Mouth dissolving tablet seminar

MDT is fast dissolving tablet in mouth only ,give quick action ,with pleasant test mainly used in journey without use of water.

1. PRESENTED BY:- HANUMAN K. NAGOLKAR M.PHARM SEM-II ROLL NO :- 507 DEPARTMENT OF PHARMACEUTICS GUIDED BY:- DR. S.V. SHIROLKAR DR. D.Y. PATIL INSTITUTE OF PHARMACEUTICAL SCIENCES AND RESEARCH, PIMPRI, PUNE- 411018 MOUTH DISSOLVING TABLET 1

2. Definitions Properties Advantages Disadvantages Need Formulation Methodology Evaluation Patented methodology Recent patents of MDTs References CONTENTS 2

3. Definitions Mouth dissolving tablet ( MDT ) It is a tablet that disintegrates and dissolves rapidly in the saliva within a few seconds without the need of drinking water or chewing. A mouth dissolving tablet usually dissolves in the oral cavity within 15 s to 3 min. Most of the MDTs include certain super disintegrants and taste masking agent. According to European pharmacopoeia, these MDTs should dissolve/disintegrate in less than three minutes. US FDA defined MDTs as “A solid dosage form containing medicinal substances or active ingredients which disintegrates rapidly within a few seconds when placed up on tounge . 3

4. Ideal properties of MDTs Mouth dissolving t ablet should not require water or other liquids to swallow. Easily dissolve or disintegrate in saliva within a few seconds. Have a pleasing taste. Leave negligible or no residue in the mouth when administered. Be portable and easy to transport. Be able to be manufactured in a simple conventional manner within low cost. Be less sensitive to environmental conditions like temperature and humidity 4

5. No need of water to swallow the tablet.   Can be easily administered to  pediatric , elderly and mentally  disabled patients.  Accurate dosing as compared to liquids . Excellent mouths feel property produced by use of flavours and sweetners . Convenient to administer during travelling without need of water . Fast disintegration of tablets leads to quick dissolution and rapid absorption which may produce rapid onset of action. Advantages of MDT’s 5

6. It is hygroscopic in nature so it must be kept in dry places. Packaging of tablet requires special equipments and it is difficult to pack. High dose cannot be incorporated into tablet. Eating and drinking may become restricted. Buccal tablet are moisture sensitive. Disadvantages 6

7. Orally disintegrating dosage forms are particularly suitable for patients find it inconvenient to swallow traditional tablets and capsules with glass of water. Pediatric and geriatric patients Patients who are unwilling to take solid preparation due to fear of choking A patient with persistent nausea, who may be in journey, or has little or no access to water Increased bioavailability and faster onset of action are a major claim of these formulations. Need for MDTs 7

8. Superdisintegrants Bulking agents Emulsifying agents Lubricants Flavours sweetners Formulation of MDTs 8

9. Superdisintegrants   Disintegrants  play  a major role in the  disintegration and dissolution of  MDTs. Super disintegrants provide quick disintegration due to combined effect of swelling and water absorption by the formulation.  Eg.1. Croscarmelose sodium 2. Crospovidone 3. Sodium starch glycolate Formulations of MDTs 9

10. Bulking materials are important in the development of fast dissolving tablets. They contribute the functions of a diluent , filler and cost reducer. Bulking agents improve the texture of the tablets that consequently enhances the disintegration in the mouth, besides adding volume and reducing the concentration of the active in the formulation. The bulking agents for this dosage form should be more sugar-based such as mannitol , polydextrose , lactose derivatives such as directly compressible lactose (DCL) and starch hydrolysate . Bulking agents are added in the range of 10% to about 90% by weight of the final composition Bulking agents 10

11. Emulsifying agents are significant for formulating fast dissolving tablets as they help in quick disintegration and drug release without the need for chewing, swallowing or drinking water. Also, emulsifying agents stabilize the immiscible blends and increase bioavailability. A variety of emulsifying agents for fast dissolving tablet formulations include alkyl sulfates , propylene glycol esters, lecithin, sucrose esters and others. These can be added in the range of 0.05% to about 15% by weight of the final formulation. Lubricants Though not essential excipients , these can aid in making the tablets more palatable after they disintegrate in the mouth. Lubricants reduce grittiness and help in the drug transit process from the oral to the stomach. Emulsifying agents 11

12. Flavours and taste masking agents make the products more palatable and pleasing for patients. The incorporation of these ingredients assists in overcoming bitterness and undesirable tastes of some actives. Natural as well as synthetic flavours can be used to enhance the organoleptic characteristic of fast dissolving tablets. A wide range of sweeteners including sugar, dextrose and fructose, as well as non-nutritive sweeteners such as aspartame, sodium saccharin, sugar alcohols and sucralose are available. The addition of sweeteners imparts a pleasant taste as well as bulk to the formulation. Flavours and Sweeteners 12

13. 1 . Freeze drying or lyophilization 2 . Cotton candy process 3 . Spray drying 4 . Nanoionization 5 . Direct compression 6 . Sublimation Formulation Methodologies 13

14. It is a pharmaceutical process that allows the drying of heat sensitive drugs and biological under low temperature by the application of vacuum to remove water by sublimation. Drugs are dissolved or dispersed in aqueous solution of a carrier, transferred to preformed blister packs and subjected to nitrogen flush to freeze out, then placed in the refrigerator to complete the process. Characteristics of lyophilization techniques are, they possess high porosity and specific surface area, and gets dissolve rapidly in mouth presenting high drug bioavailability. Advantages The major advantage of using this technique is that the tablets produced by this technology have very low disintegration time and have great mouthfeel due to fast melting effect. Freeze Drying / Lyophilization 14

