INTRODUCTION:

The ODTs is the probably most preferred route of administration for therapeutic agents because of low cost, self-medication, accurate dose, ease of administration and non-invasive method leading to high level of patient compliance. However, patients travelling with no access of water, utility of orally administered conventional capsules or tablets. Traditional capsules and tablets administered with the help of water may be inconvenient or impractical for few geriatric patients because of changes in neurological and physiological condition associated with aging including difficulty in swallowing/dysphagia. Solid dosage form present significant administrative challenges in other patient groups, such as mentally challenged, children and un co-operative patients. Pediatric patients may suffer from problems like ingestion such as a result of nervous control and underdeveloped muscular system.

Recent one technology have result of viable dosage alternatives development popularly knowns as ODTs. ODTs are also known as fast dispersing, rapid melt, rapid dissolve, fast melting and or quick disintegrating tablet. The European pharmacoepia adopted the ODTs that disperse in mouth before swallowing less than three minutes. In blood circulation, it can be easily absorbed. The potency of ODTs have been evaluated for developing bioavailability. Conventional dosage forms may be significantly lesser than drug dissolution and absorption as well as onset of clinical effect and drug bioavailability.^1,2,3,4,5

Figure 1: Oral Dispersible Tablets

Ideal characteristics of ODTs.²⁵

· They donot require water or any other liquid during administration time.

· ODTs can be easily dissolved.

· ODTs can easily disintegrate.

· It can mask the unpleasant taste of drug.

· Drug loading capacity is high.

· It is easily administered and give better patient compliance.

· Enviromental condition like moisture should have low sensitivity.

· ODTs should have better feel in mouth.

· Be less friable and harder.

· Leave no residue after aministration in mouth.

Advantages:²⁵

· Patients compliance can be improved .

· No need of water or liquid.

· Mask the bitter and unpleasant taste of drug.

· Bioavailability can be improved.

· Easily administered for patient who are disabled and mentally ill.

· Leaves no residue or minimal after administration in mouth.

· Delightful and sweetened taste with pleasure feel in mouth.

· Drug loading is high.

· Suitable and acceptable to be manufactured.

· Commercially cheap, production low, distribution cost and packaging when compared to updated commercially available medications.

· ODTs technology used to enhanced veterinary medicines.

· Therapeutic benefits is superior.

· Safety can be improved from physical obstruction and choking in oral route of administration of conventional dosage form.

Disadvantages:

· ODTs are rapid melt tablets and have to be stored in cool dry place because of it is hygroscopic inature.

· ODTs is packaged by special packaging and is required to protect and stabilize the stable ODTs.

· Unpleasant taste and unsettling feeling in the oral cavity, if not formulated correctly.

· Mechanical strength of the tablets are low, so we have to handle carefully.

Limitations:

· Careful handling is required for ODTs because of having low mechanical strength.

· ODTs, if not formulated correctly, they may leave unpleasant taste or grittiness in mouth.

· Larger doses drug are difficult to formulate into ODTs.

· Anticholinergics medication patient may not be the best candidates for ODTs.

· Patients who is having dryness of mouth may not be good candidates for ODTs formulation due to less saliva production.

CHALLENGES IN FORMULATING ORAL DISPERSIBLE TABLETS:^6,7

· Palatability:

Drugs are unpalatable. Upon administration it dissolve or disintegrate in patients oral cavity. It release active ingredients with taste buds. It becomes critical to patient compliance due to taste masking of drugs.

· Mechanical strength:

Oral dispersible tablet disintegrate in oral cavity, they are made of either soft molded and very porous or compressed into tablets with low compression force. Because of low compression force, it makes tablets brittle, friable and difficult to handle, blister packing that add to the cost.

· Hygroscopicity:

Orally disintegrating dosage form cannot maintain physical integrity under normal condition of humidity and temperature due to hygroscopic in nature. Hence, they need specialized product packaging to protect from humidity.

· Amount of drug:

The amount of drug that can be incorporated into each unit dose by limited ODTs with the use of application of technologies. The drug must be 60mg for soluble drugs and must be less than 400mg for insoluble drug, for lyophilized dosage forms. This parameter is challenging when formulating a ODTs.

· Aqueous solubility:

They form eutectic mixtures because of various formulation challenges of water soluble drug pose, which result in freezing point depression and glassy solid formed that may collapse upon drying due to loss of supporting structure during sublimating process. By using matrix-forming excipients such as mannitol can be prevented such collapse.

· Size of tablet:

The tablet size depends on ease of administration. The easiest size of tablet to handle was one larger than 8 mm while the easiest size to swallow is 7-8mm. Hence, the tablet size that is both easy to handle and easy to take is difficult to achieve.

FORMULATIONS OF ODTs:^6,8,9,10

1. Drug:

· It should be free from bitter taste.

· Dose should not be more than 20 mg.

· Small to moderate molecular weight.

· Solubility in saliva should be good.

· Ability to penetrate through oral mucosal tissue.

