Pharmaceutics III/Pharmaceutical Dosage Forms III Tablets FALL 2024 PDF

Pharmaceutics III/Pharmaceutical Dosage Forms III PT 316/PTC 316 TABLETS FALL 2024 Prof. Dr. Amal Saber Mohammed Abu El-Enin Head of Pharmaceutics Department Believing in yourself is the first secret to success  Marks ❖...

Pharmaceutics III/Pharmaceutical Dosage Forms III PT 316/PTC 316 TABLETS FALL 2024 Prof. Dr. Amal Saber Mohammed Abu El-Enin Head of Pharmaceutics Department Believing in yourself is the first secret to success  Marks ❖ Total (100 Marks) ▪ Midterm (15 Marks) ▪ Practical (25 Marks) ▪ Final exam (50 Marks) ▪ Oral exam (10 Marks) Amal S. M. Abu El-Enin  Contents Lecturer Topics No. of lectures Hours Introduction to tablets Prof. Amal Saber Abu El-Enin 1 2 Tablet Excipients Prof. Amal Saber Abu El-Enin Tablets types 1 2 Prof. Amal Saber Abu El-Enin Manufacturing of tablets 1 2 Tablets Coating and Tablets Prof. Amal Saber Abu El-Enin 1 2 Defects Amal S. M. Abu El-Enin  Introduction Tablets: solid preparations each containing a single dose of one or more active ingredients and obtained by compressing uniform volumes of particles. They are used for local & systemic effect. Usually used for oral administration. Tablets represent about 46% of all other dosage forms. Amal S. M. Abu El-Enin  Advantages of Tablets 1. A convenient and safe way of drug administration. 2. Compared to liquid dosage form they are more physically & chemically stable. 3. Compared to liquid dosage forms → Easier to package and ship. 4. Enables more accurate dosing. Amal S. M. Abu El-Enin  5. Can easily mask bitter and unpleasant taste. 6. Low manufacturing cost. 7. Simple to identify. 8. Different types of tablets are available for variable requirements (e.g., orodispersible tablets, sustained release tablets). Amal S. M. Abu El-Enin  Disadvantages of tablet 1. It’s not suitable for poorly water-soluble or poorly absorbable drugs poor bioavailability. 2. Some drugs may cause local irritant effects or cause harm to the gastrointestinal mucosa. 3. Some drugs resist compression into tablet owing to their nature. 4. Difficulty in swallowing in some patients. Amal S. M. Abu El-Enin  Quality attributes of tablets Tablets should fulfill a number of specifications: 1. The tablet should include the correct dose of the drug. 2. The appearance of the tablet should be elegant and its weight, size should be consistent. 3. The drug should be released from the tablet in a controlled and reproducible way. Amal S. M. Abu El-Enin 4. The tablet should be biocompatible (not include excipients, contaminants and microorganisms that cause harm to patients). 5. The tablet should be sufficiently hard to withstand fracture and erosion during handling. 6. The tablet should be chemically, physically and microbiologically stable. Amal S. M. Abu El-Enin  Tablet components Active therapeutic agent (Drug) + Inactive materials (Excipients) Amal S. M. Abu El-Enin  Tablet Excipients Excipients (= Additives): are inert materials (with no therapeutic effect) added to ensure that tablets of specified quality are prepared. Excipients can be classified into two groups: Excipients help to give satisfactory compression characteristics to the formulation (diluents, binders, lubricants and glidants). Excipients help to give additional desirable physical characteristics to the finished tablet (disintegrators, colors, flavors and sweetening agents). Amal S. M. Abu El-Enin  Filler or Diluent uses: increase the bulk volume of the powder to produce tablet of acceptable size. Therefore, is not necessary if the dose of the drug per tablet is high. Most common fillers in tablets: 1. Lactose. 2. Sugar or sugar alcohol. 3. Starch. 4. Cellulose. 5. Dicalciumphosphate dihydrate. Amal S. M. Abu El-Enin  Requirements for a good filler: 1. Chemically inert and biocompatible. 2. Non-hygroscopic. 3. Good biopharmaceutical properties. (water soluble or hydrophilic). 4. Good technical properties (Good compression properties). 5. Have an acceptable taste. 6. Inexpensive Amal S. M. Abu El-Enin  Lactose The most widely used diluent in tablet Advantages: water soluble, has a pleasant taste, non-hygroscopic, non-reactive and it is a low cost diluent Disadvantage: some people have intolerance to lactose. It exists in hydrous, anhydrous and spray-dried forms. Amal S. M. Abu El-Enin  Other Sugars or Sugar Alcohols (glucose, sucrose, sorbitol and mannitol) They are used in lozenges or chewable tablets because of their pleasant taste. Mannitol has a negative heat of solution cooling sensation. Sorbitol is an optical isomer of mannitol (but hygroscopic at humidity above 65%). Amal S. M. Abu El-Enin  Starch Come from rice, wheat or potatoes. Starch 1500 is free flowing, directly compressible starch; used as diluent, binder and disintegrant (multifunctional). Amal S. M. Abu El-Enin  Cellulose One of the widely used fillers. Advantages: biocompatible, chemically inert and have good tablet-forming and disintegrating properties. Disadvantage: hygroscopic. They are also used as dry binders and disintegrants in tablets. The most common type of cellulose used in tablet formulation is microcrystalline cellulose (Avicel). Amal S. M. Abu El-Enin  Binders or adhesives Role: Ensure that granules and tablets can be formed with the required mechanical strength (glue that holds particles together). Amal S. M. Abu El-Enin  Different Ways to add a Binder: 1. Dry binder As a dry powder which is mixed with other ingredients before compaction. 