r u c t u r e s e l u c i d a t e d. R. v o l k e n s i i s t a p f root y i e l d e d t w e n t y - s i x a l k a l o i d s i n c l u d i ng two new compounds, t e t r a p h y l l i c i n e - 1 7 - O - a c e t y l and r a u v o l c i n i n e . The stem b a r k gave s e v e n t e e n a l k a l o i d s i n c l u d i n g t h e new a l k a l o id p r e - p e r a k i n e . Thirteen a l k a l o i d s were i s o l a t e d from t h e l e a v e s , four of which are new n a t u r a l p r o d u c t s i . e . m e t h o x y - p l e i o e a r p a m i n e , methoxyp l e i o c a r p a m i n e 2 : 7 d i h y d r o , methoxy-pleioearpamine N-oxide and v o l k e n s i n e . The a l k a l o i d p l e i o c a r p a m i n e and i t s d e r i v a t i v e s have not p r e v i o u s l y been i s o l a t e d from any Rauwolfia s p e c i e s. l\- o r e o g i t o n Mgf. root y i e l d e d t h i r t e e n a l k a l o i d s of which t h r ee have not been p r e v i o u s l y r e p o r t e d i n t h e p l a n t . The l e a v e s y i e l d ed t w e n t y - o n e a l k a l o i d s i n c l u d i n g f i v e new ones , akuammiline-5-formyl, o r e o g U, akuammiline 2 - d i h y d r o , d e a c e t y l akuammiline 2/4 - d i h y d r o and an i m p o r t a n t b i o g e n e t i c i n t e r m e d i a t e a l k a l o i d a d i r u b i n e a c e t a t e 19 : 20 dehydro. The i n t e r - r e l a t i o n s h i p of t h e i s o l a t e d a l k a l o i d s has been d i s c u s s ed and b i o s y n t h e t i c pathways proposed. The evidence o b t a i n e d concerning the a l k a l o i d s of t h e s e c t i o n Ophioxylanthus s p e c i e s has been used t o r e l a te t h e s e c t i o n chemotaxonomically to t h e o t h e r African Rauwolfia s e c t i o n s and t h e c l o s e l y r e l a t e d genus Cabucala.
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    BACTERICIDAL EFFECTS OF CHLOROQUINE ON ESCHERICHIA COLI : The effects of chloroquine on the viability of growing and non-growing Escherichia co1i in a MOPS (3-(N-Morpholino)-propanesulphonic acid) buffered medium, and its effect on thymidine utilisation
    (1979-05) Olurinola, Philip Folaranmi
    The bactericidal effects of chloroquine on growing and nongrowing cells of Escherichia coli NCTC 1093 were investigated under controlled experimental conditions in a MOPS buffered minimal salts medium. Changes in cell mass and viable cell numbers were determined by measurements of absorbance at 600nm, and by viable cell counts respectively. At pH 7.4, the approximate minimum bactericidal concentration of chloroquine for the organism was 1.0 x 10-3M. This concentration caused about 3 log cycles of kill within 2 hours, with an initial short lag before kill commenced. Variation in the drug concentration up to a ten-fold increase had no significant effect en the rate of kill, although the time of maintenance of that rate was increased. In nongrowing (glucose-starved) cells treated with the same drug concentrations, however, there was virtually no loss in viability for at least 3 hours, except with the highest drug concentration used. Removal of glucose from cultures treated with chloroquine did not appear to affect bactericidal activity. The effect of pH on the action of chloroquine was also examined. A four-fold increase in activity was observed with increase in pH from 6.7 to 7.7, and calculations indicated that both the monoprotonated and diprotonated forms of chloroquine were biologically active, but that the diprotonated form was only l/25th as effective as the monoprotonated Cellular uptake studies of chloroquine by a direct method, using C-labelled chloroquine suggested a biphasic uptake process, a rapid initial passive uptake followed by a slower active one. The latter apparently did not occur in the absence of glucose. The effect of the drug on the utilisation of thymidine by E. coli cells was investigated. Chloroquine rapidly and strongly inhibited both the uptake and incorporation of 14C-thymidine into the cells, and caused a breakdown of preformed DNA. This work establishes the bactericidal action of chloroquine against growing cells of E. coli, and indicates that its antibacterial activity has some similarity to the phenomenon of thymineless death
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    SOME STUDIES ON DRUG-INDUCED BEHAVIOUR IN YOUNG CHICKS
    (1980-04) SOKOMBA, ELIJAH NDAJIYA
