tablet splitting and dosage uniformity issues: a review · consumer reports best buy drugs, 8...

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Mashru et al. World Journal of Pharmacy and Pharmaceutical Sciences

TABLET SPLITTING AND DOSAGE UNIFORMITY ISSUES: A

REVIEW

Hemangi Parekh, Jitesha Patel, Parth Patel and Rajashree Mashru*

Faculty of Pharmacy, G. H. Patel Building, Donor`s Plaza, The M.S. University of Baroda,

Vadodara, 390002, India.

ABSTRACT

Tablet splitting provides variety of reason such as dose flexibility, ease

of swallowing and may minimize the costs of medication. There are

risks associated with this process like breaking difficulty, loss of mass,

unequal part of tablet. Patient characteristics and medication

characteristics are main two type of factor which influence dosage

uniformity of split tablet. Patient may experience difficulty in splitting

tablet especially if their dexterity, cognitive or eyesight is impaired.

And tablet related factor include inaccuracy in splitting, degradation of

drug as result of exposure to air, alteration in dissolution rate, size,

shape, thickness and depth of groove of tablet. FDA introduced draft

guidance on tablet scoring to advise manufacturers in order to provide

criteria needed to support applications for scored tablet. The splitting can be typically

achieved by manually using hand or mechanically using tablet splitter. Accuracy of scored

tablet can be assured by weight variation method, dose uniformity and assay. In this review,

author have compiled information from currently available literature on tablet splitting.

KEYWORDS: Tablet splitting, Weight variation, Dosage uniformity, Score tablet, Assay.

INTRODUCTION

What is Scored Tablet?

Score tablet define as tablet that have an intended line or groove. Presence of score lines on

tablet implies that the tablet can be split (as shown in fig.1(a)(b)). If divide equally, it will

contain equal percent of active ingredient in each portion. It is not recommended to break non

scored tablet (as shown in fig.1(c)). Scoring ensure that the patient able to adjust the dose by

splitting. The tablet products that are meant to be split and approved by the food and drug

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 7.421

Volume 8, Issue 8, 625-643 Review Article ISSN 2278 – 4357

*Corresponding Author

Rajashree Mashru

Faculty of Pharmacy, G. H.

Patel Building, Donor`s

Plaza, The M.S. University

of Baroda, Vadodara,

390002, India.

Article Received on

06 June 2019,

Revised on 27 June 2019,

Accepted on 17 July 2019

DOI: 10.20959/wjpps20198-14469


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administration (FDA) will have a scored line indicating the split location to ensure patient can

adjust the dose by splitting. Such score lines can be included on one or both surfaces of tablet

depending upon different tablet designs. One of the main advantages scored tablets offer is

the flexibility in dose including pediatric and geriatric patients. The other advantages include

minimize the size of the tablet for ease of swallowing and reduced medication costs by

splitting tablets to achieve multiple strengths. A score is a useful feature for the patient who,

for instance, wants to switch from a brand product to generic product and may need to half

tablet to maintain a consistent dosage regimen. Scoring has also been an issue in determining

whether a generic drug is equivalent to its Reference List Drug (RLD). Tablet splitting also

address in pharmacopeia standards. In general, there are seven types of bisect lines, from a G-

type, which is very sensitive to pressure placed on it by humans, to the purely cosmetic H-

Type. Tablet splitter is device use to split tablet. Splitters that are safer and more effective in

cutting tablets into desired portions without excessive tablet crumbling and exposure to

cutting edges.

