Nigerian Journal of Pharmaceutical Research

Design and Preliminary Characterization of Sweet Potato Starch – Urea-Borate Polymer

O. Agho — 2024-07-22

Background – Sweet potato (Ipomoea batatas) starch has been reported for its potential as a directly compressible and sustained- release polymer in its native and modified forms. Chemical modification by crosslinking with urea and borax to form starch urea-borate will enhance its drug release-retarding properties.

Objective – To design starch-urea-borate (SUB) polymer using sweet potato starch to produce a new, affordable biodegradable polymer, and carry out preliminary characterization of the polymer.

Method – Native starch was extracted from sweet potato tubers and crosslinked with urea and borax to form starchurea borate (SUB) polymer. The native and modified starches were characterized for morphology (SEM), FT-IR, DSC, pH, densities, swelling, flow properties and viscosity.

Results – Modification yielded 96.66% w/w of SUB and disrupted the granular structure of the native starch, producing significantly larger (p<0.01) granules with irregular shapes. FTIR spectrum revealed a peak at 3369.05 cm1 due to –NH2 confirming the presence of a secondary amide resulting from the polymerization reaction between urea and starch in the presence of borate. A shift in the peak of DSC endotherm was observed for SUB. Modification yielded lower particle density but higher bulk and tapped densities. The swelling index increased significantly (p<0.01). Hausner’s ratio (1.06± 0.00), Carr’s index (6.33± 0.01%) and angle of repose (26.14±1.15º) showed good flow but reduction in compressibility of SUB. Viscosity revealed shear thickening or dilatant behaviour.

Conclusion- The material and physicochemical properties of SUB polymer showed its potential for application in drug delivery systems, possibly as a release retarding polymer.

Assessment of Knowledge, Attitude and Practices of Pharmacy Clients about Antibiotic Use and Misuse in Ogun State, Nigeria

A.E. Joda — 2024-07-22

Background: The rise of antimicrobial resistance poses a global health challenge, driven by the widespread misuse of antibiotics. This misuse includes self-medication, sharing of antibiotics and failing to complete prescribed courses. This fosters an environment conducive for antibiotic resistance making future treatment less effective.

Objectives: This study aims to evaluate the knowledge, attitudes, and practices (KAP) of antibiotic use/misuse and their influencing factors among pharmacy clients in Ogun State, Nigeria.

Methods: A descriptive cross-sectional study was carried out in ten (10) community pharmacies obtained from the list provided by the Association of Community Pharmacists of Nigeria, Ogun State branch, across its five zones in Ogun State, Nigeria. Pre-tested questionnaires adapted from previous studies were used to collect data which was entered into Microsoft Excel 2016 and analyzed using the Statistical Package for Social Sciences (SPSS) version 23.0. Descriptive and inferential statistical analyses were carried out with significance level set at ≤0.05.

Results: Good knowledge and practice (KP) scores of pharmacy clients about antibiotic use of 54.5% and 56.2% but poor attitude to antibiotics (60.5%) was documented along with notable misconceptions. Several demographic factors influenced the KP levels including gender (p=0.00027), marital status (p=0.013), religion (p=0.005), and education (p=0.001) for knowledge; and religion (p=0.027) and education (p=0.006) for practices.

Conclusion: The study showed that though moderate levels of KP were obtained, there is a need for targeted interventions to improve public awareness about antibiotics and promote responsible use.

Development and Evaluation of Encapsulated Self-Emulsifying Drug Delivery System of Hydrochlorothiazide

E.S. Essien — 2024-07-22

Background: Formulation of solid self-emulsifying drug delivery system (Solid SEDDS) provides a dual benefit of improved drug stability and enhanced delivery system.

Objective: This study was aimed at developing and evaluating a solid self-emulsifying drug delivery system of hydrochlorothiazide.

Methods: Solubility of hydrochlorothiazide in some oils was determined and pseudo-ternary system of the most effective oil, water and surfactant system was constructed. Four Liquid SEDDSs were formulated to contain Tween 80/oleic acid or PEG 400/oleic acid (surfactant systems) and castor oil combined in ratio 2:8 or 3:7 based on the pseudo-ternary plot. Each preparation was made by adding the drug to the oil/surfactant system and heating up to 60 0C under continuous stirring followed by cooling to room temperature. Viscosity of each Liquid SEDDS was determined; Solid SEDDS was prepared by mixing the Liquid SEDDS with microcrystalline cellulose in 1:2 proportion and then encapsulated. Drug release profile of the Solid SEDDSs in comparison with a marketed product was studied.

