Capsule Manufacturing PDF

PHD 212 CAPSULES NURUL ALYAA BINTI IBRAHIM, RPh. DipPharm, BPharm (Hons.), MClinPharm (UiTM) Faculty of Pharmacy, UiTM Pulau Pinang (Bertam Campus)  Definition Advantages and Cachets...

PHD 212 CAPSULES NURUL ALYAA BINTI IBRAHIM, RPh. DipPharm, BPharm (Hons.), MClinPharm (UiTM) Faculty of Pharmacy, UiTM Pulau Pinang (Bertam Campus)  Definition Advantages and Cachets disadvantages Preparation of cachet in old age Capsules Hard gelatin capsule Type of capsule Soft gelatin capsule Advantages and disadvantages of capsules Gelatin Components of capsules Additives  LEARNING OUTCOME After this lecture, students should be able to : Understand cachets formulation in pharmaceutical preparations Explain advantages, disadvantages, types of capsules and its characteristics Describe quality standard, containers, labeling and storage of capsules Explain general principles involved in manufacturing and dispensing of capsules  LECTURE OUTLINE 1. Manufacturing and compounding 2. Filling of capsules 3. Quality control test 4. Calculation involved in compounding 5. Storage, stability and labelling MANUFACTURING & COMPOUNDING 1. There are large-scale manufactures of both hard and soft gelatin capsules 2. Soft gelatin capsules -> made only by an industrial process and not extemporaneously prepared 3. Only a small-scale powdered medicament can be packed by hand into hard gelatin shells  Oldest commercial Plate process method of manufacturing Production methods Common method use in Rotary die process manufacturing soft shells The ONLY machine that Accogel machine formulate dry powder into soft gelatin capsule Reciprocating die Operations similar to