Quality of chloroquine tablets available in Africa.

Malaria is the biggest killer of African children, yet it is cheaply preventable and curable with insecticides spraying, impregnated bednets and effective drugs. This study aimed to evaluate the quality of Chloroquine (CQ) tablets available in selected African countries. Twenty-six samples of antimalarial CQ tablet of 100, 150 and 250 mg were collected from 12 African countries and evaluated for their quality in the Drugs Quality Control Laboratory of Rabat, Morocco. The identification and dosage of active pharmaceutical ingredients in the tablets, dissolution rate, hardness and the friability of CQ tablets were performed according to the United States Pharmacopeia (USP) and European Pharmacopoeia (Eur.Ph.) recommended methods. The results showed that 7·7% of the sampled CQ tablets available in Burkina Faso were of low quality. Failure in dissolution profile was found in 50% of CQ tablets sampled from Benin, Burkina Faso, Comoros Union, Mali and Senegal. The findings showed poor quality of CQ tablets available in the African market. This problem may affect the efforts to control malaria in Africa. Efficient regulatory systems of drugs quality control should be implemented.

Of chloroquine and COVID-19.

Recent publications have brought attention to the possible benefit of chloroquine, a broadly used antimalarial drug, in the treatment of patients infected by the novel emerged coronavirus (SARS-CoV-2). The scientific community should consider this information in light of previous experiments with chloroquine in the field of antiviral research.

Feasibility of amlodipine besylate, chloroquine phosphate, dapsone, phenytoin, pyridoxine hydrochloride, sulfadiazine, sulfasalazine, tetracycline hydrochloride, trimethoprim and zonisamide in SyrSpend(®) SF PH4 oral suspensions.

The objective of this study was to evaluate the feasibility of 10 commonly used active pharmaceutical ingredients (APIs) compounded in oral suspensions using an internationally used suspending vehicle (SyrSpend(®) SF PH4 liquid): (i) amlodipine, (as besylate) 1.0mg/mL; (ii) chloroquine phosphate,15.0 mg/mL; (iii) dapsone, 2.0 mg/mL; (iv) phenytoin, 15.0 mg/mL; (v) pyridoxine hydrochloride, 50.0 mg/mL; (vi) sulfadiazine, 100.0 mg/mL; (vii) sulfasalazine, 100.0 mg/mL; (viii) tetracycline hydrochloride, 25.0 mg/mL; (ix) trimethoprim, 10.0 mg/mL; and (x) zonisamide, 10.0 mg/mL. All suspensions were stored both at controlled refrigeration (2-8 °C) and controlled room temperature (20-25 °C). Feasibility was assessed by measuring the percent recovery at varying time points throughout a 90-day period. API quantification was performed by high-performance liquid chromatography (HPLC-UV), via a stability-indicating method. Given the percentage of recovery of the APIs within the suspensions, the expiration date of the final products (API+vehicle) was at least 90 days for all suspensions with regard to both the controlled temperatures. This suggests that the vehicle is stable for compounding APIs from different pharmacological classes.

The quality of antimalarials available in Yemen.

BACKGROUND: Malaria has always been a major public health problem in Yemen. Several studies in developing countries have demonstrated ineffective and poor quality drugs including antimalarials. Therefore, quality assessment of antimalarial drugs is of crucial importance. This study aimed to assess the quality of antimalarials (chloroquine and sulfadoxine/pyrimethamine) available in Yemen and to determine whether the quality of these products was related to the level of the distribution chain at which the samples were collected or related to the manufacturers. METHODS: Four samples from each antimalarial product were collected from each of the various levels of the distribution chain. One sample was kept with the research team. Two were tested at Sana'a and Aden Drug Quality Control Laboratories. The fourth was sent to the Centre for Quality Assurance of Medicines in Potchefstroom, South Africa, for analysis. Quality indicators measured were the content of the active ingredient and dissolution rate (for tablets only) in comparison to standard specifications for these products in the relevant pharmacopoeia. RESULTS: The results identified several problems of sub-standard products within the drug distribution chain. They included high and low failures in ingredient content for chloroquine tablets and chloroquine syrup. There was some dissolution failure for chloroquine tablets, and high sulfadoxine/pyrimethamine tablets dissolution failures. Failures with the dissolution of the pyrimethamine were found at most of the collection points. No clear relationship neither between the quality products and the level of the distribution chain, nor between locally manufactured and imported products was observed. CONCLUSION: There are sub-standard antimalarial products circulating within the drug distribution chains in the country, which will have serious implications on the reduced therapeutic effectiveness and on the development of drug resistance. This appears to be due to non-compliance with Good Manufacturing Practice guidelines by manufacturers in the production of the antimalarials.

In vitro evaluation of marketed antimalarial chloroquine phosphate tablets.

BACKGROUND & OBJECTIVES: The aim of the present study is to investigate the physicochemical equivalence of seven brands of tablets containing chloroquine phosphate, an antimalarial purchased from different retail pharmacy outlets. METHODS: The quality and physicochemical equivalence of seven different brands of chloroquine phosphate tablets were assessed. The assessment included the evaluation of uniformity of weight, friability, crushing strength, disintegration and dissolution tests as well as chemical assay of the tablets. RESULTS: All the seven brands of the tablets passed the British Pharmacopoeia (BP) standards for uniformity of weight, disintegration and crushing strength. One of seven brands failed the friability test. One of the brands did not comply with the standard assay of content of active ingredients. Dissolution test passes the pharmacopoeial standards for chloroquine phosphate tablets. There were no significant differences in the amounts of chloroquine phosphate released from the different brands. INTERPRETATION & CONCLUSION: Out of the seven brands of anti-malarial chloroquine phosphate tablets only one brand fails to meet BP quality specifications which shows constant market monitoring of new products to ascertain their equivalency to pharmacopoeial standards.

