Because of the increase in the average human life span and the decline, with age, in swallowing ability, oral tablet administration to patients is a significant problem and has become the object of public attention. ^{4, 5}

Traditional tablets and capsules administered with an 8-oz. glass of water may be inconvenient or impractical for some patients. However, some patients, particularly pediatric and geriatric patients, have difficulty swallowing or chewing solid dosage forms⁷. Many pediatric and geriatric patients are unwilling to take these solid preparations due to fear of choking⁸. For example, a very elderly patient may not be able to swallow a daily dose of antidepressant. An eight-year-old with allergies could use a more convenient dosage form than antihistamine syrup. A schizophrenic patient in the institutional setting can hide a conventional tablet under his or her tongue to avoid their daily dose of an atypical antipsychotic. A middle-aged woman undergoing radiation therapy for breast cancer may be too nauseous to swallow her H2-blocker. Fast-dissolving/disintegrating tablets (FDTs) are a perfect fit for all of these patients⁶.

The problem can be resolved by the creation of rapidly dispersing or dissolving oral forms, which do not require water to aid swallowing. The dosage forms are placed in the mouth, allowed to disperse or dissolve in the saliva, and then are swallowed in the normal way. Less frequently, they are designed to be absorbed through the buccal and oesophageal mucosa as the saliva passes into the stomach. In the latter case, the bioavailability of a drug from fast-dispersing formulations may be even greater than that observed for standard dosage forms. Furthermore, side effects may be reduced if they are caused by first pass metabolites. ^{7, 8}

ADVANTEGES:^9,10

Ease of administration to the patient who can not swallow like mentally ill, disabled, and uncooperative, strock victim, health care facility and bedridden patients.

It allows ease of termination of therapy.

It produced rapid on set of action and pregastric absorption increase the bioavailability.pregasric absorption may also reduce the dose of drug if a significant amount of drug is lost through hepatic metabolism. as a result of reduced dosages, it may give improved clinical performance and reduction of unwanted effects.

The highly beneficial feature of this dosage form is the patient who are traveling and busy people who do not have immediate accesses of water can swallow this dosage form very easily.

Fast disintegrating tablet are considered as a new dosages form. Therefore, pharmaceutical companies may get different advantages such as line extension and life cycle management, patent life extension, exclusivity of product promotion and product differentiation.

CHARACTERISTIC AND DEVELOPMENT CHALLENGES TO FDT:

Because administration of FDT_S is different from the conventional tablet, the FDT_S should have several unique properties accommodate several properties essential to FDT_S are listed below.

Fast disintegration:

FDT_S should disintegrate in the mouth with out taking water or with a very small amount (e.g., 1 or 2 ml) of water. The disintegrating fluid is provided by the saliva of the patient. The disintegrated tablet should become a soft paste or liquid suspension which can provide good mouth feel and smooth swallowing.

Taste of active ingredient:

Because fast dissolving tablet dissolve or disintegrate in patient’s mouth the drug will be partially dissolve in close proximity to the taste bud. After swallowing, there should minimum or no residue in the mouth. A pleasant taste inside the mouth is a critical for patient acceptance. Unless the drug id taste less or does not have undesirable taste, taste masking technique should be used. An ideal taste masking technology should provide drug without grittiness and with good mouth feel.

The drug property:

For the ideal FDT_S technology, the drug property should not significantly affect the tablet property. The fast dissolving drug technology be versatile enough to accommodate unique properties of each drug.

Tablet strength and porosity:

Because fast dissolving tablets are design to have quick dissolution/disintegration time, the tablet porosity is usually maximized to ensure the water absorption in to tablets. A strategy to increase the tablet hardness without sacrificing tablet porosity or requiring a special packaging to handle fragile tablet should be provided.

Moister sensitivity:

FDT_S should have low sensitivity to humidity. This problem can be especial challenging because many highly soluble excipients are used in the formulation to enhance fast dissolving properties as well as create good mouth feel. A good package design or other strategy should make to protect FDT_S from various environmental conditions.

FORMULATION PROCESSES IN DEVELOPING FDT:

FREEZE-DRYING OR LYOPHILIZATION:

Freeze-drying (lyophilization) is a process in which water is sublimated from the product after freezing. The main advantage being that pharmaceutical substances can be processed at non-elevated temperatures, thereby eliminating adverse thermal effects, and stored in a dry state with relatively few shelf-life stability problems. Freeze-dried forms offer more-rapid dissolution times than other available solid products. The lyophilization process imparts a glassy amorphous structure to the bulking agents and, sometimes, to the drug, thereby enhancing the dissolution characteristics of the formulation.

