Different approaches of fast-melts tablets : A review

By - 10/17/2007

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Tarun Kumar Satpathy

Tarun Kumar Satpathy

Now a day’s pharmaceutical scientists get hold of a better understanding of the physicochemical and biochemical parameters relevant to their routine, hence drug delivery systems are flattering progressively refined.

Regardless of different advancements in drug delivery, the oral route remains the perfect route for the administration of therapeutic agents because the low cost of therapy and ease of administration lead to high levels of patient compliance.

Recently Fast melts drug delivery systems have started gaining popularity and receiving as one such example with amplified consumer choice, for the reason of speedy disintagration or dissolution, self administration even without water or chewing. This can be achieved by various conventional methods like direct compression, wet granulation, moulding, spray drying, freeze drying, and sublimation. Some patented technology are also there to formulate this dosage form such as Zydis technology, wowtab technology, OraSolv technology, DuraSolv technology, FlashDose technology, Flashtab technology, OraQuick technology, Quick-Dis technology and NanoCrystal technology. For masking the obnoxious taste of the drug different polymers bring into play for coating, different resins utilize for complex formation, sweeteners and flavors draw on in direct compression while formulating this form of delivery system.

Introduction-

More than 50% of pharmaceutical products are orally administered for several reasons. This route of administration is considered as the most widely used route as it offers advantages like ease of administration, versatility, patient compliance and accurate dosing. Undesirable taste is one of the important formulation problems that are encountered with such oral products¹. Difficulty in swallowing is also a common problem of all age groups, especially the elderly and pediatrics, because of physiological changes associated with these groups ^{2, 3, 4}.

Consumer satisfaction is the buzzword of the current millennium to achieve. It has been already begun in the pharmaceutical industry. Taste of a pharmaceutical product is an important parameter governing compliance. Hence taste masking of oral pharmaceuticals has become important tool to improve patient compliance and the quality of treatment especially in paediatrics. Hence formulation of taste-masked products is a challenge to the pharmacist^5,6. Consumer acceptability certainly affects the commercial success of the product in the market. Various techniques are available to mask the bitter taste or to improve the taste such as by using polymeric coatings, complexation with cyclodextrins, ion exchange resins and use of excipients like flavours and sweetners.

Faster onset of action may be very valuable for faster relief. A liquid dosage form, like a solution or dispersion will be suitable for faster action, Masking the taste of a bitter drug and improving the rate of dissolution of less soluble drug become important considerations in liquid formulation. Also, it is well known that liquid dosage forms, suffer from the drawbacks of inaccuracy of dosage and inconvenience of transportation and handling. Hence considering all the above points the solid dosage form, which can be administered or swallowed as a liquid where in the bitter taste of drug is masked would be a very ideal dosage form. One such approach is fast mouth dissolving tablet⁷.

Fast dissolving drug delivery systems have started gaining popularity and acceptance as new drug delivery systems which aim to enhance safety and efficacy of drug molecule by formulating a convenient dosage form for administration and to achieve better patient compliance. Their growing importance was underlined recently when European pharmacopoeia adopted the term “Oro-dispersible tablet” as a tablet that to be placed in the mouth where it disappears rapidly before swallowing^8,9. Orodispersible tablets are also known as quick dissolves, fast melts, fast dissolving, fast disintegrating, rapid-dissolve, or orally dissolving tablets ¹⁰.

Mouth dissolving drug delivery system emerged from the desire to provide patient with more conventional means of taking their medication. It is difficult for many patients to swallow tablets and gelatin capsules. Hence they do not comply with prescription, which results in non-compliance and ineffective therapy. In some cases such as motion sickness, sudden episodes of allergic attacks or coughing and unavailability of water, swallowing conventional tablets may be difficult. Paediatric and geriatric patients experience particularly this difficulty. Such problems can be resolved by means of mouth dissolving tablet. When put on tongue, this tablet disintegrates instantaneously, releasing the drug, which dissolves or disperses in the saliva. Some drugs are absorbed from the mouth, pharynx and esophagus as the saliva passes down into the stomach. In such cases, bioavailability of drug is significantly greater than those observed from conventional tablet dosage form.