2. Bulking materials:

Bulking material is used as diluent, filler and cost reducer. It helps to enhance disintegration in mouth, it also reduce concentration of active in the composition. Bulking agent should be sugar-based such as mannitol, lactilol, polydextrose.

3. Emulsifying agent:

These agents are more important for formulating oral dispersible tablets, they help in rapid disintegration and drug release without swallowing, chewing or drinking water. It is useful in stabilizing the immiscible blends and enhancing bioavailability. Emulsifying agent includes propylene glycol esters, alkyl sulfates, lecithin,sucrose, ester and others.

4. Lubricants:

It helps to remove grittiness. By adding of lubricants, it assists in overcoming bitterness and undesirable taste of active ingredients.

5. Superdisintegrants:

It is an excipient, which is added to a capsule or tablet blend helps in the breakup of compacted mass when it keep into fluid enviroment.

Table 1: Various superdisintegrants and their mechanism of action.

Name of disintegrant	Brand name	Concentration (%)	Mechanism of action
Sodium starch glycolate	Explotab, primogel	2-8%	Swelling
Crosspovidone	Crosspovidone	2-5%	Swelling, water wicking
Crosscarmellose sodium	Ac – Di – Sol	1-3%	Working and swelling

Selection of superdisintegrants:

The rate of disintegration affect primarily by superdisintegrants, but they can also affect mouth feel, tablet hardness and friability at high levels. Hence, various ideal factor to be considered while selecting an appropriate superdisintegrants.

· When tablet comes in contact with saliva in mouth/oral cavity. It produces rapid disintegration .

· It should be enough compactable to produce less friable tablets.

· Small particle size is preferred to achieve patient compliance because it produce good mouth feel to the patients.

· Have good flow, it improves the flow characteristics of total blend.

Technologies used for ODTs formulation:^{11-18, 21,24}

There are two technologies used in the preparation of ODTs. There are conventional technologies and patented technologies.

1. Lyophillization

2. Addition of disintegrant

3. Moulding

4. Sublimation

5. Spray – drying

6. Cotton candy process

7. Melt granulation

A. CONVENTIONAL TECHNOLOGY:

1. Lyophillization:

Lyophillization is a pharmaceutical technology which allows drying of heat sensitive drugs and biologicals at low temperature under condition that allows removal of water by sublimation. It is a process by which water gets sublimated from product after freezing. Active ingredients are dissolved in aqueous solution, transferred to performed blister and subjected to flush to freeze out with nitrogen, then placed in a refrigerator to complete the process.

Figure 2- Lyophilization Technology. Patented technology based on this process is Zydis technology

2. Addition of disintegrant:

This material added to ODTs formulation to obtain fast disintegration which has superdisintegrant property like microcrystalline cellulose derivatives and crosscarmellose sodium.

3. Moulding:

This method is one of the most suitable methods for the formulations of oral dispersible tablets. Only the water soluble ingredients are selected so that the product dissolves quickly. Here all the solid ingredients are dissolved in hydroalcoholic solvents, after that at a lower pressure the dispersible tablets are compressed. after compression the solvent is shelved by air-drying method. The resultant product is very porous in nature which offers great dissolution.

Figure 3- Sublimation technique. Evaporation of volatile agent results in formation of porous tablets thereby causing fast disintegration

4. Sublimation:

Sometimes the dissolution rate of compressed tablets is delayed due to the low porosity of tablets. In sublimation technique, the active pharmaceutical ingredient, the volatizing agent and the other adjuvant are combined to form a tablet. After compression the volatile material is evaporated by sublimation. Tablets prepared by this technique, usually disintegrates quickly .

5. Spray drying:

This technique is achieved by utilizing gelatins as supporting agents, mannitol as bulking agent, crosscarmellose as disintegrating agents, acidic and alkali materials to increase the deformation of ODTs formulations.

6. Cotton candy process:

This method includes melting suddenly of the polysaccharides matrix. Then, this candy matrix is blended with an active material and other formulation to ODTs formulation.

7. Melt granulation:

In this method, hydrophillic waxy binder is used PEG-6 stearate is used commonly as a binder, but it is not used as a binder to increase physical stength of formulation and it is used as disintegrant in ODTs formulation.

B. PATENTED TECHNOLOGY:

Diverse techniques have been developed for ODTs formulation. According to their different parameter like stability, mechanical resistance and bioavailability, finished ODTs formulation are evaluated.

Some examples are as-

1. ZYDIS:

· Process Involved: Lyophilization.

· Patent owner: R.P. Scherer Inc.

· Advantages: Incresed biovailability on ODTs, easy dissolution.

· Disadvantages: Stability problem at high temperature, and costly technique.

· Brand name drugs: Loratidine.

2. ORASOLV:

· Process Involved: Tablet compression.

· Patent owner: Cima Labs Inc.

· Advantages : Rapid dissolution on ODTs and taste masking is two fold.

· Disadvantages: Low mechanical strength.

· Brand name drugs: Paracetamol, Zolmitriptan.

3. DURASOLV:

· Process Involved: Molding.

· Patent owner: Cima Labs Inc.

