Lecture 8: Solid Dosage Forms - Tablet (3) PDF

SOLID DOSAGE FORMS Tablet (3) LECTURE 8 By Maha Mostafa Ghalwash Department of Pharmaceutics &Drug Manufacturing 1  Manufacture of Tablets Generally, tablet formulation consist of the following main process 1. Weighing 2. Granulation 3. Milling and Mixi...

SOLID DOSAGE FORMS Tablet (3) LECTURE 8 By Maha Mostafa Ghalwash Department of Pharmaceutics &Drug Manufacturing 1  Manufacture of Tablets Generally, tablet formulation consist of the following main process 1. Weighing 2. Granulation 3. Milling and Mixing 4. Compression 2  MIXING Critical step in formulation of pharmaceutical dosage form. Mixing allows uniform distribution of tablet constituents throughout the formulation Allows for adequate distribution of lubricants around tablet granules. Under mixing will probably leads to impaired content uniformity of tablet formulation and poor flow properties Over mixing will lead other tablet manufacturing problem such as poor flow properties due to lubricants will enter into the tablet granules instead of staying on the surface mixing step should be validated in a way that adequate mixing is obtained 3 Methods used for the manufacture of tablets Tablets are commonly manufactured by one of the following processes: 1- Wet granulation: (as in Granulation) 2- Dry granulation (as in Granulation) 3- Direct compression Factors affect the choice of manufacture method : 1- Physical and chemical stability of the drug during manufacturing. 2- The availability of the necessary processing equipment. 3- The cost of manufacturing process. 4- The excipients used to formulate the product. 4 Tableting methods 5  Wet Granulation Method Step 1 ; Mixing the therapeutic agent with the powdered excipients (without lubricant) ❑ Using a mixer for a sufficient specified time and speed till become homogenous. Step 2 :- Wet granulation of the powder mix to make homogenous granules 6 Description of wet granulation 1) To achieve cohesion between powders: we use a binder within the formulation either in The solid state within the powder mix or Dissolved in the binding fluid (water, isopropanol or ethanol). the wetted mass is then passed into an oscillating granulator which forces the wet mass through a metal screen under the action of an oscillatory stress. 2. Achieving wet granulation using high speed mixer/ granulator: This is more recent as in this machine single operation is employed. e.g: high shear (speed) mixer 7 3. Using fluidized bed drier for granulation and drying. Advantages of granulation step in tablet manufacture 1. Prevention of segregation of powder component during manufacture process. 2. Enhancement of the flow properties from the tablet hopper to tablet dies in the machine to prevent the variability in tablet weight. 3. Enhancement of the compaction properties due to the presence of binder on the surface of granules leading to greater intergranule adhesive interactions. 4. Lower incidence of dust production. 8 Step 3 Drying of the granules: The produced wet granules are dried in the shelf or tray drier which is similar to the design of conventional oven. Step 4 Milling of the granules: reduction of the granule size to: a) Controlling the particle size to improve the flow of granules into the tablet die and the fill of granules within the die. b)The choice of the granule size is determined by the size of the die & hence the final tablet size. The reduction of the granule size is performed by using: 1.Oscillating granulator 2. Using Quadro-Co mill. 9 Step 5 Mixing of granules with lubricant: Mix the dried and milled granules with the specified quantity of the lubricant before feeding to the tablet press hopper. 10  Advantages of wet granulation method in tablet manufacturing 1. Reduced segregation of the component during processing. 2. Useful technique for the manufacture of tablets containing low concentration of therapeutic agents. 3. Employs conventional excipients i.e. not dependent on special excipients such as direct compression method. 11  Disadvantages of wet granulation method in tablet manufacturing 1. Several proceeding steps are required increase the time , loss of material and effort. 2. Solvents which are required in this process; this may lead to different problems such as: a) Drug degradation may occur in the presence of the solvent. b) Drug may be soluble in the granulation fluid. c) Heat is required to remove the solvent; this could result degradation of the thermally labile therapeutic agents. 12  II. Dry granulation Dry granulation The formation of granules by compacting powder mixtures into large pieces or compacts which are broken down or size to granules.often refer as double compression Not widely used in tablets manufacturing 13 Advantages of dry granulation method in tablet manufacturing 1. We used conventional grades of excipients. 2. No heat or solvent is required. Disadvantages of dry granulation in tablet manufacturing 1. Special equipment are required for granulation by roller compaction. 