(a) (b) (c)

Fig.1(a) Scored Tablet - One Side, (b) Scored Tablet - Both Side, (c) Unscored Tablet.[1]

WHY TABLET SPLITTING IS REQUIRED?[2]

1. Cost Savings[2-4]

The theoretical benefit of tablet-splitting is reduced prescription cost. Splitting scored tablets

is already FDA-approved as safe and efficacious. It is cost saving if a higher dose of a

medication can be split in half, providing two doses instead of one. In some instances, the

savings may reduce the price of the medications by 50%, instructing a patient to take a half

tablet to make a 30-day paid prescription cover 60 days. Since most preparations are priced

per pill or unit, rather than the number of milligrams or dose of the pill. Scored tablets is cost

savings. Score lines on tablets reduce the number of tablets strengths needed, reducing costs

both for the producing industry as well as the pharmacy and the patient. No data are available

on the economic benefits of score lines. Savings were reported when patients broke tablets


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with a double dose to take half a tablet, instead of taking a whole tablet of the right dose. The

rationale for the savings reported was that the tablets in different strengths cost about the

same [5-6]

. However, the cost-saving effect of splitting tablets could be undone by increased

non-compliance caused by bad functioning score lines by no over- or under dosing caused by

unequal broken tablets.

2. Dose Flexibility - To adjust the dosing of your medication

Dose flexibility for dosing on need: There is need of particular lower strength of medication,

and required dose of tablet is not available or which is not Manufactured by pharmaceutical

company (see fig.2), these included olanzapine, risperidone and metoprolol. Some other low-

dose formulations were available. For example, prednisone is available in a 1-mg tablet but

not in the desired 2.5mg formulation (see table 1).

Dose flexibility on increasing and decreasing dosage schedules: Dose flexibility is the most

important advantage of scored tablets. This was reported to be particularly important for

tablets with a dose schedule that has to be dosed up or down. Example: Instance ACE-

inhibitors. need to increase or decrease the strength to obtain the best effect with least side

effect.

Dose flexibility in geriatrics and pediatrics: Some elder or children may not find the liquid

formulation suitable or the liquid formulation of medication are not covered by the

pharmaceutical benefit scheme(PBS).

In pediatrics and geriatrics, doses are used which may not be available in marketed

strengths. consider for small dosage requirements a well breakable tablet preferable to a

reformulation into a liquid dosage form.

A powder involved the risk of contaminating others than the patient.

Liquid preparation may involve formulation and stability problem.

An often-used diluent in liquid preparations is syrup, resulting in an increased sucrose

intake.

3. Ease of Swallowing: Swallowing a large pill may be difficult for older adults, and score

tablet may make it easier to swallow.

Table.1: Manufacturing limitations accounted for 80.5% of pill-splitting.


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Reasons of pill spitting Percentage of

medication split Examples

Low dose not manufacture 68.3 olanzapine, risperidone and metoprolol

Specific low dose not

manufacture 12.2 Prednisolone

ODB restriction 9.8 paroxetine, sotalol, benztropine

mesylate and captopril

Hospital formulary

restrictions 4.8 Clonazepam, simethicone.

Other(cost saving,

convenience) 4.8 Donepezil, warfarin respectively

Fig. 2: Distribution of reported reasons for pill splitting. ODB = Ontario Drug Benefit

Plan.[7]

GUIDELINE FOR TABLET SPLITTING[8]

FDA providing recommendations for application content regarding the scientific basis for

functional scoring on solid oral dosage form product to ensure the quality of both NDA and

ANDA score tablet products. They developed ―consistent and meaningful criteria by which

scored tablets can be evaluated and labeled by:

(i) Providing a harmonized approach to chemistry, manufacturing, and controls (CMC)

reviews of scored tablets;

(ii) Ensuring consistency in nomenclature (e.g., score versus bisect) and labeling; and

(iii) Providing information through product labeling or other means to healthcare providers.‖

The draft guidance’s fundamental guidelines and criteria are:


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1. Therapeutics dose of split amount: The dosage amount meant to be achieved after

splitting the tablet should not be below the minimum therapeutic dose indicated on the

approved labeling.

2. Handling of split tablet: The scored dosage form should be safe to handle and not pose

risk of unintended drug exposure.

3. Careful consideration: Modified release products for which the control of drug release can

be compromised by tablet splitting should not have a scoring feature.

