, Emmanuel A. Ubieko2
COMPARATIVE CURE AND SUPPRESSION EFFICACY OF FORMULATED
GRANULES WITH A MARKETED SIMILAR PRODUCT
Edwin A. Ubieko1*, Emmanuel A. Ubieko2
1Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences University of Port Harcourt, Choba, Port Harcourt, Rivers State, Nigeria.
2Department of Physics, Faculty of Science, University of Port Harcourt, Choba, Port Harcourt. Rivers State, Nigeria.
Abstract
Aim and Objectives: Malaria, a major global health challenge which makes antimalarial drugs one of the commonly prescribed class of drugs World-wide. The most vulnerable are the children and the women especially the expectant mothers. There is need to develop locally and readily available excipients from natural sources to replace imported ones currently being used by our local manufacturing industries. The purpose of the investigation was to test the formulated granules for oral suspension.
Methods: Some weighed albino rats were infected with Plasmodium berghei, then the standard dose of the artemether-lumefantrine oral suspension formulated, a marketed product, and distilled water were administered ; 4/24 mg artemether-lumefantrine per kg body weight per oral to weighed albino rats. Then, other groups were administered standard dose of different formulated granules, a marketed similar product and distilled water respectively. These treated albino rats were then infected with Plasmodium berghei and blood samples were withdrawn from the tail veins, stained with Giemsa stain and the Plasmodium berghei count for the untreated and treated albino rats were determined.
Results: The percentage clearance and suppression were calculated for the different formulations; pectin and its hybrid formulations, a marketed product and distilled water as a control which were 83.73, 85.2, 74.9 and 2.62, and 83.74, 85.2, 74.22, and 0% for curative and suppressive efficacies respectively.
Conclusions: The investigations revealed that the most effective was the hybrid-formulated granules were closely followed by pectin-formulated granules and the least was the marketed product.
Keywords: Artemether, characterization, clearance, extracted pectin, hybrids lumefantrine, suppression.
INTRODUCTION
Malaria is an infectious disease caused infected female anopheles mosquitoes; though preventable and curable. There are five parasite species that transmit malaria in humans; Plasmodium falciparum, Plasmodium malariae, Plasmodium vivax, Plasmodium ovule, Plasmodium knowlesi, but, two of them pose the greater threat; P. falciparum and P. vivax. In 2019, almost half of the world's population was at risk of malaria, but most of the cases and death occur in Africa. High malaria infestation was attributed to the level of poverty in the African Continent, hence the need for the increment of dosage forms and assessment of their efficacy. Ascertaining such efficacy reduces treatment failure leading to complete eradication and reduced disease states and death resulting from malaria infestation. Children under five years of age are the most vulnerable, two-third of all malaria deaths World Wide1. Malaria spreads when a mosquito becomes infected with the disease after biting an infected person, and the infected mosquito then bites a non-infected person. The malaria parasites enter that person's bloodstream and travel to the liver. When the parasites mature, they leave the liver and infect red blood cells2.
Vector control is acts of malaria control and elimination strategies and quite effective in preventing infection and reducing disease transmission. The two popular methods being used globally include the use of the insecticide - treated nets (ITNs) and indoor residual spraying (IRS). Malaria control has however being threatened by emerging resistance strains to insecticides among anopheles mosquitoes; 78 countries reported mosquito resistance to at least one of the four commonly used insecticide classes between 2010 and 2019. While 29 countries reported mosquito resistance to all the used insecticide classes1.
Prevention chemotherapies
This is using of pharmaceuticals/drugs, either singly or in combination to prevent malaria infestation and diseases. These are practiced as; Intermittent Preventive Treatment of Infants (IPTI) and Intermittent Preventive Treatment of Pregnant Women (IPTP), Seasonal Malaria Chemoprevention (SMC) and Mass Drug Administration (MDA). These measures are to complement ongoing malaria control activities1,2.
Malaria vaccine
The first vaccine for malaria has been developed after more than 30 years of work and about $1 billion in investment by Glaxo-Smithkline Plc and its partner won a recommendation from the world Health Organization, WHO today for use in children in Saharan Africa and other regions with moderate to high transmission. This vaccine administration with anti-malarial drugs has reduced malaria cases and death by about 70% among the children population3.
Symptoms of malaria
Pains in the muscle or abdomen, whole body: fever, chills, fatigue, malaise, shivering or sweating. Gastrointestinal: nausea or vomiting. Also common: headache, fast heart rate, or pale skin3,4.
Malaria management
Diagnosis and commencement of treatment reduces the disease, prevents death and reduces transmission. All suspected cases of malaria must be confirmed using parasite-based diagnostic testing (through either microscopy or a rapid diagnostic test). This is to enable health care providers distinguish between malarial and non-malarial fevers and facilitating appropriate treatment. Treatment consists of anti-malarial agents; people travelling to areas where malaria is common typically take protective drugs before, during, and after their trip. Treatment includes anti-malarial drugs. Suffice to mention that earlier resistance had been developed to anti-malarial like quinine and chloroquine, so the best available treatment particularly to P. falciparum malaria is artemisinin-based combination therapy (ACT) for quick and complete eradication of plasmodium parasites from patients’ circulatory system5,6.