2. Solution binder As a solution (granulating fluid) in wet granulation. The binding action is usually more effective when the binder is mixed in liquid form. Amal S. M. Abu El-Enin  Example of commonly used binders: 1. Dry binders as microcrystalline cellulose and cross linked pvp. 2. Solution binders as starch, sucrose and gelatin. Amal S. M. Abu El-Enin  Types of binders Polymeric Sugars materials Synthetic polymers Natural polymers Methyl, ethyl, Starches, gums and hydroxypropyl gelatin cellulose and pvp. Amal S. M. Abu El-Enin Complete: 1. …………………………. are the glue that holds powders together to form granules. 2. Starch …………………… is free flowing, directly compressible starch. 3......................................... is the most common filler in tablets 4..…………………..…. is an example of sugar alcohol. Amal S. M. Abu El-Enin  Disintegrant Role: to ensure that the tablet, when in contact with a liquid, breaks up into small fragments, which promotes rapid drug dissolution. Amal S. M. Abu El-Enin  Steps of the disintegration process First: the liquid wets the solid and penetrates the pores of the tablet the tablet breaks into smaller fragments (aggregates of primary particles). Second: the aggregates will deaggregate into their primary powder particles. Amal S. M. Abu El-Enin  Steps of the disintegration process Amal S. M. Abu El-Enin  Mechanisms of action of disintegrant 1. Disintegrants may increase the porosity and wettability of the compressed tablet matrix. In so doing GI fluids may readily penetrate the pores of the tablet and thereby enable tablet breakdown to occur. Amal S. M. Abu El-Enin 2. Disintegrants may operate by swelling in the presence of aqueous fluids increase in the internal pressure within the tablet. Disintegrants in this category are typically hydrophilic polymers. Amal S. M. Abu El-Enin 3. Tablet disintegration may also be mediated by the production of gas whenever the tablet contacts aqueous fluids. This is the mechanism of disintegration of effervescent tablets. Amal S. M. Abu El-Enin  The Methods of Disintegrant Addition 1. Mixed with other ingredients prior to granulation & thus incorporated within the granules (intragranular addition). 2. Mixed with the dry granules before the complete powder mix is compacted (extragranular addition). 3. incorporated as both an intragranular and an extragranular portion. Amal S. M. Abu El-Enin  The most commonly used disintegrant: 1. Starch. 2. Modified Starch: e.g. Explotab (sodium starch glycolate). 3. Modified cellulose: e.g. Ac-di-Sol (cross- linked form of sodium carboxymethyl cellulose). 4. Alginic acid & it’s salt (high cost). Amal S. M. Abu El-Enin  Lubricant Role: To ensure that tablet formation and ejection can occur with low friction between the solid and the die wall. (Facilitate the ejection of the tablet from the die cavity) Inadequate lubrication of this interface results in the production of tablets with a pitted surface. Amal S. M. Abu El-Enin  Lubricant concentration < 1%. Lubricant is added in the last step before granulation. Commonly used lubricants: A- hydrophobic B- hydrophilic (water-insoluble) : (water-soluble) : More common - Sodium Lauryl Sulfate - Mg stearate - Polyethylene glycol - Stearic acid (PEG) Amal S. M. Abu El-Enin  Antiadherant Role: Reduce adhesion between the powder and the punch faces &thus prevent particles sticking to the punches. Prevent sticking or picking. Sticking: (whole adhesion), Picking: (localized adhesion). Many lubricants, such as magnesium stearate, have also antiadherent properties. Also talc and starch can act as antiadherents. Amal S. M. Abu El-Enin  Glidant Role: Improve flowability of the powder by reducing friction between the particles Common Glidants: 1. Talc (at concentration 1-2 %). 2. Colloidal silicon dioxide (0.2 %). 3. Magnesium stearate(at concentration < 1%) Amal S. M. Abu El-Enin ▪ Glidants are typically hydrophobic (= insoluble lubricants) ▪ ➔ ensure that concentration of glidants does not adversely affect tablet disintegration and drug dissolution. Amal S. M. Abu El-Enin  Sorbent Def.: are substances that are capable of sorbing some quantities of fluids and remain in solid dry state. used to: a) adsorb moisture. b) whenever it is required to include a liquid or semisolid component (oily drug or flavor) within the tablet formulation. e.g. Microcrystalline cellulose & silica Amal S. M. Abu El-Enin  Flavour Give the tablet a more pleasant taste or to mask an unpleasant one. Flavoring agents are often thermolabile and so cannot be added before any operation involving heat. They are often mixed with the granules as an alcohol solution or dissolved in the granulation liquid. Amal S. M. Abu El-Enin  Colorant It is added to tablets to aid identification and patient compliance. It is added during coating. It can also be added prior to compaction. (can be added as an insoluble powder or dissolved in the granulation liquid.) Amal S. M. Abu El-Enin  Sweetener They are used in lozenges, orodispersible, and chewable tablets to exclude or limit the use of sugar in the tablets. e.g. Mannitol, 72% as sweet as sucrose. Saccharin, 500 times sweeter than sucrose. Disadv.: has a bitter after taste and carcinogenic. Aspartame, largely replace saccharin. Disadv.: lack of stability in the presence of moisture. Amal S. M. Abu El-Enin Write a substance that match with the sentence below: 1. Used as sorbent and filler in tablet. 2. Used as lubricant, ant adherent and glidant at concentration < 1%. 3. Used as disintegrant with the disadvantage of high cost. 4. Used as sweetener with the advantage of cooling sensation effect. 5. It exists in hydrous, anhydrous and spray-dried forms. Amal S. M. Abu El-Enin