    Some behavioural and electrophysiological studies were undertaken in chicks and rats using observational, EEG, EMG and evoked potential techniques. Some dopamine (DA) agonists (apomorphine, d-amphetamine, amantadine, and piribedil) induced stereotyped pecking activity and aggressive behaviour of varying intensities in chicks. On the other hand, DA, L-dopa and ergometrine did not induce characteristic stereotyped activity in the chicks. D-amphetamine and ergometrine induced distinct postural changes in chicks. Pretreatment of chicks with ergometrine and piribedil antagonized the behavioural effects of apomorphine and d-amphetamine. The results show that apomorphine d-amphetamine, amantadine and piribedil induce a similar pattern of stereotyped activity in young chicks. The results further suggest that X ergometrine exerts a predominant inhibitory influence on stereotyped behaviour , while piribedil has both DA agonistic and antagonistic effects in young chicks. Pretreatment of chicks with reserpine and 6-hydroxydoparaine (6-OHDA) potentiated apomorphine and piribedil-induced stereotyped behaviour while the effects of d-amphetamine and amantadine were inhibited. The behavioural effect of apomorphine were potentiated when chicks were pretreated with dihydroxy-phenylserine, while d-amphetamine and amantadine effects were antagonised. FLA--63 potentiated d-amphetamine and amantadine-induced stereotyped behaviour and inhibited apomorphine effects. Propranolol antagonized the behavioural effects of apomorphine and d-amphetamine, while phenoxybenzamine slightly potentiated the effects. Pimozide and haloperidol antagonized apomorphine, d-amphetamine, amantadine and piribedil-induced stereotyped behaviour. These observations indicate a primary role for VT dopaminergic system in drug-induced stereotyped behaviour in young chicks as in other species. Serotonin and quipazine antagonized apomorphine and d-amphetamine-induced stereotyped behaviour. On the other hand, cyproheptadine and parachloro-phenylalanine (PCPA) potentiated the effects of apomorphine and d-amphetamine. These results suggest that serotonergic system plays an inhibitory role in drug-induced stereotyped behaviour in chicks. Desipraraine, imipramine and amitriptyline induced biphasic locomotor effects in chicks. Aporaorphine-induced locomotor activity was potentiated when the chicKs were pretreated 30 rain, previously with amitriptyline and imipramine. When the three antidepressants were administered 1 h previously, apomorphineinduced locomotor activity was inhibited. The results suggest that tricyclic antidepressants produce a time-dependent effect on apomorphine-induced locomotor activity in XII chicks. Repeated administration of j3,i$'-iminodipropionitrile( IDPN) for five days induced specific behavioural changes in chicks. These behavioural changes were characterized by excitation which was accompanied by loud chirping, jerky head and neck movements, and circling motion (i.e. ECC-syndrome). Amphetamine potentiated the syndrome while apomorphine and piribedil enhanced the head and neck movements with minimal effect on the circling behaviour. Pimozide antagonized the ECC-syndrome and also inhibited amphetamine-induced potentiation of the syndrome. Atropine and hyoscine enhanced the ECC-syndrome and also potentiated the effects of d-amphetamine, while physostigmine antagonised the syndrome. Quipazine, in low doses, abolished and in high doses enhanced the ECC-syndrome. The latter effect was antagonised by both cyproheptadine and pimozide. Such results suggest that DA and I I serotonergic mechanisms may be involved in IDPN-induced effects in chicks. It is also possible that cholinergic system may exert an inhibitory influence on the ECC-syndroioe. Evoked responses to photic stimulation recorded under artificial light and dark adaptation from three different brain areas in conscious young chicks were compared. The magnitude of the evoked responses varied from one experiment to another, but for a particular chick consistent responses were obtained under the same behavioural state, stimulus intensity, and recording conditions. The evoked responses recorded under dark adaptation were larger in magnitude and more reproducible when compared with those recorded..under artificial light. The photic-evoked responses under dark adaptation were very sensitive to drug effects. These observations suggest that photic-evoked response (PER) could probably be utilized in the elucidation of the actions of some :v Psychoactive drugs. The influence of acute and chronic administration of phenobarbitone and ethanol on PER was studied in rats. Both phenobarbitone and ethanol produced behavioural depression. EEG synchronization and varying effects on the averaged PER recorded from the frontal cortex (FC) optic cortex (OC) and midbrain reticular formation (MBRF). In phenobarbitone- and ethanol- dependent animals, amplitude of the PER recorded from the FC and OC were enhanced while the recordings from the MBRF were reduced. On the other hand, the amplitudes of the PER from all the three brain areas were enhanced during withdrawal. The results suggest that both phenobarbitone and ethanol produce similar effects on PER in rats and that the effects may probably be characteristic of the sedative - hypnotic group of drugs.