The resulting tablets are very light and have highly porous structures that allow rapid dissolution. When placed on tongue the unit dissolves almost instantly to release the incorporated drug.

MOLDING:

Molding process includes moistening, dissolving, or dispersing the drug with a solvent then molding the moist mixture into tablets (compression molding with lower pressure than conventional tablet compression), evaporating the solvent from drug solution, or suspension at ambient pressure (no vacuum lyophilization), respectively.³The molded tablets formed by compression molding are air-dried. As the compression force employed is lower than conventional tablets, the molded tablet results in highly porous structure, which increases the disintegration and dissolution rate of the product. However, to further improve dissolution rate of the product powder mixture should be sieved through very fine screen. As molding process is employed usually with soluble ingredients (saccharides) which offers improved mouth feel and disintegration of tablets. However, molded tablets have low mechanical strength, which results in erosion and breakage during handling.¹⁷

Takeda (Osaka, Japan) has developed compression molded mixtures, containing an active ingredient, a carbohydrate, barley sufficient amount of water to moisten the surface of particles.¹⁸ After the wetted mass is compressed at low pressure and subsequently dried, porous tablets with sufficient mechanical strength is obtained. The disintegration time is about 30-50 second in mouth.

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 process¹⁹ 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 FDT. This process can accommodate high doses of drug and offers improved mechanical strength. However, high-process temperature limits the use of this process.

SPRAY DRYING:

Highly porous, fine powders are obtained by this method. Allen et al.²⁰ utilized this process for preparing FDT. The FDT formulations consisted of hydrolyzed/unhydrolyzed gelatin as supporting agent for matrix, mannitol as bulking agent, and sodium starch glycolate or croscarmellose sodium as disintegrating agent. Disintegration and dissolution were further improved by adding effervescent components, i.e. citric acid (an acid) and sodium bicarbonate (an alkali). The formulation was spray dried to yield a porous powder. The FDT made from this method disintegrated in <20 s.^21,
22

MASS EXTRUSION:

This technology involves softening 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.²³

COMPACTION:

Using conventional tablet press to make fast dissolving tablet is a very attractive method because of low manufacturing cost and ease of technology transfer. Many strategies have tried to achieve high porosity and adequate tablet strength using tablet press. First, several granulation methods were tried to obtain granules Suitable for making FDT_S. Wet granulation, dry granulation, etc. methods are used. The second approach is to select special type of excipients as the main component for FDT_S. The third approach is to compress tablet at low pressure and apply various after treatment to the soft tablets. The approaches are described in details below.

Several excipients are investigated for rapid disintegration; some of the super disintegrants employed are discussed in Table 2.

Conventional methods:

Wet granulation method:

Bonadeo et al. described a process of producing rapidly disintegrable, mouth-soluble tablets by wet granulation in fluidized bed. Granules with high porosity and low apparent density were obtained, and the tablet made by such granules had rapidly disintegration time ranging from 3 to 30 second in the saliva.²⁷

Jian et al. developed a rapidly disintegrating tablet for a poorly soluble active ingredient (28). In this method first, nanoparticles were formed. The particles were granulated water soluble or water dispersible excipient using fluid bed; granules were made in to tablet. The tablet had complete dissolution in less then 3 min.

Dry granulation method:

Eoga disclosed a method of making FDT_S by dry granulation.²⁹ Higher density alkali earth metal salt and water soluble carbohydrates do not provide quick disintegration and good mouth feel. Low density alkali metal salts and water soluble carbohydrates are difficult to compress and may cause inadequate content uniformity. So low density alkali earth metal salts or water soluble carbohydrates were pre-compacted, and the resulting granules were compressed in to tablets that could dissolve fast.

Direct compression:

Ishikawa et al. prepared rapidly disintegrating tablet using micro crystalline cellulose (PH-M Series) and low substituted-hydroxypropylecellulose or spherical sugar granules by direct compression method.³⁰

Melt granulation:

Abdelbar et al.³¹ prepared FDT by incorporating a hydrophilic waxy binder (super polystate) PEG-6-stearate. Superpolystate is a waxy material with an m.p. of 33-37⁰ C.

It not only acts as a binder and increases the physical resistance of tablets, but also helps the disintegration of tablets as it melts in the mouth and solubilizes rapidly leaving no residue. Super polystate was incorporated in the formulation of FDT by melt granulation method where granules are formed by the molten form of this material. Crystallized paracetamol was used as model drug and in addition the formulation included mannitol as a water-soluble excipient and crosscarmellose sodium as disintegrating agent.