Results: Castor oil was found to be the best solvent for hydrochlorothiazide and the viscosity of the Liquid SEDDSs was in the range of 79.41 and 187.32 mPa.s. The in vitro release studies showed 85.46 – 87.17 % drug release from the formulated SEDDSs with ratio 3:7 of surfactant mix being superior; and percentage drug release for each formulation was twice that of the marketed product.

Conclusion: The prepared Solid SEDDS of hydrochlorothiazide exhibited improved drug release characteristics, hence superior to the conventional commercial product.

Effect of Garcinia kola on Atorvastatin Dissolution Profile: An Indication for Possible Drug-Drug Interactions After Oral Administration

A. Adegbola — 2024-07-22

Background: Herb-drug interactions are of growing concern due to the widespread use of herbal supplements alongside medications. These interactions can affect therapeutic outcomes. Understanding and identifying specific interactions is crucial for ensuring safe and effective medication use.
Objective: This study investigated the impact of Garcinia kola, a common food supplement, on the dissolution of atorvastatin tablets.
Methods: The dissolution profiles of atorvastatin tablets were investigated alone and in the presence of varying concentrations of G. Kola by mixing 1, 2, or 4g of G. Kola powder respectively with the dissolution medium. Samplings were performed at predetermined time points (10, 20, 30, 45 and 60 minutes) and the amount of atorvastatin dissolved was measured using a validated HPLC method. Statistical analyses were conducted to assess the significance of the observed differences.
Results: The percentages of atorvastatin released in dissolution medium without G. kola were 31.38±11.81,46.02±8.73, 72.23±33.30, 63.55±27.10, 82.54±31.12% across the sampling time points. Whereas the percentage of drug released were 17.01±7.33, 27.02±8.42, 34.70±13.90, 39.74±13.53, 28.47±11.78% in the presence of 1g G. kola; 12.44±5.89, 11.87±1.51, 23.33±5.18, 27.33±8.50, 52.49±11.66% in the presence of 2g G. kola and 2.28±3.53, 4.94±7.21, 7.26±9.01, 4.68±7.37, 6.86±8.70% in the presence of 4g G. kola. There was a statistically significant difference in the amount of drug dissolved in conditions studied.
Conclusion: There was a significant change in the dissolution profile of atorvastatin with increasing concentrations of G. kola. This suggests a need to establish the impact of G. kola on the disposition of atorvastatin in vivo.

MAMA Decoction, Nigerian Herbal Antimalarial Preparation, Alters the Disposition of Amodiaquine in Healthy Humans

A.O. Adepiti — 2024-07-22

Background: MAMA Decoction (MD) is prepared from the leaves of Mangifera indica, Alstonia boonei, Morinda lucida and Azadirachta indica. A co-administration of MD with amodiaquine led to synergism in the clearance of malaria parasites in a previous report. The pharmacokinetic basis for this observation was the subject of another study in mice which found significant MD- induced increase in the exposure and half-life of desethylamodiaquine, the major metabolite of amodiaquine.
Objective: This study aimed at evaluating previously identified murine herb-drug interactions in healthy human volunteers.
Materials and Methods: Single oral doses of amodiaquine (10 mg/kg) with/without MD (120 mg/kg) were coadministered to 16 healthy subjects in a three-period crossover design. Five millilitres of blood samples were collected employing sparse sampling from 0.25, 0.5, 1, 2, 4, 8, 12, 24 and 48 h postdose, for each study period and analysed for amodiaquine and desethylamodiaquine contents. The effect of MD on amodiaquine disposition across study periods was investigated using a non-linear mixed-effect pharmacokinetic model which estimated population parameters with the stochastic approximation expectation maximization algorithm implemented in Monolix 2020R1.
Results: The disposition of amodiaquine and desethylamodiaquine was each described, adequately, by two- and onecompartment structural models respectively, and a first-order oral absorption rate. The co-administration of amodiaquine with MD resulted in about 41% decrease in the apparent volume of distribution of amodiaquine (VAQ/F). Pre-administration of MD prior to amodiaquine led to a 22% decrease in VAQ/F.
Conclusion: MAMA decoction appeared to decrease the tissue partitioning of amodiaquine in man. The consequence of this on effective parasite clearance in man is, not yet understood.

