Tablet Splitting Research Articles

Evaluation of the nimesulide content in splitting tablets

Nimesulide is a non-steroidal anti-inflammatory drug (NSAID) that inhibits the action of the enzyme cyclooxygenase-2 and is widely used in many countries for the treatment of pain and inflammation. It is often given on a dosage adjustment basis mainly in the elderly and children. In the present work the nimesulide tablet splitting process from three different suppliers was studied using a tablet cutter in order to verify the influence of the breakdown of the same on the content of each obtained fragment. The tests of average weight, hardness, friability, disintegration, dosage and uniformity of unit doses were performed following the official methodology established by the Brazilian Pharmacopoeia. The samples studied met the official specifications before being submitted to the partition procedure; however, after dividing the tablets, the drug content in the halves presented excessive variation, showing that this procedure should not be performed for the drug Nimesulide. In cases of need for varying administration doses of Nimesulide, it is recommended that the drug be manipulated or that another pharmaceutical form is used in order to ensure dosage in each unit of the dosage form.

Unavailability of appropriate doses and need for tablet splitting of psychotropic drugs by geriatric patients

Unavailability of appropriate doses and need for tablet splitting of psychotropic drugs by geriatric patients

Tablet splitting practice in Jordan

Tablet splitting practice in Jordan

How close is the dose? Manipulation of 10 mg hydrocortisone tablets to provide appropriate doses to children

This study explores the methodology advised by healthcare professionals and the methods used by parents/carers to identify whether there is a best practice method for manipulation of 10 mg hydrocortisone tablets to provide an accurate dose to children. Bespoke surveys were used to identify methods recommended and used in manipulation of tablets. Hydrocortisone tablets were manipulated to provide a specified dose by both naïve participants and parents/carers. The accuracy of manipulation was assessed using HPLC analysis. Competed surveys were received from 159 parent/carers reporting doses that ranged from 0.25 to 15 mg. Parents/carers most commonly reported splitting the tablet and administering the solid fraction; however more than 30% of those reporting physically splitting tablets were preparing doses that were not simply halving or quartering tablets. In a naïve population the dose accuracy, defined as percent of doses within 20% of the theoretical dose ranged from 57 to 58% depending on the tablet brand and the method of manipulation used. Almost three-quarters (74.1%) of parent/carers (n = 27) were able to produce a dose within 20% of the theoretical value and the most accurate method was to split tablets and administer the solid fraction. This study shows that a lack of age-appropriate medicines results in children being at risk of sub-optimal dosing.

Actual Versus Expected Doses of Half Tablets Containing Prescribed Psychoactive Substances: A Systematic Review.

To assess through a systematic review of the literature if the practice of splitting tablets containing psychoactive/psychotropic medications for medical or economic reasons would result in the expected doses. A MEDLINE and PsycInfo comprehensive search of English-language publications from January 1999 to December 2015 was conducted using the terms describing tablet splitting (tablet splitting, split tablets, tablet subdivision, divided tablets, and half tablets) and psychoactive substances (psychoactive medicines, psychotropic medicines, antidepressants, anxiolytics, anticonvulsants, antipsychotics, and antiparkinsonian agents). An additional supplementary search included the references from the articles found. Studies were included if splitting content was directly related to psychoactive medications and examined the effect of tablet splitting on drug uniformity, weight uniformity, and adherence of psychoactive drugs. Articles were systematically reviewed and examined regarding the study design, methodology, and results of the study. A total of 125 articles were screened, and 13 were selected. Tablet splitting implications are extensive, yet substantial deviations from the ideal weight, potency, and dose uniformity are more prone to be important to patient safety. The uneven division of tablets might result in the administration of different doses than what was prescribed, causing under- or overdosing, which might be relevant depending on the drug. In 55% of the cases, splitting psychoactive drugs was satisfactory. It cannot be generalized that splitting psychoactive drugs compromises dose accuracy, thus tablet splitting might still be employed in cases in which the advantages outweigh the disadvantages. It is recommended that alternatives be adopted to prevent the disadvantages related to tablet splitting.

Tablet splitting: implications in clonazepam dose adjustment?