Desired criteria for mouth dissolving drug delivery system¹¹

Mouth dissolving tablet should

1. Not require water to swallow, but it should dissolve or disintegrate in the mouth in matter of seconds.

2. Be compatible with taste masking.

3. Be portable without fragility concern.

4. Have a pleasing mouth feel.

5. Leave minimal or no residue in the mouth after oral administration.

6. Exhibit low sensitivity to environmental conditions as humidity and temperature.

7. Allows the manufacture of tablet using conventional processing and packaging equipment at low cost.

The several advantages ^11,12 of fast dissolving dosage formsare

1. Ease of administration for patients, those who are not co-operative.

2. Quick disintegration and dissolution of the dosage form.

3. Can be swallowed without water.

4. Allows high drug loading.

5. Can be designed to leave minimal or no residue in the mouth after administration and also provide a pleasant mouth feel.

Various techniques used for preparing mouth dissolving tablets ^11,12,13,14 are by freeze drying, moulding, sublimation,spray drying, mass-extrusion and direct compression. Patented technologies for mouth dissolving tablets are zydis technology durasolv technology, ora solv technology, flash dose technology, wow technology ,flash tab technology, Ora-quick Technology, Quick-Dis Technology and Nano-crystal Technology.

Freeze drying:

A process, in which water is sublimated from the product after freezing, is called freeze drying. Freeze-dried forms offer more rapid dissolution than other available solid products. The lyophilization process imparts glossy amorphous structure to the bulking agent and some times to the drug, thereby enhancing the dissolution characteristics of the formulation.

The influence of various formulation and process parameters on the characteristics of rapidly disintegrating tablets in freeze dried form was investigated by Corveleyn and Remon ¹⁵who concluded that maltodextrins are useful in the formulation of fast dissolving tablets made by freeze drying.

Ahmed I. S. et al ¹⁶ were to develop a ketoprofen tablet which dissolve-rapidly in the mouth, therefore, needing not be swallowed. The solubility and dissolution rateof poorly water-soluble ketoprofen was improved by preparing a lyophilized tablet (LT) of ketoprofen using freeze-drying technique. The LT was prepared by dispersing the drug in an aqueous solution of highly water-soluble carrier materials consisting of gelatin, glycine, and sorbitol. The mixture was dosed into the pockets of blister packs and then was subjected to freezing and lyophilization.

Moulding:

Tablets produced by moulding are solid dispersions. Physical form of the drug in the tablets depends whether and to what extent; it dissolves in the molten carrier. The drug can exist as discrete particles or microparticles dispersed in the matrix. It can dissolve totally in the molten carrier to form solid solution or dissolve partially in the molten carrier and the remaining particles stay undissolved and dispersed in the matrix. Disintegration time, drug dissolution rate and mouth feel will depend on the type of dispersion or dissolution.

Cherukuri et al ¹⁷ have developed the method of preparing a comestible unit which disperses quickly in the mouth. The present invention also includes the product resulting from the method. The method includes initiating crystallization of shearform matrix and combining with an additive, either before or after initiating crystallization, to form flowable, compactible micro-particulates. The combination is then subjected to compacting to form a comestible unit having high structural integrity, good appearance, and excellent release characteristics.

Mizumoto et al ¹⁸ have done a Intrabuccally dissolving compressed moldings comprising a saccharide having low moldability having been granulated with a saccharide having high moldability.The moldings of the present invention show quick disintegration and dissolution in the buccal cavity and have an adequate hardness.

No-vacuum lyophilization is onother process which involves the evaporation of a solvent from a drug solution or suspension at standard pressure. Pebley et al.¹⁹, evaporated a frozen mixture containing a gum (e.g., acacia, carageenan, guar, tragacanth, or xanthan), a carbohydrate (e.g., dextrose, lactose, maltose, mannitol, or maltodextrin), and a solvent in a tablet shaped mould.

Sublimation:

Compressed tablets composed of highly water-soluble excipients as tablet matrix material often do not dissolve rapidly in the water. Porous tablets exhibit good mechanical strength and dissolve quickly. Inert solid ingredients {ex: urea, ammonium carbonate, camphor, naphthalene) were added to other tablet excipients and the blend was compressed into tablet. Removal of volatile material by sublimation generated a porous structure.

