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Formltn. of tablets sublingual......


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Formltn. of tablets sublingual......

  2. 2. CONTENTS:- <ul><li>Introduction </li></ul><ul><li>Definition </li></ul><ul><li>Types of </li></ul><ul><li>Formulation Factors </li></ul><ul><li>Formulation Techniques </li></ul><ul><li>Processing </li></ul><ul><li>Problems & Remedies </li></ul><ul><li>Recent Review </li></ul><ul><li>Conclusion </li></ul><ul><li>Reference </li></ul>
  3. 3. INTRODUCTION:- <ul><li>Conventional Oral Dosage Form:- It is related to Oral Solid Dosage Form, Oral Liquid Dosage Form. </li></ul><ul><li>Special Solid Oral Dosage Form:- i.e. Special Tablets like Buccal Tablet , Sublingual Tablet, Chewable Tablet , Lozenges & Medicated Lozenges. </li></ul><ul><li>Also there another forms special tablets like:- Tablet Triturate, Floating Tablets, Single layered, Double Layered, Multi layered Tablets,& Tablet In Tablet. </li></ul>
  4. 4. DEFINITION & RELATED TERMS:- <ul><li>Chewable Tablet :- It is defined as oral solid dosage form which is intended to be chewed in the mouth prior to swallowing & not intended to be swallowed intact. </li></ul><ul><li>Buccal Tablet, Sublingual Tablet:- These two classes of tablets are intended to be held in the mouth, where they release the medicaments for absorption directly through the oral mucosa. Buccal (Tablets are placed bet. The cheek &teeth/ in cheek pouch) Sublingual (Tablets are placed beneath the tongue). </li></ul>
  5. 5. <ul><li>Lozenges/ Medicated lozenges :- Originally termed as PASTILLEES. These types of tablets are used in oral cavity where they are intended to exert a effect in mouth (local)/ at distant site (systemic) by absorption (sucked) of drug through gastric mucosa </li></ul><ul><li>lozenges are prepared by incorporation of drug in FLAVORED HARD CANDY BASE. </li></ul><ul><li>Another form of Lozenge is compressed lozenges i.e. TROCHES are manufactured by compression process. </li></ul>
  6. 6. LOZENGES/ MEDICATED LOZENGES:- <ul><li>TYPES:- Lozenges are classified by two way's i.e. </li></ul><ul><li>According to effect of drug at the site </li></ul><ul><li>According to manufacturing techniques. </li></ul><ul><li>According to effect of drug at the site. </li></ul><ul><ul><li>Local Effect:- ex: Antiseptics, Antibiotics. </li></ul></ul><ul><ul><li>Systemic Effect:- ex: Vitamins </li></ul></ul><ul><li>According to manufacturing techniques. </li></ul><ul><ul><li>Hard candy Lozenges (boiled) </li></ul></ul><ul><ul><li>Compressed Tablet Lozenges . </li></ul></ul>
  7. 7. HARD CANDY LOZENGES:- <ul><li>Are Discoid-shaped solid dosage form containing mixture of sugar & other carbohydrate with medicament in an amorphous/ glassy condition. </li></ul><ul><li>This form can be considered as solid syrup of sugars, gelatin (glycerinated) which contains 0.5-1.5 % moisture content. </li></ul>
  8. 8. ASPECTS:- <ul><li>CONTENTS </li></ul><ul><li>FORMULATION FACTORS </li></ul><ul><li>PROCESSING </li></ul><ul><li>FORMULATION </li></ul>
  9. 9. CONTENTS OF LOZENGES:- <ul><li>Raw material:- Sugars (Sucrose) </li></ul><ul><li>Corn syrup:- </li></ul><ul><li>Production by:- </li></ul><ul><ul><ul><ul><ul><li>Acid Hydrolysis </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Enzyme Hydrolysis </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Acid/Enzyme Hydrolysis </li></ul></ul></ul></ul></ul><ul><li>Invert Sugars:- levulose & dextrose </li></ul><ul><li>Reducing Sugars:- maltose, lactose etc </li></ul><ul><li>Acidulents:- citric acid, tartaric acid </li></ul><ul><li>Colors:- </li></ul><ul><li>Flavors:- </li></ul><ul><li>Medicaments:- </li></ul>