4. Stability of split tablet: The split tablet, when stored in standard high-density

polyethylene pharmacy bottles and cap (no seal), should meet established stability

requirements for a period of 90 days at 25º C, plus or minus 2º C/60 percent Relative

Humidity (RH), plus or minus 5 percent RH.

5. Finished product criteria: The split tablet portions should meet the same finished-product

testing requirements as for a whole-tablet product with equivalent strength. A risk

assessment should be provided to justify the tests and criteria for product with the

proposed functional score.

6. The scored tablet should be tested using the indicated patient population to ensure

patients can split the tablet correctly, as labeled.

7. Comparability of ANDA and RLD: The scoring configuration of generic drug products

should be the same as the reference drug.

8. Evalution of splitability upon scale up and post approval change: Post study data on tablet

splitability should be provided during post-approval change for any product changes per

FDA’s SUPAC guidance.

FOUR SMART STEPS FOR TABLET SPLITTING[9]

1. Get your doctor (or pharmacist) to OK it first. According to an April 2015 poll by

Consumer Reports Best Buy Drugs, 8 percent of consumers trying to save money on

medications admitted to cutting their pills in half without a doctor’s or pharmacist’s approval.

Many drugs notably most cholesterol-lowering statins, and those to treat high blood pressure

and depression can be split without losing effectiveness or causing a negative health impact,

but it can be dangerous for you to divide others.

Your doctor may have other reasons to warn you about splitting pills. It’s not advised if you

have dementia or memory problems, for example, or if you have a condition that makes it

physically difficult, such as arthritis, hand tremors, or poor eyesight.


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2. Only split pills that can be divided accurately. Most time-released, long-acting, and

combination drugs shouldn’t be split because it’s difficult to make sure that you’ll get the

proper amount of the active ingredient in each half. Pills that are coated to protect your

stomach, such as enteric-coated aspirin and ibuprofen, shouldn’t be split, either.

Those with a hard coating and capsules of any kind are best swallowed whole because they

can easily crumble, leak, or crack into pieces. Chemotherapy drugs and those that require

stable daily blood levels, such as antiseizure medication, birth-control pills, and blood

thinners, should never be split.

3. Use the right tool. Get a pill splitter, a small device that cuts with a sharp blade or by

pressing pills between two opposing edges. Studies have found that pill splitters come closest

to dividing medication into precise halves. They’re usually inexpensive and widely available

at most pharmacies and largce discount stores.

Never use a knife, scissors, a razor blade, a box cutter, an X-Acto knife, or any other sharp

tool for the job. They can create unequal parts, and using them may increase the likelihood of

an injury. Replace a splitter when it no longer divides pills easily and accurately

4. Split pills one at a time. Some pills deteriorate when exposed to air, heat, or moisture

after being split. So cut a pill just before you take it, then take the other half as your next

dose. That helps ensure that you compensate for any deviation in size. And split pills in half -

not into smaller portions, such as quarters. When in doubt, ask your doctor or pharmacist to

show you how to do it properly.

WHEN SPLITTING TABLET, BEWARE OF RISK[2]

Reported problems with scored tablets are difficulty of breaking, unequally breaking and loss

of mass upon breaking (as shown in table.2).

1. Difficulty of breaking

Difficulty of breaking scored tablets is frequently reported. Breaking scored tablets is

particularly difficult for older persons. Small scored tablets appear difficult to break.

Tested uncoated and Film coated scored tables with a claim that the tablets may be

subdivided before administration. However, in some cases the tablets were hard to break

and some study were considered not breakable.


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Two brands have differences in breakability, it was suggested that besides an effect on

bioavailability, this may have an effect on patient-compliance, because a bad performance

of the score line may be experienced by the patient as a quality defect.

Pill splitting not advised if patient have dementia or memory problems or if patient have a

condition like arthritis, hand tremors, or poor eyesight, that makes it physically difficult.

2. Unequal part

Unequally breaking tablets may result varies in strength. Two halves may look the same,

but they do not contain equal amount of drug and do not work the same way in body as

whole tablet. even the scored tablet, one half may have higher drug than the other.