process rotary die process ROTARY DIE PROCESS Can filled with liquids or semisolid Ribbons of gelatin are fed between 2 rotary dies to form pockets, simultaneously, a metered volume of capsule fill is dispensed into forming pocket Soft gelatin capsules formed  MANUFACTURING OF HARD GELATIN CAPSULES FROM GELATIN Capsule molds Once dipped, Capsule Finished (pin) are they are raised Capsules are bodies and capsules are dipped into to let bodies stripped from caps are pushed into gelatin and caps to the pins joined conveyer belt solution set and dry automatically to be collected  CAPSULE FILLING OPERATIONS Feeding of Opening of Proper Removal of Filling of Ejection empty capsule Closing orientation any non- medication of filled hard shells: filled of capsule separated into capsules gelatin splits of capsule shells into capsule capsule from the capsule body and with caps molds shells body mold shells cap  Hand operated capsule Feton capsule filling filling machine machine Capsule filling machines Semi-automatic capsule For smaller batches filling machine production Developed to fill hard Automatic capsule filling gelatin capsules with machine powders or pallets Punch method For hard fill capsules  Hand operated capsule filling machine Semi operated capsule filling machine Automated capsule filling machine Punch method CAPSULE FILLING MACHINE  COMMON STEPS IN FILLING MACHINE Replacement of Separation of Rectification of the caps over cap and body of Dosing of a fill the empty the body and empty capsule material capsule shell ejection of the shell filled capsules Orientation of capsule: e.g: Auger Principle, body oriented Dosing disc principle, downwards, and