  10. 10. Dextrose Equivalent (DE):- <ul><li>Dextrose Equivalent (DE):- is a measure of the reducing sugar content of a product calculated as dextrose & expressed as a % of total dry substances/ </li></ul><ul><li>DE is the % of pure dextrose that gives the same analytical effect as is given by the corn syrup. </li></ul><ul><li>Applications of Corn Syrup. </li></ul>
  12. 12. <ul><li>Cooking. </li></ul><ul><li>Base Candy Mfg. Principle. </li></ul><ul><li>Mixing. </li></ul><ul><li>Batch Forming. </li></ul><ul><li>Rope sizing. </li></ul><ul><li>Lozenge Forming. </li></ul><ul><li>Cooling. </li></ul><ul><li>Lozenge Sizing. </li></ul><ul><li>Lozenge storage. </li></ul><ul><li>Packaging. </li></ul>
  13. 13. COOKING:- <ul><li>Types of cookers. </li></ul><ul><ul><ul><li>Fire Cookers </li></ul></ul></ul><ul><ul><ul><li>High Speed Atmospheric Cookers. </li></ul></ul></ul><ul><ul><ul><li>vacuum Cookers: </li></ul></ul></ul><ul><ul><ul><ul><ul><li>a) Pure-Sugar cookers </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>b) Standard Vacuum Cookers </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>I. Continuous Batch Process Cookers </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Pre Cookers </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Cooking Machines </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>II. Continuous Process Cookers </li></ul></ul></ul></ul></ul>
  14. 16. COMPRESSED TABLET LOZENGES:- <ul><li>Material used in the preparation of C.T.L:- </li></ul><ul><li>1) Tablet Base/ Vehicles:- </li></ul><ul><li>- sugar &sugar base vehicles:- </li></ul><ul><li>e.g. Dextrose & its trend names (Emdex, Mor- rex, Nu-tab etc…) </li></ul><ul><li>-sugar free base vehicles:- </li></ul><ul><li>e.g. Mannitol, Sorbitol …. </li></ul><ul><li>Other Fillers:- </li></ul><ul><li>e.g. compress, Teera-allba, avicel </li></ul><ul><li>3) Binders:- </li></ul><ul><li>4) Flavors:- </li></ul><ul><li>5) Colors:- </li></ul><ul><li>Lubricants:- </li></ul><ul><li>e.g. Cab-o-cil, </li></ul><ul><li>7) Medicaments:- </li></ul>
  15. 17. MANUFACTURING STPES INVOLVED IN C.T.L:- <ul><li>DIE FILLING </li></ul><ul><li>WEIGHT ADJUSTEMENT. </li></ul><ul><li>COMPRESSION HARDNESS </li></ul><ul><li>TABLET EJECTION </li></ul>
  16. 18. SUBLINGUAL DOSAGE FORM:- <ul><li>Factors Relating To Sublingual Tablets. </li></ul><ul><li>Molded Sublingual Tablets. </li></ul><ul><ul><li>Formulation Of M.S.T. </li></ul></ul><ul><ul><li>Hand Molding Of Tablets. </li></ul></ul><ul><ul><li>Machine Molding Of Tablets. </li></ul></ul>
  17. 19. FORMULATION FACTORS:- <ul><li>SITE RELEATED:- </li></ul><ul><li>PARTITION COEFFECIENT:- </li></ul><ul><li>DOSING OF DRUG:- </li></ul><ul><li>IONIC NATURE:- </li></ul><ul><li>TASTE:- </li></ul>
  18. 20. MOLDED SUBLINGUAL TABLETS:- <ul><li>Originally Introduced By FULLER In 1878. </li></ul><ul><li>Also referred as TABLET TRITURATE . </li></ul><ul><li>FORMULATION OF M.T:- </li></ul><ul><li>DRUG </li></ul><ul><li>An EXIPENT/BASE </li></ul><ul><li>ANTIOXIDANT </li></ul><ul><li>SOLVENT </li></ul>