The risk of strength variability may be larger when tablets are split in advance because of

the risk of taking subsequently heavy or light halves. Bad score lines producing unequal

parts may also be experienced as a quality defect by the patient and this might have

consequences for the reliance on the drug-product and the compliance.

Many of the divided tablet parts showed weight deviations of more than 10% from the

target weight or theoretical weight. The relative standard deviation (RSD) of the weight

of the subdivided tablets was up to 14% and almost all the tablets would be rejected if the

test for uniformity of mass was applied to the broken tablets and only about 50% of the

investigated tablets would meet the test proposed by the investigators.

The smallest tablet was most difficult to break accurately.

Some tablets may have an unusual shape that makes unequal tablet splitting

There is very less deviation of weight of the half tablet from theoretical weight, if tablets

were scored deeply on both sides broke most evenly.

Problems are shown with two crossed score lines intended to break the tablet into

quarters. Kristensen state that breaking in quarters should be avoided. It is expected that

the variability of the mass of the broken tablets will be significantly higher than the

variability demonstrated for the halved tablets.

Splitting unscored tablets is considered ―off-label‖ because each split tablet dose may not

have equal drug strength.

3. Loss of mass

A third problem reported for scored tablets is loss of drug, due to fragmentation and

powdering at the score line when a tablet is split. Loss of mass leads to loss of dosage,

health hazards and contamination for others than the patient.


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A chewable tablet disintegrated into multiple pieces when split into half.

There is negligible weigh loss for elongated tablet compare to the round tablet

Some studies show that the weight losses up to 14% were reported when breaking tablets

into halves and up to 27% when breaking tablets into quarters. The breakability of the

optimized tablet-form was compared to the previous tablet-form and another comparative

phenytoin tablet-formulation. The loss of weight after breaking was 0.4, 0.5 and 0.7% for

the comparative-formulation, previous-formulation and optimized formulation,

respectively.

4. Confusion about correct dose

When patient purchase higher dose tablet intending to split them. But there is chance to

forgotten to split tablet, instead they took whole tablet and that is very large dose for

them.

Table 2: Problems associated with scored tablets, possible solutions and their

limitations.

Problem Possible solutions Limitations to solutions

Without change of tablet

Breaking is

difficult Instructions to patient -No limitations

Unequal parts Tablet-splitters

-Breaking accuracy not improved

-Cross-contamination if different tablets are -broken

with the same splitter

-Positioning the tablet may be difficult

-Sharp blade

Loss of mass Pre-breaking in pharmacy

-Safety concerns with hazardous substance

-Stability concerns of subdivided tablets

-Risk of taking subsequently heavy or light halves

With change of tablet

Improve functioning of

score line

-Change of appearance of tablet

-Reformulation

-Conflicting formulation parameters

Remove score line -Loss of advantages of score-line and change of

appearance of tablet

DO`s AND DON`Ts OF TABLET SPLITTING[10]

Patient characteristics

1. Patient should always talk to doctor before splitting or taking a pill and should not afraid

to ask him or her questions if not sure about the label instructions or doctor’s instructions.


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2. The agent’s suitability should be verified. Before a half tablet is prescribed, dispensed, or

administered, drug references should be checked to ensure that the agent is safe. Tablet

should FDA approved to be split. If its safety cannot be confirmed, the manufacturer

should be contacted.

a. Before half tablets are prescribe, screening the patient to ensure that they have the

required level of understanding, ability, and motivation to split the tablets.

b. Patients should understand the problems associated with splitting tablets. If a patient not

able to split a tablet, a qualified family member should be entrusted to do this. (Note: In

some states, it might not be legal for a pharmacist to split tablets if the dose is available

commercially.)

3. Split pills should be dispensed in the hospital. For the In-patient, pharmacy staff members

should dispense exact doses by either splitting pills and repackaging them or by preparing

an oral solution in a unit dose. patient need instruction upon discharge.

4. Sanitary conditions must control. Patients and doctor who split pills should wear gloves;

the practitioner should also wash their hands.