caps Dosator fill principle, oriented upwards Punch principle FETON CAPSULE FILLING DEVICES Pour the prepared powder ingredients over the top of the Using a nonautomated capsule capsules and use a special spatula filling machine (see figure A), place to direct powder into capsules. A the bodies of the capsules into the tamper is provided with the holes of the machine (Figure B). machine to press powder into capsule compactly (Figure C) FETON CAPSULE FILLING DEVICES #2 After applying the capsule lids, When each capsule has been filled, randomly select 10 completed lower the platform of the capsule capsules for weighing and machine so that the capsule lid can document the weight for quality be applied. The device can usually control. If all 10 capsules are within accommodate 100 capsules at time range of 85% to 115% of the and most efficient when used to labelled amount of drug per compound full quantity of 100 capsules, then capsules are capsules (Figure D) considered to be satisfactory (Figure E)  GENERAL METHODS OF CAPSULE COMPOUNDING 1. Occasionally hand filling capsules may be required. 2. Recommended minimum weight for filling a capsule is 100mg/capsule. 3. If smaller than required weight is smaller than this, a diluent should be added by trituration  FILLING CAPSULES There are at least 3 methods of filling capsules manually. Always work on the clean tile: remember these capsules are to be taken. a) Punch method: Place some powder onto a piece of weighing paper. The powder is arranged on a suitable surface with a spatula so that the thickness of the pile is about 1 ⁄ 3 the length of the capsule body. Hold the capsule with one hand and lift the paper