Fast Dissolving Tablets- A Review and Recent Advances in Manufacturing Technologies

 

 

K Sonu Sharma1* Rashmi Sharma3 and G Vidya Sagar2

1Suresh Gyan Vihar University, Jaipur, Rajasthan.

2Veerayatan  institute of  Pharmacy, Bhuj, Kutch, Gujarat

3Mahatama Jyoti Rao Phule University, Jaipur, Rajasthan.

 

ABSTRACT:

Tablet swallowing difficulty primarily affects the geriatric and pediatric populations whereas unpalatable taste of drugs leads to patient non-compliance. To reduce  these problems, a new dosage form known as Fast-Dissolving Tablet (FDT), is a tablet that dissolves or disintrigrants in the oral cavity without the need of water or chewing. It has been developed for oral administration, also called as  fast-melt, rapimelts, porous tablets ,or fast disintegrating or orally disintegrating tablets (ODTs). In April 2007, the FDA issued a draft guidance, Guidance for Industry: Orally Disintegrating Tablets. Fast dissolving tablets can be prepared by various conventional methods like direct compression, wet granulation, moulding, spray drying, freeze drying, Cotton Candy Process and sublimation. In 1986, the first lyophilized fast-dissolving technology Zydis® was introduced (By Cardinal formerly R. P. Scherer) after that there was a continuous growth in names by different companies, now a number of fast-dissolving formulations are in market and the technology is still improving. Present review focuses on the need of FDTs, their advantages and comparative evaluation of latest technologies.

 

 

KEYWORDS: fast dissolving tablet, orasolv, durasolv, patents

 

INTRODUCTION:

Fast dissolving tablets (FDT) are solid unit dosage forms which disintegrate or dissolve rapidly in the mouth without chewing and water. FDTs are also called as fast melt, fast disintegrating or orally disintegrating tablets. In April 2007, the FDA issued draft guidance, Guidance for Industry: Orally Disintegrating Tablets. It considers ODTs to be solid oral preparations that disintegrate rapidly in the oral cavity with an in vivo disintegration time of approximately 30 seconds or less, when based upon the USP disintegration test method or alternative.1

 

Requirements of Fast Dissolving Tablets 20

An ideal FDT should require no water for oral administration, yet dissolve / disperse/ disintegrate in mouth in a matter of seconds, have a pleasing mouth feel, have an acceptable taste masking property, be harder and less friable leave minimal or no residue in mouth after administration exhibit low sensitivity to environmental conditions (temperature and humidity)allow  the   manufacture   of  tablet   using conventional   processing  and   packaging equipments.

 

Advantages of FDTs over conventional dosage forms

FDTs have significant advantages of both solid and liquid dosage forms. FDTs remain solid till administration and possess dose accuracy and stability during storage which transform into liquid form within few seconds after its administration for easy swallowing. Besides this, rapid drug therapy intervention, convenient for administration and patient compliant for disabled, bedridden patients and for travelers and busy people, who do not always have access to water and  the risk of chocking or suffocation during oral administration of conventional formulations due to physical obstruction is also avoided.

Methodology Employed For FDT Formulations:

Melt granulation:

Melt granulation technique is a process by which pharmaceutical powders are efficiently agglomerated by a meltable binder. The advantage of this technique compared to a conventional granulation is that no water or organic solvents is needed. Because there is no drying step, the process is less time consuming and uses less energy than wet granulation. It is a useful technique to enhance the dissolution rate of poorly water-soluble drugs, such as griseofulvin.5 This approach to prepare FDT with sufficient mechanical integrity, involves the use of a hydrophilic waxy binder (Superpolystate©, PEG-6-stearate). Superpolystate© is a waxy material with a melting point of 33–37°C and a HLB value of 9. So it will not only act as a binder and increase the physical resistance of tablets but will also help the disintegration of the tablets as it melts in the mouth and solublises rapidly leaving no residues.6

 

Phase transition process:

It is concluded that a combination of low and high melting point sugar alcohols, as well as a phase transition in the manufacturing process, are important for making FDTs without any special apparatus. FDT were produced by compressing powder containing erythritol (melting point: 122 °C) and xylitol (melting point: 93 95 °C), and then heating at about 93 °C for 15 min. After heating, the median pore size of the tablets was increased and tablet hardness was also increased. The increase of tablet hardness with heating and storage did not depend on the crystal state of the lower melting point sugar alcohol.7