The highly porous mouth dissolving tablets of Domperidone was studied by Mane Avinash R.et al ²⁰, they formulated by using meltable binder polyethylene glycol-4000, a diluent mannitol and a component which sublimes readily camphor/ ammonium carbonate and later is removed from the tablet by sublimation process after compression.

Spray-Drying:

Highly porous and fine powders can be produced by spray drying process, as the processing solvent is evaporated rapidly during spray drying. For fast dissolving tablets, they developed formulation by using mannitol as bulking agent, hydrolysed and non-hydrolysed gelatin as support matrix, sodium starch glycolate as disintegrant and acidic material (ex. citric acid) and/or alkali material (ex.NaHCO₃) to enhance disintegration and dissolution. When immersed in an aqueous medium, the tablets compressed from spray-dried powder, disintegrated within 20 seconds).

Spray drying technique has been employed by Allen and Wang ²¹ to prepare fast dissolving tablet. They developed formulation by using mannitol as bulking agent, hydrolyzed or non hydrolyzed gelatin as support matrix, sodium starch glycollate as disintegrant citric acid and NaHCO3 to enhance the disintegration and dissolution.

Mass-Extrusion:

This technology involves softening the active blend using the solvent mixture of water soluble polyethylene glycol using methanol and 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. The dried cylinder can also be used to coat granules of bitter tasting drugs and thereby masking their bitter taste.

Dandagi P.M. et al ²²developed mouth disintegrating tablets of ofloxacin using aspartame as sweetener, sodium starch glycolate disintegrant and isopropyle alcohol as granulating agent and by mass extrusion technique using eudragit E100 as taste masking agent along with avicel 102 and ethanol.

Rapidly disintegrating domperidone tablets were formulated by Dandagi P.M²³.using two methods as mass extrusion technique and treated agar. In mass extrusion formulations sodium starch glycolate, eudragit E-100, low substituted hydroxyl propyl cellulose, lactose and in treated agar formulations mannitol, treated agar, lactose, aspartame were used as exciepients.

Direct Compression:

It is the easiest way to manufacture tablets. Conventional equipment, commonly available excipients and a limited number of processing steps are involved in direct compression. Directly compressed tablets disintegration and solubilization depends on single or combined action of disintegrants, water soluble excipients and effervescent agent. Disintegrant efficacy is strongly affected by tablet size and hardness. Large and hard tablets have disintegration time more than that usually required. As consequences, products with optimal disintegration properties often have medium to small size and /or high friability and low hardness. Breakage of tablet edges during handling, tablet rupture during the opening of blister alveolus all results from insufficient physical resistance.

Disintegrants have major role in the disintegration and dissolution process of mouth dissolving Tablets made by direct compression. To ensure a high dis- integration rate, choice of suitable type and an optimal amount of disintegrant is important. Other formulation components such as water-soluble excipients or effervescent agents can further enhance dissolution or disintegration properties. But main drawback of using effervescent excipients is their highly hygroscopic nature.

The understanding of disintegrant properties and their effect on formulation has advanced during last few years, particularly regarding so called super-disintegrants¹⁰. Disintegration efficiency is based on force equivalent concept, which is the combined measurement of swelling force development and amount of water absorption. Force equivalent expresses the capability of disintegrant to transform absorbed water into swelling force. The optimisation of tablet disintegration was defined by means of disintegrant critical concentration. Below this concentration, the tablet disintegration time is inversely proportional to disintegrant concentration and above that disintegration time remains approximately constant or even increases.

Koizumi k. et al ²⁴developed a direct compression method for the preparation, using mannitol and camphor, of a meclizine (antidinic agent) tablet with high porosity which dissolves rapidly in saliva. These compressed tablets which have high porosity (approximately 30%) rapidly dissolved within 15 s in saliva in the mouth.

Gilis et al ²⁵ were make a fast-dissolving tablet for oral administration comprising as an active ingredient a therapeutically effective amount of galanthamine hydrobromide (1:1) and a pharmaceutically acceptable carrier, characterized in that said carrier comprises a spray-dried mixture of lactose monohydrate and microcrystalline cellulose (75:25) as a diluent, and a disintegrant; and with a direct compression process of preparing such fast-dissolving tablets.