with the other and scoop the powder into the capsule. Or the capsule is pressed into the powder with a slight rotation as it enters the powder and reaches the working surface to aid in packing the powder. After filling and weighing a few capsules, you will obtain a ”feel“ for the resistance required for the amount of fill required.  FILLING CAPSULES #2 b) Place some powder onto a piece of weighing paper and fill the capsule using chemical spatula. c) Weigh 200mg of powder onto a piece of weighing paper, which has been folded in half. Using the weighing paper to pour the powder into the capsule. Remember! Use of gloves provides a more hygienic environment and helps recommended to minimize contact with the powder and to avoid fingerprints on the capsules Cleaning capsules is difficult if they have become moist or sticky. The capsules should be handled so that they retain their dryness and shiny appearance. QUALITY CONT ROL TESTS ON CAPSULE Weight variation test Moisture permeation test Content uniformity Dissolution test Disintegration test  CALCULATION QUESTIONS You receive a prescription in your pharmacy with the following details for each patient. Consider 2-3 extra for manipulative loss, calculate the required amount (in mg) for each ingredient including the trituration steps involved in compounding the dosage forms. Use lactose as diluent. Note: Minimum weighable quantity by using class B balance is 100 mg. Patient 1: Mr Murugan a/l Subramaniam Age: 65 Prescription: Atropine 0.6 mg capsule Ft: cap no. 3 Mitte: VIII Sig: 1 cap q.i.d / p.r.n  CALCULATION #1 Atropine Sulphate Information given  Make 8 + 2 extra = 10 capsules, each containing 0.6 mg of