A divisão de comprimidos permite o ajuste de dose e retirada gradual de medicamentos, principalmente para pacientes psiquiátricos e geriátricos. O objetivo deste estudo foi investigar a exatidão e precisão de doses das porções provenientes da divisão de comprimidos de clonazepam utilizando-se faca e cortador de comprimidos. Comprimidos inteiros e porções foram pesados individualmente para determinação da variação de peso e perda de peso. Apesar de uma divisão exata (próxima a 100%), a análise da precisão indicou alta variabilidade entre o peso das porções (DPR>6%), variando em torno de ± 25% para o cortador de comprimidos e ± 18% para a faca. Não houve diferença significativa entre as técnicas utilizadas quanto à exatidão e perda de peso. Esses dados preliminares indicam que dividir comprimidos de clonazepam tanto com o cortador de comprimidos quanto com a faca pode resultar em uma divisão aparentemente exata, apesar da falta de precisão entre as porções obtidas. Estudos são necessários para investigar se tais variações nas doses diárias de clonazepam resultariam em um desfecho clínico comprometendo esquemas de ajuste de doses.

Subdivision of aspirin tablets? Use your hands: a study on aspirin tablet subdivision using four different methods

AbstractBackground/AimLow‐dose aspirin therapy (1 × 75–150 mg) is used in the secondary prevention of cardiovascular diseases. Recently it has been suggested that a twice daily regimen is more effective (2 × 40–75 mg). We therefore compared the precision of four subdivision methods.MethodA total of 280 aspirin tablets (acetylsalicylic acid 80 mg) were subdivided using four different methods (PillTool, hand, knife and Pilomat). Precision was compared using a difference score and loss of mass. The accuracy (uniformity of weight) was evaluated according to an adapted version of the European Pharmacopoeia test. Loss of mass was analysed using the criteria of the US Food and Drug Administration.ResultsEvaluating the difference score (mean ± SD: PillTool 22 ± 14; hand 14 ± 8; knife 36 ± 23; and Pilomat 20 ± 13), the knife method was less precise than the PillTool, the hand method and the Pilomat (for all p < 0.001). Furthermore, the hand (p < 0.001) and the PillTool (p < 0.001) had statistically significantly a smaller loss of mass (mg) than the knife and the Pilomat (median (interquartile range): PillTool 1 (2), hand 0 (2), knife 4 (6) and Pilomat 3 (5)). Only breaking by hand complied with the adapted European Pharmacopoeia test. Tablets broken by PillTool and hand fulfilled the criteria of the US Food and Drug Administration test for loss of mass.ConclusionBased on the results of our study, we recommend hand breaking and to avoid a knife for the best weight uniform tablets. If a tablet splitting device is necessary we advise use of the PillTool.

A Review on Tablet Scoring: Background, History and Current Regulatory Considerations

Tablet splitting or breaking of tablets into multiple strengths has been a common practice across the world. Splitting of tablet offers various advantages such as dose flexibility and ease of swallowing in different population including geriatric and pediatric patients (wide patient acceptance) and cost saving on medications (economic advantage) The tablet products that are meant to be split and approved by the Food and Drug Administration (FDA) will have a scored line indicating the split location to ensure patient can adjust the dose by splitting and such splitting information will be included in the patient package insert. Having a consistent scored reduces difficulty in dose related problems especially when using products made by different manufacturers such as Generic compared to Reference Listed Drugs (RLD). Physical characteristics such as shape, size and tablet score may affect tablet splitability. Currently, various regulatory bodies (FDA, USP, and EP) provide consistent and useful information to the pharmaceutical industry. In this review, authors have compiled information from currently available resources on tablet scoring.

Tablet Splitting: Public Perception and Quality Attributes of Two Common Cardiovascular Drugs

Our study aims to assess the perception and public practice of tablets splitting, and to evaluate the weight variation, weight loss and drug content of manual and splitter-produced tablet halves from selected commercially available cardiovascular products, which are furosemide (F) and atenolol (A) tablets. A cross-sectional online survey was conducted on a sample of 309 participants from both genders aged over 18 years old. The survey included 10 questions to assess the public perception of splitting of tablets, manually or by a splitter. The second part of the study was an experimental analysis of furosemide scored uncoated tablets and atenolol scored coated tablets (brands F and A respectively). Both medications were split manually and by a splitter. The resulting split halves were subjected to weight variation test according to USP 2018 and drug content assays according to BP 2018. The percentage of weight loss and weight variation assessment were calculated, while chemical analysis involved the determination of drug content in the split halves of each tablets. The survey results revealed that 95.0% of participants were familiar with tablet splitting and most of them reported that the need for tablets splitting is related mainly to either dose adjustment (51.1%) or difficulty in swallowing (36.6%). The majority of participants split their tablets manually (68.1%) and many were unsure about getting exactly the half amount of drug after splitting (44.3%). The statistical analysis of the experimental part showed significant difference in drug content between both halves as following: F Manually, A Manually, A Splitter (p < 0.001) and F Splitter (p= 0.0078). However, there was no significant difference between the weights of right halves and left halves, but some tablets were observed to lose fragments upon splitting and deviate from the allowed range of each half. Customers are aware about tablets splitting and the majority perform this manually despite their doubts about the accuracy of the dose. If required, tablet splitter should be recommended for splitting scored tablets.