Phase transition process:

Kuno et al.³² investigated the disintegration of FDT by phase transition of sugar alcohols using erythritol (m.p.122^o C), xylitol (m.p.93-95^o C), trehalose (97^o C), and mannitol (166^o C). Tablets were produced by compressing a powder containing two sugar alcohols with high- and low-melting points and subsequent heating at a temperature between their melting points. Before heating process, the tablets do not have sufficient hardness because of low compatibility. The tablet hardness was increased after heating process, due to the increase of inter particle bonds or the bonding surface area in tablets induced by phase transition of lower melting point sugar alcohol.

Sublimation:

The presence of a highly porous structure in the tablet matrix is the key factor for rapid disintegration of FDT. Even though the conventional tablets contain highly water-soluble ingredients, they often fail to disintegrate rapidly because of low porosity. To improve the porosity, volatile substances such as camphor can be used in tableting process, which sublimated from the formed tablet.

Koizumi et al.³³ developed FDT utilizing camphor, a subliming material that is removed from compressed tablets prepare using a mixture of mannitol and camphor. Camphor was sublimated in vacuum at 80⁰ C for 30 min after preparation of tablets.

Humidity Treatment:

It is known that certain type of sugar change from amorphous state to crystalline state when their solution is spray-dried or used as a binder solution. Further investigations have shown that when an amorphous suger is treated to go through the humidification and drying process, It change to a crystalline state. This change increase the tablet strength substantially. Liu et al. disclosed a system for making fast dissolving tablets by humidity treatment.⁵¹

In formulating FDTs, one of the important components is the super disintegrants. Several excipients are

Investigated for rapid disintegration of FDTs, some of the super disintegrants employed are discussed in Table 2.

PATENTED TECHNOLOGY:

Zydis technology:

The Zydis technology was described in issued to Gregory et al of John Wyeth and Brother, Ltd.^11-12 and Yarwood et al. of R.P. Scherer.¹³ In the Zydis formulation the drug is physically trapped in matrix which is composed of two components. One is a water soluble mixture of saccharides (e.g., mannitol) and the other is a polymer (e.g., gelatin). Other carrier polymers commonly used in the Zydis system include partially hydrolyzed gelatin, hydrolyzed dextran, dextrin, alginates, poly (vinyl alcohol), poly- vinylpyrrolidone, acacia, and the mixtures. An especial peelable backing foil was used to package the Zydis unit. Because the water content in the final freeze dried product is to low for microbes grow, the Zydis formulation is also self preserving.¹⁴

Quicksolve:

It is a porous solid form also prepared by freeze drying method. In the Quicksolve formulation, the matrix compositions are first dissolve in the first solvent (usually water) and then the solution is frozen. At the temperature when the first solvent remains in the solid form, the frozen solution contacts the second solvent which is substantially miscible with first solvent. The matrix composition should be immiscible to the second solvent. Thus, the first solvent is substantially removed after a few hours of contacting the second solvent to result in a usable matrix ¹⁵.

Freeze drying is relatively expensive manufacturing process and the final dosages forms are very fragile, lacking physical resistance in standard blister packs. Moreover, this method does not allow accommodating high amount of active drugs. Also, the formulation has poor stability at higher temperature and humidity. ¹⁶

Nanocrystal technology: ³⁴

This is patented by Elan, King of Prussia. Nanocrystal technology includes lyophilization of colloidal dispersions of drug substance and water-soluble ingredients filled in to blister pockets. This method avoids manufacturing process such as granulation, blending, and tableting, which is more advantageous for highly potent and hazardous drugs. As manufacturing losses are negligible, this process is useful for small quantities of drug.

Flashtab technology:³⁵

This is patented by Ethypharm France. This technology includes granulation of excipients by wet or dry granulation method and followed by compressing 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. Disintegration time is within 1 min.

Orasolv technology: ^36-37

This technology is patented by CIMA Labs. This includes use of effervescent disintegrating agents compressed with low pressure to produce the FDT. 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. As tablets are prepared at low compression force, they are soft and fragile in nature. This initiated to develop Paksolv,³⁸ a special packaging to protect tablets from breaking during storage and transport. Paksolv is a dome-shaped blister package, which prevents vertical movement of tablet with in the depression. Paksolv offers moisture, light, and child resistance packing.