atropine Capsule size 3 = 200 mg/ capsule. To make 10 capsules  Total weight = 200 mg/ capsule x 10 = 2000 mg total  CALCULATION #2 For active ingredients (Atropine); 1. Total weight atropine (A) required < MWQ 0.6 mg / capsule X 10 capsule = 6mg A (100mg) 2. Select some multiple of 6mg A that can be weighed with desired degree of accuracy (e.g., you can stick to MWQ 100mg OR select multiple 20, easier for calculation) > MWQ 6mg A x 20 = 120mg A (100mg)  CALCULATION #3 3. Select the size of aliquot portion to be taken to contain 6mg of drug A (You can select multiple of 6 or any nearest whole numbers for easier calculation) 100mg, 120 mg, 140mg, 160mg, 180mg, 200mg Same as Powder Calculation ! (Method 1) 𝑡𝑡𝑜𝑜𝑡𝑡𝑎𝑎𝑙𝑙 𝑎𝑎𝑚𝑚𝑜𝑜𝑢𝑢𝑛𝑛𝑡𝑡 𝑜𝑜𝑓𝑓 𝑡𝑡𝑟𝑟𝑖𝑖𝑡𝑡𝑢𝑢𝑟𝑟𝑎𝑎𝑡𝑡𝑖𝑖𝑜𝑜𝑛𝑛 𝑎𝑎𝑙𝑙𝑖𝑖𝑞𝑞𝑢𝑢𝑜𝑜𝑡𝑡 𝑐𝑐𝑜𝑜𝑛𝑛𝑡𝑡𝑎𝑎𝑖𝑖𝑛𝑛𝑠𝑠 𝑑𝑑𝑒𝑒𝑠𝑠𝑖𝑖𝑟𝑟𝑒𝑒 𝑎𝑎𝑚𝑚𝑜𝑜𝑢𝑢𝑛𝑛𝑡𝑡 𝑜𝑜𝑓𝑓 𝑎𝑎𝑐𝑐𝑡𝑡𝑖𝑖𝑣𝑣𝑒𝑒 𝑖𝑖𝑛𝑛𝑔𝑔𝑟𝑟𝑒𝑒𝑑𝑑𝑖𝑖𝑒𝑒𝑛𝑛𝑡𝑡𝑠𝑠 = 𝑀𝑀𝑊𝑊𝑄𝑄 𝑜𝑜𝑓𝑓 𝑎𝑎𝑐𝑐𝑡𝑡𝑖𝑖𝑣𝑣𝑒𝑒 𝑖𝑖𝑛𝑛𝑔𝑔𝑟𝑟𝑒𝑒𝑑𝑑𝑖𝑖𝑒𝑒𝑛𝑛𝑡𝑡𝑠𝑠 (𝑚𝑚𝑔𝑔) 𝑑𝑑𝑒𝑒𝑠𝑠𝑖𝑖𝑟𝑟𝑒𝑒 𝑎𝑎𝑚𝑚𝑜𝑜𝑢𝑢𝑛𝑛𝑡𝑡 𝑎𝑎𝑐𝑐𝑡𝑡𝑖𝑖𝑣𝑣𝑒𝑒 𝑖𝑖𝑛𝑛𝑔𝑔𝑟𝑟𝑒𝑒𝑑𝑑𝑖𝑖𝑒𝑒𝑛𝑛𝑡𝑡𝑠𝑠 (𝑚𝑚𝑔𝑔) (Method 2) 𝑡𝑡𝑜𝑜𝑡𝑡𝑎𝑎𝑙𝑙 𝑎𝑎𝑚𝑚𝑜𝑜𝑢𝑢𝑛𝑛𝑡𝑡 𝑜𝑜𝑓𝑓 𝑡𝑡𝑟𝑟𝑖𝑖𝑡𝑡𝑢𝑢𝑟𝑟𝑎𝑎𝑡𝑡𝑖𝑖𝑜𝑜𝑛𝑛 𝑎𝑎𝑙𝑙𝑖𝑖𝑞𝑞𝑢𝑢𝑜𝑜𝑡𝑡 𝑐𝑐𝑜𝑜𝑛𝑛𝑡𝑡𝑎𝑎𝑖𝑖𝑛𝑛𝑠𝑠 𝑑𝑑𝑒𝑒𝑠𝑠𝑖𝑖𝑟𝑟𝑒𝑒 𝑎𝑎𝑚𝑚𝑜𝑜𝑢𝑢𝑛𝑛𝑡𝑡 𝑜𝑜𝑓𝑓 𝑎𝑎𝑐𝑐𝑡𝑡𝑖𝑖𝑣𝑣𝑒𝑒 𝑖𝑖𝑛𝑛𝑔𝑔𝑟𝑟𝑒𝑒𝑑𝑑𝑖𝑖𝑒𝑒𝑛𝑛𝑡𝑡𝑠𝑠 = 𝑀𝑀𝑊𝑊𝑄𝑄 𝑜𝑜𝑓𝑓 𝑎𝑎𝑐𝑐𝑡𝑡𝑖𝑖𝑣𝑣𝑒𝑒 𝑖𝑖𝑛𝑛𝑔𝑔𝑟𝑟𝑒𝑒𝑑𝑑𝑖𝑖𝑒𝑒𝑛𝑛𝑡𝑡𝑠𝑠 (𝑚𝑚𝑔𝑔) 𝑑𝑑𝑒𝑒𝑠𝑠𝑖𝑖𝑟𝑟𝑒𝑒 𝑎𝑎𝑚𝑚𝑜𝑜𝑢𝑢𝑛𝑛𝑡𝑡 𝑎𝑎𝑐𝑐𝑡𝑡𝑖𝑖𝑣𝑣𝑒𝑒 𝑖𝑖𝑛𝑛𝑔𝑔𝑟𝑟𝑒𝑒𝑑𝑑𝑖𝑖𝑒𝑒𝑛𝑛𝑡𝑡𝑠𝑠 (𝑚𝑚𝑔𝑔)  ATROPINE SULFATE (METHOD 1) 𝑡𝑡𝑜𝑜𝑡𝑡𝑎𝑎𝑙𝑙 𝑎𝑎𝑚𝑚𝑜𝑜𝑢𝑢𝑛𝑛𝑡𝑡 𝑜𝑜𝑓𝑓 𝑡𝑡𝑟𝑟𝑖𝑖𝑡𝑡𝑢𝑢𝑟𝑟𝑎𝑎𝑡𝑡𝑖𝑖𝑜𝑜𝑛𝑛 𝑎𝑎𝑙𝑙𝑖𝑖𝑞𝑞𝑢𝑢𝑜𝑜𝑡𝑡 𝑐𝑐𝑜𝑜𝑛𝑛𝑡𝑡𝑎𝑎𝑖𝑖𝑛𝑛𝑠𝑠 𝑑𝑑𝑒𝑒𝑠𝑠𝑖𝑖𝑟𝑟𝑒𝑒 𝑎𝑎𝑚𝑚𝑜𝑜𝑢𝑢𝑛𝑛𝑡𝑡 𝑜𝑜𝑓𝑓 𝑎𝑎𝑐𝑐𝑡𝑡𝑖𝑖𝑣𝑣𝑒𝑒 𝑖𝑖𝑛𝑛𝑔𝑔𝑟𝑟𝑒𝑒𝑑𝑑𝑖𝑖𝑒𝑒𝑛𝑛𝑡𝑡𝑠𝑠 = 𝑑𝑑𝑒𝑒𝑠𝑠𝑖𝑖𝑟𝑟𝑒𝑒 𝑎𝑎𝑚𝑚𝑜𝑜𝑢𝑢𝑛𝑛𝑡𝑡 𝑎𝑎𝑐𝑐𝑡𝑡𝑖𝑖𝑣𝑣𝑒𝑒 𝑖𝑖𝑛𝑛𝑔𝑔𝑟𝑟𝑒𝑒𝑑𝑑𝑖𝑖𝑒𝑒𝑛𝑛𝑡𝑡𝑠𝑠 (𝑚𝑚𝑔𝑔) 𝑀𝑀𝑊𝑊𝑄𝑄 𝑜𝑜𝑓𝑓 𝑎𝑎𝑐𝑐𝑡𝑡𝑖𝑖𝑣𝑣𝑒𝑒 𝑖𝑖𝑛𝑛𝑔𝑔𝑟𝑟𝑒𝑒𝑑𝑑𝑖𝑖𝑒𝑒𝑛𝑛𝑡𝑡𝑠𝑠 (𝑚𝑚𝑔𝑔) ? 