2. Segregation may occur post mixing. 3. The final tablet produced by dry granulation tends to be softer than these of wet granulation rendering them difficult for further process such as coating. 4. Slugging or roller compaction may lead to the generation of dust. 5. May affect the disintegration and dissolution of drug as there is double lubrication and compaction 14  Direct Compression Special case of tablet formulation. ❑ No granulation step; only mixing ingredients and excipients and compressed directly without modifying the physical nature of materials itself. ❑ Avoids many of the problems associated with wet and dry granulation. ❑ It requires certain properties of the active ingredients to be able to produce a good tablet. ❑ Crystalline in nature and easy to be compressed drugs are fit for this method ❑ Ex:- Sodium chloride, potassium salts of iodide or chloride 15  Note: ❑ Direct Compression method are being to be used increasingly in recent years due to:- The development in manufacturing machine technology. Discovering of new excipients; ❑ Used specially for a drug which are effective in a very low dose because this method ensure ”better” content uniformity than other method. 16 17 Advantages of direct compression:- 1. The process is required few steps so ❑ There are no batch-to-batch variation ❑ Need a smaller number of workers, so is less cost 2. No need for liquid and no need for heat, hence the stability of the therapeutic agent is ensured. 3. The lubrication is performed in the same vessel of powder mixing. decrees number of equipment used. 18 Disadvantages of Direct Compression 1. Special excipients are required. Which more expensive. 2. The final tablet produced may be softer than that produce by wet granulation 3. If the therapeutic agent in the final formula is high dose the compression properties of the final tablet may be affected 4. In some cases, the physical properties of the drug may be unsuitable for compression by their methods (crystalline and amorphous drugs) 5. Direct compression is not used if deep colorant is required as this will produce molted tablet. 19  Tablet Compression Machine ❑ The tablet press is a high-speed mechanical device. ❑ It compresses the ingredients into the required tablet shape with extreme precision. ❑ It can make the tablet in many shapes, although they are usually round or oval. ❑ Also, it can press the name of the manufacturer or the product into the top of the tablet. ❑ Tablet punching machines work on the principle of compression. 20 The basic unit of any tablet press consisting of 1. Two Punches 2. a die which is called a station. The die determines the diameter or shape of the tablet; the punches. Upper and lower come together in the die that contains the tablet formulation to form a tablet. 21  Basic components of Tablet Presses 1. Hopper for holding & feeding powder or granules to be compressed. 2. Dies which define the size & shape of the tablet. 3. Punches for compressing the granules within the dies. 4. Cam tracks for guiding the movement of the punches. 5. Feed frame(s) for distributing the formulation to the dies. 22 23 24 25  1. Single Punch Machine A single-punch press possesses one die and one pair of punches. The powder is held in a hopper which is connected to a hopper shoe located at the die table. The hopper shoe moves to and from over the die, by either a rotational or a transitional movement 26 27 28  Compression sequence in single punch machine 1. The upper punch is raised, and lower punch is dropped. 2. Feed shoe (hopper) has moved forward over die and granules fall into die, then moved back. 3. Upper punch has come down compressing granules into tablet. 4. Upper punch has moved upwards and lower punch has moved upwards to eject tablet. 5. The cycle repeated. 29 30 31  2. Multi-Station (Rotary) Machine ❑ It are employed for the large-scale manufacture of tablets production up to 10000 tablet/minute. ❑ It is composed of series of upper and lower punches (up to 60 / machine) housed in a circular die tablet which rotates in circular motion. ❑ The head of the tablet machine that holds the upper punches, dies and lower punches in place rotates. 32 33 34 35  Tablet Testing Quality Control Test (Tablet Evaluation Parameter): These tests evaluate each step of formulation and the finished product to obtain good quality products. There are several tests for the evaluation of tablets. A. Non-official test B. Official Test General Appearance Weight Variation Size and shape Disintegration Test Thickness Test Dissolution Test Hardness Test Content Uniformity Friability Test 36  Non-official test. General Appearance: The general appearance of a tablet is its identity and "elegance," which is essential for consumer acceptance. It involves size, shape, color, odor, taste, and surface texture. 