capsule manufacturing and ipqc.pptx

Capsule manufacturing and flowcharts.
Capsule ipqc and fpqc

1. M. Pharm Sem-I Presentations Title:- MANUFACTURING,MANUFACTURING FLOWCHARTAND IPQC OF NON STARILE DOSAGE FORM-CAPSULE . SUBMITTED TO SAVITRIBAI PHULE, PUNE UNIVERSITY , PUNE FOR PARTIAL FULFILMENT OF REQUIREMENTS FOR THE AWARD OF MASTER OF PHARMACY IN THE SUBJECT Pharmaceutical Quality Assurance IN THE FACULTY OF SCIENCE AND TECHNOLOGY Bhujbal Knowledge City, MET’s Institute of Pharmacy, Adgaon, Nashik, 422003. Maharashtra, India Academic Year--2021-2022- 1 Presented By- Mandlik Amruta Anil. Guided By- Dr. Sapna Ahirrao.

2. Manufacturing process, manufacturing flowchart, IPQC of non sterile product:- Capsule Contain:- Introduction to capsules Advantages of capsule Disadvantages of capsule Manufacturing process and flowcharts In Process Quality Control tests Reference 2

3. Introduction :- Capsules are solid dosage form in which drug substance is enclosed within hard or soft soluble shell generally formed from gelatine. The term capsule is derived from Latin word Capsula means small container. Capsules may be classified as either har d or soft depending on nature of capsule shell . Soft gelatine capsules are one piece , hermetically sealed, soft gelatine shell containing liquid, suspension, or semisolid. Hard gelatine capsules are of two piece , they are manufactured and filled in completely separate operations. Hard gelatine capsules are typically filled with powder, granules, or pellets. 3

4. Advantages of capsules:- Capsules mask the taste and odour of unpleasant drug and can be easily administered. They are slippery when moist and hence easy to swallow. The shells are physiologically inert and easily and quickly digested in GI track. They are economical. The shells can be opacified (with titanium dioxide) or coloured to give protection from light. They are easy to handle . 4

5. Manufacturing of capsule shells:- Hard gelatin capsules are also known as dry filled capsule or two piece capsule. Hard gelatine capsule consist of 2 parts known as capsule body (longer part) and the capsule cap (shorter part). The drug substance is placed in the body and the cap is slides over it. Hence enclosing the drug substance. Manufacture:- The manufacturing equipment consist of pins and pegs made up of stainless steel to produce the capsule shells of desired shapes and sizes. About 50 of these pins are attached to the plate which are movable. Both caps and bodies prepared simultaneously. 5

6. Steps:- 1. Dipping:- Gelatin solution of required viscosity is taken in a reservoir. The plate holding the pins is lowered into the reservoir to the suitable depth for the certain period of time. This helps in achieving proper length and thickness of shells. 2. Drying:- The plate holding the pins is slowly raised from the gelatin solution and is subjected to blow drying with air having controlled temperature and humidity. During this period the gelatin sets or gels over pins. 6

7. 3. Stripping: The desired capsule shells are then stripped (removed) off from the pins by using jaws made up of bronze. 4. Trimming: The stripped capsules shells are then trimmed (shortened) by stationary knives to the required length. 5. Joining of capsule caps and bodies: Finally, the trimmed caps and body parts are joined and released from the machines. The width of walls of the capsule shells is to be strictly controlled for accurate fitting of caps over the bodies. 7

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9. Manufacturing of Soft gelatin capsules:- Production by two processes 1.Plate process 2.Rotary or reciprocating die processes 1.Plate process: It is a semi autonomic process in which a warm sheet of soft gelatin is laid over a plate having die pockets. Vacuum is applied from underside of this plate to pull the gelatin sheet into the pockets. The liquid medication is poured into these dies and another sheet of soft gelatin of similar or a different color is laid over it. Finally, a die press which upon application of pressure seals and cuts off the capsules simultaneously. The capsules are removed and washed with a volatile solvent. Washing is done to removed the adhering oil from the capsules. 9