5. Drugs should be prescribed according to the patient’s weight. Prescribers should order the

drug strength and dose in milligrams, when possible, to avoid misreading an order for a

half tablet.

6. Patient counseling is recommended, when prescriptions for medications that require half

pill.

7. Don't use scissors or kitchen knives to cut tablets - This causes uneven splitting and

crumbling, which changes the correct dose. ―Don’t split your pills with a knife. Studies

show that doing so too often leads to unequal half. Patients need the right tools by which

to split tablet. Tablet splitting device use to improve accuracy. tablet splitters are safe and

easy to use. In many cases, a tablet splitter may be appropriate. However, some tablets

may not be acceptable for this method because of their unique size and shape even if they

appear to be scored. It is important to discuss this issue with your healthcare professional

to determine what is best for you. it should be washed after use to remove any powder or

particles. [11]

8. When patient switch from one brand of drug to another, doctor should verify whether the

newly prescribed pill can be split or not, even if the original tablet could be split. The

same medicament can be manufactured differently, thus may not have been developed to

be split.


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9. ―Don’t split your pills in advance. Some pills may be subject to stability issues like

degradation when exposed to air and hygroscopic absorption of water and affect shelf life.

pre-breaking may increase fragmentation and friability. So for medications taken on a

regular basis, Both half are taken before splitting the next pill.it ensure that any deviation

in the size of one dose is compensated in the next.[11]

Medication characteristics

Is the tablet scored or unscored?

Is the tablet modified or extended release?

Is the tablet a single or combination product?

Is the tablet a critical dose product?

Is the tablet film-coated or modified to mask taste or for some other reason?

Does the tablet crumble when split?

Some pills are not meant for splitting. Drugs that are time-released or long-lasting and tablets

that contain a combination of drugs probably shouldn't be split, because it's difficult to ensure

a proper amount of active ingredient in each half. Pills with a coating to protect your

stomach, and pills that crumble easily or irritate your mouth shouldn't be split either. For

example, oxycodone (OxyContin) is controlled release medicament use for pain. Patient may

get an overdose, if they split it.[9,11]

a) Coated and controlled release tablets. The way that tablets dissolve and are absorbed into

the body changes when they are split, especially coated and controlled release tablets. By

changing the way of medication absorbed can decrease its positive effects or increase its

negative effects. (Ex., How long it takes for the medication to enter the body, how strong

it is at any one time, how long it stays in the body.)[12]

b) Extended release medications are designed to have an effect over a long period of time.

Some extended release medications can be split without affecting the designed release

profile (Ex. isosorbide mononitrate), but other extended release medications cannot be

split (Ex. tramadol).[12]

c) Some drugs are coated in another substance to hide the taste of the drug. By splitting the

tablet and thus breaking the coating, the drug’s taste may be exposed.

d) Anticancer agents (Ex. cytotoxic drugs or chemotherapy drugs) are potentially

harmful. Healthy individuals should have as little contact with them as possible, either by

skin contact or air-borne particles. Breaking the coating of tablet containing antineoplastic

https://healthengine.com.au/info/medical-glossary/cytotoxic-agent

https://healthengine.com.au/info/chemotherapy


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agents may compromise safety. Therefore, tablets containing anticancer should not be

split, crushed or broken.[13]

e) Scoring Tablets are usually scored when it is acceptable to cut them, leaving a groove in

the surface of the tablet along which a break may form. However, not all tablets are easy

to break even though they are scored. The tablet’s size and shape, and the type of scoring,

will determine the accuracy of the dose obtained when the tablet is cut. It is important to

note that not all tablets that are scored are suitable for splitting.

