out period of at least 7 days was used. Methods: An open-labeled, balanced, single-dose with food, two-treatment, two-period, two-sequence, rando- mized crossover study was conducted in 18 healthy male volunteers. Each volunteer received a 480mg Lumefantrine tablets of the reference or test drug respectively. On the day of dosing, blood samples were collected before dosing and at vari- ous time points up to 216 hours after dosing. Anal- ysis of Lumefantrine concentrations was per- formed using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) me- thod. The pharmacokinetic parameters including C max , AUC 0-t , AUC 0-inf , T max , t 1/2 and K el were ana-
Different formulae were used to prepare Artemether/Lumefantrinetablets using direct compression and wet granulation methods of preparation. Tablets of Lumefantrine and Artemether were prepared in different concentrations with: Microcrystalline cellulose (as diluent), HPMC and Polyvinylpyrrolidone (as binder), Croscarmellose sodium, Crospovidone and starch 1500 (as disintegrant), Colloidal Silicon dioxide (as glident), Polysorbate 80 (as surfactant), PEG (as dissolution enhancer), Magnesium stearate and sodium stearylfumarate (as lubricant).The different formulations of Artemether and lumefantrine tablets were evaluated for: weight variation, uniformity of tablets thickness and diameter, friability, hardness, disintegration and dissolution for Artemether and Lumefantrine.
Background: Widespread resistance has been recorded with the use of mono-therapy in the management of malaria. In 2000, Ghana initiated the process of using Artemisinin-based combination therapy (ACT) following the World Health Organization’s (WHO) recommendation. Globally and in Ghana, there stands a high risk of development of resistance to the ACTs due to the act of counterfeiting or substandard drugs. In 2009, there was a report that fake Coartem, an ACT had been found in Ghana by the Drug Quality and Information (DQI) Program; this is a serious national problem that needs redress thus the need to conduct this study to check if there are any substandard or counterfeit Artemether/ Lumefantrine tablets on the Ghanaian market. Method: Using Representative sampling method, a total of nine different brands or samples of artemether/lumefantrine tablets were sampled from nine different Pharmacies in Accra. The sam- ples were analyzed using a validated MVHimagePCv8.exe colour software technology. Results: The International Con- ference on Harmonization (ICH) and United States Pharmacopoeia (USP) recommend that for assay of tablets, the per- centage concentration should fall within 80% - 120%. After the analysis, seven out of the nine samples passed the test to varying degrees. Two samples (AL-S4 and AL-S6) however failed the test with AL-S4 recording artemether concen- tration (126.07%) above and Lumefantrine concentration (78.38%) below the recommended figure while AL-S6’s 51.53% failed to meet the minimum allowable concentration for lumefantrine in a tablet. Conclusion: The results pre- sented show that some Artemether/Lumefantrine tablets on the Ghanaian market still have issues with regards to quality or level of active ingredients. There would therefore be the need for further studies to be conducted into these products especially those that failed the test.
International Pharmacopoeial stipulation of less than 30 minutes for uncoated tablets with sample H having the highest disintegration time of 22.7 minutes. Disintegration test is a measure of the time required under a given set of conditions for a group of tablets to disintegrate to particles. The difference in crushing strength and disintegration times, among the different sample brands could be as a result of the type and quantity of binders, disintegrants, lubricants, and compressional force used by the different companies during production (20). In this study, sample brands B, C, D, E and F failed the BP 2009 hardness test specification for uncoated tablets. The percentage violation of hardness requirements for the failed brands ranged from 41% - 92% for the lower range and 20% - 46% for the upper range with sample E showing the highest percentage violation. Tablet hardness affects disintegration time and invariably the dissolution and then the bioavailability of the active ingredient and consequently affect overall therapeutic efficacy of a particular drug. If a tablet is too hard or above specified limit, it may not disintegrate at the required period of time and thus affect bioavailability of the active ingredient. Worse still the tablet may be passed out in the feaces undissolved. Hence, there is a strong correlation between disintegration time and the rate of dissolution.  If the tablet is too soft, it will not withstand the handling during subsequent packaging and shipping thereby causing breakage or chipping of tablet parts resulting in decreased amount of active ingredients in the formulated drug product. Friability is another property that is related to hardness of the tablet and it indicates the ability of the tablets to withstand agitation and chippings or breakage during transportation. In this study, all the brand samples exhibited % friability within the official specifications of British Pharmacopoeia 2009.