Efficacy and tolerability of a low-dose mefloquine-sulfadoxine-pyrimethamine combination compared with chloroquine in the treatment of acute malaria infection in a population with multiple drug-resistant Plasmodium falciparum.

The efficacy and tolerability of single, low-dose mefloquine, sulfadoxine-pyrimethamine (MSP) combination was compared with chloroquine (CQ) for malaria treatment in a malaria-endemic area of Nigeria with multiple drug-resistant Plasmodium falciparum. The two drug regimens (MSP and CQ) were tested in a 12-month prospective population study. The patients were divided into two groups. Group 1 patients were treated presumptively, based on malaria symptoms. Group 2 patients were treated based on a parasitologic diagnosis using the World Health Organization seven-day in vivo test and extended to a 28-day follow-up period. Tolerability was assessed by the incidence and intensity of adverse events. One thousand nine hundred thirty-five patients visiting 10 health facilities, including the University of Calabar Teaching Hospital, were enrolled. The study showed that the low-dose MSP was efficacious, with day 7 response rates of 95% and 91% for (presumptive) Group 1 and (in vivo) Group 2, respectively, while CQ had day 7 response rates of 82% and 66% in Groups 1 and 2, respectively. The low-dose MSP was significantly (P < 0.0001) more efficacious, with faster fever and parasite clearance times than CQ in this area of CQ-resistant P. falciparum malaria. Eight patients treated with CQ, including seven severe cases (RII-RIII) were successfully re-treated with MSP. Adverse events were generally more common among those treated with MSP (29%) than those treated with CQ (17%). However, the adverse events caused by both drugs were mild to moderate and self-limited. The MSP combination appears to be a good substitute for CQ, in view of multiple drug resistance, especially in areas with severe (RII-RIII) malaria.

Quality of oral and parenteral chloroquine in Kampala.

Malaria remains an important public health problem in Uganda. The mainstay of treatment is still chloroquine. However, recently there have been several reports of poor response to chloroquine treatment. We do not know whether the reported poor response is due to true resistance or poor quality of the drug in the market. This study was done to assess the quality of chloroquine dosage forms in Kampala. The study was cross-sectional; end-point designed to assess the amount of the active ingredient in the tablet and injection dosage forms of the drug. The quality assay was based on the BP, 1988 standard, using both visual and potentiometric analysis technique. The study demonstrated that there is a problem with the quality of chloroquine in the market. Upto 30% of the tablet samples and 33% of injection samples contained less than the stated amount of the active ingredient. This may be one of the reasons for the reported poor response of malaria to chloroquine treatment in Uganda. Given that routine laboratory testing of active ingredients in pharmaceuticals is not practised in Uganda, this study has demonstrated the necessity for establishment of a drug quality control laboratory in the country.

Determination of the percentage purity, active ingredients and other parameters in paracetamol and chloroquine syrups.

In this paper the percentage purity, active ingredients, specific gravity and the pH of paracetamol and chloroquine syrups were determined. For paracetamol the percentage purity ranged from 102.6-106.67, while the active ingredients (in mg/5 ml base) ranged from 123.2-128. The specific gravity ranged from 1.13-1.24 and the pH from 4.16-5.32. For the chloroquine the percentage purity ranged from 97-106.3, and the active ingredient 48.5-53.13, the specific gravity 1.17-1.27 and the pH 2.44-4.17. The results are discussed in relation to the purity, active ingredients and sources of the drugs. The drugs were coded. The paracetamol had a code of 1p-5p while the chloroquine was coded from 1c-5c.

Comparative bio-availability characteristics of different brands of chloroquine available in Nigeria.

The disintegration, dissolution and bio-availability characteristics of six of the most popular brands of chloroquine used in Nigeria were determined in order to test the hypothesis that there are no significant differences among the different brands. The disintegration times of all the six brands ranged from 8.9 to 40.4 min while the dissolution times ranged from 17.5 to 60 min. All passed the U.S. Pharmacopoiea (USP) XX disintegration test. Bio-availability studies done on two brands, Avloclor (ICI) with the fastest dissolution rate and Pfizerquine (Pfizer) with the slowest dissolution rate, showed similar areas under the curve (AUC). Furthermore, their peak height concentration (Cmax) and time of peak height concentration (Tmax) did not show any significant differences. Consequently, statements about any of these six brands of cloroquine having a greater efficacy than the other may be pure conjecture.

Chloroquine in the Ugandan market fails quality test: a pharmacovigilance study.

BACKGROUND: Antimalaria treatment failure has been partly attributed to poor quality antimalarials in the drug market. A 1998 survey in Kampala showed that 55% of tablets and 62% of injection forms of chloroquine failed the quality test. OBJECTIVE: This study was carried out as a follow-up to establish the quality of chloroquine tablet and injection dosage forms in the Ugandan drug market from June - November 2001. METHODS: Chloroquine tablets and injection dosage forms, randomly purchased from pharmacies and drug shops in the four regions of Uganda, were assayed for content of the active ingredient according to the USP standard, using the HPLC method. RESULTS: Of the tablets samples surveyed, 39% failed the content test with 11% having sub-normal and 28% having supra-normal amounts, whilst 51% of the injection samples failed with 40% and 11% having sub-normal and supra-normal amounts respectively. CONCLUSION: There was overall improvement in the quality of chloroquine in Uganda compared with the 1998 figures, but the failure rates are still unacceptably high. The variations in the chloroquine amounts in both the tablet and injection forms may contribute to chloroquine toxicity or poor response during treatment. More vigorous pharmacovigilance on drugs entering the Ugandan drug market is needed.