The immunosuppressant azathioprine is cytotoxic, yet the tablets are scored. These are

not suitable for splitting. Before splitting any of your medications, talk to your health care

professional to find out if they are suitable to be split.

f) The stability of the tablet when it is cut is also an important factor to consider. The cut

surface of some medications may be sensitive to light, heat or air. This is of particular

concern when a medication is separated into individual dose administration aids.

g) Do not use any medication that has changed color, consistency or shape. These may be

ineffective or have negative side effects. [13]

h) Combination tablets that contain two or more drug, in which the amount of one active

ingredient changes from one tablet size to the next, but the amount of the other does

not.[11]

NOTE: Women should NOT handle crushed or broken finasteride tablets if pregnant or

possibly pregnant. Broken tablets lose some of the protective outer coating, thus allowing

absorption of finasteride through the skin. The drug may cause birth defects.

―There is no official or complete list of medicaments that can be split. And it can be risky to

split some drugs. For example, Birth control pills. [10]

It is usually safe drugs that treat:

• High cholesterol (―statins‖)

• High blood pressure

• Depression

https://healthengine.com.au/info/chemotherapy/08


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Can Split That Tablet? [9]

Tablets that CAN be

Split Tablets that CANNOT be Split

Atorvastatin(Lipitor) Oxycodone (OxyContin) for pain

Doxazosin (Cardura) Omeprazole (Prilosec) for heartburn

Finasteride (Proscar) Cetirizine (Zyrtec) for allergies

Amlodipine (Norvasc) Chemotherapy drugs and anti-seizure medicines

Quinapril (Accupril) Birth control pills

Sertraline (Zoloft) Blood thinners (Coumadin, warfarin)

Lovastatin (Mevacor) Capsules containing powders or gels

Simvastatin (Zocor) Pills with hard outside coatings

Sertraline (Zoloft) Pills that release the drug throughout the day

(extended-release)

Tadalafil (Cialis) Pills that crumble easily

Paroxetine (Paxil) Pills that irritate the mouth or taste bitter

Lisinopril (Zestril) Pills with strong dyes that could stain your teeth and

mouth

Atenolol (Tenormin) Combination Tablets

Citalopram (Celexa) Amlodipine/Atorvastatin (Caduet)

Clonazepam (Klonopin) Amlodipine/Olmesartan (Azor),

Levothyroxine (Synthroid) Amoxicillin/Clavulanic acid (Augmentin, and others),

Metformin (Glucophage) Ezetemibe/Simvastatin (Vytorin),

Nefazodone (Serzone) Irbesartan/Hydrochlorothiazide (Avalide)

Metoprolol (Toprol) Oxycodone/Acetaminophen (Percocet, and others)

Olanzapine (Zyprexa) Sitagliptin/Metformin (Janumet)

Pravastatin (Pravachol) Anti-seizure medicines

Quinapril (Accupril) Time-release pills designed to release medication over

time in your body

Rosuvastatin (Crestor) Enteric Coated tablet

Sildenafil (Viagra)

Vardenafil (Levitra)

METHOD OF SPLITTING

1. Pill Crusher: Pulverizes pill into a powder that can be mixed with food or drink.

2. Mortar and Pestle: Crushes pill into a fine powder that can be easily dissolved in liquids

or stirred into soft food.

3. Pill Splitter: It is device use to practice of divide pill and provide a lower dose of active

ingredient.

A tablet-splitter may relieve the difficulty of breaking tablets by hand (see fig. 3(a)(b)). It is

simple and inexpensive device. The patient’s acceptance of tablet-splitters was studied by

Carr Lopez. Most patients reported that the tablet-splitter was easy to use, did not waste

medication and did not affect their compliance. Problems reported regarding tablet-splitters


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are potential injury due to the sharp steel blade and the possibility of cross contamination

when different tablets are split.

Having the right equipment is very important too. Don't use a knife or scissors to cut your

pills in half. It can cause you to split them unevenly resulting in two pieces with very

different dosages, which can be dangerous. a proper pill cutter that has a cover and a V-

shaped pill grip that holds the pill securely in place.

(a) (b)

Fig. 3(a) (b) Tablet Splitter.