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    STUDIES INVOLVING INTERACTION BETWEEN ALPHAMETHYLDOPA AND COWPEA (VIGNA SINENSIS) USING BOTH NORMOTENSIVE . AND SPONTANEOUSLY HYPERTENSIVE RATS.
    (1980-11) KOLAWOLE, SIMEON OLATUNDE
    The effect of cowpea and its possible interactions with alphamethyldopa on the b.p. and heart rate of normotensive and spontaneously hypertensive rats have been studied. ii ) Cowpea (60%w/w of Pfizer feed) increased the b.p. of normotensive rats (NTR), but had no such effect on spontaneously hypertensive rats (SHR). In addition the heart rate of SHR was significantly elevated while that of NTR was not affected. The sympathomimetic agents further elevated the b.p. in the NTR than in the controls, but the b.p. elevation in the SHR was much lower than in the controls. The heart rate of both NTR and SHR were not consistently affected. lii) Cowpea (20%w/w of Pfizer feed) did not alter the b.p. of NTR, but increased the heart rate. On the other hand, the b.p. of SHR was reduced, while the heart rate was apparently not affected. Noradrenaline and tyramine elevated the b.p. of this group lower than in controls, particularly with the SHR. The results obtained with other sympathomimetics on both NTR and SHR were not consistent. iv) Alphamethyldopa did not alter the b.p. of the NTR but lowered that of SHR. The heart rate uf both NTR and SHR was significantly elevated by alphamethyldopa. The b.p. elevating effect of the sympathomimetics were not significantly more than those obtained in the controls. V) Coadministration of alphamethyldopa and cowpea (60% and 20°/oW/w) had no effect on the b.p. of NTR, but reduced that of SHR, Interaction of alphamethyldopa with cowpea (20%w/w) increased the heart rate of both NTR and SHR. Similarly, cowpea (60%w/w) elevated the heart rate of SHR, but had no such effect on NTR. The sympathomimetic effects followed the pattern of responses obtained when administered to rats (NTR and SHR) treated with only cowpea (20% and 60%w/w) . The treatment apparently had no influence on the effects of the sympathomimetics,
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    FACTORS AFFECTING DRUG DISTRIBUTION IN GRANULES
    (1980-12) OJILE, JOSEPH ELUGBE
    The formulation and processing variables affecting the distribution of a low dose drug in granules prepared by the massing and screening method have been investigated. Five granule formulations were used to elucidate the effect of the "relative solubilities" on the drug distribution in granules. These were borax/lactose, sodium salicylate/ lactose, sulphadimidine/lactose, sodium salicylate/dibasic calcium orthophosphate (d.c.o.) and sulphadimidine/d.c.o. Water was used as the binder for the formulation containing lactose diluent and PVP binder for d.c.o. Relative dissolution ratio R was derived. This was found to govern drug distribution in granules. The effect of dose variation for a soluble drug was shown to affect R which also explained why dosage uniformity in granules was more problematic in micro-dose than high dose drugs. The effect of the massing action on dosage uniformity throughout the granule sizes has been elucidated. A higher R value in the granule formulation was found to cause some solute dissolution including the drug in the initially overwetted region. The binder distribution from this region now containing dissolved components enriched the drier area of the mix with the solutes. This action was found to be further enhanced by solute migration during drying. Thus the peak, drug concentration was obtained in the intermediate sized granules. For an appreciably high R value as in sodium salicylate/lactose formulation, a snow-balling action was envisaged to counteract the massing action to a certain extent. This allowed a further low drug concentration in the fines. The d.c.o. diluent which showed a lesser degree of surface wetness was found to reduce this snow-balling action. Massing a dry mix with a binder, of constant composition throughout the massing period, e.g. a solution simultaneously saturated with part of the drug and diluent, led to a directly related drug concentration with the granule size. Also massing sulphadimidine/d.c.o. dry mix with PVP binder caused a constant PVP binder composition during the massing as both components are poorly soluble. This led to an inverse relationship between the drug concentration and the granule size on account of the dilution effect of the directly related binder content with granule size. A formulation containing a drug with an R value lower than unity but a markedly higher diluent relative solubility, as in sulphadimidine/lactose granulation, produced the most uniform drug distribution in the granules. Although the lactose