Substandard artemisinin-based antimalarial medicines in licensed retail pharmaceutical outlets in Ghana.

BACKGROUND & OBJECTIVES: The artemisinin-based antimalarial medicines are first line medicines in the treatment of severe and uncomplicated falciparum malaria. Numerous brands of these medicines manufactured in various countries are available in the Ghanaian market. The study was aimed at evaluating the authenticity and quality of selected brands of artemisinin-based antimalarial medicines marketed in Ghana. METHODS: In all, 14 artemisinin-based antimalarial medicines were purchased from pharmacies (P) and licensed chemical shops (LCSs) in the Kumasi metropolis, Ghana. Simple field tests based on colorimetry and thin layer chromatography were employed in determining the authenticity of the samples. Important quality assessment tests, namely uniformity of mass, crushing strength, disintegration time, and the percentage content of active pharmaceutical ingredients (APIs) were determined. RESULTS: All the brands tested contained the stipulated APIs. Artesunate tablet AT2 failed the uniformity of mass test while artesunate tablets AT3 & AT4 as well as amodiaquine tablets AM4 & AM6 failed the crushing strength test. All the six artemether-lumefantrine tablet brands passed the uniformity of mass, crushing strength and disintegration tests. Only artemether-lumefantrine tablet brand AL1 contained the correct amount of the drugs. The other 13 artemisinin products contained either a lower (underdose) or higher (overdose) amount of the specified drug. Artesunate monotherapy tablets were readily available in pharmacies and licensed chemical shops. INTERPRETATION & CONCLUSION: All the artemisinin-based medicines tested (except AL1) were of substandard quality. The results demonstrate the need for continuous monitoring and evaluation of the quality of artemisininbased antimalarials in the Ghanaian market. Also, the practice of artemisinin antimalarial monotherapy is prevalent in Ghana. Determined efforts should, therefore, be made to eradicate the practice to prevent the development of resistance to the artemisinins.

Resveratrol nanosuspensions: interaction of preservatives with nanocrystal production.

The effect of six different preservatives on the production process and stability of resveratrol nanosuspensions was investigated. Nanosuspensions of the anti-oxidant resveratrol were prepared by high pressure homogenization (1,500 bar, 20 homogenization cycles). The preservatives used were: caprylyl glycol (0.75%), Euxyl PE 9010 (1.0%), Hydrolite-5 (2.0), Phenonip (0.75%), Rokonsal PB-5 (0.5%) and MultiEx Naturotics (2.0%). Preservation is essential for oral and dermal nanosuspensions, but can impair the stability. The effect of the preservatives on stability as a function of cycle numbers was determined by size measurements (photon correlation spectroscopy (PCS), laser diffraction (LD) and light microscopy). Zeta potential measurements were performed for determination of the Stern potential (measurements in water) and as stability criterion (measurements in original dispersion medium), to elucidate the mechanism of destabilization. The preservatives could be placed into three groups. Hydrolite-5 did not affect the production process and the short term stability, sizes were practically identical to the preservative-free nanosuspension (e.g. PCS diameters 196 nm and 184 nm, respectively). All other preservatives impaired the stability medium to pronounced, being most pronounced for MultiEx Naturotics. Hydrolite-5 is recommended as preservative of choice. A mechanistic model was developed to explain the absence and the different degrees of destabilization. In general, when screening for suitable preservatives, suspensions are produced, different preservatives added and the size changes are monitored over long-term. The destabilizing effect of the preservatives on nanosuspensions became evident when added in the production process immediately, thus this can be used as a screening tool for optimal, non-destabilizing preservatives, replacing or minimizing time-consuming long-term stability studies.

Resveratrol nanosuspensions for dermal application--production, characterization, and physical stability.

Nanosuspensions of the anti-oxidant resveratrol (5%) were produced for dermal application. Production was performed by high pressure homogenization, applying 1.500 bar up to 30 cycles. Four nanosuspensions were investigated using the stabilizers Tween 80, Poloxamer 188, Plantacare 2000 and Inutec SP1, 1% and 2% respectively. The nanosuspensions were characterized regarding size (photon correlation spectroscopy, laser diffraction), zeta potential and crystallinity. Nanocrystal sizes were about 150 nm (Poloxamer, Plantacare) and about 200 nm (Tween, Inutec); no amorphous fraction could be detected in the nanocrystals. In a short-term stability study (30 days, room temperature), the nanosuspensions with 2% stabilizer proved to be either less stable or at least had no stability advantage over the 1% formulations. All formulations with 1% stabilizer were stable in the short-term study, Plantacare and Inutec showing best stabilization. The stabilization is attributed solely or mainly to steric stabilization, because the measured zeta potentials in the original dispersion media were close to zero (-1 to -5 mV, Tween, Poloxamer, Plantacare) or around -20 mV (Inutec).