𝑡𝑡𝑜𝑜𝑡𝑡𝑎𝑎𝑙𝑙 𝑎𝑎𝑚𝑚𝑜𝑜𝑢𝑢𝑛𝑛𝑡𝑡 𝑜𝑜𝑓𝑓 𝑡𝑡𝑟𝑟𝑖𝑖𝑡𝑡𝑢𝑢𝑟𝑟𝑎𝑎𝑡𝑡𝑖𝑖𝑜𝑜𝑛𝑛 120𝑚𝑚𝑔𝑔 𝑎𝑎𝑙𝑙𝑖𝑖𝑞𝑞𝑢𝑢𝑜𝑜𝑡𝑡 𝑜𝑜𝑓𝑓 𝑡𝑡𝑟𝑟𝑖𝑖𝑡𝑡𝑢𝑢𝑟𝑟𝑎𝑎𝑡𝑡𝑖𝑖𝑜𝑜𝑛𝑛 = 120𝑚𝑚𝑔𝑔 𝑎𝑎𝑡𝑡𝑟𝑟𝑜𝑜𝑝𝑝𝑖𝑖𝑛𝑛𝑒𝑒 (𝐴𝐴) 6𝑚𝑚𝑔𝑔 𝑎𝑎𝑡𝑡𝑟𝑟𝑜𝑜𝑝𝑝𝑖𝑖𝑛𝑛𝑒𝑒 𝑇𝑇𝑜𝑜𝑡𝑡𝑎𝑎𝑙𝑙 𝑎𝑎𝑚𝑚𝑜𝑜𝑢𝑢𝑛𝑛𝑡𝑡 𝑜𝑜𝑓𝑓 𝑡𝑡𝑟𝑟𝑖𝑖𝑡𝑡𝑢𝑢𝑟𝑟𝑎𝑎𝑡𝑡𝑖𝑖𝑜𝑜𝑛𝑛 = ? 𝑚𝑚𝑔𝑔 𝑑𝑑𝑖𝑖𝑙𝑙𝑢𝑢𝑒𝑒𝑛𝑛𝑡𝑡 + 120 𝑚𝑚𝑔𝑔 𝐴𝐴 Can we solve the equation? Sure !  ATROPINE SULFATE (METHOD 1) 4. Solve for the total trituration amount 𝑡𝑡𝑜𝑜𝑡𝑡𝑎𝑎𝑙𝑙 𝑎𝑎𝑚𝑚𝑜𝑜𝑢𝑢𝑛𝑛𝑡𝑡 𝑜𝑜𝑓𝑓 𝑡𝑡𝑟𝑟𝑖𝑖𝑡𝑡𝑢𝑢𝑟𝑟𝑎𝑎𝑡𝑡𝑖𝑖𝑜𝑜𝑛𝑛 (𝑥𝑥) 120𝑚𝑚𝑔𝑔 𝑎𝑎𝑙𝑙𝑖𝑖𝑞𝑞𝑢𝑢𝑜𝑜𝑡𝑡 𝑜𝑜𝑓𝑓 𝑡𝑡𝑟𝑟𝑖𝑖𝑡𝑡𝑢𝑢𝑟𝑟𝑎𝑎𝑡𝑡𝑖𝑖𝑜𝑜𝑛𝑛 = 120𝑚𝑚𝑔𝑔 𝑎𝑎𝑡𝑡𝑟𝑟𝑜𝑜𝑝𝑝𝑖𝑖𝑛𝑛𝑒𝑒 (𝐴𝐴) 6𝑚𝑚𝑔𝑔 𝑎𝑎𝑡𝑡𝑟𝑟𝑜𝑜𝑝𝑝𝑖𝑖𝑛𝑛𝑒𝑒 𝑋𝑋 = 120𝑚𝑚𝑔𝑔 𝑎𝑎𝑙𝑙𝑖𝑖𝑞𝑞𝑢𝑢𝑜𝑜𝑡𝑡 𝑜𝑜𝑓𝑓 𝑡𝑡𝑟𝑟𝑖𝑖𝑡𝑡𝑢𝑢𝑟𝑟𝑎𝑎𝑡𝑡𝑖𝑖𝑜𝑜𝑛𝑛 𝑥𝑥 120𝑚𝑚𝑔𝑔 𝐴𝐴 6𝑚𝑚𝑔𝑔 𝑎𝑎𝑡𝑡𝑟𝑟𝑜𝑜𝑝𝑝𝑖𝑖𝑛𝑛𝑒𝑒 𝑋𝑋 = 2400𝑚𝑚𝑔𝑔 5. Determine weight of diluent (lactose) required to prepare the trituration by subtracting weight of atropine from trituration weight 𝑇𝑇𝑜𝑜𝑡𝑡𝑎𝑎𝑙𝑙 𝑎𝑎𝑚𝑚𝑜𝑜𝑢𝑢𝑛𝑛𝑡𝑡 𝑜𝑜𝑓𝑓 𝑡𝑡𝑟𝑟𝑖𝑖𝑡𝑡𝑢𝑢𝑟𝑟𝑎𝑎𝑡𝑡𝑖𝑖𝑜𝑜𝑛𝑛 = ? 𝑚𝑚𝑔𝑔 𝑑𝑑𝑖𝑖𝑙𝑙𝑢𝑢𝑒𝑒𝑛𝑛𝑡𝑡 + 120𝑚𝑚𝑔𝑔 𝑎𝑎𝑡𝑡𝑟𝑟𝑜𝑜𝑝𝑝𝑖𝑖𝑛𝑛𝑒𝑒 ? 𝑚𝑚𝑔𝑔 𝑑𝑑𝑖𝑖𝑙𝑙𝑢𝑢𝑒𝑒𝑛𝑛𝑡𝑡 = 2400𝑚𝑚𝑔𝑔 − 120𝑚𝑚𝑔𝑔 𝑎𝑎𝑡𝑡𝑟𝑟𝑜𝑜𝑝𝑝𝑖𝑖𝑛𝑛𝑒𝑒 𝑇𝑇𝑜𝑜𝑡𝑡𝑎𝑎𝑙𝑙 𝑑𝑑𝑖𝑖𝑙𝑙𝑢𝑢𝑒𝑒𝑛𝑛𝑡𝑡 = 2280𝑚𝑚𝑔𝑔  ATROPINE SULFATE (METHOD 1) 6. Fill the prescription (Rx) Determine the weight of lactose which must be added to the aliquot portion of trituration to make 10 capsules with each capsule 200mg/capsule 200𝑚𝑚𝑔𝑔 𝑥𝑥 10 𝑐𝑐𝑎𝑎𝑝𝑝𝑠𝑠𝑢𝑢𝑙𝑙𝑒𝑒𝑠𝑠 = 2000𝑚𝑚𝑔𝑔 𝑑𝑑𝑟𝑟𝑢𝑢𝑔𝑔 + 𝑙𝑙𝑎𝑎𝑐𝑐𝑡𝑡𝑜𝑜𝑠𝑠𝑒𝑒 2000𝑚𝑚𝑔𝑔 − 120𝑚𝑚𝑔𝑔 = 1880𝑚𝑚𝑔𝑔 𝑙𝑙𝑎𝑎𝑐𝑐𝑡𝑡𝑜𝑜𝑠𝑠𝑒𝑒 ATROPINE SULFATE (METHOD 2) 𝑡𝑡𝑜𝑜𝑡𝑡𝑎𝑎𝑙𝑙 𝑎𝑎𝑚𝑚𝑜𝑜𝑢𝑢𝑛𝑛𝑡𝑡 𝑜𝑜𝑓𝑓 𝑡𝑡𝑟𝑟𝑖𝑖𝑡𝑡𝑢𝑢𝑟𝑟𝑎𝑎𝑡𝑡𝑖𝑖𝑜𝑜𝑛𝑛 𝑎𝑎𝑙𝑙𝑖𝑖𝑞𝑞𝑢𝑢𝑜𝑜𝑡𝑡 𝑐𝑐𝑜𝑜𝑛𝑛𝑡𝑡𝑎𝑎𝑖𝑖𝑛𝑛𝑠𝑠 𝑑𝑑𝑒𝑒𝑠𝑠𝑖𝑖𝑟𝑟𝑒𝑒 𝑎𝑎𝑚𝑚𝑜𝑜𝑢𝑢𝑛𝑛𝑡𝑡 𝑜𝑜𝑓𝑓 𝑎𝑎𝑐𝑐𝑡𝑡𝑖𝑖𝑣𝑣𝑒𝑒 𝑖𝑖𝑛𝑛𝑔𝑔𝑟𝑟𝑒𝑒𝑑𝑑𝑖𝑖𝑒𝑒𝑛𝑛𝑡𝑡𝑠𝑠 = 𝑀𝑀𝑊𝑊𝑄𝑄 𝑜𝑜𝑓𝑓 𝑎𝑎𝑐𝑐𝑡𝑡𝑖𝑖𝑣𝑣𝑒𝑒 𝑖𝑖𝑛𝑛𝑔𝑔𝑟𝑟𝑒𝑒𝑑𝑑𝑖𝑖𝑒𝑒𝑛𝑛𝑡𝑡𝑠𝑠 (𝑚𝑚𝑔𝑔) 𝑑𝑑𝑒𝑒𝑠𝑠𝑖𝑖𝑟𝑟𝑒𝑒 𝑎𝑎𝑚𝑚𝑜𝑜𝑢𝑢𝑛𝑛𝑡𝑡 𝑎𝑎𝑐𝑐𝑡𝑡𝑖𝑖𝑣𝑣𝑒𝑒 𝑖𝑖𝑛𝑛𝑔𝑔𝑟𝑟𝑒𝑒𝑑𝑑𝑖𝑖𝑒𝑒𝑛𝑛𝑡𝑡𝑠𝑠 (𝑚𝑚𝑔𝑔) 1000𝑚𝑚𝑔𝑔 ? 