10. Manufacturing of Soft gelatin capsules flowchart:- Spread gelatin sheet over plate having die pocket Apply vaccum (to create die) Pour liquid medicament in die Another sheet of gelatin laid over it Apply pressure to seal and cut of capsules Wash with solvents 10

11. 2. Rotary Die Process: This process is developed in the year of 1933. The capsule prepared by this process have uniformly filled medications with accurate doses. It is fully automatic continuous process. Liquid mixture of gelatin is placed in one hopper and liquid medicament in another hopper. Two rotating dies rotate in 2 opposite direction the fluid gelatin mixture enters into the machine and produce 2 continuous ribbons. Half shell of capsule is formed, at this stage the measured quantity of medicament is filled into it with stroke of pump and subsequent movement of the dies other half capsule formed. Two half of capsules are sealed together by the heat and pressure of the rotating dies. As the die rolls rotate, the convergence of the matching die pocket seals and cutout the filled capsules. 11

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13. Flowchart:- Hopper1 contain gelatin soln. Gelatin mass spread by gravity to meter device Gelatin ribbon of controlled thickness formed Ribbon then fed down between wedge and die rolls Hopper2 conatain medicament Laid into the gelatin ribbon in unit dose capsule is about half sealed 13

14. Cont … Medicament filled with stock Subsequent moment of dies form other half capsule 2 half parts of capsule sealed together by heat and pressure Die pocket seals and cutoff the capsule Capsules are spread on trays and dry with infrared dryers 14

15. IPQC TESTS FOR CAPSULES:- Appearance Size and shape Disintegration test Weight variation Moisture permeation test Bloom strength of gelatine Viscosity and iron content Content uniformity Dissolution test 15

16. Appearance:- Capsule produced on a small or large scale should be uniform in appearance. Visual or electronic inspection should be undertaken to detect any flaws in the integrity and appearance of the capsule. Evidence of physical instability is demonstrated by gross change in appearance including hardening or softening, cracking, swelling, mottling, printing mistake, or discolouration of shell. Defective capsules should be rejected . 16

17. 2. Size and Shape:- Hard capsules are made in a range of sizes, the standard industrial ones in use today for human medicines range from size from 000 (the largest, 1.40 ml/ 950 mg) to 5 (the smallest, 0.13ml/ 100 mg) are commercially available. 0 to 5 size capsules are for human use. Soft gel capsules are available in variety of shapes such as spherical (0.05-5ml). Ovoid (0.005-7ml). Cylindrical (0.15-25ml) tubes (0.5-0ml). Pear (0.3-5ml) etc. 17

18. 18 3. Bloom strength of gelatin:- Bloom is a test to measure the strength of a gel or gelatin. The test was originally developed and patented in 1925 by Oscar T. Bloom. The test determines the weight in grams needed by a specified plunger to depress the surface of the gel by 4 mm without breaking it at a specified temperature. The number of grams is called the bloom value, and most gelatins are between 30 and 300gm bloom. The higher a bloom value, the higher the melting and gelling points of a gel, and the shorter its gelling times.

19. 19 Gelatin bloom tester

20. 20 4. Viscosity and iron content:- Viscosity of gelatin is measure of molecular chain length and determines the molecular characteristics of gelatin film. Viscosity of 6% gelatin solution is determine in water at 60°C by measuring the flow time of 100ml of solution through the standard pipette. Viscosity of gelatin range from 25-45 milipoise. Iron content : iron content of gelatin use in manufacturing of capsules, should not contain more than 15ppm.

