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REVIEW ARTICLE
INTRODUCTION
Despite of tremendous innovations in drug delivery, the
oral route remains the preferred route for administration of
therapeutic agents because of accurate dosage, low cost
therapy, self medication, non invasive method and ease of
administration leading to high level of patient compliance
1
. However, traditional tablets and capsules administered
with a glass of water may be inconvenient or impractical
for some geriatric patients because of changes in various
physiological and neurological conditions associated with
aging including difficulty in swallowing/dysphagia, hand
tremors, deterioration in their eyesight, hearing, memory,
risk of choking in addition to change in taste and smell.
Solid dosage forms also present significant administration
challenges in other patient groups, such as children,
mentally challenged, bed ridden and uncooperative
patients. Paediatric patients may suffer from ingestion
problems as a result of underdeveloped muscular and
nervous control. Moreover, patients travelling with little or
no access to water, limit utility of orally administered
conventional tablets or capsules.
Therefore, to cater the needs of such patients, recent
advancements in technology have resulted in development
of viable dosage alternatives popularly known as orally
disintegrating tablets (ODTs)[1,2].During the past decade,
the FDT (fast dissolving tablet) technology, which makes
tablets dissolve or disintegrate in the mouth without
additional water intake, has drawn a great deal of attention.
The technology is also referred to as fast disintegrating
tablet, fast dispersing tablet, rapid dissolve tablet, rapid
melt tablet, quick disintegrating tablet, and orally
disintegrating tablet. The FDT formulation is defined by
the Food and Drug Administration (FDA) as a solid
dosage form containing medicinal substances which
disintegrates rapidly, usually within a matter of
seconds, when placed upon the tongue. The tablets
disintegrate into smaller granules or melt in the mouth
from a hard solid structure to a gel like structure, allowing
easy swallowing by the patients. The disintegration time
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Aqueous solubility
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Superdisintegrants:
A disintegrant is an excipient, which is added to a tablet or
capsule blend to aid in the breakup of the compacted mass
when it is put into a fluid environment.
Table 1: Enlists various existing superdisintegrants and also their mechanism of action
Name of disintegrant
Sodium Starch Glycolate
Micro crystalline cellulose
Cross linked povidone
Low substuted hydroxy
propyl cellulose
Crosscarmellose sodium
Brand name
Explotab,Primogel
Avicel, Celex
Cross povidone
LH-11, LH-12 (Grades)
Concentration (%)
2-8%
2-15%
2-5%
1-5%
Mechanism of action
Swelling
Water wicking
Swelling, Water wicking
Sweling
Ac-Di-Sol
Pregelatinized starch
Starch 1500
1-3%Direct compression
2-4% wet granulation
1-20%
Swelling
flowability.
SELECTION OF SUPERDISINTEGRANTS:
Although superdisintegrants primarily affect the rate of
disintegration, but when used at high levels they can also
affect mouth feel, tablet hardness and friability. Hence,
various ideal factors to be considered while selecting an
appropriate superdisintegrants for a particular
formulationshould:
Produce rapid disintegration, when tablet comes in
contact with saliva in the mouth/oral cavity.
Be compactable enough to produce less friable tablets.
Produce good mouth feel to the patients. Thus, small
particle size is preferred to achieve patient compliance.
Have good flow, since it improves the flow
characteristics of total blend.
Lyophilization
Moulding
Direct Compression
Cotton Candy Process
Spray Drying
Sublimation
Mass Extrusion
Nanonization
Fast Dissolving Films
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Advantages
Disadvantages
Figure 5: Lyophilization Technology. Patented technology based on this process is Zydis technology
Tablet Moulding9,11
Moulded tablets invariably contain water-soluble
ingredients due to which the tablets dissolve completely
and rapidly. Following are the different tablet moulding
techniques:
Compression Moulding Process
This manufacturing process involves moistening the
powder blend with a hydroalcoholic solvent followed by
pressing into mould plates to form a wetted mass
(compression moulding). The solvent is then removed by
air drying, a process similar to the manufacture of tablet
triturates. Such tablets are less compact than compressed
tablets and possess a porous structure that hastens
dissolution.