Durasolv technology: ³⁹

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, non direct compression fillers, and lubricants.Nondirect compressible fillers are dextrose, mannitol, sorbitol, lactose, and sucrose, which have advantage of quick dissolution and avoid gritty texture, which is generally present in direct compressible sugar. The tablets obtained are strong and can be packed in conventional packing in bottles and blisters. Nondirect compressible fillers generally used in the range of 60-95%, lubricant in 1-2.5%.

WOW tab technology:^40-41

Yamanouchi patented this technology. WOW means with out water. This technology utilizes conventional granulation and tableting methods to produce FDT employing low- and high-moldability saccharides.

Low moldability saccharides are lactose mannitol, glucose, sucrose, and xylitol. High-moldability saccharides are maltose, maltitol, sorbitol, and oligosaccharides. When these low- and high-moldable saccharides used alone tablets obtained do not have desired properties of rapid disintegration and hardness, so combinations are used.

This technology involves granulation of low-moldable saccharides with high-moldable saccharides as a binder and compressing into tablets followed by moisture treatment. Thus tablets obtained showed adequate hardness and rapid disintegration.

Dispersible tablet technology: ⁴²

Lek, Yugoslavia patents this technology. It offers development of FDT with improved dissolution rate by incorporating 8-10% of organic acids and disintegrating agents. Disintegrating agent facilitates rapid swelling and good wetting capabilities to the tablets that results in quick disintegration.

Disintegrants include starch, modified starches, microcrystalline cellulose, alginic acid, cross-linked sodium carboxy methyl cellulose and cyclodextrins. Combination of disintegrants improved disintegration of tablets usually less than 1 min.

Pharmaburst technology:⁹

SPI Pharma, New Castle, patents this technology. It utilizes the co processed excipients to develop FDT, which dissolves within 30-40 s. This technology involves dry blending of drug, flavor, and lubricant followed by compression into tablets. Tablets obtained have sufficient strength so they can be packed in blister packs and bottles.

Frosta technology: ⁹

Akina patents this technology. It utilizes the concept of formulating plastic granules and compressing 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 usually mixing the porous plastic material with water penetration enhancer and followed by granulating with binder. The tablets obtained have excellent hardness and rapid disintegration time ranging from 15 to30 s depending on size of tablet.

Oraquick:

This technology is patented by K.V Pharmaceuticals.⁴³ It utilizes taste masking micro sphere technology called as micromask, which provides superior mouth feel, significant mechanical strength, and quick disintegration/dissolution of product. This process involves preparation of microparticles in the form of matrix that protects drug, which can be compressed with sufficient mechanical strength. Low heat of production in this process makes it appropriate for heat sensitive drugs. Oraquick product dissolves within few seconds.

Ziplets/advatab: ⁴⁴

This technology is patented by Pessano con Bornago, Italy. It utilizes water-insoluble ingredient combined with one or more effective disintegrants to produce FDT with improved mechanical strength and optimal disintegration time at low compression force. This technology handles high drug loading and coated drug particles and does not require special packaging, so they can be packed in push through blisters or bottles.

Flash heat process:

Fuisz has introduced the shearform technology to make FDT_S.²⁴ The shearform technique utilizes a unique spinning mechanism to produce floss like crystalline structure, much like cotton candy. In this process the feedstock is subjected to the centrifugal force and to a temperature gradient simultaneously. An internal flow is created by this condition to force the flowing mass out of the opening provided in the perimeter of a spinning head. The mass is cooled down as it comes out of the opening to form a discrete fiber structure, as seen in cotton candy. The speed of spinning is about 3,000–4,000 rpm, and the temperature gradient is about 180-250⁰ C. The carrier material includes the saccharides, poly sacchrides, and mixture thereof.

The produced floss needs to be recrystllized to form free flowing granules of self binding properties. There are two system used to create shearform floss, having self binding properties. ^25-26

In the first system, mixture of xylitol, a mixture of saccharide-based carrier and one more additional sugar alcohol, preferably with sorbitol, were used to create shearform. This system named as “single floss” or “uni floss”. The second system utilizes two separate flosses, one is xylitol-containing binder flosses and other is base flosses which contain different sugar alcohol or saccharides. The two flosses are combined together, and this system is termed as “dual floss”.

Approach for Taste masking:

For conventional tablet formulation, taste masking is not a critical issue to be addressed, because tablets are supposed to be swallowed quickly with plenty of water. FDT_S stay in mouth longer then the conventional tablets. Some FDT_S take up to more then one minute in mouth. Taste masking is must for bitter drugs.