Dosage
It is a function of the severity of the case and the clinical manifestation of the patient. However, the standard dose is general 4/24 mg artemether/ lumefantrine per kg body weight respectively per day, administered 12 h (WHO 2021).
MATERIALS AND METHODOLOGY
These include, but, not restricted to albino rats, distilled water, 0.5 mL syringe/needle, heparinized tubes, Giemsa stain, P. berghei infected albino rats, P. berghei obtained from Nnamdi Azikiwe University, Awka. Antimalarial curative study of the optimized formulated and marketed granules for oral suspension was carried out according to animal model study by Peter, 1975 with some modifications. In this model of study, a total of twenty male albino mice of weight 20± 2 g in groups of five mice. Blood was collected from the mouse infected with the parasite, P. berghei by oculus puncture and was diluted with 0.9 %w/v sodium chloride that 0.2 mL contains approximately 107 infected erythrocytes. All the animals in each group were infected with the parasite by single intra-peritoneal administration of 0.2 mL of the diluted blood and left for 72 h7. Then each of the four groups was administered with 0.2 mL of distilled water, D/W, the normal dose 4/24 mg artemether-lumefantrine per kg body weight of the marketed product, N, optimized formulations with the extracted pectin, M and the hybrid, G, respectively for three days. A thin film of blood made from the tail blood stained with a Giemsa stain and was examined for parasitemia on day 4 and 7 respectively.
The survived mice had their parastemia levels examined on day 8, 12, 15, and 30 post treatments with much care and observations of signs and behavior.
Ethical approval
Issued on the 8 December, 2023 by the Ethical committee of University of Port harcourt. Rivers State.
Statistical analysis
Results were expressed as mean ± standard deviation and the differences compared using one-way ANOVA.
RESULTS AND DISCUSSION
The essence of designing a formulation is to enhance its efficacy and/or therapeutic effects. Results from the animal study indicated that the three formulations, optimized formulations M and G, and the marketed product, N administered were efficacious. However, the order of efficacy was N<M<G as shown in Figure 2. The formulation of the marketed product has the least percentage clearance, but the formulation with the hybrid, G had the highest percent clearance. Though, the clearing ability of the hybrid formulation in the plasma similar to that formulated with pectin, but, pectin is more readily available in the country and will definitely be less costly than the hybrid formulation which contains xanthan gum which is not readily/ locally available8,9. Evaluation of the chemoprophylactic potential of the formulated artemether-lumefantrine fixed- dose therapy was performed according to Peter, W, 1975 with some modifications. Four groups of five mice each group was administered with standard dose of formulated products, (pectin and its hybrid) and a marketed product (N) of 4/24 mg artemether/ lumefantrine respectively. The control group was administered with 1 mL of distilled water. The mice were inoculated with 0.2 mL of Plasmodium berghei parasitized erythrocytes such that the 0.2 mL contained 1x107 parasitized cells. After 72 h of inoculation blood samples were collected from the tail vein and thin films of the blood sample were made, fixed and viewed under the microscope using x 10 magnification.
The prophylactic effects of the distilled water, D/W was less than that of the marketed product, N which in turn was less than that of the pectin formulated artemether-lumefantrine granules, M, which is also less than the hybrid formulated artemether-lumefantrine granules for oral suspension. This is in agreement with earlier report10,11.
Limitations of the study
Formulation and analysis of the artemether-lumefantrine fixed-dose granules for oral suspension, and evaluation of the in-vivo activity of the formulated artemether-lumefantrine granules; some pharmaco-kinetic properties.
CONCLUSIONS AND RECOMMENDATION
The in-vivo studies carried out indicated that the percentage clearance and/or suppression of the optimized granules were higher than those of the marketed product, and more effective than earlier antimalarial agents such as quinine and chloroquine. Further animal studies are required to determine the suitability of the extracted pectin and/or its hybrids as suspending agents to be used to production of granules for oral suspension.
ACKNOWLEDGEMENTS
Our profound gratitude goes Mr. Amadi, Industrial Pharmacy Laboratory, Madonna University, Elele, and all the staff of Pharmaceutical Technology Laboratory, University of Port Harcourt, especially, Mr. Samson Bekweri, Mr. Madighiode Oghaaphemugh Pharmacology Department and Mr. Vite Toobari Monday of Basic Medicals, University of Port Harcourt. We acknowledge the Managing Directors/Chief Executive Officers of SABHEIK and EMZOR Pharmaceutical Companies in Port Harcourt and Lagos respectively for their assistance in various ways.
AUTHOR’S CONTRIBUTION
Edwin AU: formulation development, determinations of the pharmacokinetic properties. Emmanuel AU: determination of the polymer properties of the extracted pectin, statistical analysis. Both authors reviewed the article and approved the final version.
CONFLICT OF INTEREST
None to declare.
REFERENCES