  19. 21. HAND MOLDING & MACHINE MOLDING:- <ul><li>HAND MOLDING </li></ul><ul><li>Powder Mix. Blended by mortar. Then solvent mix. Is added to form damp mass. This mass is pressed in molding plates </li></ul><ul><li>&molded tablets are formed. </li></ul><ul><li>Same pri. Is involved in machine molding tablets . Here the machines are used. </li></ul><ul><li>MOLDING PROBLEMS </li></ul><ul><li>Solvents:- </li></ul><ul><li>Aqueous solvent </li></ul><ul><li>Drying :- </li></ul>
  20. 22. MOLDING PLATE:-
  21. 23. COMPRESSED SUBLINGUAL TABLET:- <ul><li>Generally Molded S.T get easily absorbed &give better effect but Compressed S.T. also disintegrate rapidly & allow the ingredients to dissolved in saliva &to available for absorption without requiring the complete solution of all ingredients of the formulation. </li></ul><ul><li>E.g.:- Compressed nitroglycerin tablet. </li></ul><ul><li>This type have less weight variation &better content uniformity. Also are harder & less fragile than Molded tablets. </li></ul><ul><li>According to USP the disintegration time should be 3-7 sec. </li></ul><ul><li>Formulation aspects are same as that of Compressed Tablet Lozenges. </li></ul>
  22. 24. BUCCAL TABLETS:- <ul><li>Developed by H.S.Russel. </li></ul><ul><li>Basic principle behind this is same that of Sublingual Tablet. </li></ul><ul><li>Buccal tablets are most often used when replacement hormonal therapy is goal. </li></ul><ul><li>Flat, ellipitcal/ capsule shaped tablets are used. </li></ul><ul><li>Circular &concave depression in each side of major surfaces. Flexible in nature. </li></ul><ul><li>Compressed Buccal Tablets are prepared either by Wet granulation/ Direct compressed method. </li></ul><ul><li>Main factor relating to B.T is that swallowing of drug is not allowed as the drugs are not allowed to absorbed from G.I.T. /they get destroyed by G.I.T./liver enzymes. </li></ul>
  23. 25. CHEWABLE TABLETS:- <ul><li>Chewable Tablet :- It is defined as oral solid dosage form which is intended to be chewed in the mouth prior to swallowing & not intended to be swallowed intact. </li></ul>
  24. 26. <ul><li>Formulation factors </li></ul><ul><li>Organoleptic properties </li></ul><ul><li>Taste </li></ul><ul><li>Flavor </li></ul><ul><li>Mouth feel </li></ul><ul><li>After effect </li></ul><ul><li>2.Physical properties </li></ul><ul><li>Amount of Drug </li></ul><ul><li>Flow </li></ul><ul><li>Compressibility </li></ul><ul><li>Compatibility </li></ul><ul><li>Desired product attribute </li></ul><ul><li>Good taste& mouth feel </li></ul><ul><li>Acceptable bioavailability </li></ul><ul><li>Acceptable stability& </li></ul><ul><li>Quality </li></ul><ul><li>Economical formula& </li></ul><ul><li>Process. </li></ul><ul><li>Formulation Techniques </li></ul><ul><li>Micro encapsulation </li></ul><ul><li>Adsorption </li></ul><ul><li>Ion exchange </li></ul><ul><li>Spray congealing& coating </li></ul><ul><li>Granulation& coating </li></ul><ul><li>Amino acids& protein hydrolysates </li></ul><ul><li>Formation of salts </li></ul><ul><li>Formulation approaches </li></ul><ul><li>Artificial sweeteners </li></ul><ul><li>Flavoring </li></ul><ul><li>coloring </li></ul>
  26. 28. MICROENCAPSULATION:- <ul><li>Coating of drug particles/ liquid droplets with edible polymeric materials there by masking the taste &forming of free flowing microcapsules of 5-5000 µm size. </li></ul><ul><li>Steps involved in micro encapsulation:- </li></ul><ul><li>Formation of three immiscible phases:- vehicle (liquid) phase, core (drug) phase, coating material phase. </li></ul><ul><li>Depositing the liquid polymer coating by sorption around the core material by mixing three phases. </li></ul><ul><li>Rigidizing the coating by chemical cross-linking/ desolvation techniques to form a microcapsules. </li></ul><ul><li>phase-separation& co-acervation technique is used for Microencapsulation. </li></ul>