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8] Aika AA Omari et al, 2009 43 The Cochrane Collaboration. Published by JohnWiley & Sons, Ltd. Artemether-lumefantrine [six-dose regimen] for treating uncomplicated falciparum malaria.Malaria is a parasitic disease, spread by mosquitoes. It affects millions of people worldwide, and causes significant illness and mortality. Uncomplicated malaria presents with symptoms such as fever, headache, muscle pain, and vomiting. The parasite has become resistant to a number of previously effective drugs, and so combinations of drugs are used to try increase cure and to prevent further resistance.Artemether-lumefantrine is one such drug combination. This review of trials showed that the six-dose regimen of artemether- lumefantrine was associated with high cure rates and was more effective that most other drug combinations used for uncomplicated malaria. Further research is needed to properly assess adverse outcomes. The fixed-dose combination of artemether- lumefantrine, called co-artemether, contains 20mg of artemether and 120mg of lumefantrine [previously called benflumetol]. It was initially developed by scientists at the Academy ofMilitaryMedical Sciences in China before the pharmaceutical company Novartis [Switzerland] became a partner and was licensed to market it as Coartem® or Riamet. This oral preparation has been designed for use against chloroquine-resistant falciparum malaria.
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Present work Bi-layered tablet of Artemethar and Lumefantrine were prepared by wet granulation method, using superdisintegrants for immediate release layer and polymer like HPMC K4M and HPMC K100M for sustained release layer. Best formulations of each layer were selected for bi-layered tablet and bi-layered tablet were prepared. Bi-layered tablet of Artemethar and Lumefantrine were subjected to hardness, weight variation, friability, drug content uniformity, in vitro drug release and drug polymer interaction. FTIR and DSC studies indicated that the drug is compatible with all the excipients. Both immediate and sustained release layer were prepared by wet granulation method and punched separately. The prepared tablets of both layers were evaluated for post compression parameters. According to the in vitro dissolution profile date one formulation of each layer were selected for bi-layered tablet. IRF2 from immediate release formulations as they showed 96.62% drug release within 20 minute. SRF1 from sustained release formulation as they showed 98.18% drug release within 18 hours. The bilayer tablets were prepared using the selected immediate and sustained release layer. The prepared tablets were found to be good and free from chipping and capping. The percentage drug content was uniform in all the formulations of prepared bi-layered tablets. In vitro drug release pattern of the bi-layered tablets were same as individual layer tablets. The stability study showed that no significant changes in tablets after 3 months‟ study. Based on the observations, it can be concluded that the formulated bi-layered tablets of Artemether and Lumefantrine using superdisintegrants, release retardant polymers and different excipients was capable of exhibiting all the
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After several trials of different medium it is concluded that addition of surfactant is needed for both the drugs. As solubility of both drugs differ drastically it is very difficult to carried out dissolution in a single medium, hence it is decided to use two different dissolution medium for each of artemether and lumefantrine. Medium 0.5% SLS in sodium phosphate buffer pH adjusted 7.2 is chosen for artemether and 1% BKC in 0.1N HCl is chosen for lumefantrine. Both the drug substances require approximately 300-325ml of the medium to dissolves 20mg & 120mg in respective medium. To achieve sink condition minimum 3 times of volume required than what is required to soluble maximum dose hence volume 1000ml is decided per jar. This selection was found to be ok for lower strength of lumefantrine but at higher strength, results of lumefantrine were found to be poor (up to 40% at a decided time). In an attempt to understand the origin of the method variability at, a visual observation of the tablet behavior in the dissolution vessel was performed. The results found showed that after a certain point precipitation was found to occur and it was increasing with time. According to definition of saturation, up to a certain point the solubility increases and after that point precipitation forms and goes on increasing. To increase the solubility one available option was to increase the volume of dissolution media i.e. from 1000 ml to 2000 ml or increase the surfactant quantity or increase the time. Increasing volume to 2000ml was having practical problem of dissolution apparatus. Hence, 2% BKC was used instead of 1% BKC which showed adequate results for all strengths. Then dissolution profile was carried out having 15 minutes interval up to 2 hours. The results showed that up to a certain point, the dissolution increases, after which it showed drastic drop it is because of precipitation of lumefantrin due to super saturation. Therefore the time selected is time at which absorption was found to be maximum was selected .