There is invention provides a device for measuring the force required to break a tablet,

wherein the device comprises a tablet holding means comprising a base, a tablet splitting

edge in the base and an area for holding a tablet in an inclined cantilevered position such that

at least a portion of the cantilevered segment of the tablet extends over the tablet splitting

edge. Means are provided for exerting a force substantially normal to a portion of the

cantilevered segment of the tablet extending over the splitting edge to thereby create a

moment of force about the tablet splitting edge sufficient to break the tablet. The device

includes means for measuring the force required to break the tablet.

The device of this invention thus not only measures the force required to break a tablet, but

also gives a measure that is representative of the force required for a human to break a similar

tablet. As will be apparent from the description that follows, the device of the invention is

simple to operate and can be adapted for use with a variety of different size tablets.

4. Multiple methods of crushing medications have been used. The common practice of

crushing medication in a plastic bag can be unsafe for patients. It is difficult to extract all of


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the drug particle from the bag and their corners. Consequently, the correct dosage of the drug

is not delivered. The device should be clean after each medicament to avoid drug interactions.

Each of these methods is appropriate with the choice of a method based on patient preference

and ability to correctly use the device.

It's also important to know that pills are only safely split in half, and never into smaller

portions such as into thirds or quarters

Factor Affecting Tablet Splittting[22]

A full factorial design was used to evaluate the influence of five variables of pills:

(i) filler (lactose mono-hydrate or dibasic calcium phosphate 600 mg/tablet),

(ii) binder (hydroxyl propyl-methyl cellulose or polyvinyl pyrollidone; 32 mg/tablet),

(iii) disintegrating agent (sodium carboxy methyl cellulose or microcrystalline cellulose; 80

mg/tablet),

(iv) tablet hardness (low or high),

(v) tablet surface (with or without score line).

(vi) score on one side or both side.

We studied the effect of these variables on the weight variation of split pills and on pill

weight resulting from splitting. The resulting half tablets were weighed to determine the

weight variability between them. No significant influence of tablet hardness and binder type

was observed on weight variability or weight loss. Scored tablets exhibited a significantly

lower weight variation and weight loss as compared to the unscored tablets. Tablets prepared

with dibasic calcium phosphate as the filler and those prepared with microcrystalline

cellulose as the disintegrating agent also showed a significantly lower weight variability and

weight loss upon splitting as compared to the tablets prepared with either lactose

monohydrate as the filler (p < 0.005 for both endpoints) or sodium carboxymethyl cellulose

as the disintegrating agent (p < 0.015 for both endpoints). A number of other factors,

including mass production techniques and use of different drugs and excipients may affect

the weight variability and weight loss because of pill splitting. However, the study highlights

the importance of score line on the tablet surface in limiting the weight variability among

split tablets and weight loss during the tablet splitting when compared to the unscored tablets

prepared from the same formulation under identical conditions. The practice of splitting

tablets when they are not scored should be discouraged for better therapeutic outcomes.


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Patients reporting severe vision impairment, missing arms or digits, or disabling arthritis. which

affects tablet splitting. Alprazolam (kalma), benztropine (Cogentin), clozapine (clozaril) are

scored on single side. Digoxin, temazepam are small size tablet. And some irregular shape tablets

are fosinapril, lamotrigine, auranofin, alendronate.

ACCURACY OF TABLET SPLITTING

Methods

Spectrophotometric scanning: To determine maximum absorption wavelength.

Calibration curve: A standard curve was created for drug, using API powder diluted to three

known concentrations within range of respective drug. These standard curves were

established to verify accurate analysis of the drug. Ex. Salbutamol sulphamet (range between

0.0096 and 0.0478 mg/ml).

Scanning Electron Microscope: A Scanning Electron Microscope (SEM) is a type of

electron microscope that images a sample by scanning it with a high energy beam of

electrons in a raster scan pattern. The electrons interact with the atoms that make up the

sample producing signals that contain information about the sample’s surface topography,

composition, and other properties such as electrical conductivity.

