Orodispersible tablets

Novel drug delivery system- fast dissolving tablet

1. ORODISPERSIBLE TABLETS

2. Content 2 Introduction History Merits Demerits Formulation strategies Evaluation parameters References

3. Introduction Delivery of the drug to the target site is the most important consideration presently for achieving the fastest therapeutic effect. Researchers and formulation scientist has made the many approaches for the fastest delivery of the drug to attain pharmacological responses soon especially in case of an emergence conditions like cardiac arrest, heart attack, asthma, convulsions , etc . In the market, several dosage form are present with their high effectiveness of delivering the drug. Among all the route of drug administration, oral route is the route which is highly acceptable and it is choosen at priority by medical practitioner for administering the drug. Oral route is a prominent, simple and a convenient route of a drug administration and it is most preferable by the working populations. But , in case of, pediatrics and gediatrics populations, some disadvantages are also associated with it. Majorly ‘ dysphagia ’ i.e difficulty in swallowing is the problem which is commonly found in this age group . 3

4. 4 To beat this problem, there is a need arises for the development of the novel drug delivery system which shows its effect by simply putting the dosage form in the mouth cavity and the effect obtained within the matter of seconds. Development of orodispersible tablets overcome the shortcomings of conventional dosage form. Orodispersible tablets can be defined as the dosage form which get disintegrated within a matter of seconds after putting simply on a tongue. Fast dissolving tablets, mouth dissolving tablets, orally disintegrating tablet, orodispersible tablets, quick dissolving tablets, rapimelts , etc are the alternative synonyms of orodispersible tablets. They are beneficial for paediatrics, gediatrics , unconscious and uncooperative patients.

5. History The first ODT form of a drug to get approval from USFDA was a ZYDIS ODT formulation of Claritin ( loratadine ) in December1996 . It was followed by a ZYDIS ODT formulation of Klonopin ( clonazepam ) in December 1997 and a ZYDIS ODT formulation of Maxalt ( rizatriptan ) in June 1998. FDA guidance issued in Dec 2008 is that ODT drug should disintegrate in less than 30 sec. 5

6. Merits Ease of administration. No need of water to swallow the dosage form unlike conventional dosage forms. This is very useful for patients who are travelling or do not have immediate access to water and thus, provide improved patient compliance. Provide accurate dosing, easy portability and manufacturing, good physical and chemical stability. Acceptable taste masking property for pediatric patients is achieved. Bioavailability is enhanced through pregastric absorption of drugs from mouth, pharynx and oesophagus as saliva passes down and it leads to reduce dose, improved clinical performance through a reduction of unwanted effects. 6

7. 7 Have a pleasant mouth feel and leave minimal or no residue in the mouth after drug administration. Have rapid dissolution and absoption of the drug which will produce quick onset of action. No specific packaging is required. It combines advantages of solid dosage form in terms of stability and liquid dosage form in term of bioavailabilty .

8. Demerits FDTs usually have insufficient mechanical strength. Hence, it requires careful packaging and handling. FDTs may leave unpleasant taste and/or grittiness in mouth if not formulated properly. Fast dissolving dosage forms are hygroscopic in nature and more susceptible to degradation by humidity and temperature. Some time it possesses mouth feeling. MDT requires special packaging for properly stabilization & safety of stable product. Drugs difficult to formulate into FDT with relatively larger doses. Drugs with short half-life and frequent dosing and those whom require controlled or sustained release are unsuitable candidates of FDTs. 8

9. Ingredients used in preparation of ODTs 1 Super disintegrants The most important ingredients of a mouth dissolving tablets are Super disintegrants , which play a major role in the disintegration and dissolution of MDT. Sodium starch glycolate, Ac‐ di ‐sol ( Crosscarmellose sodium), Crospovidone , Microcrystalline cellulose, Pregelatinised starch are some of the examples of disintegrants . 2 Flavours Flavours and taste-masking agents make the products more palatable and pleasing for patients. The addition of these ingredients assists in overcoming bitterness and undesirable tastes of some active ingredients. For example, example Peppermint flavour , cooling flavor, flavor oils and flavoring aromatic oil, peppermint oil, clove oil, bay oil, anise oil, etc. Aspartame, Sugars derivatives are used as sweeteners. 3 Fillers Selection of filler also had an important role in deciding the disintegration time. Some examples of fillers are directly compressible spray dried Mannitol, Sorbitol , xylitol , calcium carbonate, magnesium carbonate, calcium. 9