15. This process is so named as it utilises a unique spinning mechanism to produce a floss-like crystalline structure, which mimics cotton candy. Cotton candy process involves the formation of Matrix of polysaccharides or saccharides by the 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 FDTs. Cotton candy process 15

16. In this method hydrolyzed and nonhydrolyzed gelatin were used as supporting matrix. Mannitol as bulking agent Acidic substances (citric acid) or alkali substance (sodium bicarbonate) further increase disintegration and dissolution. Sodium starch glycolate or crosscarmellose sodium as superdisintegrant . Disintegration time < 20 sec Spray drying 16

17. Nanomelt technology involves reduction in the particle size of drug by proprietary wet-milling technique. Nanocrystals of the drug are stabilized against agglomeration by surface adsorption on selected stabilizers, which are then incorporated into MDTs. Advantages For poor water soluble drugs. Fast disintegration/dissolution of nanoparticles leads to increased absorption and bioavailability. Reduction in dose. cost effective manufacturing process. Nanoionization 17

18. direct compression is the most preferred technique to manufacture the tablets due to certain advantages: The easiest way to manufacture the tablets. A limited no. of processing steps are involved. Cost effectiveness. MILLING SIEVING MIXING COMPRESSION fig. Process of direct compression Direct compression 18

19. Schematic  Diagram of Sublimation Technique for  Preparation of MDT   Tablets produce by this method exhibit good mechanical strength and dissolved within 15 seconds in saliva. Sublimation 19

20. Analgesics and Anti-inflammatory Agents: e.g. Indomethacin , Phenylbutazone,etc . Anthelmintics e.g. Albendazole , Mebendazole etc. Anti-coagulants: e.g.Dicoumarol , Nicoumalone etc . Anti-bacterial Agents : e.g. Penicillin, Ciprofloxacin, Clarithromycin , Erythromycin . Drugs Formulated Into MDT’s 20

21. Anti-Epileptics : e.g. Carbamazepine , Clonazepam etc . Anti-Fungal Agents: e.g. Amphotericin , Clotrimazole , Econazole Nitrate, Fluconazole Etc. 21

22. 1. Thickness Measured using Vernier calipers . 2. Hardness Force required to break a tablet by compression in the radial direction. Pfizer hardness testers Monsanto hardness tester Evaluation of Mouth dissolving tablets 22

23. 20 tablets randomly take from lot and weighted individually to check for weight variation. Weight variation specification as per IP. 3. Uniformity of weight Average weight of tablet % Deviation 80 mg or less ± 10 More than 80 mg but less than 250 mg ± 7.5 250 mg or more ± 5 23

24. 4. In-vitro dispersion time test Drop a tablet in a beaker containing 50ml of phosphate buffer pH 6.8 & time required for complete dispersion was determined 24

25. Determined using Roche friabilator . Subjected to 100 revolutions ( 25rpm) formula :- Where , F - Friability, W - Weight of the tablets before the test and W- Weight of the tablet after the test. 6. In vivo Disintegration time Time required for complete disintegration of tablets in oral cavity determined by administering tablets to 10 healthy volunteers . 5. Friability test F = (1- W / W) × 100 25

26. Tablet is placed on a piece of tissue paper folded twice and kept in a Petri dish (ID = 6.5 cm) containing 6 ml of water, and the time for complete wetting is measured. 8. Dissolution test Dissolution study performed using USP II apparatus ( paddal speed 50rpm). USP monographs dissolutions conditions should be followed in addition 0.1N HCl , pH 4.5 & 6.8 buffers should be evaluated. 7. Wetting time 26

27. Patented Technology Basis of Technology Technology developed by Company Active Ingredient (Brand Names) Zydis Lyophilization R.P.Scherer,Inc Loratidine (Claritin Reditab and Dimetapp Quick Dissolve) Quicksolv Lyophilization Janssen pharmaceutics Risperidone ( Risperdal Mtab ) Lyoc Lyophilization Farmalyoc Phloroglucinol Hydrate ( Spasfon Lyoc ) Orasolv Direct compression Cima Labs,Inc . Zolmitriptan ( Zolmig Repimelt ), Patented technologies for MDTs 27

28. Sr.N TITLE PATENT NUMBER YEAR 1 Orally disintegration tablet ( Ticagrelor ) significant proportion of patients with stroke have difficulty swallowing in the acute phase, and many have ongoing problems. WO2017182589 26.10.2017 2 Orally disintegrating tablet containing ( Asenapine ) treatment of adults with schizophrenia and acute treatment of manic or mixed episodes associated with bipolar I disorder with or without psychotic features in adults US2017014367 25.05.2017 3 Tofacitinib orally disintegrating tablets , use in moderate-to- severe forms of rheumatoid arthritis. It helps to decrease pain, tenderness, swelling in the joints. WO2017017542 02.02.2017 Recent patent of MDTs 28

29. Ashish Masih , Amar Kumar, Shivam Singh, Ajay Kumar Tiwari . Fast Dissolving Tablets: A Review. Int J Curr Pharm Res 2017;9(2):8-18. Dali Shukla , Subhashis Chakraborty , Sanjay Singh, Brahmeshwar Mishra . Mouth Dissolving Tablets I: An Overview Of Formulation Technology Sci Pharm. 2009; 77: 309–326 http:patentscope.wipo.int/search REFERENCES 29

30. 30