Comparison of Treatment Response Achieved by Tablet Splitting Versus Whole Tablet Administration of Levothyroxine in Patients with Thyroid Cancer.

Objective(s):TSH suppression by Levothyroxine consumption is a mainstay of thyroid cancer treatment. Tablet-splitting is a worldwide approach in dose adjustment in patients. However, it is highly recommended to evaluate the validity of tablet splitting for each distinctive drug by clinical trials before routinely using tablet halves in clinical practice. In this study we compared the effect of 150 µg dose of Levothyroxine by use of a100 and a 50 µg tablets or one and half 100 µg tablets in Differentiated thyroid cancer (DTC) patients.Methods:One hundred DTC patients treated with one and half 100 µg Levothyroxine tablets were randomly divided into two groups. The first group continued taking medication as before and the second group received the same daily dose by taking one 100 and one 50 microgram Levothyroxine tablets. The mean changes in TSH and T3 levels and patients weight were compared between the groups.Results:91 patients completed the study. Levothyroxine consumption pattern, age, gender distribution, weight and TSH levels were comparable between groups at the beginning of the study. The mean change of body weights, serum levels of T3 and TSH showed no significant difference between groups in different time points during the study (P>0.05). Conclusion:This study showed similar efficacy of tablet splitting and two tablets administration for Levothyroxine; however, patients preferred two tablets at the end of the study. It can be concluded that tablet splitting can be used as an alternative way when the 50 µg tablet is not available.

EVALUATION OF QUALITY ATTRIBUTES OF PROPRANOLOL SPLIT TABLETS: FOCUS ON DOSE VARIABILITY

Tablet splitting is a widespread practice among patients and health professionals aiming the administration of lower doses and the reduction of the cost of prescriptions. Nevertheless, potential concerns such as weight variation, stability and uneven drug content of the halves are related to this practice. The objective of this study was to evaluatethe uniformity of half-tablets regarding weight and drug content in three different commercial products containing propranolol. Also, it was assessed drug content for whole tablets. Weight variation and drug content uniformity tests were evaluated for whole and split tablets, as well as the weight loss due to the splitting process. Drug contentevaluation for whole tablets showed that all products were satisfactory. All the products were approved in the weight variation and drug content uniformity tests before splitting, with results close to 100%, but the halves of all products failed the tests, presenting a high variability between the portions. In one of the products, halves ranged from 75.5to 120.4% of the target drug content, indicating that when administered to patients, daily doses may vary around 45%. Splitting propranolol tablets might compromise clinical treatment, affecting blood pressure and consequently producing side effects. Clinical implications due to tablet splitting might not be critical in some cases. Nevertheless,the high variability between doses should be considered by healthcare professionals when prescribing a therapy involving this practice.

Comparative analysis of package inserts of local and imported antihypertensive medications in Palestine

BackgroundPackage inserts (PIs) as a reliable reference for patients and health care providers should provide accurate, complete and up-to-date information. The purpose of the current study is to assess and compare the PIs of antihypertensive agents locally produced in Palestine and their imported counterparts.MethodsThirty-five PIs were assessed for the presence of 31 information statements using a scoring method. Word counting of 20 headings and subheadings was used to evaluate and compare local and imported PIs for information quantity.ResultsNone of the analysed PIs fulfilled the criteria. All of them included the brand name, active ingredients, indications, directions for use, adverse drug reactions, drug–drug interactions, pregnancy and lactation considerations, and storage. Whereas none of them, either local or imported PIs, included the shelf life and instructions to convert tablets or capsules into liquid forms. Additionally, only one (5%) imported and no (0%) local PIs mentioned the duration of therapy. Moreover, 93.4% of local PIs were deficient in areas regarding the inactive ingredients and date of last revision, and 86.7% did not mention the drug dose and possibility of tablet splitting. Furthermore, the maximum dose was not indicated in 90% of imported and 86.7% of local PIs. In general, imported PIs contained more detailed information than their local counterparts, where the range of differences in medians between the local and imported PIs was from 1.5-fold for pregnancy considerations to >42.00-fold for the effect on the ability to drive and use machines.ConclusionsThe findings of this study revealed the superiority of imported over local PIs in both quality and quantity of information provided. This emphasises the need for appropriate measures to be taken by the Ministry of Health and local manufacturers to ensure efficiency of local PIs in providing accurate, complete and up-to-date information.