10. 4 Surface active agents The presence of esterase or bile salts (sodium doecyl sulfate, sodium lauryl sulfate, polyoxy ethylene sorbitan fatty acid esters) like surface active agents plays a role in drug release. 5 Lubricants Lubricants remove grittiness and assist in the drug transport mechanism from the mouth down into the stomach. Some examples are Stearic acid, Magnesium stearate, Zinc state, calcium state, talc, polyethylene. 6 Binder Binders are added to tablet to add cohesiveness to powders, thus providing the necessary bonding to form granules, which under compaction form a cohesive mass or a compact which is referred to as a tablet. Polyvinyl pyrrolidone , Polyvinylalcohol , Hydroxy propyl methyl cellulose. 7 Colour Sunset yellow, Amaranth, etc. 10

11. Evaluation parameters 1 . Thickness The thicknesses of the formulated tablets were measured by using Vernier callipers . 2 . Weight variation The formulated tablets were tested for weight uniformity. For this 20 tablets were weighed collectively and individually. From the collective weight, average weight was calculated. Each tablet’s weight was then compared with average weight to ascertain whether it was within permissible limits or not. % Weight variation = Average weight Average weight-Individual weight ×100 3 . Hardness Hardness of tablets was measured using Pfizer type hardness tester. Three tablets were selected from each formulation randomly and their hardness was measured. The mean ±SD of hardness values were calculated. 11

12. 4. Friability Friability of the tablets was determined by using Roche friabilator . The weight of 20 tablets (initial weight) was subjected to friabilator at 25 revolutions per 4 min. Tablets were then dedusted , reweighed (final weight) and percentage loss was calculated. Friability is obtained by the following formula: % Friability = Initial weight Initial weight-Final weight ×100 5. Wetting time and water absorption ratio A double folded tissue paper was placed in a Petri dish. 6 mL of water containing a water-soluble dye (eosin) was added to the Petri dish. A tablet (pre-weighed) was carefully placed on the surface of tissue paper. The time required for water to reach the upper surface of the tablet was noted as the wetting time. The wetted tablet was then weighed and the water absorption ratio (R) was determined by using the equation: R=100 ( Wb-Wa )/ Wb Where Wa and Wb are the weights of tablet before (dry weight) and after water absorption (wet weight) respectively. 12

13. 6. Drug content Twenty tablets were weighed and powdered. The quantity of powder equivalent to 50 mg of diclofenac sodium was dissolved in phosphate buffer pH 6.8 diluted to 100 mL with the same and the solution was filtered and suitably diluted. The drug content was estimated spectrometrically at 276 nm. 7. In vitro disintegration test In vitro disintegration time was determined by using disintegration test apparatus ( Electrolab , USP model ED2L, Mumbai) without disk for six tablets. The disintegration medium was 900 mL of distilled water kept at (37.0±0.5) °C and stirred at a rate of (30±2) r/min. The time was measured in seconds for complete disintegration of the tablet with no palpable mass remaining in the apparatus. The test was carried out in triplicate. 8. In vitro dissolution studies Dissolution rate was studied by using USP type II paddle dissolution apparatus, in 900 mL of phosphate buffer pH 6.8 at (37.0±0.5) °C at 75 r/min. Aliquot of dissolution medium was withdrawn at regular time intervals and the same volume of pre-warmed (37.0±0.5) °C fresh dissolution medium was replaced. The samples were filtered and drug content of diclofenac sodium in each sample was analyzed after suitable dilution by Shimadzu UV-spectrophotometer at 276 nm. 13

14. References 1.Lohithasu Duppala , Shabari Girinath K.And D. Midhun Kumar. Fast Dissolving Dosage Forms: An Overview. World Journal of Pharmaceutical Research 2016;5(10):1184-1200. 2.Internet Sources- Google 3.M. Uday Kumar, M. Kishore Babu . Design And Evaluation of Fast Dissolving Tablets Containing Diclofenac Sodium Using Fenugreek Gum As A Natural Superdisintegrant. Asian Pac J Trop Biomed 2014; 4( suppl 1):S329-S334. 14

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