𝑎𝑎𝑙𝑙𝑖𝑖𝑞𝑞𝑢𝑢𝑜𝑜𝑡𝑡 𝑐𝑐𝑜𝑜𝑛𝑛𝑡𝑡𝑎𝑎𝑖𝑖𝑛𝑛𝑠𝑠 𝑑𝑑𝑒𝑒𝑠𝑠𝑖𝑖𝑟𝑟𝑒𝑒 𝑎𝑎𝑚𝑚𝑜𝑜𝑢𝑢𝑛𝑛𝑡𝑡 𝑜𝑜𝑓𝑓 𝑎𝑎𝑐𝑐𝑡𝑡𝑖𝑖𝑣𝑣𝑒𝑒 𝑖𝑖𝑛𝑛𝑔𝑔𝑟𝑟𝑒𝑒𝑑𝑑𝑖𝑖𝑒𝑒𝑛𝑛𝑡𝑡𝑠𝑠 120𝑚𝑚𝑔𝑔 𝑎𝑎𝑡𝑡𝑟𝑟𝑜𝑜𝑝𝑝𝑖𝑖𝑛𝑛𝑒𝑒 (𝐴𝐴) = 6𝑚𝑚𝑔𝑔 𝑎𝑎𝑡𝑡𝑟𝑟𝑜𝑜𝑝𝑝𝑖𝑖𝑛𝑛𝑒𝑒 𝐴𝐴𝑙𝑙𝑖𝑖𝑞𝑞𝑢𝑢𝑜𝑜𝑡𝑡 𝑐𝑐𝑜𝑜𝑛𝑛𝑡𝑡𝑎𝑎𝑖𝑖𝑛𝑛𝑠𝑠 𝑑𝑑𝑒𝑒𝑠𝑠𝑖𝑖𝑟𝑟𝑒𝑒 𝑎𝑎𝑚𝑚𝑜𝑜𝑢𝑢𝑛𝑛𝑡𝑡 𝑜𝑜𝑓𝑓 𝐴𝐴𝑃𝑃 = 1000𝑚𝑚𝑔𝑔 𝑥𝑥 6𝑚𝑚𝑔𝑔 120𝑚𝑚𝑔𝑔 𝑎𝑎𝑡𝑡𝑟𝑟𝑜𝑜𝑝𝑝𝑖𝑖𝑛𝑛𝑒𝑒 (𝐴𝐴) MWQ, cannot < 𝐴𝐴𝑙𝑙𝑖𝑖𝑞𝑞𝑢𝑢𝑜𝑜𝑡𝑡 𝑐𝑐𝑜𝑜𝑛𝑛𝑡𝑡𝑎𝑎𝑖𝑖𝑛𝑛𝑠𝑠 𝑑𝑑𝑒𝑒𝑠𝑠𝑖𝑖𝑟𝑟𝑒𝑒 𝑎𝑎𝑚𝑚𝑜𝑜𝑢𝑢𝑛𝑛𝑡𝑡 𝑜𝑜𝑓𝑓 𝐴𝐴𝑃𝑃 = 50𝑚𝑚𝑔𝑔 weight or use 50mg aliquot What to do? Stick to MWQ, dilute 100mg aliquot  ATROPINE SULFATE (METHOD 2) 𝑇𝑇𝑟𝑟𝑖𝑖𝑡𝑡𝑢𝑢𝑟𝑟𝑎𝑎𝑡𝑡𝑖𝑖𝑜𝑜𝑛𝑛 1 𝑇𝑇1 : 120𝑚𝑚𝑔𝑔 𝐴𝐴 + 880 𝑚𝑚𝑔𝑔 𝑙𝑙𝑎𝑎𝑐𝑐𝑡𝑡𝑜𝑜𝑠𝑠𝑒𝑒 → 1000𝑚𝑚𝑔𝑔 𝑇𝑇1 Since we use 120mg A In 1000mg T1, it contains 120mg A In 100mg T1, it contains 12mg A -> How? Further dilution! Trituration 1 (T1) Atropine 120mg Lactose 880 mg Total 1000mg In 1000mg of T1, it contain 120mg A In 100mg of T1, it contain 12mg A (need 6mg of atropine, hence need further dilution)  ATROPINE SULFATE (METHOD 2) 𝑇𝑇𝑟𝑟𝑖𝑖𝑡𝑡𝑢𝑢𝑟𝑟𝑎𝑎𝑡𝑡𝑖𝑖𝑜𝑜𝑛𝑛 2: 100𝑚𝑚𝑔𝑔 𝑇𝑇1 + 100𝑚𝑚𝑔𝑔 𝑙𝑙𝑎𝑎𝑐𝑐𝑡𝑡𝑜𝑜𝑠𝑠𝑒𝑒 → 200𝑚𝑚𝑔𝑔 𝑇𝑇2 In 200mg T2, it contains 12mg A To have 6mg of A, how much T2 you need? 12𝑚𝑚𝑔𝑔 6𝑚𝑚𝑔𝑔 = 200𝑚𝑚𝑔𝑔 𝑥𝑥 𝑥𝑥 = 100𝑚𝑚𝑔𝑔 𝑇𝑇2 Trituration 2 (T2) T1 100mg Lactose 100 mg Total 200mg In total of 100mg of T2, it contain 12mg A Each 100mg of T2, it contain 6mg A  ATROPINE SULFATE (METHOD 2) To make 10 capsules, 200 mg each (200 mg/capsule) What is the total weight? 200 mg x 10 = 2000 mg As you have used 100 mg T2, how much lactose you need to make the 10 capsules? Lactose to make 10 capsules = 2000 -100 mg = 1900 mg 1 capsule 10 capsules Atropine 0.6mg T1 T2 100mg Lactose 194mg 1900mg Total 200mg 2000mg  COMPOUNDING PROCEDURE Weigh lactose for Weigh 120mg atropine trituration accordingly Mix atropine sulfate and sulfate and triturate to a (amount depends on lactose by geometric fine powder method 1/2) dilution Weigh 1880 or Remove 120mg T1 Fill capsules size 3 1900mg lactose and (method 1) or 100mg weighing 200 mg each mix with 120mg or T2 (method 2) of with punch method. 