Antimicrobial activity of extracts and topical products of the stem bark of Spathodea campanulata for wound healing.

The antibacterial activity of the aqueous, ethanol, methanol and petroleum ether Soxhlet extracts of sundried stem bark of Spathodea campanulata P. Beauv. (Bignoniaceae) was investigated by testing the extracts against B. subtilis, E. coli, P. aeruginosa and S. aureus. The minimum inhibitory concentration (MIC) of the methanol extract was determined against the four bacteria strains and C. albicans using the broth dilution method. Four topical products were prepared by incorporating the methanol extract of S. campanulata (20 % w/w) into aqueous cream, soft paraffin, emulsifying ointment and simple ointment bases and evaluated for their in vitro antimicrobial efficacy. The effect of storage time on the activity of the methanol extract of S. campanulata and S. campanulata extract incorporated in aqueous cream base was also investigated. The methanol and ethanol extracts showed good activity while the aqueous and petroleum ether extracts exhibited little activity. The methanol extract showed the best antibacterial activity. The MIC of the methanol extract of S. campanulata was: C. albicans (45 - 50 mg/ml), B. subtilis and E. coli (50 - 55 mg/ml), P. aeruginosa (60 - 65 mg/ml), S. aureus (145 - 150 mg/ml). Antimicrobial activity of S. campanulata in the topical bases was in the order: aqueous cream > emulsifying ointment > simple ointment > white soft paraffin. Antimicrobial activity of S. campanulata in aqueous cream decreased (p < 0.05) upon storage at room temperature for 6-months. The antifungal activity of the methanol extract of S. campanulata was reduced (p < 0.05) upon storage while antibacterial activity was largely unaffected.

Quality of Artesunate Tablets Sold in Pharmacies in Kumasi; Ghana

Purpose: The study was carried out to evaluate the quality of artesunate tablets sold in retail and wholesale pharmacies in Kumasi; Ghana. In particular; the study sought to ascertain the presence or otherwise of counter-feit artesunate tablets in Kumasi. Method: Artesunate tablets were purchased from pharmacies in Kumasi for the study. The mechanical properties of the tablets were evaluated; namely: uniformity of weight; breaking strength; friability and rate of disintegration in aqueous medium. Colorimetric methods were used to determine the presence of artesunate and to assay the tablets. Result: None of the artesunate tablets sampled was found to be a counterfeit. Most of the brands had acceptable mechanical properties in terms of mass uniformity; hardness; friability and disintegration time. However; the artesunate content of the tablets was variable (47.9-99.9). Six (35.3) of the samples passed the International Pharmacopoeia content uniformity test (93.7-99.9) while 11 (64.7) failed the test (47.9-89.4). However; only 3 (17.6) of the samples met the European Pharmacopoeia (Ph. Eur.) content requirements while 14 (82.4) failed to meet the requirements. Conclusion: The presence of substandard artesunate tablets on the Ghanaian market should alert drug regulatory authorities to be vigilant and continually monitor the quality of this life-saving drug

Biphasic drug release: the permeability of films containing pectin, chitosan and HPMC.

The permeabilities of mixed films of pectin/chitosan/HPMC have been studied to assess their value in producing a dosage form with biphasic drug release characteristics. The inclusion of chitosan enhanced the properties of the films, rendering them stable at all physiological pH values. Pectin/HPMC films were soluble at pH values above 3.0. All pectin/chitosan/HPMC films were permeable to a model drug, paracetamol. HPMC initially increased the permeability of the films and subsequently reduced it at higher concentrations. The minimum permeability was obtained at pH 3 and at an HPMC level of 5% where the potential for polyelectrolyte complex formation between pectin and chitosan exists. The permeabilities of the films increased when they were exposed to pectinolytic enzymes, a system designed to mimic conditions in the colon. The film formulation thus show the potential for biphasic delivery with an initial, controllable slow phase that can be manipulated by changes in the formulation followed by a faster phase under conditions pertaining in the colon.