Phytochemical and Anticonvulsant Activity of the Ethanol Root Bark Extract of Mimosa pigra L. (Fabaceae) in Laboratory Animals

O.M. Aiyelero — 2024-07-22

Background and objectives: Various parts of Mimosa pigra (MPG) are used in traditional medicines to treat convulsive disorders. The objective of this study was to investigate the anticonvulsant properties of Mimosa pigra ethanol root extract (EREM).
Methods: The acute toxicity of the extract was investigated using OECD 423 protocol of 2002. The anticonvulsant properties of EREM at 200,400 and 800 mg/kg were evaluated using Maximal Electroshock Test (MEST) in chicks; strychnine (SCN-) and pentylenetetrazole (PTZ)-induced seizures in mice.
Results: The extract at 400 and 800 mg/kg significantly (p<0.05) prolonged the mean onset of clonic and tonic convulsions in mouse model of SCN-induced seizure. In PTZ-induced seizure, the extract at 400 mg/kg significantly (p<0.05) increased the mean onset of clonic seizure, while at 800 mg/kg, there was significant (p<0.05) prolongation in the mean onset of clonic and tonic seizure compared to control. The extract did not protect the chick against MEST but significantly (p < 0.05) reduced the mean recovery time at the of 200, 400 and 800 mg/kg. The extract offered 60 and 100% protection at 400 and 800 mg/kg respectively in SCN-induced seizure. Similarly, EREM offered 20 and 40% protection at 400 and 800 mg/kg respectively in PTZ-induced seizure. Diazepam (10 mg/kg), a reference drug significantly (p<0.05) prolonged the onset of clonic-tonic seizure and protected against SCN-, and PTZ-induced convulsion in mice.
Conclusion: These findings indicated that EREM may possess anticonvulsant activity in SCN-, and PTZ-induced seizure in mice. Thus, lend scientific credence to the anticonvulsant claim of EREM in ethnomedicine.

In Silico Identification of Canthin-6-one as a Pancreatic Lipase Inhibitory Anti-Obesity Drug Lead from Hibiscus Sabdariffa

O.S. Ajala — 2024-07-22

Background: The therapeutic use of the only Pancreatic Lipase (PL) - inhibiting anti-obesity drug available in clinical practice, orlistat, is bedevilled with unbearable side effects, necessitating the discovery of new and better-tolerated ones. Hibiscus sabdariffa, a folkloric anti- obesity plant is a plausible repertoire from which such agents could be sought.

Objective: The main objective of this work was to evaluate in silico the phytochemicals of Hibiscus sabdariffa for a possible identification of potential leads for PL inhibitory anti-obesity drug discovery.

Methods: Phytoligands from H. sabdariffa were subjected to a series of in silico evaluations including site directed docking, MM/GBSA calculations, SwissADME drug-likeness screening, Protox II-based toxicity evaluations and a 20 ns molecular dynamics (MD) simulation.

Results: MM/GBSA ranking of docked phytoligands and SwissADME evaluations produced three PL inhibitor hits. One of them, canthin-6-one, demonstrated minimal end-organ toxicity with a 1200 mg/kg LD₅₀; its PL complex generated stability-implying root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg) and solvent accessible surface area (SASA) plots, after the 20 ns MD simulation.

Conclusion: Hibiscus sabdariffa-based canthin-6-one has demonstrated, in silico, high human PL binding affinity, impressive drug-likeness/toxicity profiles and stability-implying MD simulation parameters. It is therefore, herein, recommended as lead for further in vitro, in vivo and molecular modification studies for possible development into a clinical PL inhibitory anti-obesity drug.

Effect of Hibiscus Sabdariffa (Linn) Water Extract on the Pharmacokinetics of Lisinopril in Healthy Human Volunteers

I. Nasir — 2024-07-22

No Abstract

Antifungal Activity of Alchornea cordifolia and Ficus exasperata Leaves Against Trichophyton mentagrophyte and Trichophyton verrucosum

C.O. Akpo — 2024-07-22

Background: The use of plant based natural products as alternative remedy for mycosis has gained global prominence, hence the need to explore the antifungal potentials of readily available herbs.

Aim: To compare the antifungal activity of the ethanol leaf extracts of Alchornea cordifolia and Ficus exasperata against Trichophyton mentagrophyte and Trichophyton verrucosum with that of conventional griseofulvin.

Method: Plant samples were extracted with ethanol via maceration. Phytochemical screening was carried out using standard techniques. The ethanol extract of the fresh and dried leaves of Ficus exasperata and Alchornea cordifolia were compared with griseofulvin (0.03mg/ml) for activity against Trichophyton mentagrophyte and Trichophyton verrucosum using agar well diffusion method at varying concentrations.