  27. 29. ADSORPTION:- <ul><li>The drug is going to be adsorbed on a suitable substrates which is capable of keeping drug adsorbed while in the mouth but releasing them eventually in the stomach/G.I.T. </li></ul><ul><li>e.g. Dextromethorphan HBr on Mg.trisilicate </li></ul><ul><li>adsorbate Adsorbent </li></ul><ul><li>impart undesirable taste </li></ul>
  28. 30. ION EXCHANGE:- <ul><li>Substrate Resin (Cationic/ Anionic) possesses affinity for oppositely charged drug molecule, this form a complex which is stable in mouth for longer time. </li></ul><ul><li>e.g. resin bound form of Vit.B12. in presence of Vit.C (Ascorbic acid) </li></ul><ul><li>Amberlite (cation exchange resin) </li></ul><ul><li>SPRAY CONGEALING &SPRAY DRYING:- </li></ul><ul><li>Cooling (congealing) of melted substances in the form of fine particles during their travel from a spray nozzle to the distant vicinity of a spraying chamber held at temp. below the melting point . </li></ul>Vitamins Coating agent %W/W Thiamine mononitrate Mono& diglycerides- 33.3 Riboflavin -Of Fatty- 33.3 Pyridoxime -acid 33.3 Niacinamide Stearic acid 33.3
  29. 31. SPRAY DRYING:- <ul><li>THIS Process Involves Evaporation of solvent from a solution of coating material leaving a film of the coating material on the particle of substance being coated. </li></ul><ul><li>e.g. Coating of ANTIBIOTICS (sod. Dicloxacillin) by means of ethyl cellulose. </li></ul><ul><li>FORMATION OF DIFFERENT SALTS:- </li></ul><ul><li>The modification of chemical composition of the drug substance is done to form a salt/ derivative which it self render it less soluble in saliva & there by less stimulating for taste buds. </li></ul>
  30. 32. COATING BY CONVENTIONAL GRANULATING METHOD:- <ul><li>Direct granulation method. </li></ul><ul><li>Dry granulation method. </li></ul><ul><li>Wet granulation method. </li></ul><ul><li>USE OF AMINO ACIDS & PROTEIN HYDOLYSATE:- </li></ul><ul><li>By combining Amino acids /its salts it is possible to substantially reduce the bitter taste of the drug (PENICILLIN ). </li></ul><ul><li>Some used Amino acids:- Sarcosine, Alanine, Taurine, Glutamic acid, & Glycine. </li></ul>
  31. 33. MATERIAL USED IN FORMULATION OF CH.TAB.:- <ul><li>Direct compression vehicle. </li></ul><ul><li>Flavor. </li></ul><ul><li>Colors. </li></ul><ul><li>Active in gradients. </li></ul><ul><li>DIRECT COMPRESION VEHICLE :- </li></ul><ul><li>Characteristics required for D.C.V. </li></ul><ul><li>Moisture uptake characteristic </li></ul><ul><li>Loading potential </li></ul><ul><li>Hardness of tablets with vehicles </li></ul><ul><li>Relative sweetness of the vehicle & Auxillary sweetness </li></ul>
  32. 34. MOISTURE UPTAKE CHARACTERISTICS:- <ul><li>EQUILIBRIUM MOISTURE CONTENT(E.M.C):- </li></ul><ul><li>E.M.C. By given vehicle is defined as its ability of vehicle remain in equilibrium under the presence of moisture. </li></ul><ul><li>e.g. Graphic representation of Mannitol, Sucrose, Lactose, Xylitol, Sorbitol, Fructose, at 50, 65, 75, &85% RH. </li></ul><ul><li>Mannitol remain unchanged under any %RH while Fructose & lactose having high tendency to absorbed more moisture under %RH. </li></ul><ul><li>Mannitol/ Lactose < Sucrose< Dextrose/Xylitol < fructose/Sorbitol </li></ul>