 

Sublimation

In this method a subliming material like camphor, is removed by sublimation from compressed tablets and high porosity is achieved due to the formation of many pores where camphor particles previously existed in the compressed tablets prior to sublimation of the camphor. A high porosity was achieved due to the formation of many pores where camphor particles previously existed in the compressed mannitol tablets prior to sublimation of the camphor. These compressed tablets which have high porosity (approximately 30%) rapidly dissolved within 15 seconds in saliva.8 Granules containing nimusulide, camphor, crospovidone, and lactose were prepared by wet granulation technique. Camphor was sublimed from the dried granules by vacuum exposure.9 Conventional methods like dry granulation, wet granulation and direct compression with highly soluble excipients, super disintegrants and/or effervescent systems can also be used.

 

Three-dimensional Printing (3DP):

Three-dimensional printing (3DP) is a rapid prototyping (RP) technology. Prototyping involves constructing specific layers that uses powder processing and liquid binding materials. A novel fast dissolving drug delivery device (DDD) with loose powders in it was fabricated using the three dimensional printing (3DP) process. Based on computer-aided design models, the DDD containing the drug acetaminophen were prepared automatically by 3DP system.10 It was found that rapidly disintegrating oral tablets with proper hardness can be prepared using TAG. The rapid disintegration of the TAG tablets seemed due to the rapid water penetration into the tablet resulting from the large pore size and large overall pore volume.11

 

Mass Extrusion:

This technology involves softening of the active blend using the solvent mixture of water-soluble polyethylene glycol and methanol and subsequent expulsion of softened mass through the extruder or syringe to get a cylinder of the product into even segments using heated blade to form tablets.

 

Spray Drying:

Maximum drug release and minimum disintegration time were observed with Kollidon CL excipient base as compared to tablets prepared by direct compression, showing the superiority of the spray dried excipient base technique over direct compression technique.12

 

Cotton Candy Process:

This process is so named as it utilizes a unique spinning mechanism to produce floss-like crystalline structure, which mimic cotton candy. Cotton candy process involves formation of matrix of polysaccharides or saccharides by simultaneous action of flash melting and spinning. The matrix formed is partially recrystallized to have improved flow properties and compressibility. This candy floss matrix is then milled and blended with active ingredients and excipients and subsequently compressed to ODT. This process can accommodate larger drug doses and offers improved mechanical strength. However, high-process temperature limits the use of this process.

 

Molding:

The molding technology results in tablets with an appropriate dissolution time, even though they are characterized by poor mechanical properties (hardness).

 

Lyophilization or Freeze-Drying:

Freeze-drying allows immediate dissolution of the tablets because of their high porosity, and enhances drug stability, especially for moisture-sensitive substances; on the other hand, a porous network is associated with low physical resistance and high friability. Special packaging is required in some cases.

 

Patented FDTs Technologies:

Zydis technology:

Zydis® was introduced By R. P. Scherer Corporation (a wholly owned subsidiary of Cardinal Health, Inc.) in 1986. The Zydis process requires the active ingredient to be dissolved or suspended in an aqueous solution of water-soluble structure forming additives then the mixture is poured into the preformed blister pockets of a laminate film and freeze-dried. This results in a tablet shaped dosage form that spontaneously disintegrates in mouth in seconds. The two most commonly used structural additives are gelatin and mannitol although some other (e.g., starches, gums, etc.) may be used depending on the properties of the active ingredient. As a general rule, the best physical characteristics are achieved by using a mixture of a water-soluble polymer and a crystalline sugar alcohol or amino acid at a typical combined concentration of 10% w/w in the matrix solution. The polymer gives the strength and resilience while the crystalline component gives the hardness and texture.13

 

Lyoc (Laboratoires L. Lafon, Maisons Alfort , France ) :

Lyoc utilizes a freeze drying process but differ from Zydis in that the product is frozen on the freeze dryer shelves. To prevent in homogeneity by sedimentation during this process, these formulations require a large proportion of undissolved inert filler (mannitol), to increase the viscosity of the in process suspension. The high proportion of filler reduces the potential porosity of the dried dosage form and results in denser tablets with disintegration rates that are comparable with the loosely compressed fast melt formulations.13

 

Flashtab technology:

This is patented by Ethypharm France . This technology includes granulation of excipients by wet or dry granulation method followed by compression into tablets. Excipients used in this technology are of two types. Disintegrating agents include reticulated polyvinylpyrrolidine or carboxy methylcellulose. Swelling agents include carboxymethylcellulose, starch, modified starch, microcrystalline cellulose, carboxy methylated starch, etc. These tablets have satisfactory physical resistance

 

Orasolv technology:

This technology is patented by CIMA Labs. This includes use of effervescent disintegrating agents compressed with low pressure to produce the ODT. The evolution of carbon dioxide from the tablet produces fizzing sensation, which is a positive organoleptic property. Concentration of effervescent mixture usually employed is 20-25% of tablet weight.

 

Durasolv technology:

This technology is patented by CIMA Labs. The tablets produced by this technology utilize the conventional tableting equipment. Tablets in this are formulated by using drug, nondirect compression fillers, and lubricants.

 

WOW tab technology:

Yamanouchi patented this technology. WOW means without water. This technology utilizes conventional granulation and tableting methods to produce ODT employing low- and high-moldable saccharides. It is used for both water-soluble and insoluble drugs, the breakthrough WOWTAB™ technology provides quick, convenient and consistent dosing for patients of all ages having swallowing difficulties.

 

Pharmaburst technology:

Pharmaburst™ is a “Quick Dissolve” delivery system patented by SPI Pharma. Pharmaburst is a co-processed excipient system with specific excipients, which allows rapid disintegration and low adhesion to punch faces.14

 

Advantol™ 200:

Advantol™ 200 is a directly compressible excipient system offering "Soft-Melt" functionality and specially formulated for nutraceutical applications. SPI Pharma’s Advantol platform uses proprietary co-processing technology. Advantol requires no special manufacturing equipment or tooling. Advantol formulations utilize a standard rotary tablet press with standard tooling under normal tableting temperature and humidity conditions to make robust “soft-melt” tablets.15

 

 

Frosta technology:

Akina patents this technology. It utilizes the concept of formulating plastic granules and compressing them at low pressure to produce strong tablets with high porosity. Plastic granules composed of porous and plastic material, water penetration enhancer, and binder. The process involves mixing the porous plastic material with water penetration enhancer followed by granulating with binder. The tablets obtained have excellent hardness and rapid disintegration time ranging from 15 to 30 sec depending on size of tablet.

 

Advatab:

AdvaTab tablets disintegrate rapidly in the mouth, typically in less than 30 seconds, to allow for convenient oral drug administration without water. These tablets are especially suited to those patients that experience difficulty in swallowing capsules and tablets. AdvaTab is distinct from other ODT technologies as it can be combined with Eurand’s complimentary particle technologies like its world leading Microcaps® taste-masking technology and its Diffucaps® , controlled release technology. The pairing of AdvaTab with Microcaps creates products that offer the dual advantage of a patient preferred dosage form, together with a superior taste and smooth mouth feel. This is a critical advantage as the unpleasant taste of drugs is a significant restriction in the application of other ODT technologies.16

 

Drugs To Be Promising In Corporated In Fast Dissolving Tablets:17-19

There are no particular limitations as long as it is a substance which is used as a pharmaceutical active ingredient.

 

Analgesics and Anti-inflammatory Agents:

Aloxiprin, Auranofin, Azapropazone, Benorylate, Diflunisal, Etodolac, Fenbufen, Fenoprofen Calcim, Flurbiprofen, Ibuprofen, Indomethacin, Ketoprofen, Meclofenamic Acid, Mefenamic Acid, Nabumetone, Naproxen, Oxaprozin, Oxyphenbutazone, Phenylbutazone, Piroxicam, Sulindac.

 

Anthelmintics :

Albendazole, Bephenium Hydroxynaphthoate, Cambendazole, Dichlorophen, Iverrnectin, Mebendazole, Oxarnniquine, Oxfendazole, Oxantel Embonate, Praziquantel, Pyrantel Embonate, Thiabendazole.