Heat-Moulding Process
Heat-moulding process involves setting the molten mass
containing a dispersed drug. This process uses agar
solution as a binder and a blister packaging well as a
mould to manufacture the tablet. A suspension containing
drug, agar and sugar is prepared followed by pouring the
suspension into the blister packaging well, solidifying the
agar solution at room temperature to form a jelly and
finally drying at approximately 30 C under vacuum.
Moulding
by
Lyophilization
Vacuum
Evaporation
without
Ideal requirements
Flowability
Compressibility
Dilution Potential
Reworkability
Stability
Controlled Particle Size
Advantages
Cost effective production
Better stability of API
Faster dissolution
Less wear and tear of punches
Simple validation
Low microbial contamination
Disintegrants
In many MDT products based on DC process, the
disintegrants mainly affect the rate of disintegration and
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Limitations
Segregation
Variation in functionality
Low dilution potential
Reworkability
Poor compressibility of API
Lubricant sensitivity
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Mass-Extrusion17
This technology involves softening of the active blend
using the solvent mixture of water soluble polyethylene
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Nanonization17
Wetting time:
%
Total weight of tablet before Total weight of tablets after
100
Total weight of tablets
Wa Wb
100
Wb
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Sulphapyridine,
Anti-Fungal Agents:
Amphotericin, Butoconazole Nitrate, Clotrimazole,
Econazole Nitrate, Fluconazole, Fiucytosine, Griseofulvin,
Itraconazole, Ketoconazole, Miconazole, Natamycin,
Nystatin, Sulconazole Nitrate, Terbinafine, Terconazole,
Tioconazole, Undecenoic Acid.
Anti-Gout Agents:
Allopurinol, Probenecid, Sulphinpyrazone.
Anti-Hypertensive Agents:
Amlodipine,
Carvedilol,
Benidipine,
Darodipine,
Dilitazem, Diazoxide, Felodipine, Guanabenz Acetate,
Indoramin, Isradipine, Minoxidii, Nicardipine, Nifedipine,
Nimodipine,
Phenoxybenzamine, Prazosin, Reserpine, Terazosin.
Anti-Malarials:
Amodiaquine, Chloroquine, Chlorproguanil, Halofantrine,
Mefloquine, Proguanil, Pyrimethamine, Quinine Sulphate.
Anti-Migraine Agents: Dihydroergotamine Mesyiate,
Ergotamine Tartrate, Methysergide Maleate, Pizotifen
Maleate, Sumatriptan Succinate.
Anti-Neoplastic Agents and Immunosuppressants:
Aminoglutethimide, Amsacrine, Azathiopnne, Busulphan,
Chlorambucil, Cyclosporin, Dacarbazine, Estramustine,
Etoposide, Lomustine, Melphalan, Mercaptopurine,
Methotrexate, Mitomycin, Mitotane, Mitozantrone,
Procarbazine, Tamoxifen Citrate, Testolactone.
Anti-Thyroid Agents:
Carbimazole, Propylthiouracil.
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Sulphafurazole, Sulphamethoxazole,
Tetracycline, Trimethoprim.
Benorylate,
Calcim,
Flurbiprofen,
Ibuprofen,
Indomethacin,
Ketoprofen, Meclofenamic Acid, Mefenamic
Nutritional Agents:
Betacarotene, Vitamin A, Vitamin B 2 , Vitamin D,
Vitamin E, Vitamin K.
Opioid Analgesics:
Acid,
Nabumetone,
Naproxen,
Oxaprozin,
Oxyphenbutazone, Phenylbutazone, Piroxicam, Sulindac.
Codeine,
Dextropropyoxyphene,
Dihydrocodeine, Meptazinol, Methadone,
Anthelmintics :
Albendazole,
Bephenium
Hydroxynaphthoate,
Cambendazole, Dichlorophen, Iverrnectin, Mebendazole,
Oxarnniquine,
Oxfendazole,
Oxantel
Embonate,
Praziquantel, Pyrantel Embonate, Thiabendazole.