Although children less than five years of age are the major target of anti-malarial drug therapy in malaria endemic regions, the available oral paediatric formulations of ACT are not optimal for this high-risk population; young chil- dren cannot swallow whole tablets and sometimes spit out the drug, because of the bitter taste of the crushed tab- lets. In addition, AL tablets are not recommended for patients weighing less than 5 kg. These drug administra- tion problems influence prescription of ACT by health workers and patient adherence, resulting in either under- dosing or over-dosing. Within the context of home-based management of malaria, 10 – 20% of participants were either non-adherent or administered incorrect doses of AL tablets [12-14]. There is an urgent need for oral prepara- tions of ACTs for young children, which are easy to administer and stable under tropical conditions. Evalua- tion of an AL paediatric dispersible tablet has been com- pleted, showing good efficacy (Salim Abdulla, personal communication). Artemether/lumefantrine powder for suspension is a fixed-dose combination of the two anti- malarials developed by Dafra Pharma NV in 2004 and manufactured by Manufacturing Packaging Farmaca (MPF) b.v. in the Netherlands under GMP. AL suspen-
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This multi-center, comparative, randomized, open-label, parallel-group clinical trial followed WHO guidelines . Study drugs were pyronaridine-artesunate granules (60/20 mg) supplied in aluminium sachets (Shin Poong Pharmaceutical Company, Ltd., Ansan, Korea), and artemether-lumefantrine tablets (20/120 mg), supplied in blister packs (Novartis SA, Basel, Switzerland). Patients were recruited from local hospitals and clinics at seven centers: Koupèla, Burkina Faso; Kinshasa, Democratic Republic of Congo; Lambaréné, Gabon; Anonkoua-koute, Côte d’Ivoire; Siaya, Kenya; Bougoula, Mali; and Puerto Princesa, the Philippines.
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The oral route of administration remains the most convenient route of administration but the major disadvantage is dysphagia (difficulty in swallowing) to overcome these problems novel drug delivery systems have developed mouth dissolving tablets with improved patient compliance. Mouth dissolving tablets are solid dosage forms which dissolve rapidly when kept in mouth. The first choice of drugs for pediatric, geriatric, mentally disable patients and also for patients who are traveling can administer the tablet any time without the need for water. Conventional technologies and patented technologies are the two different technologies used in the manufacturing of MDTs. This review describes the various aspects of MDT formulation, super disintegrants, and technologies used for developing MDT, along with evaluation
www.wjpr.net Vol 7, Issue 05, 2018. 983 The FDT formulation is defined by the Food and Drug Administration (FDA) as “a solid dosage form containing medical substances whish disintegrates rapidly, usually within a seconds, when placed upon the tongue.  According to European Pharmacopoeia, “the FDT should disperse/disintegrate in less than three minutes. Fast dissolving tablets are also called as mouth-dissolving tablets, melt-in mouth tablets, Oro-dispersible tablets, porous tablets, quick dissolving etc.  The basic approach in development of FDT is the use of superdisintegrants, which provide instantaneous disintegration of tablet after putting on tongue and release the drug in saliva. The fast dissolving tablets are rapidly dissolved or disintegrate by the use of superdisintegrants.  The faster the drug into solution, quicker the absorption and onset of clinical effect. Some drugs are absorbed from the mouth, as the saliva passes down into the stomach. In such cases, bioavailability of drug is significantly greater than those observed from conventional tablets dosage form. The advantage of mouth dissolving dosage forms are increasingly being recognized in both, industry and academics. The basic approach in development of FDT is the use of superdisintegrant like cross linked carboxy methyl cellulose (croscarmellose), sodium starch glycolate (primogel, explotab), polyvinylpyrollidone (polyplasdone) etc, which provide instantaneous disintegration of tablet after putting on tongue, thereby release the drug in saliva. 
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The formulations contained hydrolyzed and unhydrolyzed gelatin as a supporting specialists for the lattice, mannitol as a building operators and sodium starch glycolate/croscaramellose as a disintegrant. Breaking down and disintegration were further im- proved by including a corrosive (e.g.,citric corrosive) or a soluble base (e.g., sodium bicarbonate). The suspen- sion of above excipients was spray-dried to yield a per- meable powder which was packed into tablets. Tablets made by this technique deteriorated in < 20 secs in a wa- tery medium. 6
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The aim of the present work is to formulate and develop orodispersible tablets of lamotrigine using different super disintegrating agent by direct compression method. The objective of the study is to increase rapid onset of action of lamotrigine in treatment of epilepsy. The orodispersible tablets of lamotrigine were prepared by diect compression method using different concentration of sodium starch glycolate, crosscarmellose sodium, crospovidone, polyplasdone, indion. The tablet were evaluated for various parameters and results were found to be satisfactory. Total 15 formulations were prepared out of which f13, has shown good results.