Bi et al.²⁶ and Watanbe et al.,²⁷ used microcrystalline cellulose (MCC) and low substituted hydroxypropyl cellulose (HPC) to manufacture rapidly disintegrating tablets. The ratios of MCC to HPC varied from 8:2 to 9:1.

Zydis Technology:^{28, 29}

Using concept of Gregory et al.³⁰ Scherer has patented the Zydis technology. Zydis, the best known of the fast-dissolving/disintegrating tablet preparations, was the first marketed new technology tablet. Zydis formulation is a unique freeze dried tablet in which drug is physically entrapped or dissolved within the matrix of fast-dissolving carrier material. When zydis units are put into the mouth, the freeze-dried structure disintegrates instan- taneously and does not require water to aid swallowing. The zydis matrix is composed of many materials designed to achieve a number of objectives. To impart strength and resilience during handling, polymers such as gelatin, dextran or alginates are incorporated. These form a glossy amorphous structure, which imparts strength.

Durasolv Technology:³¹

Durasolv is the patented technology of CIMA labs. The tablets made by this technology consist of a drug, fillers and a lubricant. Tablets are prepared by using conventional tableting equipment and have good rigidity. These can be packaged into conventional packaging system like blisters. Durasolv is an appropriate technology for products requiring low amounts of active ingredients.

Orasolv Technology:

CIMA labs have developed Orasolv technology. In this system active medicament is taste masked. It also contains effervescent disintegrating agent. Tablets are made by direct compression technique at low compression force in order to minimize oral dissolution time. Conventional blenders and tablet machine is used to produce the tablets. The tablets produced are soft and friable and packaged in specially designed pick and place system.

Ora-Solv technology has been developed by Mishra T.K. et al.³². In this system active medicament is taste masked by using effervescent disintegrating agent. Tablets were made by direct compression technique at low compression force in order to minimize oral dissolution time.

Flash Dose Technology:

Flash dose technology has been patented by Fuisz and is known as Shearform. The final product has a very high surface area for dissolution. It disperses and dissolves quickly once placed onto the tongue. Nurofen Meltlet, a new form of Ibuprofen as melt-in-mouth tablets. Flash dose tablets consist of self-binding shear form matrix termed as "floss". Shear form matrices are prepared by flash heat processing.

Wowtab Technology:

Wowtab technology is patented by Yarnanouchi Pharmaceutical Co. WOW means "With out water". In this process, combination of low mouldability saccharides and high mouldability saccharides is used to obtain a rapidly melting strong tablet. The active ingredient is mixed with a low mouldability saccharide and granulated with a high mouldability saccharide and compressed into tablet. The Wowtab product dissolves quickly in 15 seconds or less³³.

Wow tab technology was developed by yarwood et al³⁴.Wow means “Without water”. In this process combination of low mouldability saccharides and high mouldability saccharides is used to obtain a rapid melting strong tablet. The active ingredient is mixed with a low mould ability saccharide and granulated with a high mould ability saccharide and compressed in to tablet.

Flashtab Technology:

A Prographarm laboratory has patented the Flashtab technology. Tablets prepared by this system consist of an active ingredient in the form of microcrystals. Drug micro granules may be prepared by using the conventional techniques like coacervation, microencapsulation, and extrusion. All the processing utilized conventional tableting technology.

Mouth dissolving tablets are also developed by Flash tab technology. Mizumoto et al ¹⁸ utilized active ingredient in the form of microcrystals. Drug micro-granules may be prepared by using conventional techniques like coacervation, microencapsulation and extrusion.

Oraquick Technology:

KV pharmaceutical has patented this technology. Here the test masking process does not utilize solvents of any kind and therefore leads to faster and more efficient production. This claims quick dissolution in a matter of seconds, with good taste masking.^{35, 36}. KV pharmaceutical has products in development such as analgesics, scheduled drugs, cough and cold, psychotropics, and anti-infective.

Quick-Dis Technology:³⁷

The novel intraoral drug delivery system system, trademarked Quick-Dis^TM, is Lavipharm’s proprietary patented technology and is a thin, flexible, and quick-dissolving film. The typical release profile of an active ingredient exhibited by a Quick-Dis^TMdrug delivery system is 50 % released within 30 seconds and 95 % within 1 minute.