Tablet splitting for antipsychotics: a cost-saving initiative

Tablet splitting for antipsychotics: a cost-saving initiative

Weight and content uniformity study of captopril half-tablets

Dose-related adverse effects of medications are a major problem in modern medical practice. The dose, based on drug company guidelines in package inserts, may not be correct for many patients. Tablet splitting or dividing has been an accepted practice for many years as a means of obtaining the prescribed dose of medication. As model tablets for this investigation, three brands of captopril scored tablets labeled to contain 50 mg were used. Tablets were split by hand, tablet splitter, or knife. The percentages by which each whole tablet’s or half-tablet’s drug content and weight difference from sample mean values were compared with Ph. Eur. specification ranges for drug weight and content. Using tablet splitter, the results showed that 13.3% and 5.83 % of half-tablets fell outside of the proxy Ph. Eur specification for weight and content respectively. In case of hand and knife splitting, the percentage of half-tablets that fell outside of the proxy Ph. Eur specification increased to 62.5% (weight) and 20% (content).

Accuracy of tablet splitting and liquid measurements: an examination of who, what and how.

To examine factors that might affect the ability of patients to accurately halve tablets or measure a 5-ml liquid dose. Eighty-eight participants split four different placebo tablets by hand and using a tablet splitter, while 85 participants measured 5 ml of water, 0.5% methylcellulose (MC) and 1% MC using a syringe and dosing cup. Accuracy of manipulation was determined by mass measurements. The general population was less able than pharmacy students to break tablets into equal parts, although age, gender and prior experience were insignificant factors. Greater accuracy of tablet halving was observed with tablet splitter, with scored tablets split more equally than unscored tablets. Tablet size did not affect the accuracy of splitting. However, >25% of small scored tablets failed to be split by hand, and 41% of large unscored tablets were split into >2 portions in the tablet splitter. In liquid measurement, the syringe provided more accurate volume measurements than the dosing cup, with higher accuracy observed for the more viscous MC solutions than water. Formulation characteristics and manipulation technique have greater influences on the accuracy of medication modification and should be considered in off-label drug use in vulnerable populations.

Dose Uniformity of Scored and Unscored Tablets: Application of the FDA Tablet Scoring Guidance for Industry.

This U.S. Food and Drug Administration (FDA) laboratory study examines the impact of tablet splitting, the effect of tablet splitters, and the presence of a tablet score on the dose uniformity of two model drugs. Whole tablets were purchased from five manufacturers for amlodipine and six for gabapentin. Two splitters were used for each drug product, and the gabapentin tablets were also split by hand. Whole and split amlodipine tablets were tested for content uniformity following the general chapter of the United States Pharmacopeia (USP) Uniformity of Dosage Units <905>, which is a requirement of the new FDA Guidance for Industry on tablet scoring. The USP weight variation method was used for gabapentin split tablets based on the recommendation of the guidance. All whole tablets met the USP acceptance criteria for the Uniformity of Dosage Units. Variation in whole tablet content ranged from 0.5 to 2.1 standard deviation (SD) of the percent label claim. Splitting the unscored amlodipine tablets resulted in a significant increase in dose variability of 6.5-25.4 SD when compared to whole tablets. Split tablets from all amlodipine drug products did not meet the USP acceptance criteria for content uniformity. Variation in the weight for gabapentin split tablets was greater than the whole tablets, ranging from 1.3 to 9.3 SD. All fully scored gabapentin products met the USP acceptance criteria for weight variation. Size, shape, and the presence or absence of a tablet score can affect the content uniformity and weight variation of amlodipine and gabapentin tablets. Tablet splitting produced higher variability. Differences in dose variability and fragmentation were observed between tablet splitters and hand splitting. These results are consistent with the FDA's concerns that tablet splitting can have an effect on the amount of drug present in a split tablet and available for absorption. Tablet splitting has become a very common practice in the United States and throughout the world. Tablets are often split to modify dose strength, make swallowing easier, and reduce cost to the consumer. To better address product quality for this widely used practice, the U.S. Food and Drug Administration (FDA) published a Guidance for Industry that addresses tablet splitting. The guidance provides testing criteria for scored tablets, which is a part of the FDA review process for drugs. The model drugs selected for this study were amlodipine and gabapentin, which have different sizes, shapes, and tablet scores. Whole and split amlodipine tablets were tested for drug content because of a concern that the low-dose strength may cause greater variability. Whole and split gabapentin tablets were tested for weight variation because of their higher dosage strength of 600 mg. All whole tablets met the acceptance criteria for the Uniformity of Dosage Units based on the guidance recommendations. When unscored amlodipine tablets were split by a splitter, all formulations did not meet the acceptance criteria. When fully scored gabapentin tablets were split by hand and by splitter, they met the acceptance criteria. The findings of this FDA study indicated physical characteristics such as size, shape, and tablet score can affect the uniformity of split tablets.