solubility is appreciable, its R value is still low due to its presence as a high dose, 987o w/w, diluent. A formulation was designed to make R value equal to 1. This was, as expected, found to lead to a uniform drug distribution irrespective of granule size or granule bed depth. Other variables which were studied were drying temperature, binder concentration and binder type, intermediate granule screening during drying, excessive massing time, granule packing density during drying, granule bed thickness or height, particle size of both components and drying method. The action of initial larger drug particle sizes for a moderately or poorly soluble drug was due to lack of ease of wetting for bonding to the initially overwetted mass and slower dissolution rate as in borax. The former action led to a lower concentration in the larger granules in the batch but the latter a higher concentration. For a readily wettable drug e.g. sodium salicylate the rate of dissolution with particle size was found to be sufficiently rapid to cause a non-rate determining step. Intermediate screening of borax/lactose produced granules with a high borax concentration in the larger granules depending on the moisture content remaining as well as the sieve mesh used in the rescreening process. This was apportioned to abrasion and bonding of the wet fines to granules. The action of excessive (60 minute) massing time was found to produce the same effect as the increase in the binder volume. This was a further decrease in borax concentration in larger granules with a shift of the peak concentration in finergranules. A comparative study of the drying method showed that the highest borax concentration was obtained in the larger granules dried by freeze drying, then vacuum drying, hot air oven and fluidised drying. The freeze dried granules further substantiates the distribution of the borax rich binder from the overwetted to the drier region of the wet mass during massing. It also showed that solute migration in a batch of granules dried on the tray caused a further depletion of borax from the larger to the intermediate granules. The effect in the granules dried by fluidisation was an abrasive action while that of the other drying methods was due to solute migration during drying. All the factors affecting drug distribution during the drying in the hot air oven were found to be connected with the degree of solute migration. A denser packing of granules increased solute migration; a higher drying temperature decreased the migration; an increase in the height of granule bed increased the migration and led to a direct relationship between borax concentration and the mean granule size. An increase in the particle size of the diluent increased the effective volume of the binder in the pores available to increase the quantity of the dissolved drug and increase the solute migration of the drug. The larger pores in larger granules entrapped a higher quantity of the drug in the larger granules. The concentration of drug in granules is therefore the net effect of the massing action and solute migration during drying.
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    STUDIES ON THE NEUROMUSCULAR EFFECTS OF THE EXTRACTS OF ABRUS PRECATORIUS LINN
    (1982-09) AMOSUN, SEYI-'LADELE
    Abrus precatorius Linn. was reported to be a medicinal plant (Ghosal & Dutta, 1971). The seeds of the plant have been reported to cause paralysis in horses (Nwude, 1979). In order to determine if this plant contributes to paralysis observed in humans at the Physiotherapy Department, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria, an investigation was carried out on the neuromuscular effects of the crude water, petroleum ether and ethanol extracts of the seeds, leaves and root of Abrus precatorius Linn. Isolated toad's rectus abdominis, rat's phrenic nerve-diaphragm muscle preparation, as well as chicks were used in this study. Isometric contractions of the muscle preparations were recorded by Ugo Basile recording microdynamometer (model No. 7050) . Only the ethanol extracts antagonised the effect of acetylcholine on the isolated tissues.. The ethanol extract of the seeds (0.1 - 1.6 mg/ml) inhibited (32.00 - 84.33%) acetylcholine-induced contractions of toad's rectus abdominis mucole. Similarly, the ethanol extract of the leaves (1.0 - 8.0 mg/ml) inhibited (21.77 - 80.02%) the acetylcholine-induced contraction of the toad's rectus abdominis, while the ethanol extract of the roots (0.5 - 4.0 mg/ml) also inhibited (20.75 - 85.80%) the contraction of the tissue. The antagonism was reversible. On the rat's tissue, the ethanol extract of the seeds (0.1 - 0.8 mg/ml) inhibited (0.1+2 - 77.50%) the contraction of the diaphragm elicited by electrical