  33. 35. HARDNESS OF TABLET WITH DEXTROSE, MANNITOL, SUCROSE…. <ul><li>For chewable tablets the hardness should be greater than regular tablet. In above e.g. it is indicated that Hardness of the given tablet upon storage going to decrease even at low humidity. </li></ul><ul><li>In such cases an Auxillary dry binder (M.C.C) is added in gran. Process to avoid softening. </li></ul>Vehicles Initial hardness (Sc) Hardness (sc unit) after 12 days 43%RH 65.%RH 75%RH 100%RH Lactose (Ah) 14.0 12.0 11.2 10.8 7.9 Mannitol 9.9 7.5 4.9 3.6 1.7 Sorbitol 14.7 12.2 8.1 6.4 4.2 Dextrose 15.6 11.4 6.2 4.0 1.8 Sucrose 15.1 7.2 2.3 1.2 0.2
  34. 36. LOADING POTENTIAL:- <ul><li>LOADING POTENTIAL:- It is defined as the ability of D.C.V. to accept other materials in the formulation including active drug & other agents. </li></ul><ul><li>It is expressed as % w/w of the vehicle weight. </li></ul><ul><li>Greater the L.P. The more economical formula. </li></ul><ul><li>For given vehicle the L.P should be dependent on each specific formulation </li></ul><ul><li>E.g. VIT.C. formulation. Sorbitol having L.P. of 45% & that of Dextrose having 33%. </li></ul><ul><li>The L.P. is also dependent on inherent compr. Character of drug. E.g. acetaminophen. </li></ul>
  35. 37. RELATIVE SWEETNESS OF VEHICLE /AUXILLARY SWEETENER:- <ul><li>Acceptance of D.C.V. mainly depend upon their ability to mask the bad taste of drug </li></ul><ul><li>The D.C.V should require the property of sweetness. </li></ul><ul><li>Auxillary sweeteners :- necessary in order to supplement the natural sweetness of vehicle. </li></ul><ul><li>E.g. neo hesperdin diHcl, Saccharin etc. </li></ul>
  36. 38. 2). FLAVORING AGENTS:- <ul><li>Natural flavors </li></ul><ul><li>Spray dried flavors </li></ul><ul><li>Adsorbed flavors </li></ul><ul><li>Microencapsulated flavors </li></ul><ul><li>The selection of flavors depends upon </li></ul><ul><li>Therapeutic agents </li></ul><ul><li>Active drug formulation </li></ul><ul><li>Formulation </li></ul><ul><li>Dose/ tablet & frequency of administration </li></ul><ul><li>Intended patient population </li></ul><ul><li>Marketing preference. </li></ul>
  37. 39. RECENT DEVELOPMENT & ASPECTS CHEWING GUMS (chewable tablets):- <ul><li>AIM:-Data from medicines monitoring unit (MEMO) at university of DUNDEE finds that 1/3 rd of patients:-fully compliance with drug prescription </li></ul><ul><li>1/3 rd of patients:- non compliance </li></ul><ul><li>Remaining patients:-fully non compliance </li></ul><ul><li>FLARER SA based company developed a system of chewing gum(3 TAB GUM) </li></ul><ul><li>Advantages:- </li></ul><ul><li>Dissolved in saliva:- compliance, bioavailability, readily available for absorption. </li></ul><ul><li>Use to act locally:- oral cavity disease treatment. </li></ul><ul><li>Administration of lower dosage:- side effects. </li></ul>
  38. 40. <ul><li>4) Gastric mucosa will not suffer:- risk of intolerance/erosion. </li></ul><ul><li>5) If gum is swallowed :-mechanism of release of drug is negated. </li></ul><ul><li>6) Separate process of formulation technique:- prevent gum base heating, avoid destruction of API. </li></ul><ul><li>7) Useful for combination of two/more API:-i.e.imcompatible / immediate, slow releasing drugs. </li></ul>
  39. 41. FORMULATION ASPECT:- <ul><li>NATURE OF CHEWING GUMS </li></ul><ul><li>Chewing gum(3TAB GUM) is divided into 3 layers:- upper & lower external layer & core layer (Drug). </li></ul><ul><li>Upper & lower layer mainly composed of anti adhesive excipients. </li></ul>External layers % Core layer % Antiadherant layer 70-90 Active 0.1-8 Compression adj. 1-10 Gum base 70-80 Sweetener 1-10 Compr. adj. 1-10 Flavors 1-10 Sweetener 1-10 Flavors 2-20
