Browsing by Author "Obese, Ernest"

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    Antinociceptive, anti-inflammatory and anticonvulsant evaluation of the hydroethanolic leaf extract of calotropis procera (ait) r. Br. (apocynaceae)
    (KNUST, 2019-11) Obese, Ernest
    ABSTRACT Pain, inflammation, and epilepsy remain a real and currently, a major problem in clinical medicine which requires new agents with improved efficacy for more effective therapy. Plant sources can serve as a basis for the search for these novel drugs. The analgesic, anti-inflammatory and anticonvulsant effects of hydroethanolic extract 70% v/v of Calotropis procera (CPE) which is widespread in Ghana and other tropical areas in the subregion was evaluated. A primary neurological assessment revealed that CPE has some central nervous system depressant and analgesic effects. It also showed impairment on motor coordination in the rotarod test. The extract potentiated duration of sleeping time in the pentobarbitone interaction test and analgesic properties were also further confirmed in the tail immersion test while it delayed pentylenetetrazole-induced convulsions. The anti-inflammatory assessment showed that CPE was able to significantly reduce both carrageenan-induced (F4,15=6.24, P=0.0105) and formalin-induced inflammation (F4,15=100.9, P<0.0001) in rats. The analgesic effects were demonstrated in the acetic acid-induced writhing and formalin-induced paw licking tests. Writhing induced by acetic acid was significantly reduced (F4,15=24.14, P<0.0001) on treatment with oral doses of CPE (30-300 mg/kg). The extract significantly inhibited both phase 1 and phase 2 states induced by injection of formalin (F4,60=12.21, P<0.0001) comparable to morphine, the standard analgesic used. The extract significantly attenuated hyper-nociception induced by tumour necrosis factor-alpha, interleukin 1β, bradykinin, and prostaglandin E2. The anti-nociceptive effect exhibited by CPE in the formalin test was reversed by systemic administration of naloxone and theophylline. The extract was further evaluated for anticonvulsant activity in rodents using animal models, picrotoxin–induced convulsions, strychnine-induced convulsions, and pilocarpine-induced status epilepticus. CPE (100–300 mg/kg) exhibited anticonvulsant effect against strychnine-induced clonic seizures by significantly reducing the duration (F6,20=4.196, P=0.0068) and frequency (F6,21=5.438, P=0.0016) of convulsions. The extract (100-300 mg kg-1) caused a profound dose-dependent delay in the onset of clonic convulsions induced by picrotoxin (F6,25=17.43, P<0.0001) and tonic convulsions (F6,20=43.45, P<0.0001) in mice. The duration of convulsions was reduced significantly (F6,19=41.71, P<0.0001). CPE (100-300 mg kg-1), showed profound anticonvulsant effect and protected against death induced the pilocarpine. ED50 (~ 0.1007) and Emax values calculated from the dose-response curves demonstrated that the extract was less potent than diazepam in reducing the duration and onset of convulsions but had comparable efficacies. Flumazenil – a GABAA receptor antagonist, did not reverse the onset or duration of convulsions produced by the extract in the picrotoxin-induced seizure model. Overall, the hydroethanolic leaf extract of Calotropis procera possesses analgesic, anti-inflammatory, and anticonvulsant properties.
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    Formulation and In-Vitro Evaluation of Oral Sustained-Release Diclofenac Sodium Matrix Tablets Using Hydrophilic Polymer Blends
    (2012-06-15) Obese, Ernest
    A sustained effect of diclofenac is required for the treatment of some chronic conditions like rheumatoid arthritis, osteoarthritis and chronic pain. Sustained release matrix tablets of diclofenac sodium were formulated using the natural gums, xanthan gum and cashew gum together with the semi–synthetic release modifier, hydroxypropylmethylcellulose (HPMC). Crude and purified cashew gums were found to have satisfactory moisture content and insoluble matter. The gums were analysed for their rheological property and found to show pseudoplastic flow. Fifteen (15) different batches of matrix tablets of diclofenac sodium (dose 100 mg) were produced by wet granulation. Different ratios (100:0, 80:20, 60:40, 20:80, 0:100) of Xanthan: HPMC, Xanthan: Cashew and Xanthan: Cashew: HPMC were used. The flow properties of the granules and the physical properties of the compressed tablets namely, weight uniformity, crushing strength, drug content, friability and tablet thickness were evaluated. In – vitro release studies of the drug was performed in phosphate buffer, pH 7.5 over 24 hours with Voltaren Retard as the reference diclofenac sodium tablet. The granules produced had good flow properties as evidenced by their angles of repose, Hausner ratio and Carr’s index values. All the physical characteristics of the formulated tablets fell within acceptable limits. The swelling index of Batch 2 tablets containing only xanthan gum exhibited the highest swelling index followed by Batch 10 tablets containing xanthan and cashew gums in the ratio, 80:20. Different dissolution models were applied to the drug release data in order to evaluate the release mechanism and kinetics. The drug release data fitted well to the Higuchi square root model (R2 = 0.8308 – 0.9750).The n value obtained for most of the batches ranged from 0.45 to 0.89 which indicates that drug is released through an anomalous or non – Fickian transport. Overall, drug release was found to be a complex mixture of diffusion, swelling and erosion. The similarity factor (f2) obtained for batches 7 to 15 fell in the range 50 – 100 meaning the drug release profile of the batches was similar to the reference drug. Batches 7 to 13 and 15 had difference factors in the range 0 – 15 signifying a minor difference in the dissolution profile of those batches and the reference drug. From the results obtained, the gums and HPMC used individually could not sufficiently produce sustained release so must be combined in various ratios for effective sustained release to be achieved.