100mg aliquot by aliquot from the geometric dilution trituration (contain 6mg (doubling up) atropine sulfate)  CALCULATION EXERCISE HOSPITAL UITM PULAU PINANG Name: Mr XA Date: 28th Okt 2024 Age: 70 years Address: No 33A, Jalan Bendahara 2, Bertam Rx Minoxidil 0.8mg Ft: cap no. 0 Mitte: XIV Sig: 1 cap OD 2/52 Signed/stamp Dr. NIB Note: MWQ: 100mg  PACKAGING/CONTAINERS Blister packs/strip packs Amber glass or plastic containers Preferably with a child resistant closure for domestic use Protection from humidity (desiccant use) – particularly important since it will cause softening of the gelatin Blister pack/strip packs Plastic container Various design for child resistant closure Amber glass container Child resistant closure  LABELLING IMPORTANT labelling for capsules Emptying content of capsule onto food or into water for easy swallowing is not advisable because it MAY AFFECT the release characteristics of the dosage form Capsules should be swallowed whole with a glass of water or other liquid Store in a cool and dry place  STORAGE AND SHELF LIFE Capsules are manufactured in special environments and usually attract a long shelf life Commercially prepared and packed capsules Store according to the manufacturers’recommendations, are generally very stable Extemporaneous prepared capsules should not be stored for long periods without stability data If prepared extemporaneously, an expiry of up to 3 months, consideration to each individual formulation may be given Stability of the ingredients Susceptibility to microbial contamination Store in a cool and dry place THANK YOU [email protected] Level 4, Room 77