stimulation of the phrenic nerve. Similarly, the ethanol extract of the leaves (0.5 - 4.0 mg/ml) antagonised (0.99 - 89.83%) the contraction of the diaphragm muscle via phrenic nerve stimulation, while the ethanol extract of the roots (0.3 - 2.4 mg/ml) inhibited (4.89 - 86.47%) the same contraction. The antagonism in each case was potentiated by d-tubocurare and reversed by eserine. The inhibitory effect of the ethanol extracts on the nerve-induced contraction of the rat's diaphragm was potentiated in the presence of reduced Ca++ (1.25 mM), elevated Mg++ (2.50 mM) or reduced K+ (0.9 mM). The hot water extracts of the seeds, leaves and roots, and the petroleum ether extract of the seeds induced spastic paralysis in five day old chick;;. On the other hand, the ethanol extracts of the seeds., leaves and roots caused flaccid paralysis when injected intravenously into chicks. The ethanol extract of the seeds was most toxic, whereas that of the leaves was least toxic on weight basis. The ethanol extracts showed a similarity to d-tubocurare vis-a-vis the pattern of neuromuscular blockade. The present data indicate that the ethanol extracts of the seeds, leaves and roots of Abrus precatorius possess neuromuscular blocking effects.
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    The Effect of Temperature Fluctuation In The Tropics On The Viscoelastic Properties of Clotrimazole (an antifungal) Cream Bases
    (1983-03) ABUBAKAR, MUSA
    The physicochemical factors affecting semi-solids and in particular emulsified creams have been reviewed. Temperature, humidity, pH changes, Oxidation-rednction processes and microbial contamination are such factors that generally affect the stability of Pharmaceutical and Cosmetic creams. The flow properties and types of flow of various types of pharmaceutical fluids and semi-solids have also been outlined. An investigation on the macroscopical and rheological properties such as apparent plastic viscosity, yield stress and thixotropy using Ferrenti-Shirley cone and plate viscometry was carried out on various cream bases at different temperatures. Cetostearyl alcohol/Cetyltrimethyl Ommonium oromide were used as mixed emulsifier. The effects of alcohol/surfactant ratio and the total mixed emulsifier concentrations on the viscoelastic properties have also been investigated, The results of these investigations indicated that temperature fluctuations common to tropical climates affect the physical stability of the creams drastically. It was found that the consistency usually increases with rise in temperature to a maximum of around 20° - 27° and decreases with further increase therefrom. An exact temperature of maximum stability of 20° was also found to be the same for the commercial sample "Canesten Cream" in the comparative studies conducted in this work,
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    ANTHRACENE DERIVATIVES IN TISSUE CULTURE OF SOME NIGERIAN CASSIA SPECIES
    (1983-06) RAI, PREM PRAKASH
    This study was undertaken to determine the nature and quantity of anthraquinones produced in callus cultures of four Nigerian species of Cassia: C. nodosa Roxb., c. alata L., .C. occidentalis L. and C. podocarpa Guill. 4 Perr. A visual selection procedure for a high yielding anthraquinone cell line from callus cultures of C. podocarpa was attempted for the first time. The use of plant tissue culture for secondary product biosynthesis, particularly in plants of pharmaceutical importance, holds promise for the controlled production of plant constituents. In all of the Cassia cultures studied, only hydroxyanthraquinones, anthrones, dianthrones, and anthraquinone monoglycosides were produced and the most pharmacologically active dianthrone glycosides based on rhein were particularly absent. Callus cultures from seedling hypocotyls and cotyledons of Cassia nodosa,
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    INFLUENCE OF LEVODOPA, APOMORPHINE AND 3,4-
    (1984-10) GAMANIEL, KARNIYUS
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    SOME ANTHELMINTIC AND OTHER PHARMACOLOGICAL ACTIONS OF DIETHYL ETHER EXTRACT OF THE SEEDS OF CARICA PAPAYA LINN
    (1985-09) BILLEYA, JAMES PANINGA