2. Size and Shape: It depends upon the die and punches used for making tablets. Generally, they are biconvex, oval, circular, oblong, and flat. 3. Thickness: Tablet thickness must be maintained within a ±5% range of the reference value. It is measured by Micrometer by a vernier caliper or screw gauge. 37 4. Hardness test: Tablets must be capable of withstanding mechanical handling shocks during the manufacturing, packaging, and shipping processes and are resistant to friability. Hardness generally measures the tablet crushing strength.. It's the amount of energy necessary to disintegrate a tablet. 38 Why hardness of the Tablet is essential? ❑ It is measured to determine the need for adjustment of compression pressure. ❑ If the Tablet is too hard, then it should not disintegrate easily. ❑ If the Tablet is too soft, it causes problems during coating, handling, packaging, and transportation. ❑ Generally, if the Tablet's hardness is too high, we first check its disintegration before rejecting the Batch. If the disintegration is within the limit, we accept the Batch. 39 What are the factors affecting the hardness? ❑ Compression of the Tablet and compressive force ❑ Quantity of binder used. Hardness will increase if more binder is used during the manufacturing of tablets. ❑ Method of granulation during tablet manufacturing. The wet granulation method gives more hardness than the direct compression method. 40 5. Friability Test: This test aims to evaluate the tablets' physical adaptability during handling and transportation. This test is applicable for compressed tablets and uncoated tablets. This test is official according to U.S.P. but not in I.P. The Roche friabilator can be used in a laboratory to verify a tablet's friability. mainly composed of a plastic chamber that rotates at 25 rpm and drops the tablets into the friabilator six inches away. The friabilator is then turned on for 100 revolutions, which takes four minutes to complete. Acceptable compressed tablets lose less than 0.5 to 1.0% of their total weight 41  Official Test Weight Variation Test: Uniformity of weight: ❑ The weight variation of tablets measured routinely helps to ensure that the Tablet contains the proper amount of the drug. ❑ The variation test is applicable when the Tablet contains 50 mg or more of the drug substance (weight). IP Standard: Average Weight of Tablet % deviation Less than 80 or 80 mg ±10% 80 mg to 250 mg ±7.5% More than 250 mg ±5% USP Standard: Average Weight of Tablet % deviation Less than 130 or 130 mg ±10% 130 mg to 324 mg ±7.5% More than 324 mg ±5% 42 Disintegration Test: ❑ That is the time it takes for the Tablet to disintegrate. The disintegration test calculates how long it takes for a batch of tablets to break up into smaller pieces under particular circumstances. ❑ The time required to disintegrate the Tablet is called disintegration time. ❑ A disintegration test is not performed for controlled & sustained-release tablets. 43  OFFICIAL TESTS ❑ The disintegration apparatus contains a water bath and beaker filled up to mark. A basket rack holding six plastic tubes is open at the top, and the bottom is covered with a 10-mesh screen. The test requires that the Tablet break up and that every particle go through the ten mesh screen in the allowable amount of time. If any residue is left, it needs to be soft in mass. Disintegration Apparatus 44 Dissolution Test: Dissolution tests are in vitro experiments that quantify the rate and degree of pharmaceutical product substance release or dissolution from an aqueous medium—under predetermined conditions.. It mainly depends on the aqueous solubility of the drug. The aqueous solubility increases, increasing the rate of dissolution of the drug. So, this test is performed to predict the time required for a given amount of drug to be released into the solution. It also helps to determine the bioavailability of a drug. The size, shape, and surface area of particles have a significant impact on how quickly a drug dissolves. 45  Dissolution is based on four processes – 1. wetting 2. Solubility 3. Swelling 4. Diffusion. It consists of a cylindrical vessel with a hemisphere bottom and is made up of transparent glass with a 1000 ml capacity. The vessel is fitted with a cover having four holes: one for the shaft, one for the thermometer, and two for the sample. According to I.P. 2022 Appratus I: Basket Appratus II: Paddle 46 Dissolution Apparatus 47 Tablet Manufacture problems and their correction 48 2- Capping is prevented by using flat punches 49 3- 50 How to solve or to treat the problem : 1-Fluffy materials may be identified by increasing the amount of binder or by changing to a solvent system which increases the wetting of the granulation. 2-The granulation may be too dry and a certain percentage of water is sometimes essential to good compaction. 3-The addition of a hygroscopic substance e.g. sorbital, methylcellulose or polyethylene glycol 4000 can help to maintain the proper moisture level. 51 4- 52 53 54 55