Weight Variation: A total of 20 whole pills were randomly selected. Weight the tablets

individually. Ten of the 20 selected pills were divide in halves using a pill splitter and the

another 10 pills were split in half by hand. All 10 whole tablets and 40 half tablets were

weighted using analytical balance. The difference between the tablet weight before splitting

and the sum of the weights of the two halves after splitting was used to calculate the weight

loss during tablet splitting. The individual weight was compared with an average weight. Not

more than two of the individual weights deviated from the official standard (limit ±7.5%).

Also comparison between hand splitting and tablet splitter. Assay parameters for each drug

taken directly from USP monographs. [15]

Content Uniformity: First the 10 whole tablets of 2 mg and 20 half-tablets selected from 40

halves were dissolved individually using a combination of shaking and sonication techniques

in 25 ml of 0.1 N HCl. Then the samples were mixed well before filtration through a

membrane filter. All tablets were assayed in accordance with developed and validated

spectrophotometric method for determining content uniformity for whole tablets. Assay


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parameters for each drug were taken directly from USP monographs. The samples of each

solution were assayed for drug concentration via UV system using a spectrometer. The drug

content was quantified by calculating the concentrations from the absorbance readings

obtained through UV analysis of whole and half-tablet samples.

To assess the amount and acceptability of variations in drug content and weight, several

measures were calculated. The measured drug content expressed as a percent of label claim

was calculated for both whole and half-tablets. Individual values for whole tablets should be

in the range of 85–115% for the drugs studied (proxy USP specification for drug content).

Relative standard deviation expressed as a percentage (%RSD), was calculated for whole

tablets (drug content and weight) and for half-tablets (drug content and weight). The %RSD

is widely used to assess the repeatability and precision of the assays used to analyse drug

content. Individual medication lots for whole tablets are targeted to have a %RSD less than

6% (proxy USP specification for %RSD).[15]

Statistical Analysis

1. t-Test

2. f-Test

Statistical analysis of the data was performed using the analysis of variance function in the

JMP software. Statistical tests of significance of preexisting condition (age, gender, grip and

finger pinch strength, finger size) on results of tablet splitting.

Measurements

1. Grip strength was measured using a hydraulic hand dynamometer

Patient need a lot of dexterity to cut tablet accurately as possible. Otherwise, the tablet is

unevenly split, or a lot of waste is produced as tablets break into fragments. If patient suffer

from arthritis or Parkinson’s disease, cutting tablets may be difficult due to impaired manual

dexterity or reduced grip strength. Alzeimer’s patients may also face problems due to

decreased cognitive function, and may not remember how to split a tablet properly. Before

splitting. The subject sat with arms resting on a table and palms facing medially The

dynamometer was set at level 1 with the indicator at zero. The subject was instructed to

squeeze the dynamometer as hard as possible using one hand and a slow, steady grip. This

procedure was repeated 3 times for each hand, and the subject’s mean grip strength was

calculated.

https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/drug-concentration

https://healthengine.com.au/info/rheumatoid-arthritis/

https://healthengine.com.au/info/parkinsons-disease/

https://healthengine.com.au/info/alzheimers-disease


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2. Pinch strength was documented using a standard pinch test gauge

Pinch strength was documented using a standard pinch test gauge. The subject sat at a table

with arms pronated. The indicator on the pinch test gauge was set to zero. The gauge was

placed between the subject’s thumb and distal phalanx of the index finger. The subject slowly

compressed the pinch tester, and the maximum value was recorded. This procedure was

repeated 3 times for each hand, and the subject’s mean pinch strength was calculated.

REMEMBER: Tablet splitting should be done only under the supervision of a healthcare

profession.

CONCLUSION

The review shows that only score tablet can be split. By using tablet splitter gives more

accuracy than hand splitting, knife and scissor. Some safety point should keep in mind while

splitting tablet. Patient should advise about appropriate storage of split tablets. A patient’s

state of health might affect the ability to properly split tablets. Scoring configuration of

generic drug product should be same as the RLD (Reference Listed Drug). This thing should

be taken care by guideline before splitting the scored tablet.

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