    The anthelmintic property of the extract of Carical Papaya seeds against Nippostrongylus braziliensis and Hymenolepls nana were studied using rats. In addition, pharmacological properties of the seed extract on skeletal, smooth and cardiac muscles were investigated. The extract (0.5 - 2 g/kg) used once daily for three days, or once followed by purging with magnesium sulphate (4.6 g/kg) 2 and 2k hours later, did not show any activity against N. braziliensis. The activity of bephenium hydroxynapthoate (150 - 200 mg/kg) against N. braziliensis. was significant. On the other hand, the extract exhibited activity both in vitro and in vivo against H. nana. The LD50 for extract and niclosamide in vitro were 36 ug/ml and 120 ng/ml respectively. The extract at concentrations above 100 ug/ml either paralysed the worms or killed them. A similar effect was observed with niclosamide (>1.9 ug/ml). The activity of extract was significant at concentrations above 0.5 g/kg when used once daily for three days against H. nana. When used once, followed by purging with magnesium sulphate, it was significant at 1.0 g/kg and highly significant at 2.0 g/kg. Niclosamide (600 mg/kg) once daily for three days showed complete deparasitization of all the rats used. The results of the extract suggest that it could be a cestocidal agent hut its use as a general vermifuge is not justified in ankylostomiasis. The extract (> 32 ug/ml) affects isolated skeletal muscle preparations directly resulting in permanent contracture, suggesting that it could be acting at a point beyond the neuromuscular junction. It is likely to be interfering with the process involved in, either sequestering of released Ca2+ or the storage of Ca2+ thereby making Ca continously available for sustained and irreversible contracture. The extract (0.5 mg/ml)contracted and desensitized both oestrous and non-oestrous rat uterine smooth muscle to oxytocin and acetylcholine. The activity may be related to a possible effect of the extract on the fluxes of calcium or other ions. On the cardiac muscle, the extract (0.2 mg/ml) produced initial positive chronotropic and inotropic effects followed by gradual decrease in force and rate of contraction of the heart. It also desensitized the heart to acetylcholine and adrenaline. The cardiac effect of the extract may be due to its interference with enzyme systems (e.g. c-AMP, c-GMP) responsible for the mobilization of Ca2+. When acute toxica logical studies with chicks and mice were conducted, the extract (2 g/kg) did not produce any observable toxic effects. BITC was qualitatively determined by its hydrolysis to yield hydrogen sulphide and carbon dioxide gases. It is therefore likely that the observed effects of the extract in this project may be principally attributed to BITC content of the seed extract.
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    EFFECT OF ULTRA VIOLET RADIATION ON THE STABILITY OF PROGUANIL AND PYRIMETHAMINE
    (1985-09) UKO, NNENNA OYIDIA
    The influence of UV radiation (366nm) on the stability of proguanil hydrochloride and pyrimethamine sulphate in tablet formulations and in phosphate buffer solutions of different pH values has been evaluated in the present study, UV spectroscopic method for estimating drug content in the various dosage forms was employed. The effect of pH on the UV spectrum of the drugs was investigated» The influence of reaction vessel and pH on the irradiated phosphate buffer solutions was also studied, In-vitro dissolution rate studies of the drugs were carried out including those tablets that had been subjected to UV irradiation. The UV spectrum of proguanil hydrochloride was found to be stable at pH values above 2.0 in phosphate buffer solutions. Below pH 2,0 the spectral peak at 232nm disappeared while the peak at 253nm flattened out giving a plateau. Proguanil hydrochloride was found to enter into photochemical reaction in phosphate buffer solution when subjected to continuous UV irradiation at 366nm. Evidence of photochemical reaction was shown by loss of spectral peaks in phosphate buffer, appearance of a precipitate, colour change of solution, spectral shift and increase in absorbance of the irradiated solution. The photochemical reaction was found to be influenced by the pH of the solution and the type of glassware in which the reaction was performed. Assay of irradiated proguanil hydrochloride tablets indicated loss of drug content with time. Dissolution rate studies of the irradiated tablets showed decrease in dissolution rate: with time The UV spectrum of pyrimethamine sulphate remained stable at different Values. Pyrimethamine sulphate appeared not to readily enter into photochemical reaction. The formulations used showed signs of degradation by colour change of tablets but there was no loss of drug content on assay. The dissolution rate of the irradiated pyrimethamine tablets produced by Wellcome Nig. Ltd. increased with time in phosphate buffer solution pH 4.5 while the dissolution rate of irradiated pyrimethamine tablets produced by Quality Control Unit A.B.U. Zaria decreased with time in phosphate buffer solution pH 4.5. This difference observed in the dissolution rates of the formulations has been attributed to the influence of the different excipients used by the different manufacturers.