Nanocrystal Technology:³⁸

This technology has patented by Elan, which can enable formulation and improve compound activity and final product characteristics. Decreasing particle size increases the surface area, which leads to an increase in dissolution rate. Nanocystal particles are small particles of drug substance, typically less than 1000 nanometers (nm) in diameter, which are produced by milling the drug substance using a proprietary wet milling technique.

Formulation of Fast-melts tablets by using polymers as taste masking agent: -

Expert has proficiency in the practical application of polymers to a variety of industries involved with cosmetics, pharmaceuticals, biomedical products, flooring, photographic materials, roofing, and plastics. In pharmaceuticals polymers has been used in coating of materials, taste-masking materials, different drug delivery like sustained release, control release, transdermal release etc. In orodispersible tablet formulation the big challenge is to mask the taste. So many works has done in this content by using different polymers. Some of them has cited here.

Shishu and Bhatti A ³⁹have done a study where the attempt has been made to mask the bitter taste of Diazepam by microspheres formulation with eudragit E-100 and to formulate into a more accessible and patient compliant mouth disintegrating tablets

The Azithromycin dihydrate could be successfully taste masked using the technique of complexation was developed by Joshi SR et al ⁴⁰, they described that taste masked drug polymer complex could effectively incorporated into patient compliant oral suspension as well as dispersible tablets.

Ishikawa T et al ⁴¹ was prepare tablets which can rapidly disintegrate in saliva (rapidly disintegrating tablet), of drugs with bitter taste (pirenzepine HCI or oxybutynin HCI). The taste-masked granules were prepared using aminoalkyl methacrylate copolymers (Eudragit E-100®) by the extrusion method. The prepared tablets (compressed at 500 kgf) containing the taste-masked granules have sufficient strength (the crusing strength: oxybutynin tablet, 3.5 kg; pirenzepine tablet, 2.2 kg), and a rapid disintegration time (within 20 s) was observed in the saliva of healthy volunteers. None of the volunteers felt any bitter taste after the disintegration of the tablet which contained the taste-masked granules.

Ishikawa T et al ⁴² were prepared rapidly disintegrating tablets using microcrystalline cellulose (Avicel PH-M series), a new type of pharmaceutical excipient that is spherical and has a very small particle size (particle size, 7-32 microm), instead of conventional microcrystalline cellulose (PH-102) and spherical sugar granules (NP) used in the formulation of tablets containing acetaminophen or ascorbic acid as model drugs for tableting study and got the good disintegration time with a excellent mechanical strength.

Formulation of Fast-melts tablets by using ion-exchange resins as taste masking agent:-

Ion exchange resins have been increasingly used for the taste masking of bitter taste drug and help to prepare oro-dispersible tablets.^{43, 44}.

Ion exchange resins are solid and suitably insolubilized high molecular weight polyelectrolytes that can exchange their mobile ions of equal charge with the surrounding medium reversibly and stochiometrically. They are available in desired size ranges. Bitter cationic drugs can get adsorbed on to the weak cation exchange resins of carboxylic acid functionally to form the complex which is non bitter. Further resinates can be formulated as lozenges, chewing gum, suspension or dispersible tablet and mask the taste⁴⁵.

Drug can be bound to the resin by either repeated exposure of the resin to the drug in prolonged contact of resin with the drug solution. Drugs are attached to the oppositively charged resin substrates or resinates through weak ionic bonding so that dissociation of the drug-resin complex doesnot occur under salivary pH conditions. This suitably masks the unpleasant taste and odour of drugs⁴⁶.

Drug release from the resin depends on the two factors.

a)The ionic environment (i.e., pHand electrolyte concentration) with in the gastrointestinal tract.

b)The properties of resin.

Ion exchange resins can be classified into four major groups⁴⁷.

1. Strong acid cation exchange resin

Eg: - Amberlite IRP-69, Indion-224.

2. Weak acid cation exchange resin

Eg: - Amberlite IRP-65, Indion-204, Indion-234.

3. Strong base anion exchange resin

Eg: - Amberlite IRP-276.

