Tablets: Dosage Forms and Manufacture - Tablet Ingredients PDF

Tablets PHAR 7624 L. Garcia-Contreras, Ph.D. Pharmaceutics II Spring 2025 1  LEARNING OBJECTIVES: Tablets 1. Name the ingredients of a tablet and to explain their function within the formulation 2. Explain the steps involved in the 3 proc...

Tablets PHAR 7624 L. Garcia-Contreras, Ph.D. Pharmaceutics II Spring 2025 1  LEARNING OBJECTIVES: Tablets 1. Name the ingredients of a tablet and to explain their function within the formulation 2. Explain the steps involved in the 3 procedures to manufacture compressed tablets 3. Recognize the factors that influence the optimal outcome in each step to manufacture compressed tablets 4. Explain the rationale for tablet coating and describe the different coating types 5. Name the different types of compressed tablets and identify the particular excipients that differentiate them 6. Identify the reasons for possible tablet defects and propose solutions to each of these 7. List the quality control test that tablets are subject to and explain the rationale for each 2  Outline Introduction Tablet types Ingredients/ excipients Tablet Manufacturing – Pre-formulation – Unit processes – Granulation – Compression (Dice and Punches) – Coating Possible problems during manufacturing procedures Specialized tablets Packaging and storage Quality control 3  Tablets “Solid pharmaceutical dosage forms of many shapes and sizes containing ‘active principle(s)’ with or without suitable diluents which are prepared by compression or molding methods” RE King and JB Schwartz, 1985 – Compressed- large scale – Molded- smaller scale 4  Tablets: Advantages ‘Simplicity’ and economy of manufacture Can accommodate a large range of dose sizes Stability Convenience in packaging, shipping and dispensing Convenient for patient – Dosage accuracy – Compactness – Portability – Tasteless – Ease of administration 5  Tablet types Compressed tablets – Uncoated – Coated Sugar Film Molded tablets Gelatin Tablet triturates Enteric Hypodermic tablets – Multiple compressed Dispensing tablets Specialized tablets – Chewable – Effervescent – Controlled release/ Extended release – Sublingual – Buccal 6  LEARNING OBJECTIVES: Tablets 1. Name the ingredients of a tablet and to explain their function within the formulation 2. Explain the steps involved in the 3 procedures to manufacture compressed tablets 3. Recognize the factors that influence the optimal outcome in each step to manufacture compressed tablets 4. Explain the rationales for tablet coating and describe the different coating types 5. Name the different types of compressed tablets and identify the particular excipients that differentiate them 6. Identify the reasons for possible tablet defects and propose solutions to each of these 7. List the quality control test that tablets are subject to and explain the rationale for each 7  Tablet Ingredients Active pharmaceutical ingredient (API, or ‘active’) Diluent Impart satisfactory processing and Binder* compressing characteristics to the Lubricant formulation Glidant *Mainly for wet granulation Disintegrant Give additional Color desirable physical characteristics to Flavor the finished tablet Sweetening agent 8  Tablet Ingredients: Diluent Inert substance added to increase bulk to make a tablet of practical size for compression, or to adjust its size ‘Dilutes’ the ‘active’ allowing handling of small quantities Usually subjected to previous processes to give them flow-ability and compressibility Examples: – Lactose * – Mannitol – Di-calcium phosphate – Calcium phosphate – Microcrystalline cellulose (Avicel®) 9  Tablet Ingredients: Diluent Diluents can also be called “excipients” Warning: Need to test compatibility of ‘active’ with excipient – E.g.: Calcium salts interfere with absorption of tetracycline in the GI tract Water soluble diluents can be used to increase bioavailability of ‘actives’ with low solubility 10  Tablet Ingredients: Binder Imparts cohesive qualities to the powdered material (promotes adhesion of particles) Ensures tablet remains intact after compression (maintains integrity of the tablet) Improves powder flow-ability Quality of binder influences tablet characteristics: – Too much or too strong binder → strong/hard tablet that won’t disintegrate easily and can cause excessive wear of tableting machine 11  Tablet Ingredients: Binder For wet or dry granulation or direct compression (*) – Wet: Made into a paste or solution – Dry: Blended with remaining ingredients before compression Examples: – Starch paste (10-20% paste) – Gelatin (10-20% solution) – Sugar solution (sucrose, dextrose, lactose, molasses) – Natural or synthetic gums (acacia, sodium alginate) – Carboxy methyl cellulose (CMC), methyl cellulose (MC), polyvinyl pyrrolidone (PVP) – Alcohol, water ( not really binders, but act like binders when reacting with sugars) – Microcrystalline cellulose (Avicel®) (*) Warning: the use of different binders with tolbutamide influenced the hypoglycemic effects observed clinically 12 Diagram of how the tablet ingredients fit together + + Mix / Blend Active (PURE DRUG) Diluent Binder GRANULATE  Tablet Ingredients: Lubricant Generally hydrophobic materials Prevents adhesion of the powder formulation to the surfaces of the dice and punches of tableting machine Reduce inter-particle friction Facilitates ejection of tablets from dice cavity Improves rate of flow of granulate Should be added to the granulated material, not during granulation 14  Tablet Ingredients: Lubricant Examples: – Talc (~ 1-5%) – Magnesium stearate – Calcium stearate – Stearic acid Poor selection may result in : – ‘water-proofing’ tablet – Poor tablet disintegration – Poor dissolution – Decreased stability: Aspirin + talc (with high calcium content) → Aspirin decomposition 15 Diagram of how the tablet ingredients fit together + + Mix / Blend Active (PURE DRUG) Diluent Binder GRANULATE + Lubricant Blend  Tablet Ingredients: Glidant Improves flow characteristics of powder mixture Should be added in DRY state just prior to powder compression Examples: – Talc – Colloidal silicon dioxide (CAB-O-SIL® M-5P, Cabot, Corp) (