PILL SCORING

(DOES IT REALLY INFLUENCE THE TABLET EFFICACY)

Drug delivery is a technique of administering a mass of an entity that is predetermined to produce an optimum therapeutic effect in its lowest possible dose. There are many dosage forms present for the delivery of drug but it depends on various properties to design such as nature, factors influencing, excipient compatibilities of drug and there are also other patient related factors which are considered prior to the development of dosage form. The most advantageous, easiest, cheapest, patient compliant unit dosage forms are oral dosage forms (tablets). There are different types of tablets present and there are huge manufacturing practices for its preparation. The most important problem addressed in its preparation is dose adjustment in consideration with size, shape, weight and content uniformities. But in the present wide variety of disease burden; some diseases, in case of maintenance dose, patient incompatibility to high effective dose and some other drug (dose tapering) and patient related ( pediatrics, geriatrics and cost mitigation) factors may require a low fraction of dose than the marketed drug dose in that case a situation arises called as tablet scoring or splitting. 

PILL/TABLET SCORING

Tablet scoring is an engraved line across the planar surfaces of the tablet that provides capability to split a tablet into equal doses precisely. The tablet scoring is facilitated by some factors during its preparation such as particle size, blend uniformity and compression/tooling design. 

HISTORY OF TABLET SPLITTING 

The practice of tablet splitting was in demand during 2009 and 2010 due its dose flexibility and cost saving which lead the Centre for Drug Evaluation and Research/ Food and drug administration (CDER/FDA) to evaluate such practice as they were no specific regulatory requirements to address tablet scoring. As such dosage forms may produce lower efficacy and higher risk of adverse drug reactions due to inaccurate dosing. In 2002, The European Pharmacopeia introduced a new test on accuracy of subdivision of scored tablets which was followed by all European countries. But there were no standard tests for weight uniformity of split halves of tablet. In 2011, FDA introduced draft guidance for manufacturers regarding tablet scoring. In 2013, a final tablet splitting guidelines was published by FDA concerning “Tablet scoring: Nomenclature, labelling and data for evaluation”. 

FDA GUIDELINES AND CRITERIA TO SPONSORS OF NDA/ANDA

•      Split tablet should not be below the minimum therapeutic dose indicated on the approved labelling

•      Safe to handle and should not pose unintended drug exposure

•      Modified release products for which control of drug release can compromised should not have scoring feature

•      Split tablet when stored in pharmacy dispensing containers should demonstrate adequate stability for a period of 90 days at 25±2^o C/60±5 RH

•      The label should encompass the therapeutic dose

•      Generic drug should be scored if RLD is scored

•      Criteria of dose uniformity, tablet splitability (mechanical &non-mechanical), dissolution for immediate release and modified release oral dosage forms should be contended.

CONCERNS FOR EVALUATION OF TABLET SCORING 

•      Approach to chemistry, manufacturing and controls (CMC) review 

•      Tablet uniformity, weight variation, disintegration, dissolution, stability issues and availability of drug for absorption

•      Scoring configurations (generic drugs should be similar to reference listed drug (RLD))

•      Should fulfill FDA guidelines of nomenclature & labelling for functional scoring.

•      All the other physical attributes should meet the criteria of quality target product profile (QTPP) 

•      The tablet splitability should be ensured during post approval period as per scale-up and post approval changes (SUPAC) guidance 

•      Should probably meet all finished product specifications.

Some examples of marketed generic drugs at their commercially available doses and being partitioned in conditions (Indications of use):

DRUG	CATEGORY	LOWEST MARKETED DOSE	SCORED DOSE	INDICATIONS OF SCORED TABLET
Atenolol	Antihypertensive	25mg	12.5mg	Post myocardial infarction
Clonazepam	Benzodiazepine	0.5mg	0.25mg	Panic disorders
Levothyroxine	Hypothyroid	25mcg	12.5mcg	Mild hypothyroidism with cardiovascular disease
Gabapentin	Anti-epileptic	600mg	300mg	Neuralgia
Escitalopram	Anti-depressant	10mg	5mg	Insomnia
Haloperidol	Anti-psychotic	0.5mg	0.25mg	Schizophrenia
Glyburide	Hypoglycemic	2.5mg	1.25mg	Type II Diabetes mellitus
Furosemide	Loop diuretic	40mg	20mg	Edema associated with congenital heart disease

Besides the above-mentioned generic drugs some other commonly marketed scored drugs of different brands are: aceon, endocet, lanoxin, Skelaxin, toprol xl, univasc, Valtrex and Zoloft.

Note: There are also different scored tablets of both generic and brand-named medications  

Advantages:

•      Facilitates ease of administration (in case of large tablet, dysphagia, pediatric and geriatric patients)

•      Facilitates cost reduction 

•      Facilitates ease of adjusting & altering the dose in conditions requiring dose tapering.

•      Facilitates to overcome insurance policies that deny payments for lower strength tablets.

The tablet can be split by non-mechanical means (by hand) and mechanically (tablet splitter), apart from tablet scoring assessments as per FDA, yet the problems with scoring emerges and the most regular ones are discussed below.

Limitations:

•      Misleading score lines

•      Inadmissible splitting (geriatrics)

•      Ineffective drug dose

•      Unintended drug exposure 

•      Storage issues (stability & relative humidity) and lack of awareness about scoring of a tablet.

In order to overcome the issues associated with tablet scoring, the clinical pharmacist can make out some of the best practices that are mentioned below.

Best practices by clinical pharmacist: 

As the clinical pharmacist has sound knowledge in both healthcare and industrial sectors, he/she can contribute the knowledge to enlighten the patients regarding the scored tablet.

In health care sector:

Usage of scored tablet, use of tablet splitters especially in case of geriatrics, storage of tablet, splitting of the next tablet only after consuming the previous halves that are split.

Non-mechanical and mechanical splitting of tablet.

In industrial sector:

Regarding the design of formulation, selection of excipients, processing parameters, geometry of score line and the stability of storing a scored drug, possible impurities & product degradation.

  CONCLUSION

As it is an emerging concept the standard regulatory guidance on tablet scoring and treating different conditions requiring the scored dose should be well defined particularly in high potency and narrow therapeutic index drugs and use of other possible strategies such as micronization should be implemented

 

 

                                                                                                                 K. Shravani & S. Ashwini                                                                                                                               5^th Pharm D                                                                                                                      sherlaashwini@gmail.com                                            inavarhs247@gmail.com