4. Weak base anion exchange resin

Eg: - Dimethyl amine resin.

Strong acid cation exchange resins can be used for masking the taste of basic drugs as they function through out the entire pH range. Weak acid cation exchange resins functions at pH value above 6. Strong base anion resin function throughout the entire pH range. Weak base amino resins function below pH 7.

Polystyrene matrix cation exchange resins (Indion CRP-244, Indion CRP- 254) have been used to mask the bitter taste of Chlorpheniramine maleate, Ephedrine hydrochloride, Di phenhydramine hydrochloride.

Co-polymers of acrylic and methacrylic acid with divinyl Benzene (Indion-234) has been successfully used to mask the bitter taste of Chloroquine phosphate⁴³. Ciprofloxacin was also effectively taste masked using Indion 234⁴⁸. A mixture of coated and non-coated sulfuric acid cation exchange resins crosslinked with divinyl benzene is used to mask the taste of Dextromethorphen⁴⁹.

Avari JG and Bhalekar ⁵⁰ have worked on taste masking and rapid dissolution of Sparfloxacin by using cation exchange resins and they found that Indion-204 yielded maximum complexation for Sparfloxacin its drug resinate complex being taste less.

Amin Purnima et al ⁵¹ introduce Indion 414, an ion exchange resin, as a new superdisintegrant for pharmaceutical dosage forms. Indion 414 is a pharmaceutical grade weak acid cation exchange resin. Model drugs belonging to various classes were taste masked and formulated into palatable mouth dissolve tablets. Experiments were carried out to evaluate the disintegrant property of Indion 414 by incorporating Indion 414 in fast disintegrating dosage form like mouth dissolve tablets. Indion 414 was compared with the conventional disintegrants to determine its relative efficacy.

Wadhwani K et al ⁵² were studied by using ion exchange resins complexation with Roxithromycin and formulated in to taste masked mouth dissolving tablet.

Conclusion –

To deliver the drug is the main aim of a pharmacist while manufacturing the products. But the delivery system which will aim to improve the patient compliance and convenience is the better one. Now a day’s patient demand is increasing to get the drug in smooth ways. More over this fast melts delivery is the solid dosage form, which is the oldest and convenient in its own ways. It has been accepted by all types of patients except geriatrics and pediatrics as it has discussed in earlier part of this article. This fast melts delivery system give all advantage of solid as well as liquid dosage form by overcoming the disadvantage of the both dosage form. Keeping all the advantages of this delivery system in mind, in near future these forms are anticipated to become more well-liked drug delivery system.

Reference:

Hiremath JG, Shastry CS, Srinath MS. “Pharmaceutical approaches of taste masking in oral dosage forms”, Indian drugs, 2004, 41(5), 253-57.
Lindegreen S. and Janzon L. Dysphagia: “Prevalence of swallowing complaints and clinical findings”, Medical Clinics of North America, 1993, 77, 3-5.
Bhushan S.Y., Sambhaji S.P., and Kakasaheb R.M., “New drug delivery system for elderly”, Indian Drugs, 2000, 37, 312-18.
Slowson, M., Slowson, S., “What to do when patients cannot swallow their medications”, Pharm. Times, 1985, 51, 90-96.
Amita nanda R, Kandarapu, Garg S., “An update on taste masking technologies for oral pharmaceuticals” Indian J Pharm Sci, 2002, 64(1), 13-17.
Tony Nunn and Julie Williams, “Formulation of medicines for children”, British Journal of Clinical Pharmacology, 2005, 59 (6), 674–676
Reddy LH, Bijaya ghos, Bhadhan AC. “Mouth dissolve tablets of Sumatriptan succinate”, Indian J Pharm sci, 2004; 66(2): 238-40
US Food and Drug Administration”, CDER Data Standards Manual, 2003, http://www.fda.gov/cder/dsm/DRG/drg00201.htm
“European Directorate for the Quality of Medicines”, Pharmeuropa, 1988, 10 (4), 547, http://www.pheur.org/
Wayne C., Dipan R., Ann D., “Selecting superdisingrants for orally disintegrating tablet formulations”, Pharmaceutical Technology, Oct 1, 2006, http://www. Pharmtech. com/pharmtech/article/articleDetail.jsp?id=378398
Ms. Parul B. Patel, Amit Chaudhary, Dr. G. D. Gupta , “Fast Dissolving Drug Delivery Systems :An Update", Sunday, 02 July 2006,http://www.pharmainfo.net/ exclusive/ reviews/fast_dissolving_drug_delivery_systems:_an_update/
Kaushik D. Dureja H. and Saini T.R., “Mouth dissolving tablets: A Review, Indian Drugs”, 2004, 41(4) , 188
William R. Pfister, Tapash K. Ghosh, “Orally Disintegrating Tablets Products, Technologies, and Development Issues”, Pharmaceutical Technokogy, Oct 2, 2005, http://www.pharmtech.com/pharmtech/article/articleDetail.jsp?id=185957
Robin H. Bogner, Meghan F. Wilkosz, “Fast Dissolving Tablets”, US Pharmacist, A Jobson Publication, http://www.uspharmacist.com/oldformat.asp?url=newlook/ files/Feat/ FastDissolving.htm&pub_id=8&article_id=842
Remon; Jean Paul, Corveleyn; Sam, “Freeze-dried disintegrating tablets”, United States Patent, 6, 010, 719, 2000.
Ahmed, I. S.; Nafadi, M. M.; Fatahalla, F. A.^“Formulation of a Fast-Dissolving Ketoprofen Tablet Using Freeze-Drying in Blisters Technique”, Drug Dev and Ind Pharm, 2006, 32 (4), 437-442.
Cherukuri, Subraman R.; Myers, Garry L.; Battist, Gerald E.; Fuisz, Richard C., “Process for forming quickly dispersing comestible unit and product therefrom”,United States Patent, 5, 587, 172, 1996
Mizumoto, Takao; Masuda, Yoshinori; Fukui, Muneo., “Intrabuccally dissolving compressed moldings and production process thereof”, United States Patent, 5, 576, 014, 1996.
Pabley, W.S., Jager, N.E. and Thompson S.J., “Rapidly Disintegrating Tablet”,United States Patent, 5, 298, 261, 1994
Mane Avinash R, Kusum devi V and Asha AN. “A novel technique for preparation of mouth dissolving tablets of Domperidone” Indian drugs, 2003; 40(9), 544-6.
Allen LV, Wang B: “Particulate support matrix for making a rapidly dissolving tablet”, US patent, 5, 595,761, 1997
Dandag P.M., Sreenivas S.A., Manvi F.V., Patil M.B., Mastiholimath V.S., and Gadad A.P., “Taste masked ofloxacin mouth disintegrating tablets”, Indian drugs, 2005, 42(1), 52-55.
Dandag P.M., Halakatti P.K., Mastiholimath V.S., Patil M.B. and Manvi F.V., “Rapidly disintegrating domperidone tablets”, Indian drugs, 2006, 43(7), 594-597
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
Gilis, Paul Marie Victor; De Conde, Valentin Florent Victor, “Fast-dissolving galanthamine hydrobromide tablet”, United States Patent, 6,099,863, 2000.
Bi, Y. et al., “ Preparation and Evaluation of a Compressed Tablet Rapidly Disintegrating in the Oral Cavity”, Chem. Pharm. Bull., 1996, 44 (11), 2121-2127.