Tablet Splitting of Antiepileptic Drugs in Pediatric Epilepsy: Potential Effect on Plasma Drug Concentrations.

Tablet splitting is the process of dividing a tablet into portions to obtain a prescribed dose of medication. Very few studies have investigated whether split parts of a tablet deliver the expected amount of drug to patients. Our objectives were to evaluate the split parts of adult-dose tablet formulations for percentage of weight deviation, weight uniformity, weight loss, drug content, and the content uniformity of four antiepileptic drugs (AEDs) prescribed to pediatric patients. We also measured AED plasma concentrations in the children. We chose to study first-line AEDs (phenytoin sodium [PHE], sodium valproate [SVA], carbamazepine, and phenobarbitone) as they are routinely prescribed in India. We asked caregivers to perform the same splitting process they follow in their homes on three whole tablets during their routine visit to the outpatient department. After caregivers split the tablets, we studied the weight and content of the split parts. We also used high-performance liquid chromatography to study plasma drug concentrations in children who had received split AEDs for at least 4months. A total of 168 caregivers participated in the study, and we analyzed 1098 split tablet parts. In total, 539 (49.0%) split parts were above the specified limit of the 2010 Indian Pharmacopeia (IP) acceptable percentage weight deviation (PHE 169 [48.8%], SVA 187 [51.9%], carbamazepine 56 [41.1%], phenobarbitone 127 [49.6%]); 456 (41.5%) split parts were outside the proxy IP specification for drug content (PHE 135 [39.0%], SVA 140 [38.8%], carbamazepine 51 [37.5%], phenobarbitone 130 [50.7%]), and 253 split parts were outside the acceptable content uniformity range of <85% and >115% (PHE 85 [24.5%], SVA 98 [27.2%], carbamazepine 14 [10.2%], phenobarbitone 56 [21.8%]). In total, 130 (72.2%) patients had plasma drug concentrations outside the therapeutic range (PHE 36 [72.0%], SVA 39 [78.0%], carbamazepine 34 [68.0%], phenobarbitone 21 [70.0%]). Splitting adult-dosage formulations of AEDs results in patients not receiving the optimal dose. Plasma drug concentrations are also not optimal. Pediatric dosage formulations should be preferred to splitting adult-dosage formulations in pediatric epilepsy.

Liquid chromatographic-mass spectrometric method for determination of drug content uniformity of two commonly used dermatology medications in a split-tablet dosage form