To overcome this problem various approaches are studied.⁴⁵

Incorporation of sweeteners and flavors:

To provide pleasant taste and mouth feel Sweeteners and flavors are used in many FDT formulations.

Sugars have been the main component in most of the FDT formulation. The pleasant taste and fast dissolving can help to overcome bad taste.

Mannitol is most widely used excipient in formulating FDT. Aspartame and citric acid are most commonly used along with various flavorants mint favor, orange flavor, strawberry flavor, peppermint flavor to produce pleasant taste, and mouth feel.

Encapsulation or coating of drug:

Some of the unpleasant drugs can not be mask by incorporation of sweeteners and flavors, in such cases alternative method for masking the taste is encapsulating or coating of drugs

Various technique utilized includes:

CIMA’S taste masking technique use coating of drug with dissolution retarding material.

In OraSolve formulation a effervescence couple was added to provide a tingling effect as carbon dioxide is generated during disintegration, as these tablets compressed at low pressure, the coating on the drug particle remain intact during compression. This contributes to better taste masking.

Phase separation approach for taste-masked microcapsules.⁵⁷

Micro caps process used micro encapsulation technology.

· Extrusion method.

· Flash tab technology.

· Blending with cyclodextrin⁵⁸

Coating crystals, granules and pellets with aqueous dispersions of methacrylic acid polymers.

Determination of disintegration time of FDTS:

FDT_S should be strong enough to survive rough handling during manufacturing and shipping process, and yet friable enough to instantly dissolve or disintegrate into small particles to quickly release their active ingredients in patient mouth. Conventional disintegration taste for ordinary tablets may not allow precise measurement of the disintegration time of FDT_S.

Generally, the method described in U.S. Pharmacopoeia can produce data for evaluation of the disintegration time. It is also possible to evaluate the tendency of disintegration kinetics by visual examination. However these examinations are not sufficiently objective.⁵⁹

In order to predict the disintegration time of FDT_S and effects of different formulation parameters, a few method have been proposed.^59-62

In vivo Determination of Disintegration time:

It can be conducted on volunteers. Volunteers are usually randomized to receive the treatment and then directed to clean their mouth with water.⁶² Tablets are placed on their tongues, and then time for disintegration is measured by immediately starting a stopwatch. The volunteers are allowed to move FDT_S against the upper roof of the mouth with their tongue and to cause a gentle tumbling action on the tablet without biting on it or tumbling it from side to side. Immediately after the last noticeable granule has disintegrated, the stopwatch is stopped and the time recorded.

In vitro determination of disintegration time:

Modified U.S. Pharmacopoeia Method:

Instead of using the disintegration apparatus described in the U.S. Pharmacopoeia, a modified method has been proposed.^{60, 61} The disintegration apparatus was same as the USP dissolution test apparatus 2, which uses a paddle stirring element

And 1000 ml cylinder vessel at 37⁰ C. Distilled water was chosen for disintegration medium, instead of buffer solution. A tablet to be tasted put on the bottom of the sinker, which was placed on the middle of the vessel and hung by a hook to the lid of the vessel with a distance of 6 to 8.5 cm. Disintegration time was determined at the point at which the tablet disintegrated and passed through the screen of sinker completely. The opening of mesh of sinker was 3-3.5 mm in height and 3.5-4 mm in width.

Method Using Texture Analyzer:

A Texture Analyzer (Stable Micro System, U.K.) was applied to measure the beginning and ending time of disintegration.⁶² A tablet was adhere to the bottom of a probe, which was attached to the load cell, with a very thin layer of glue or double-sided scotch tape. The tablet under a constant force was immersed in a definite volume of distilled water. The time for the tablet to disintegrate was determined by measuring the distance the probe traveled into the tablet. Typical time distance profiles generated by the Texture Analyzer software enabled the calculation of beginning and ending of disintegration time.

Method Using a CCD Camera:

This CCD camera apparatus is comprised of two distinct sections, a disintegration component and a measurement device.⁵⁹ The mode of measurement involves the continuous of pictures by the CCD camera to record the disintegration time course. The acquired picture are simultaneously transferred to the computer and stored. The key point of this apparatus is to combine the detailed picture obtained by the CCD camera.

Evaluation of FDT_S:

Evaluation parameters are discussed as follow

Hardness/crushing strength:

The limit of crushing strength of FDT_S usually kept in lower range to facilitate early disintegration in mouth. The crushing strength of the tablet may be measured using conventional hardness taster.