 

Anti-Arrhythmic Agents:

Amiodarone, Disopyramide, Flecainide Acetate, Quinidine Sulphate,

 

Anti-bacterial Agents:

Benethamine Penicillin, Cinoxacin, Ciprofloxacin, Clarithromycin, Clofazimine, Cloxacillin, Demeclocycline, Doxycycline, Erythromycin, Ethionamide, Imipenem, Nalidixic Acid, Nitrofurantoin, Rifampicin, Spiramycin, Sulphabenzamide, Sulphadoxine, Sulphamerazine, Sulphacetamide, Sulphadiazine, Sulphafurazole, Sulphamethoxazole, Sulphapyridine, Tetracycline, Trimethoprim.

 

Anti-coagulants:

Dicoumarol, Dipyridamole, Nicoumalone, Phenindione. Anti-Depressants: Amoxapine, Ciclazindol, Maprotiline, Mianserin, Nortriptyline, Trazodone, Trimipramine Maleate., Acetohexamide, Chlorpropamide, Glibenclamide, Gliclazide, Glipizide, Tolazamide, Tolbutamide.

Anti-Epileptics:

Beclamide, Carbamazepine, Clonazepam, Ethotoin, Methoin, Methsuximide, Methylphenobarbitone, Oxcarbazepine, Paramethadione, Phenacemide, Phenobarbitone, Phenytoin, Phensuximide, Primidone, Sulthiame, Valproic Acid.

 

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-Muscarinic Agents:

Atropine, Benzhexol, Biperiden, Ethopropazine, Hyoscine Butyl Bromide, Hyoscyarnine, Mepenzolate Bromide, Orphenadrine, Oxyphencylcimine, Tropicamide.

 

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 Protozoal Agents:

Benznidazole, Clioquinol, Decoquinate, Diiodohydroxyquinoline, Diloxanide Furoate, Dinitolmide, Furzolidone, Metronidazole, Nimorazole, Nitrofurazone, Omidazole, Tinidazole.

 

Anti-Thyroid Agents:

Carbimazole, Propylthiouracil.

 

Anxiolytic, Sedatives, Hypnotics And Neuroleptics:

Alprazolam, Amyiobarbitone, Barbitone, Bentazeparn, Bromazepam, Bromperidol, Brotizoiam, Butobarbitone, Carbromal, Chlordiazepoxide, Chlormethiazole, Chlorpromazine, Clobazam, Clotiazepam, Clozapine, Diazepam, Droperidol, Ethinamate, Flunanisone, Flunitrazepam, Fluopromazine, Flupenuiixol Decanoate, Fluphenazine Decanoate, Flurazepam, Haloperidol, Lorazepam, Lormetazepam, Medazepam, Meprobamate, Methaqualone, Midazolam, Nitrazepam, Oxazepam, Pentobarbitone, Perphenazine Pimozide, Prochlorperazine, Suipiride, Temazepam, Thioridazine, Triazolam, Zopiclone.

Tj-Blockers :

Acebutolol, Alprenolol, Atenoiol, Labetalol, Metoptolol, Nadolol, Oxprenolol, Pindolol, Propranolol.

 

Cardiac Inotropic Agents:

Amrinone, Digitoxin, Digoxin, Enoximone, Lanatoside C, Medigoxin.

Corticosteroids:

Beclomethasone, Betamethasone, Budesonide, Cortisone Acetate, Desoxymethasone, Dexamethasone, Fludrocortisone Acetate, Flunisolide, Flucortolone, Fluticasone Propionatu, Hydrocortisone, Methylprednisolone, Prednisolone, Prednisone, Triamcinolone.

 

Diuretics:

Acetazolarnide, Amiloride, Bendrofluazide, Bumetanide, Chlorothiazide, Chlorthalidone, Ethacrynic Acid, Frusemide, Metolazone, Spironolactone, Triamterene. Enzymes : All The Enzymes.

 

Anti-Parkinsonian Agents:

Bromocriptine Mesylate, Lysuride Maleate.

 

Gastro-Intestinal Agents:

Bisacodyi, Cimetidine, Cisapride, Diphenoxylate, , Domperidone, Famotidine, Loperamide, Mesalazine, Nizatidine, Omeprazole, Ondansetron, Ranitidine, Sulphasaiazine.

 

Histamine H,-Receptor Antagonists:

Acrivastine, Astemizole, Cinnarizine, Cyclizine, Cyproheptadine, Dimenhydrinate, Flunarizine, Loratadine, Meclozine, Oxatomide, Terfenadine, Triprolidine.

 

Lipid Regulating Agents:

Bezafibrate, Clofibrate,Fenofibrate, Gemfibrozil, Probucol.