21. 5. Disintegration test:- The USP disintegration apparatus consist of 6 glass tube that are 3 inches long, open at the top, and held against a 10 mesh screen at the bottom end of the basket rack assembly. To test for disintegration time, one capsule is placed in each tube and the basket rack is positioned in specified medium at 37 ± 2°C such that capsule remains 2.5cm below the surface of the liquid on their upward movement and descend not closer than 2.5 cm from the bottom of the beaker. A standard motor driven device is used to move the basket assembly containing capsules up and down through distance of 5-6cm at a frequency of 28-32 cycles per minute. 21

22. The capsule complies with the test according to USP if all of capsules disintegrated completely. If 1 or 2 capsules fails to disintegrate completely, repeat the test on 12 additional capsules. The requirement is met if not less than 16 of the total 18 capsules tested are disintegrated according to IP and BP disintegration time of various capsules are given in table. 22

23. Disintegration time of various capsules according to IP and BP according to IP disintegration test is not applicable to modified release capsule. 23 Capsule Disintegration time (min) BP Disintegration time (min) IP Hard capsule 30 30 Soft capsule 30 60 Enteric capsules 60 60 Rectal capsule 30 -

24. Weigh 20 intact capsules individually and average weight is determine. Test requirement are met if none of the individual weights are less than 90% or more than 110% of the average if the original 20 do not met the criteria the individual weights are determine this are averaged and the difference are determine between each individual net content and the average. The test requirement are met 1. if not more than 2 of the individual differences are greater than 10% of average or 2. if in no case any difference is greater than 25% 24 6. Weight variation:-

25. If more than 2 but less than 6 net weights determined by the test deviate by more than 10% but less than 25% the net content are determined for additional 40 capsule, and average calculated for entire 60 capsule. Sixty deviation from new average is calculated. the requirement are met 1 if the difference dose not exceed 10% of average weight in more than 6 of 60 capsule and 2 if in no case any difference exceed 25% Two new piece equipment, rotoweigh and vericap 1200, determined the weight of capsules, providing the automatic rejection of overfilled and underfilled capsules

26. Average mass (mg) Percentage deviation (%) Less than 300 10 300 or more 7.5 26 IP and BP limits for uniformity of mass:-

27. 27 7. Moisture permeation test:- The degree and rate of moisture permeation penetration determine by packaging the dosage unit together with a color reveling desiccant pellet. Expose the packaged unit to known relative humidity over a specified time. Observe the desiccant pallet for color change. Any change in color indicates absorption of moisture. By measuring pre test and protest weight of pellet amount can be calculated.

28. 28 8. Content uniformity:- As per USP and BP Select randomly 30 capsule (soft or hard) 10 of which are assayed by specified procedure. The requirements are met if 9 of the 10 are within specified potency range of 85 to 115% and 10 th is not outside 75 to 125% . If more than 1, but less than 3,of first 10 capsule fall outside the 85 to 115% limits, the remaining 20 capsule are assayed. The requirement are met if all 30 capsule are within 75 to 125% of specified potency range,and not less than 27 of the 30 are within the 85 to 115% range.

29. 29 9. Dissolution test :- Dissolution test is carried out using dissolution apparatus official in both USP and IP The capsule is placed in basket and basket immersed in dissolution medium and temperature is maintained at 37°c±5°c 6 capsule are tested and accepted if each of them is not less than monograph specified i.e.. Q±5. if it fails additional 6 capsules are tested the result is accepted if avg. of 12 capsule is greater than or equal to Q and none of them is less than Q-15. If capsule still fails the test additional 12 capsules are tested and are accepted if the avg. of 24 is greater than Q, if not more than 2 less than Q-15% and none of them is less than Q-25%

30. 30 Acceptance table Stage Number of capsules Acceptance criteria S1 6 Each unit is ≥Q+5% S2 6 Average of 12 units is ≥ Q, NMT 2 units are < Q-15% S3 12 Average of 24 units is ≥Q, NMT 2 units are <Q-15% and no single unit is less than Q-25%.

31. 31 Reference:- L. Lachman, HA Lieberman, JL Kanig. The Theory and Practice of Industrial Pharmacy, 3 rd Edition, Lea AND Febiger, Philadelphia, 1986, 374-398. Indian Pharmacopoeia Commission. Indian Pharmacopoeia. 7 th ed. Ghaziabad: Indian Pharmacopoeia Commission : 2014. United States Pharmacopeial Convention. United Stated Pharmacopoeia 33- National Formulary 28. USA : Stationary office; 2010. British Journal of Pharmaceutical Research 9(2); 1-9, 2016, article no. BJPR 22044 ISSN; 2231-2919.

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