Purpose : To develop and validate a simple, efficient and reliable Liquid chromatographic-mass spectrometric (LC-MS/MS) method for the quantitative determination of two dermatological drugs, Lamisil® (terbinafine) and Proscar® (finasteride), in split tablet dosage form. Methods : Thirty tablets each of the 2 studied medications were randomly selected. Tablets were weighed and divided into 3 groups. Ten tablets of each drug were kept intact, another group of 10 tablets were manually split into halves using a tablet cutter and weighed with an analytical balance; a third group were split into quarters and weighed. All intact and split tablets were individually dissolved in a water: methanol mixture (4:1), sonicated, filtered and further diluted with mobile phase. Optimal chromatographic separation and mass spectrometric detection were achieved using an Agilent 1200 HPLC system coupled with an Agilent 6410 triple quadrupole mass spectrometer. Analytes were eluted through an Agilent eclipse plus C8 analytical column (150 mm × 4.6 mm, 5 μm) with a mobile phase composed of solvent A (water) containing 0.1% formic acid and 5mM ammonium formate pH 7.5, and solvent B (acetonitrile mixed with water in a ratio A:B 55:45) at a flow rate of 0.8 mL min-1 with a total run time of 12 min. Mass spectrometric detection was carried out using positive ionization mode with analyte quantitation monitored by multiple reaction monitoring (MRM) mode. Results : The proposed analytical method proved to be specific, robust and adequately sensitive. The results showed a good linear fit over the concentration range of 20 - 100 ng mL-1 for both analytes, with a correlation coefficient (r2) ≥ 0.999 and 0.998 for finasteride and terbinafine, respectively. Following tablet splitting, the drug content of the split tablets fell outside of the proxy USP specification for at least 14 halves (70 %) and 34 quarters (85 %) of FIN, as well as 16 halves (80 %) and 37 quarters (92.5 %) of TBN. Mean weight loss, after splitting, was 0.58 and 2.22 % for FIN half- and quarter tablets, respectively, and 3.96 and 4.09 % for TBN half- and quarter tablets,respectively. Conclusion : The proposed LC-MS/MS method has successfully been used to provide precise drug content uniformity of split tablets of FIN and TBN. Unequal distribution of the drug on the split tablets is indicated by the high standard deviation beyond the accepted value. Hence, it is recommended not to split non-scored tablets especially, for those medications with significant toxicity Keywords : Tablet splitting, Finasteride, Terbinafine, Drug content uniformity, LC-MS/MS

Raman spectroscopy for the analytical quality control of low-dose break-scored tablets

Quality control of solid dosage forms involves the analysis of end products according to well-defined criteria, including the assessment of the uniformity of dosage units (UDU). However, in the case of break-scored tablets, given that tablet splitting is widespread as a means to adjust doses, the uniform distribution of the active pharmaceutical ingredient (API) in all the possible fractions of the tablet must be assessed. A general procedure to accomplish with both issues, using Raman spectroscopy, is presented. It is based on the acquisition of a collection of spectra in different regions of the tablet, that later can be selected to determine the amount of API in the potential fractions that can result after splitting. The procedure has been applied to two commercial products, Sintrom 1 and Sintrom 4, with API (acenocoumarol) mass proportion of 2% and 0.7% respectively. Partial Least Squares (PLS) calibration models were constructed for the quantification of acenocoumarol in whole tablets using HPLC as a reference analytical method. Once validated, the calibration models were used to determine the API content in the different potential fragments of the scored Sintrom 4 tablets. Fragment mass measurements were also performed to estimate the range of masses of the halves and quarters that could result after tablet splitting. The results show that Raman spectroscopy can be an alternative analytical procedure to assess the uniformity of content, both in whole tablets as in its potential fragments, and that Sintrom 4 tablets can be perfectly split in halves, but some cautions have to be taken when considering the fragmentation in quarters. A practical alternative to the use of UDU test for the assessment of tablet fragments is proposed.

Dividing the Tablets for Children – Good or Bad?

Introduction: To investigate the dosing accuracy using split tablets in paediatric patients. Methods: Five brands of tablets (Alvedon ® (paracetamol), Catapresan ® (clonidine), Hydrocortone ® (hydrocortisone), Prednisolon ® (prednisolon) and Tavegyl ® (clemastine) were split into halves and quarters by hand or by using a tablet splitter. The resulting halves and quarters were weighed. Results: Three out of the five tablet brands passed the test in the Ph. Eur. (European Pharmacopoeia) for subdivision of tablets when split once and when split twice to yield quarters only one of the tablets passed the test. When also applying the limit for relative standard deviation (RSD) from the US Pharmacopoeia only one of the tablet halves passed and the other two was just outside the limit. None of the tablet quarters passed the RSD limit. Conclusion : Our results indicate that tablets larger than 8 mm might be split once. Tablets should not be split more than once, due to uncertainty in dose accuracy. There is a need for more commercially available age-appropriate formulations. Extemporaneously prepared formulations should be considered as an alternative to the use of split tablets. Key words: Dosing accuracy, Manipulation of drugs, Paediatric patients, Subdivision of tablets, Tablet splitting