Methods used for the manufacture of tablets

methods for the preparation of manufacturing of tablets

1. METHODS USED FOR THE MANUFACTURE OF TABLETS Prepared By: DR. ANANDA KUMAR.CH Assoc. Prof Department of pharmaceutics Lydia college of pharmacy Subject: Pharmaceutical Formulation Pharma . D IIIrd Year

2. CONTENTS DEFINITION WET GRANULATION DRY GRANULATION DIRECT COMPRESSION

3. DEFINITION OF TABLETS A tablet is a pharmaceutical dosage form. It comprises of a mixture of active substances and excipients, usually in powder form, passed are compacted into a solid dose. Excipients: Diluents, binders or granulating agents, glidents and lubricants to ensure efficient tabletting; Disintegrates: to promote tablet break up in the digestive tract; Sweeteners or flavours: to enhance the taste; Polymer coating: it is to applied to make the tablet smoother and easier to swallow, to control the release rate of the active ingredient, to make it more resistant to the environment.

4. MANUFACTURE OF TABLETS There are three methods by which tablets are manufactured; Wet granulation Dry granulation Direct compression Manufacturing process is dependent on several factors, including the compression properties of the therapeutic agents, the particle size of the therapeutic agent, excipients and the chemical stability of the therapeutic agent during the manufacturing process.

5. MANUFACTURE OF TABLETS STEPS Mixing of the therapeutic agents with the excipients Granulation of the mixed powders(this is not performed in direct compression) Mixing of the powders or granules with other excipients(mostly lubricants) Compression into tablets The details of each of these steps will vary depending on the manufacturing method used.

6. Wet granulation It is most commonly used method for the manufacturing of tablets. Water is frequently used as the granulation fluid (and heat is employed to dry the formed granules), it is important to ensure that the therapeutic agent is chemically stable during the granulation process. The wet granulation exhibit sufficient mechanical properties to be subsequently exposed to other unit operations, Eg : film coating. Tablet quality is directly affected by the choice and concentration of binder and the type and volume of granulation fluid. Due to the number of unit operations to the required, the manufacture of tablets by wet granulation is not as efficient as other methods. eg : direct compression

7. Advantages & disadvantages Reduced segregation of formulation components during storage and processing. Leading to reduced intra and inter batch variability. It uses low concentration of therapeutic agent. It is not dependent on the inclusion of special grades of excipients (is spray dried excipients used in direct compression method). Tablets produced by wet granulation are amenable to post processing unit operations, eg : tablet coating techniques. Disadvantages: It has several processing steps Solvents are required in the process: this leads to a number of concerns, eg : drug degradation may occur in the presence of the solvent. This is particularly relevant if water is used as the granulation medium due to the susceptibility of some drugs to hydrolysis

8. Advantages & disadvantages To overcome this concern, a hydroalcoholic (water/alcohol) or an alcohol (ethanol or isopropanol) granulation medium should be used. 3. The drug may be soluble in the granulation fluid. During the drying process the drug will then precipitate/ crystallise , resulting in possible changes in the polymorphic form. If the drug and some excipients soluble in the granulation medium, subsequent drying will result in deposition of these components on the surface of the insoluble particles and in so doing, this may enhance the hardness of the granule 4. Heat is required to remove the solvent. This may result in the degradation of thermo labile therapeutic agents. In addition drying is a costly operation and furthermore, if alcohols are used in the granulation medium, there are issues regarding solvent recovery and flammability.

9. DRY GRANULATION When tablet ingredients are sensitive to moisture and unable to withstand elevated temperature during drying and when the tablet ingredient have insufficient cohesive properties, slugging may be used to form granules. This technique is used in preparation of aspirin, aspirin combination, acetophenetidin. Excipients used in this method: 1. Diluents/ filler: anhydrous lactose/ lactose monohydrate, starch, dibasic calcium phosphate, and MCC 2. Disintegrants: Starch, MCC, Sodium starch glycolate, Croscarmellose sodium, Crospovidone. 3. Lubricants: Stearates (Mg. stearate, steric acid), Glyceryl fatty acid esters, polyoxyethylene stearates, SLS. 4. Glidants: Talc, Colloidal silicon dioxide. 5. Miscellaneous Excipients: Colours, sweetening agents, etc.

10. Advantages & disadvantages This technique popularity has decreased in recent years, having been superseded by direct compression. However both slugging and roller compaction are still employed in tablet manufacture. Advantages: Both roller compaction and slugging require conventional grades of excipients. These methods are not generally associated with alterations in drug morphology during processing. No heat or solvent are required.

11. Advantages & disadvantages Disadvantages: Specialist equipment is required for granulation by roller compaction. Segregation of components may occur during post mixing. There may be issues regarding powder flow. The final tablets produced by dry granulation tend to be softer than those produced by wet granulation, rendering them more difficult to process using post tabletting techniques, eg : film coating. Slugging and roller compaction lead to the generation of considerable dust. Therefore there may be a reduction in the yield of tablets.

12. Direct compression Wet granulation and dry granulation methods having series of unit operations, both time consuming and potentially costly. Potentially more attractive option for the manufacture of tablets involves powder mixing and subsequent compression of the powder mix, thereby obviating the need for granulation. This process is called direct compression. The mechanism of particle-particle interactions in tablets produced by direct compression are similar to those operative in tablets produced by dry granulation and roller compaction.

13. Direct compression Excipients: 1. Diluents/filler: spray dried lactose(lactopress spray dried, lactopress), spray dried 250, Dicalcium phosphate, M annitol, S orbitol, MCC. 2. Disintegrants: MCC ( eg : Avicel ) pregelatinised starch (starch1500), Sodium starch glycolate, Croscarmellose and Sodium Crospovidone. 3. L ubricants: Magnesium stearate, stearic acid, Sodium stearyl fumarate. 4. Glidants: Talc, Colloidal Silicon dioxide.

14. Advantages & disadvantages Advantages: There are fewer processing steps and therefore the method is potentially more cost effective than other methods. Direct compression does not require the use of water or other solvents. Therefore negates potential problems regarding the stability of therapeutic agents in the presence of the solvents. In addition heating is not required in direct compression. Lubrication is performed in the same vessel as powder mixing, thereby reducing both transfer losses and contamination of equipment.

15. Advantages & disadvantages Disadvantages: Special grade excipients are required. The quality and uniformity of the final dosage form depends on the excipients. There may be issues regarding powder flow into the tableting machine. The final tablets produced by direct compression tend to be softer than those produced by wet granulation, rendering them more difficult to process using post tableting techniques, eg : film coating It is not used if a colourent is required in the formulation due to the mottled appearance of the resulting dosage form.