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    PHYTOCHEMICAL AND BIOLOGICAL STUDIES OF THE BARK OF SCLEROCARYA BIRREA (A. RICH,) HOCHST.
    (1986) EZZELDIN, MUKHTAR ABDURAHMAN
    Sclerocarya birrea (A. Rich.) Hochst is a Savannah tree belonging to the family Anacardiaceae.. The different parts of the plant, especially the plant bark, have long been used by traditional healers in the northern parts of Nigeria for treating dysentery, hemorrhoids and skin diseases. A thorough literature survey indicated that there has been no systematic phytochemical or biological study of the chemical constituents of this plant. The phytochemical study of the bark involved a preliminary phytochemical screening and a detailed phytochemical study of its various extracts (water, ethanol and petroleum ether) for isolation and characterisation of the major constituents. Some of the constituents were also quantitativel}' estimatedi The phytochemical examination of the bark revealed the presence of carbohydrates, simple phenolic compounds and sterols. Sucrose, gallic acid and a sterol (characterised as cholesterol) were isolated from the bark. Various pharmacological properties of the bark's crude water extract were separately studied using isolated rabbit duodenum, guineapig ileum, rat uterus and frog rectus abdominis. Acute toxicity of its water extract was also investigated, In addition, the water extract of the bark was also tested for its antimicrobial activity. The crude water extract of the bark contracted the smooth muscles of rabbit duodenum, guineapig ileum and rat uterus,. It also contracted the skeletal muscles of the frog rectus abdominis. The median lethal dose (intraperitoneal) of the water extract of the bark was 1.44g/kg. The isolated cholesterol sample and the pure cholesterol sample relaxed the smooth muscles of rabbit duodenum only and did not produce any significant effects on any other tissues. However, the similar behaviour of these two cholesterol sampler provided additional support to the phytochemical identity of the isolated sterol as cholesterol. The microbiological studies indicated that the water extract of the bark has a wide antimicrobial activity against both gram positive and gram negative microorganisms. All these results have been reported and discussed in this thesis in relation to the traditional uses of the bark. In conclusion it has been derived that these findings offer a rational basis for the use of the bark bytraditional healers for treating gastrointestinal diseases and microbial infections.
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    ISOLATION, IDENTIFICATION AND PHARMACOLOGICAL SCREENING OF THE ALKALOIDS.OF THE LEAVES OF SYNCLISIA SCABRIDA MEIRS
    (1986-10) BAKO, UMARU FAROUQ
    The leaves of Synclisia scabrida (Menispermaceae), a plant used in the treatment of gynaeco-obstetrical and mental problems in traditional medicine was investigated for its alkaloidal content. The alkaloidal fractions of the ethanolic extract of the leaves of Synclisia scabrida showed the presence of five alkaloids by TLC. Three of the alkaloids were isolated and designated as alkaloids D, E and F. Alkaloid D m.p. 276-278°C was identified as isochondodendrine from colour reactions, spectral data and methylation experiments. This is the first report of occurence of isochondodendrine in Synclisia scabrida. Alkaloid F m.p. 268-270°C was identified as cycleanine from colour reactions, spectral data and comparison with authentic sample. This is the first report of the isolation of cycleanine from the leaves of Synclisia scabrida. The colour reactions and spectral properties of alkaloid E m.p. 230-232°C have been studied. In order to obtain further information about structure, alkaloid E was methylated to the O-methyl derivative (alkaloid E-M). The spectral properties of alkaloid E-M were studied. From the available information some suggestions have beer; made regarding the structure of alkaloid E, but no definite structure could be predicted for this alkaloid. Pharmacological screening showed that alkaloid D antagonised acetylcholine induced contractions of the frog rectus abdominis tissue. It showed weak antagonism to oxytocin induced contractions of the rat uterus. Anti-psychotic tests showed that apomorphine induced stereotyped behaviour in chicks was suppressed by alkaloid D. Alkaloid E showed no effect on acetylcholine induced contractions of the frog rectus abdominis tissue but it produced a weak antagonism to ocytocin induced contractions of the rat uterus.