 

Local Anaesthetics:

Lidocaine

 

Neuro -Muscular Agents:

Pyridostigmine.

 

Nitrates And Other Anti-Anginal Agents:

Amyl Nitrate, Glyceryl Trinitrate, Isosorbide Dinitrate, Isosorbide Mononitrate, Pentaerythritol Tetranitrate.

 

Nutritional Agents:

Betacarotene, Vitamin A, Vitamin B 2 , Vitamin D, Vitamin E, Vitamin K.

 

Opioid Analgesics:

Codeine, Dextropropyoxyphene, Diamorphine, Dihydrocodeine, Meptazinol, Methadone, Morphine, Nalbuphine, Pentazocine.

 

Oral Vaccines:

Vaccines Designed To Prevent Or Reduce The Symptoms Of Diseases Of Which The Following Is A Representative

Influenza, Tuberculosis, Meningitis, Hepatitis, Whooping Cough, Polio, Tetanus, Diphtheria, Malaria, Cholera, Herpes, Typhoid, Hiv, Aids, Measles, Lyme Disease, Travellers Diarrhea, Hepatitis A, B And C, Otitis Media, Dengue Fever, Rabies, Parainfluenza, Rubella, Yellow Fever, Dysentery, Legionnaires Disease, Toxoplasmosis, Q-Fever, Haemorrhegic Fever, Argentina Haemorrhagic Fever, Caries, Chagas Disease, Urinary Tract Infection Caused By E.Coli, Pneumoccoccal Disease, Mumps, File://H:\Gits Mdt\Fast Dissolving Tablet The Future Of Compaction And Chikungunya.

 

Proteins, Peptides And Recombinant Drugs:

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).

 

Sex Hormones:

Clomiphene Citrate, Danazol, Ethinyloestradiol, Medroxyprogesterone Acetate, Mestranol, Methyltestosterone, Norethisterone, Norgestrel, Oestradiol, Conjugated Oestrogens, Progesterone, Stanozolol, Stiboestrol, Testosterone, Tibolone.

 

Stimulants:

Amphetamine, dexamphetamine, dexfenfluramine, fenfluramine, mhazindol, pemoline.

 

There are no particular limitations on the amount of these drugs to be mixed as long as it is the usual effective treatment amount. It should be around 50 weight/weight % or below of the entire tablet, and is preferably 20 weight/weight % or below.

 

Optimal disintegration properties often have medium to small size and /or high friability and low hardness. Breakage of tablet edges during handling and tablet rupture during the opening of blister alveolus, all result from insufficient physical resistance.

 

Evaluation Of Fast Dissolving Tablet21, 22

The mouth disolving tablets are to be evaluated for following tests:

General appearance, size and shape, table in vivo dsintegration testt thickness, uniformity of weight, tablet hardness, friability, wetting time,  and stability testing of drug (temperature dependent stability studies)

 

Marketed Fast Dissolving Tablets in India

Name of the
Product

Active
Ingredients

Imodium Lingual

Imodium

Pepcidin Rapitab

Quick releasing antiulcer
preparation of pepcid

Mosid – MT

Mouth melt tablet of Mosapride
citrate.

Calritin Reditabs

Immediate Dissolving formulation of Calritin

Nimulid – MD

Nimesulide

Zyrof Meltab

Rofecoxib

Claritin Reditab

micronized loratadine

Feldene Melt

piroxicam (10 or 20 mg),

Maxalt-MLT

rizatriptan (5 or 10 mg),
peppermint flavour

Pepcid RPD

famotidine (20 or 40 mg),

Zyprexa Zydis

olanzapine (5, 10, 15 or 20 mg),

Zofran ODT

ondansetron (4 or 8 mg),
strawberry flavor

Remeron Soltab

mirtazepine (15, 30, or 45 mg),
orange flavor

 

CONCLUSIONS:

The FDTs have potential advantages over conventional oral dosage forms with their improved patient compliance; convenience, bioavailability and rapid onset of action which drawn the attention of many manufactures over a decade. FDT formulations obtained by some of these technologies have sufficient mechanical strength, quick disintegration/dissolution in the mouth. Many drugs can be incorporated in FDT especially unpalatable drugs. The research is still going on. More products need to be commercialized to use this technology properly. Thus FDT may be developed for most of the available drugs in near future.