  40. 42. MELT-IN-MOUTH TABLETS BY SUBLIMATION TECHNIQUE:- <ul><li>Melt-in-mouth tablets:-Novel slid dosage form. </li></ul><ul><li>Disintegrate & dissolved rapidly in saliva, No need of water for administration. </li></ul><ul><li>Melt-in-mouth tablets overcome the feeling of rough texture (Side effect of compressed tablets, disintegrating agent). </li></ul><ul><li>MECHANISM :-It involves sublimation of volatile oils/sublimating agent, which causes pre formation in the tablet saliva enter in this pores &causes the rapid disintegration of tablet in oral cavity. </li></ul><ul><li>Compressible Mannitol (PEARLITOL SD200):-used as diluent, sweetener </li></ul><ul><li>subliming </li></ul><ul><li>agent pores created on sublimation </li></ul><ul><li>Compressed tablet </li></ul><ul><li>sublimation at appropriate condition e.g. olanzapine tablet (Anti-psychotic) </li></ul>
  41. 43. Name of Ingredients Forml n SO 1 SO 2 SO 3 Olanzapine 5.0 5.0 5.0 Pearlitol SD200 113.12 94.375 75.625 Ammo. bicarbonate - 18.750 37.500 Aspartame 3.125 3.125 3.125 Flavour 1.875 1.875 1.875 Aerosil 200 0.625 0.625 0.625 Magnesium Stearate 1.250 1.250 1.250 Formulation code Disint. Time in sec. In Oral SO 1 80 +/-5 80+/-5 SO 2 75 +/-5 60+/-5 SO 3 80 +/-5 35+/-5
  42. 44. MOUTH DISSOLVING TABLETS:- <ul><li>Mouth dissolving tablet (MDT)/ Orally disintegrating tablets (ODT) have emerged as Novel solid oral dosage form, which dissolve/ disintegrate/ disperse in saliva within few seconds. According to European Pharmacopoeia, the ODT disintegrate less than three minutes. MDT/ODT basically contains super disintegrating agent like Cross linked carboxymethylcellulose (Croscarmellose), Sodium starch glycolate (Primogel, explotab) ,Polyvinylpyrrolidone (Polyplasdone) etc. </li></ul>
  43. 45. TECHNOLOGIES FOR PREPARING MDT:- <ul><li>1) FREEZ DRYING METHOH:- </li></ul><ul><li>2) MOULDING:- </li></ul><ul><li>3) SUBLIMATION:- </li></ul><ul><li>4) SPARY DRYING:- </li></ul><ul><li>5) DIRECT COMPRESSION:- </li></ul>
  44. 46. QUIT SMOKING LOZENGES:- <ul><li>Quit smoking lozenges are a popular stop smoking aid. They are in the form of a small candy that are a) easy to carry with you, b) keep your mouth occupied and c) help you quit smoking of course. </li></ul><ul><li>Quit smoking lozenges are particularly good for people who light up their first cigarette in less than half an hour other they wake up in the morning. Most lozenges come in various forms depending on this time-factor. </li></ul><ul><li>well-know fact that the nicotine addiction and the cessation symptoms (nervousness, anxiety, sweating, headaches, depression, etc) are the two things making smoking cessation an impossible task for many smokers. </li></ul><ul><li>Q.M.L. will reduce the withdrawal symptoms thus leaving the person more stop-smoking-stress-free time to cope with yourself. Moreover the use of quit smoking lozenges will reduce the cravings. </li></ul><ul><li>Quit smoking lozenges are particularly preferred by women who often postpone smoking cessation because they are afraid of gaining weight one of the most popular brands quit smoking lozenges are the Commit stop smoking lozenges. </li></ul><ul><li>E.g. Bupropion Hydrochloride </li></ul><ul><li> </li></ul>
  46. 48. <ul><li>Learn to say </li></ul><ul><li>THANK YOU </li></ul><ul><li>Say some time </li></ul>