· Advantages: Higher mechanical resistance.

· Disadvantages: It cannot be used with low potency for active ingredients.

· Brand name drugs: Hyoscyamine sulfate, Zolmitriptan.

4. FLASHTAB:

· Process Involved: Lyophilization.

· Patent owner: Ethypharm.

· Advantages: Only conventional tableting technology.

· Brand name drugs: Ibuprofen.

5. ORAQUICK:

· Process Involved: Micro-mask taste masking.

· Patent owner: K V Pharm. Co, Inc.

· Advantages: Appropriate for heat sensitive and easy production.

· Brand name drugs: Hyoscyamine sulfate.

6. FLASH DOSE:

· Process Involved: Cotton candy method.

· Patent owner: Fuisz Technology.

· Advantages: High surface area on ODT.

· Disadvantages: It needs high temperature for melting matrix.

· Brand name drugs: Tramadol HCl

EVALUATION OF ODTS.^19,20,22,23

The following evaluation test are as for ODTs formulation.

1. General appearance:

It includes size, shape, color, taste, odour, surface texture.

2. Size, shape, thickness and diameter:

Size and shape can be dimensionally described and controlled. Thickness of tablet is dimensionally described and controlled. Thickness of tablet is counting by using filling equipment. Some filling equipment utilizes uniform thickness of tablet as a counting mechanism. Their thickness is measured by vernier caliper by taking 10 tablets.

3. Uniformity of weight:

Ten or twenty tablets were taken and their weight was determined individually and collectively on a digital weighing balance. Then, average weight of tablet is required to find from collective weight. The weight variation test would be satisfactory method of determining drug content uniformity.

4. Hardness of tablet:

It is defined as the force applied across the diameter of the tablet in order to break the tablet. Hardness of tablet of each formulation is to be determined using Monsanto hardness tester.

5. Friability of tablets:

It consist of plastic chamber which revolves at 25 rpm, dropping those tablets at distance of 6 inches will each revolution. Tablets should be rotated in the friabilator for at least 4 min. At the end, these tablets required to be deducted and reweighed, the loss in the tablet is measured of friability and is expressed in percentage as –

Percentage Friability = (initial weight – final weight) / initial weight ×100

6. Disintegration time:

According to European pharmacopoeia, oral dispersible tablet or fast disintegration tablet should be disintegrate within 3 min without leaving any residue on screen. As described in pharmacopoeia, tablets are placed in disintegration tube and time is noted.

7. In-Vitro disintegration test:

The disintegration test apparatus is generally used for determination of disintegration time of tablets under test. Sis tablets are taken from the batch under evaluation and are placed into the six tubes of the apparatus. These tubes contain a suitable dissolution medium as specified in the pharmacopoeia and the temperature of the medium must be maintained within 37°±2°C. After maintaining all the conditions the apparatus is started. After completing the test, the result is to be concluded.

8. In-Vitro dissolution study:

The dissolution testing of orodispersible tablets can be performed in the same manner as employed for conventional tablets. The procedure given in the monograph for a particular drug in the conventional tablet form can also be considered for the dissolution testing of that drug in oro-dispersible form. Other media such as 0.1M HCl and buffer (pH 4.5 and 6.8) can be evaluate for ODT much in the same way as their ordinary tablet counterparts. Most probably the USP 2 paddle apparatus can be utilized for orally disintegrating tablets, with a paddle speed of 50rpm.

9. Wetting time:

Take five circular tissue paper of diameter 10cm and placed in petridish with a 10cm diameter. A water soluble dye is required to add in petridish. Then tablet placed carefully on the surface of tissue paper. The time required to reach upper surface of tablet is noted.

10. Water dispersion ratio:

Fold a piece of tissue paper twice and place in petridish containing 6ml of water. Tablet place on paper and record time required for complete wetting. Note down the wetted tablet weight. Finally ratio of water absorption (R) is find out by using following equation,

R = 10 (Wa)/(Wb)

Where,

Wb = weight of tablet before water absorption

Wa = weight of tablet after water absorption

11. Stability studies:

Various stability studies like immediate stability study, acclerated stability study and long term stability studies were done during preformulation. The tablet is to be subjected to higher humidity or temperature or both, to know their impact on the stability of ODTs.

CONCLUSION:

While comparing the ODTs with conventional oral dosage forms, we can conclude that they have potential advantages with their improved patient compliance, convenience, higher bioavailability and rapid onset of action. ODTs have few disadvantages like short disintegration time, limited tablet weight, high cost. ODTs are formulations obtained by technology which is having quick disintegration/ dissolution in the mouth without water and have sufficient mechanical strength. ODTs are designed to disintegrate or dissolve in saliva in less than 60 seconds. ODTs can be evaluated as a first option for geriatric and pediatric patients who are having swallowing problem and also it is convenient for regular patient.

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Received on 05.08.2022 Modified on 07.04.2023

Asian J. Pharm. Ana. 2023; 13(4):298-302.

DOI: 10.52711/2231-5675.2023.00048