Results: Both crude drugs contains flavonoids, saponins, tannins, and cardiac glycosides. Ficus exasperata extracts also contains phlobatannin and terpene. The extracts exhibited a dose dependent fungal inhibition. The highest concentration (150mg/ml) of A.cordifolia and F.exasperata extracts exerted the highest zones of inhibition (16.7mm, 19.3mm, and 19.00mm, 19.7mm respectively) against T.mentagrophyte. The zones of inhibition of the test drugs against T.verrucosum were 20mm, 19.3mm, and 21.3mm, 24.7mm respectively. The least mean zone of inhibition was observed at 25mg/ml. Minimum inhibitory concentration (MIC) of 50mg/ml was obtained for Alchornea cordifolia fresh and dried leaves and Ficus exasperata dried leaves while minimum inhibitory concentration of 25mg/ml was obtained for the Ficus exasperata (fresh) leaves.

Conclusion: These results clearly elucidates the potentials of fresh and dry extracts of A.cordifolia and F.exasperata as a good source of antifungal compounds.

Antibacterial, Antibiofilm Activities and Toxicity of Uvaria chamae P. Beauv (Annonaceae)

B.B. Oluremi — 2024-07-22

Background: Bacteria biofilms are a serious global health concern. The rapid increase of antimicrobial resistance in diarrheagenic bacteria due to biofilm formation has limited the clinical usefulness of some antibiotics in circulation.

Objectives: Uvaria chamae has shown broad spectrum antibacterial activity, hence the need to study its antibiofilm activity against enteroaggregative Escherichia coli (EAEC) strains implicated in paediatric diarrhoea.

Methods: Samples of authenticated U. chamae root, stem and leaf were collected, air-dried, ground and extracted by cold maceration in dichloromethane and methanol separately. The EAEC strains tested were; O42, DH5α, MN5DE, D25D and D28I. The plant extracts were subjected to quantitative and qualitative phytochemical screening and the 50% lethality (LC50) brine shrimp assay carried out. Extracts were screened for antibacterial activity using agar diffusion method, while agar dilution and broth dilution methods were used to determine minimum inhibitory and bactericidal concentrations, respectively. Biofilm inhibition of the active extracts was investigated by crystal violet method.

Results: All the EAEC strains were multi-drug resistant, but susceptible to gentamicin and azithromycin. Dichloromethane leaf extract (DLE) and methanol leaf extract (MLE) inhibited the growth of the tested EAEC strains with the MIC of MLE D28I being MIC 3.75 mg/mL. The percentage biofilm inhibition by MLE against EAEC strains O42, MND5E and D25D were 72%, 74.5%, and 63%, respectively. Alkaloids were the most abundant in the methanol leaf extract of U. chamae (MLE). The extracts had LC50 >1000 μg/ mL.

Conclusion: Uvaria chamae is non-toxic and possesses antibiofilm potential that could be further developed as a natural remedy for diarrhoea.

Physico-Mechanical and Tableting Properties of Metronidazole Obtained by Crystallo Co-Agglomeration Technique

A.K. Abdullahi — 2024-07-22

Background: Due to its simplicity and cost-effectiveness, direct compression has become the approach most frequently used to create tablet. Nonetheless, the active pharmaceutical ingredient should have acceptable flow and good compaction qualities in order to use direct compression in tablet manufacture. Crystallo coagglomeration (CCA) technique has shown to be efficient in improving the earliest stages of tablet manufacture. By combining crystallization (primary particles design) and agglomeration (secondary particles design), it increases the product’s added value.

Objectives: This study exploits the CCA approach to boost the physico-mechanical and tableting properties of metronidazole tablet.

Methods: Metronidazole co-agglomerates was formulated with hydrophilic polymers using CCA technique. The dilution potential of the produced agglomerates was assessed to obtain suitable concentration that was used to prepare metronidazole tablet by direct compression method after which the tablet properties were evaluated.

Results: Metronidazole agglomerate powder had a very good flow rate and angle of repose, low bulk and tapped densities as well as improved Carr’s compressibility index, 15.00±0.14% and Hausner’s ratio 1.18±0.03 compared to pure metronidazole (27.54±0.14% and 1.38±0.04 respectively). The CSFR/Dt ratio for batches F3 and F4 showed higher compactability and functionality. The dissolution profiles of batches F3 and F4 of metronidazole exhibited improved dissolution behaviour than pure drug containing batches (batches F1 and F2).

Conclusion: The CCA technique yielded metronidazole with increased particle size and compactability resulting in excellent flowability and packability due to reduced inter- particulate friction, which exhibited improved compressibility, dilution potential, disintegration and dissolution rate.