 

REFERENCES:

1.     http://www.fda.gov/cder/guidance/5909dft.htm

2.     Ed L Hamilton, Eugene M Lutz. Orally disintegrating tablets, Drug Delivery Technology 2005, 5(1).

3.     Jamali F, Aghazadeh H A. Rapidly dissolving formulations for quick absorption during pain episodes: ibuprofen, Int J Clin Pharmacol Ther. 2008, 46(2):55-63.

4.     http://www.drugdeliverytech.com/cgi-bin/articles.cgi?idArticle=164

5.     Dong Y, Kulkarni R, Behme R J, Kotiyan PN. Effect of the melt granulation technique on the dissolution characteristics of griseofulvin, International Journal of Pharmaceutics 2007, 329 (1-2) :72-80.

6.     Abdelbary G, Prinderre P, Eouani C, Joachim J, Reynier J P, Piccerelle P. The preparation of orally disintegrating tablets using a hydrophilic waxy binder, International Journal of Pharmaceutics 2004, 278(2): 423-433.

7.     Kuno Y, Kojima M, Ando S, Nakagami H. Evaluation of rapidly disintegrating tablets manufactured by phase transition of sugar alcohols, Journal of Controlled Release 2005, 105(1-2): 16-22.

8.     Koizumi K, Watanabe Y, Morita K, Utoguchi N, Matsumoto M. New method of preparing high-porosity rapidly saliva soluble compressed tablets using mannitol with camphor, a subliming material, International Journal of Pharmaceutics 1997, 152(1): 127-131.

9.     Gohel M, Patel M, Amin A, Agrawal R, Dave R, Bariya N. Formulation design and optimization of mouth dissolve tablets of nimesulide using vacuum drying technique, AAPS PharmSciTech 2004, 5(3): 10-15.

10.   Yu DG, Shen XX, Han J, Zhu LM, Branford-White C, Li XY, Yang XL. Oral Fast-Dissolving DDD Fabricated Using 3DP, Bioinformatics and Biomedical Engineering, 2008. ICBBE 2008. The 2nd International Conference 16-18 May 2008 :1602 – 1605.

11.   Ito A, Sugihara M. Development of oral dosage form for elderly patients: use of agar as base of rapidly disintegrating oral tablets, Chem Pharm. Bull. 1996, 44(11):2132-6.

12.   Mishra DN, Bimodal M, Singh SK, Vijaya Kumar SG. Spray dried excipient base: a novel technique for the formulation of orally disintegrating tablets. Chem Pharm Bull 2006, 54(1):99-102.

13.   Patrick Kearney (ed.), The zydis oral fast dissolving dosage form; In: Modified release drug delivery technology. New York , Marcel Dekker.2003; 192-194.

14.   http://www.spipharma.com/default.asp?contentID=617

15.   http://www.spipharma.com/default.asp?contentID=621

16.   http://www.eurand.com/Technologies/Dosage-Form-Technology/AdvaTab/

17.   15.Francesco Cilurzo, 2005,  Fast-dissolving mucoadhesive microparticulate delivery system containing piroxicam, Eur. J. Pharm. Sci., 24, 355-361.

18.   16.Rasetti-Escargueil, C., Grange, V., 2005, Pharmacokinetic profiles of two tablet formulations of piroxicam., Int. J. Pharm., 13, 129-34.

19.   17.Abdelbary, G., Eouani, C., Prinderre, P., Joachim, J., Reynier, J., and Piccerelle, P., 2005, Determination of the in vitro disintegration profile of rapidly disintegrating tablets and correlation with oral disintegration,Int.J.  Pharm., 292, 1-2, 29-41.

20.   Bradoo, R., Fast Dissolving Drug Delivery Systems, JAMA India, 2001, 4 (10), 27-31.

21.   .Kuchekar, B. S., Mahajan, S., and Bandhan, A. C., Mouth dissolve tablets of sumatriptan, Indian Drugs, 2004, 41(10), 592-598.

22.   20.Lalla. J K.,  Mamania, H. M.,  2004, Fast dissolving rofecoxib tablets, Indian J. Pharm. Sci.,59(4), 23-26.

 

 

 

Received on 19.12.2009

Accepted on 12.02.2010   

© A&V Publication all right reserved

Research Journal of Pharmaceutical Dosage Forms and Technology. 2(2): March –April. 2010, 120-124