Wantanabe, Y. et al., “ New Compressed Tablet Rapidly Disintegrating in the Mouth using Crystalline Cellulose and a Disintegrant”, Biol. Pharm. Bull., 1995, 18 (9), 1308-1310.
Seager, H., “ Drug-deliver Products and the Zydis Fast-dissolving Dosage Form”, J. Pharm. and Pharmacol., 1998, 50, 375-382.
Schering Corporation. Product Information for Claritin Brand of Loratadine, September 2000, 6.
Gregory, G.K.E., Peach, J.M. and Du Mayna, J.D., United States Patent, 4, 371, 516, 1983.
CIMA Labs, Inc. CIMA--Technologies. 25 May 2001 http://www.cimalabs.com/tech.htm
Mishra TK, Cuming ton JW, Kamath SV, Sanghvi PP, Sisak JR and Rajan MG: “Fast-dissolving comestible units formed under high-speed/high-pressure condition”, US patent, 5, 869, 098, 1999
Yamanouchi Pharma Technologies, Inc. WOWTAB. 20 June 2001 http://www.ypharma.com/wowtab.shtml
Yarwood RJ, Kearny P and Thomson AR, “Process for preparing solid pharmaceutical dosage forms”, US patent. 5, 738, 875, 1998.
KV Pharmaceutical Company. Drug Delivery Technologies (technical bulletin) found in part at KV Pharmaceutical Company. OraQuick, 27 May 2001 http://www.kvpharma.com/tech/3_1_oraquick.html and KV Pharmaceutical Company. Quick-Dissolving Tablets. 27 May 2001.
Proulx SM and Melchiorre HA. New Dosage Forms Lead to Confusion. US Pharm. 2001, 26(2), 68-70.
Liang AC, Chen, Li-Lan H, Fast-dissolving Intraoral drug delivery systems, Expert Opinion, 2001, 11(6), 981-986.
www. ElanNanoCrystal_Technology.htm
Shishu and Bhatti A., “fast disintegrating tablets of diazepam”, Indian drugs, 2006, 43(8), 643-648.
Joshi SR, Prabhu MV, Bhalla AS, Patravale VB. “Taste masked Azithromycin dosage forms”, Indian J Pharm Sci, 2004, 66(4), 508-09
Ishikawa T.; Watanabe Y; Utoguchi N.; Matsumoto M; “Preparation and evaluation of tablets rapidly disintegrating in saliva containing bitter-taste-masked granules by the compression method”, Chem. Pharm. Bull, 1999, 47(10), 1451-1454.
Ishikawa T, Mukai B, Shiraishi S, Utoguchi N, Fujii M, Matsumoto M, Wataabe Y., “Preparation of rapidly disintegrating tablet using new types of microcrystalline cellulose (PH-M series) and low substituted-hydroxypropylcellulose or spherical sugar granules by direct compression method”, Chem Pharm Bull. Feb 2001, 49(2), 134-9.
Agarwal R, Mittal R, Singh A., “Studies of ion-exchange resin complex of chloroquine phosphate”, Drug Dev Ind Pharm., 2000, 26(7), 773-6.
Manek S .P. Kamat V.S. “Evaluation of Indion CRP 244 and Indion CRP 254 as sustained release and taste masking agents”, Ind. J.Pharm.Sci., 1981, 26, 773-776
Avari JG, Bhalekar M. “Cation exchange resins for taste masking and rapid dissolution of Sparfloxacin” Indian drugs, 2004, 41(1), 19-23.
Harmik sohi, Yasmin sultana and Roop K Hars. “Taste masking technology in oral pharmaceuticals:Recent development and approaches”, Drug Dev Ind Pharm. 30, 429-48.
Ashwini R. Madgulkar, Mangesh R Bhalekar, Nitin D. Wable, Vinay J. Kolhe, and Krishna G. Patel, “Ion Exchange Resins in Formulation, An Update”, 25 Feb 2007,http://www.pharmainfo.net/exclusive/reviews/ion_exchange_resins_in_formulation_:_an_update/
Pisal S, Zainnuddin R, Nalawade P, Mahadik K, Kadam S. “Molecular Properties of Ciprofloxacin-Indion 234 Complexes”, AAPS PharmSciTech., 2004, 5(4), Article 62.
Wen, Betty, Ramsay, Michael P, Scheurer, Hein rich dokuzovic, Val, Lam, Vincent. “Antussive drugs delivered by ion exchange resins”, United State patent, 6, 001, 392, 1997.
Avari JG, Bhalekar M. “Cation exchange resins for taste masking and rapid dissolution of Sparfloxacin” Indian drugs, 2004, 41(1), 19-23.
Amin Purnima, Prabhu Namita, Wadhwani Anita, “Indion 414 as superdisintegrant in formulation of mouth dissolve tablets”, Indian Journal of Pharmaceutical Sciences, 2006, 68, 1, 117-119.
Wadhwani AR, Amin PD. “Mouth dissolve tablets of Roxithromycin” Indian J Pharm Sci, 2002, 64(3), 295-6.

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