Joshua Boateng

As part of our ongoing study to screen local herbs for their possible usefulness as anti-infectives, we assessed extracts from 16 medicinal plants for their antibacterial properties and their influence on the activity of amoxicillin. The minimum inhibitory concentrations (MIC) of amoxicillin against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli and Salmonella typhi were determined alone and in the presence of sub-inhibitory concentrations of the extracts by the Kirby–Bauer agar diffusion method of antibacterial assay. Eleven out of 18 extracts exhibited antibacterial activity with MIC values below 20 mg/ml against at least one of the test bacteria employed. Amoxicillin activity against Staph. aureus was significantly (p<0.05) enhanced by the presence of sub-inhibitory concentrations of 5 extracts (Mallotus oppositifolius, Bidens pilosa, Morinda lucida, Croton membranaceus and Jatropha curcas). B. subtilis also became significantly susceptible to amoxicillin in the presence of 10 μg/ml extracts of B. pilosa, Hibiscus sabdariffa, M. oppositifolius, Momordica charantia, Anoclesta nobilis, Cryptolepis sanguinolenta and Moringa oleifera. Spathodia campanulata, M. lucida, M. oleifera and J. curcas leaf extracts also significantly reduced the MIC of amoxicillin against E. coli while S. typhi susceptibility was enhanced by the presence of A. nobilis, M. charantia and J. curcas extracts. We hereby report that sub-inhibitory concentrations of some plant extracts can enhance amoxicillin activity and these plants may provide lead compounds that may serve as cheap alternative adjuvants to clavulanic acid in amoxicillin formulations for the treatment of resistant opportunistic bacterial infections usually encountered among HIV/AIDS patients.

Objective of this dissertation was to investigate heavy metals in the salivary samples of smokers and non-smokers using inductively coupled plasma mass spectrometry (ICP-MS) as an application of mass spectrometry. 11 salivary samples were collected by spitting from 5 non-smokers and 6 smokers. All the samples were treated with nitric acid for the digestion. All treated samples were analysed for 10 heavy metals 52 Cr, 59 Co, 60 Ni, 66 Zn, 75 As, 111 Cd, 115 In, 139 La, 202 Hg, and 208 Pb. Among which, 66 Zn, 75 As and 208 Pb were found to be differing significantly in smokers and non-smokers. Zinc is the potent regulator of a protein called gustin. Gustin is the key component that maintains taste.

This study aimed to develop films for potential delivery of omeprazole (OME) via the buccal mucosa of paediatric patients. Films were prepared using hydroxypropylmethylcellulose (HPMC), methylcellulose (MC), sodium alginate (SA), carrageenan (CA) and metolose (MET) with polyethylene glycol (PEG 400) as plasticiser, OME (model drug) and L-arg (stabiliser). Gels (1% w/w) were prepared at 40°C using water and ethanol with PEG 400 (0-1% w/w) and dried in an oven (40°C). Optimised formulations containing OME and L-arg (1:1, 1:2 and 1:3) were prepared to investigate the stabilisation of the drug. Tensile properties (Texture analysis, TA), physical form (differential scanning calorimetry, DSC; X-ray diffraction, XRD; thermogravimetric analysis, TGA) and surface topography (scanning electron microscopy, SEM) were investigated. Based on the TA results, SA and MET films were chosen for OME loading and stabilisation studies as they showed a good balance between flexibility and toughness. Plasticised MET films were uniform and smooth whilst unplasticised films demonstrated rough lumpy surfaces. SA films prepared from aqueous gels showed some lumps on the surface, whereas SA films prepared from ethanolic gels were smooth and uniform. Drug-loaded gels showed that OME was unstable and therefore required addition of L-arg. The DSC and XRD suggested molecular dispersion of drug within the polymeric matrix. Plasticised (0.5% w/w PEG 400) MET films prepared from ethanolic (20% v/v) gels and containing OME: L-arg 1:2 showed the most ideal characteristics (transparency, ease of peeling and flexibility) and was selected for further investigation.

The majority of active pharmaceutical ingredients (APIs) found in oral dosage forms have a bitter taste. Masking the unpleasant taste of bitter, APIs is a major challenge in the development of such oral dosage forms. Taste assessment is an important quality-control parameter for evaluating taste-masked formulations of any new molecular entity. Hot-melt extrusion (HME) techniques, have very recently, been accepted from an industrial compliance viewpoint in relation to both manufacturing operations and development of pharmaceuticals. HME achieves taste masking of bitter APIs via various mechanisms such as the formation of solid dispersions and inter-molecular interactions and this has led to its wide-spread use in pharmaceutical formulation research. In this article, the uses of various taste evaluation methods and HME as continuous processing techniques for taste masking of bitter APIs used for the oral delivery of drugs are reviewed.

The evaluation of the effects of different media ionic strengths and pH on the release of hydrochlorothiazide, a poorly soluble drug, and diltiazem hydrochloride, a cationic and soluble drug, from a gel forming hydrophilic polymeric matrix was the objective of this study. The drug to polymer ratio of formulated tablets was 4:1. Hydrochlorothiazide or diltiazem HCl extended release (ER) matrices containing hypromellose (hydroxypropyl methylcellulose (HPMC)) were evaluated in media with a pH range of 1.2-7.5, using an automated USP type III, Bio-Dis dissolution apparatus. The ionic strength of the media was varied over a range of 0-0.4M to simulate the gastrointestinal fed and fasted states and various physiological pH conditions. Sodium chloride was used for ionic regulation due to its ability to salt out polymers in the midrange of the lyotropic series. The results showed that the ionic strength had a profound effect on the drug release from the diltiazem HCl K100LV matrices. The K4M, K15M and K100M tablets however withstood the effects of media ionic strength and showed a decrease in drug release to occur with an increase in ionic strength. For example, drug release after the 1h mark for the K100M matrices in water was 36%. Drug release in pH 1.2 after 1h was 30%. An increase of the pH 1.2 ionic strength to 0.4M saw a reduction of drug release to 26%. This was the general trend for the K4M and K15M matrices as well. The similarity factor f2 was calculated using drug release in water as a reference. Despite similarity occurring for all the diltiazem HCl matrices in the pH 1.2 media (f2=64-72), increases of ionic strength at 0.2M and 0.4M brought about dissimilarity. The hydrochlorothiazide tablet matrices showed similarity at all the ionic strength tested for all polymers (f2=56-81). The values of f2 however reduced with increasing ionic strengths. DSC hydration results explained the hydrochlorothiazide release from their HPMC matrices. There was an increase in bound water as ionic strengths increased. Texture analysis was employed to determine the gel strength and also to explain the drug release for the diltiazem hydrochloride. This methodology can be used as a valuable tool for predicting potential ionic effects related to in vivo fed and fasted states on drug release from hydrophilic ER matrices.