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the conventional dosage forms (tablet and capsule) have wide acceptance upto 50-60 % of the total dosage forms. Tablet is still most popular dosage form existing forms existing because of ease of self administration, compact in nature, easy to manufacture and it can be delivered in accurate dose. One drawback of solid dosage form is difficulty in swallowing (dysphasia) and chewing in some patients particularly in geriatric and paediatric patients. The problem of choking is common phenomenon in geriatric patients due to fear of choking, hand tremors, dysphasia (Habib et al ,2000). Orally disintegrating tablets are also called as Orodispersible tablets, quick disintegrating tablets, mouth dissolving tablets, fast disintegrating tablets, fast dissolving tablets, rapid dissolving tablets, porous tablets, and rap melts. However, of all the above terms, United States pharmacopoeia (USP) approved these dosage forms as ODTs. Recently, European pharmacopoeia has used the term orodispersible tablet for tablets that disperses readily and within 3 min in mouth before swallowing (Sastry et al,2000).
Early diagnosis and timely treatment of malaria with an effective drug is an important strategy to control the disease . However, the emergence of antimalarial drug resistance is one of the challenges towards controlling malaria . In the early 1990s, a chloroquine-resistant P. falciparum strain was the main threat to malaria preven- tion and control in Ethiopia . A failure rate of above 85%for chloroquine was reported in the late 1990s. This event triggered the change of first-line treatment to sulphadoxine-pyrimethamine in 1998 [9, 10]. However, a study conducted on sulphadoxine-pyrimethamine through- out the country in 2003 reported a 72% treatment failure rate . After the occurrence of a large-scale malaria epidemic in 2003  and the concomitant recognition of widespread resistance to sulphadoxine-pyrimethamine [11, 13], the Federal Ministry of Health of Ethiopia adopted artemether-lumefantrine (AL) as the first-line treatment of uncomplicated P. falciparum malaria in 2004 . At that time, the baseline efficacy of AL was 99.1%, which showed a treatment failure rate of under 1% .The commonly used brand name of a drug containing AL in Ethiopia is coartem.
We have demonstrated that the mAb-based dipstick as- says for detecting artemisinin and its derivatives in ACT drugs performed well in field conditions without the requirement for technical training of the test per- formers. Compared to most of the currently available assays for quality control of artemisinin-containing drugs at field sites, this method offers several advan- tages. First, it has a very simple sample preparation step, which involves crushing drug tablets, dissolving the drug powder in ≥95 % alcohol, and further diluting the solution with water. Second, the protocol is fast
Stability studies: The selected formulation (HC2 & HC3) was tested for 3 Months at the storage conditions. At room temperature and 40°C at 75% RH, were analyzed for their drug content105. The residual drug contents of formulations were found to be within the permissible limits, as shown in the Table. The tablets showed satisfactory physical stability at room temperature and 40°C at 75% RH. No appreciable changes were found in any of the formulations. The tablets were also subjected to IR studies to determine compatible the drug with the recipients used in the tablets. The IR studies showed that there are no interactions between the drug and polymers109.
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hardness ranged from 5.97 ± 1.26 to 6.66 ± 1.28 kgf for A1 and A3 tablets, while the reference showed hardness of 7.46±1.74 kgf, significantly different from paracetamol tablets formulated with starch co-precipitate as disintegrant. The results of tablets hardness presented in Table 3 also showed that the tablets exhibited good hardness properties and passed the test for tablets hardness. However, the reference batch containing Ac-di- sol exhibited higher hardness properties more than the test tablets (p < 0.05). However, tablet hardness may be a function of the physical properties of granule such as hardness of the granules and deformation under load which may be affected by the type and quantity of binder and lubricant and compression pressure.
Department of Pharmaceutics 19 JKKMMRF’s College Pharmacy purposes. Starch is a “mild” tablet disintegrant. In the past, there was concern that tablet compression forces should not exceed certain limits or tablet crushing strengths 70 to 80 N because of the probability of prolonged disintegration times. However, with the advent of modern excipients, mechanically strong tablets with 200 to 300 N crushing strengths can be produced, and these tablets will disintegrate within five minutes or less using the super- disintegrants. Super-disintegrants are materials added to tablet formulations in a range of 1% to 5% to assure disintegration within 1 to 10 minutes. Among these are sodium carboxymethyl starch (ExplotabTM, Mendell, U.S.A.), cross-linked sodium carboxymethylcellulose (PharmacelTM XL, DMV, Netherlands), and cross-linked PVP (17) (KollidonTMXL, BASF). The rank order of the degree of swelling in water in two minutes for those disintegrants has been reported to be sodium carboxymethyl starch >sodium carboxymethyl cellulose > L-HPC 11 > cross-linked PVP > starch > MCC.
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Among the drugs that are administered orally, solid dosage form represents the predefined class of product. They are versatile, flexible in dosage strength relatively stable, present lesser problem in formulation and packaging and it is convenient to manufacture, store handle and use. Solid dosage forms provides best protection to the drug against temperature, humidity, oxygen light and stress during transportation of two solid dosage forms i.e. tablets and capsules. The tablets are in wide use. 2
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