Oral Vaccines:
Anti-Arrhythmic Agents:
Ciprofloxacin,
Demeclocycline,
Doxycycline,
Erythromycin,
Ethionamide, Imipenem, Nalidixic Acid, Nitrofurantoin,
Rifampicin, Spiramycin, Sulphabenzamide, Sulphadoxine,
Sulphamerazine,
Sulphacetamide,
Sulphadiazine,
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Diamorphine,
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Insulin
(Hexameric/Dimeric/Monomeric
Forms),
Glucagon, Growth Hormone (Somatotropin), Polypeptides
or Their Derivatives, (Preferably With A Molecular
Weight from 1000 To 300,000), Calcitonins And Synthetic
Modifications
Thereof,
Enkephalins,
Interferons
(Especially Alpha-2 Inter Feron For Treatment Of
Common Colds).
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have
sufficient
mechanical
strength,
quick
disintegration/dissolution in the mouth without water.
There is a clear opportunity for new enhanced oral
products arising within this market segment.
Approximately one-third of the population, primarily the
geriatric and pediatric populations, has swallowing
difficulties, resulting in poor compliance with oral tablet
drug therapy which leads to reduced overall therapy
effectiveness.. These tablets are designed to dissolve or
disintegrate rapidly in the saliva generally within <60
seconds (range of 5- 50seconds). The development of a
fast-dissolving tablet also provides an opportunity for a
line extension in the marketplace, A wide range of drugs
(e.g., neuroleptics, cardiovascular drugs, analgesics,
antihistamines, and drugs for erectile dysfunction) can be
considered candidates for this dosage form. As a drug
entity nears the end of its patent life, it is common for
pharmaceutical manufacturers to develop a given drug
entity in a new and improved dosage form. A new dosage
form allows a manufacturer to extend market exclusivity,
while offering its patient population a more convenient
dosage form or dosing regimen.
Sex Hormones:
Clomiphene
Citrate,
Danazol,
Ethinyloestradiol,
Medroxyprogesterone Acetate, Mestranol,
Methyltestosterone, Norethisterone, Norgestrel, Oestradiol,
Conjugated Oestrogens, Progesterone, Stanozolol,
Stiboestrol, Testosterone, Tibolone.
CONCLUSION:
The FDTs have potential advantages over conventional
dosage forms, with their improved patient compliance,
convenience, bioavailability and rapid onset of action had
drawn the attention of many manufactures over a decade.
FDTs formulations obtained by some of these technologies
REFERENCES
1) Kaur et al., Mouth dissolving tablets: A novel approach to drug
delivery, International Journal of Current Pharmaceutical
Research, 20011; 3:1-7.
2) Seong Hoon Jeong, Kinam Park., Material properties for making
fast dissolving tablets by a compression method. Journal of
Materials Chemistry; 2008; 18: 35273535.
3) McLaughlin Rosie,Banbury Susan,Crowley Kieran., Orally
Disintegrating Tablets The Effect of Recent FDA Guidance on
ODT
Technologies
and
Applications,
Pharmaceutical
Technology:Sep.(2009)
4) D. Shukla et al., Mouth Dissolving Tablets I: An Overview of
Formulation Technology, Scientia Pharmceutica. 2009; 76; 309
326.
5) Hirani et al., Orally Disintegrating Tablets: A Review, Tropical
Journal of Pharmaceutical Research, April 2009; 8 (2): 163
6) Rish RK et al., A review on fast dissolving tablets techniques. The
Pharma Review 2004; 2: 32.
7) Kuchekar BS, Atul, Badhan C, Mahajan HS., Mouth dissolving
tablets: A novel drug delivery system., PharmaTimes 2003; 35: 79.
8) Bhaskaran S, Narmada GV. Rapid dissolving tablets a novel
dosage form. Indian Pharmacist 2002; 1: 912.
9) H . Seager., Drug-delivery Products and the Zydis Fast-dissolving
Dosage Form., J. Pharm. Pharmacol. 1998; 50: 375-382.
10) Vummaneni. V et. al., Mouth Dissolving Tablets: A Review,
American Journal of Pharmatech Research; 2012; 2(3).
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