Friability:

To achieve % friability within limit for an FDT is the challenge to the formulator science all methods of manufacturing FDT are responsible for increasing % friability values. Thus it is necessary that this parameter should be evaluated and the results are with in bound limits (0.1-0.9%).

Wetting time and water absorption ratio:

Wetting time of a dosages form is related with the contact angle. Lower wetting time give a quicker disintegration of tablet.

The wetting time of a tablet can be measured using a simple procedure.⁶³ Five circular tissue paper of 10 cm diameter are placed in a Petridish with a 10 cm diameter. Ten milliliter of water soluble dye (eosin) solution is added to pertidish. A tablet is placed on the surface of tissue paper. The time required for the water to reach the upper surface is noted as wetting time.

For measuring water absorption ratio the weight of tablet before keeping in petridish is noted (W_b). The wetted tablet from the Petridish is taken and reweigh (W_a). The water absorption ratio then can be determined according to the following equation

R = 100 ( W_a- W_b) / W_b

Moister uptake study:

Ten tablets from each formulation were kept in a desiccator over calcium chloride at 37⁰ C for 24 h. The tablet is then weighed and exposed to 75% relative humidity, at room temperature for 2 weeks. Required humidity was achieved by keeping saturated sodium chloride solution at the bottom of the desiccator for 3 days. One tablet as control (without superdisitegrant) was kept to access the moister uptake due to the other excipients. Tablets were weighed and % increase in weight was recorded.

Disintegration Test:

The time of disintegration for FDT is < 1 min and actual disintegration time that patient can experience ranges from 5 to 30 sec. The standard procedure for performing disintegration test for these dosages form has several limitations. Various disintegration methods developed are discussed above.

Dissolution Test:

Dissolution medium such as 0.1 N HCl and buffers (p H 4.5 and 6.8) should be evaluated for FDT same way as conventional tablets. USP dissolution apparatus 1 and 2 can be used. USP basket 1 apparatus may have some applications, but some times tablet fragments or disintegrated tablet masses may become trapped on the inside top of the basket at the spindle where little or no effective stirring occurs, yielding irreproducible dissolution profile. Kancke ⁶⁴ proposed USP 2 paddle apparatus, which is most suitable and common choice for FDT_S, with a paddle speed of 50 rpm commonly used. Typically, the dissolution of FDT is very fast when using USP monograph conditions; hence slower paddle speed may be utilized to obtain a profile.

The USP 2 paddle apparatus at 50-100 rpm is suitable for dissolution testing of taste-marked drug as well. The media used for taste-masked drug should match that of the finished product to maximize the value of the test. High-performance liquid chromatography is required to analyze dissolution aliquots due to the presence of UV absorbing components, specially flavors and sweeteners.

Clinical studies:

In vivo studies were performed on oral fast-disintegrating dosage forms to investigate their behavior in the oral esophageal tract, their pharmacokinetic and therapeutic efficacy, and acceptability. Zydis’s residence time in the mouth and stomach, and its transit through the esophageal tract, was investigated using gamma-scintigraphy. Its dissolution and buccal clearance was rapid;⁶⁵ the esophageal transit time and stomach emptying time were comparable with those of traditional tablets, capsules, or liquid forms.^66,67 A decreased intersubject variability in transit time also was observed ⁶⁶. Zydis also showed good therapeutic efficacy and patient acceptability — particularly in children ^68,
69 or when easy administration and rapid onset of action were required (such as for patients undergoing surgery).^{70, 71}

The fast-disintegrating forms examined showed improved pharmacokinetic characteristics when compared with reference oral solid formulations. For example, the absorption rate of the acetaminophen Flashtab was higher than that of the brand leader, while having the same bioavailability.⁷² Increased bioavailability and improved patient compliance were observed in Lyoc formulations for different drugs such as phloroglucinol ⁷⁴, glafenine , spironolactone ⁷⁴, and propyphenazone.⁷⁴ Using Zydis, all the drugs that can be absorbed through the buccal and esophageal mucosa exhibited increased bioavailability and side-effect reduction. This is helpful particularly in actives with marked first-pass hepatic metabolism. Finally, the suitability of FDTs for long-term therapy also was assessed. Lyoc formulations containing aluminum were positively tested in patients with gastrointestinal symptoms.⁷³

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Received on 11.06.2009

Accepted on 19.08.2009

Research Journal of Pharmaceutical Dosage Forms and Technology. 1(2): Sept.-Oct. 2009, 71-79