capsules

Introduction,advantages, disadvantages,capsule manufacturing and evaluation

1. CAPSULES Presenter: Amruta Balekundri M.Pharm 2 nd semester, Department of Pharmaceutical Quality Assurance, KLE College of Pharmacy, Belagavi .

2. CONTENT Introduction Advantages Disadvantages Manufacturing process Hard gelatin capsules Soft gelatin capsules Evaluation of capsules

3. INTRODUCTION Capsules are solid dosage forms in which drug substance is enclosed within hard or soft soluble shell. The shells are generally formed from gelatin . Capsules are of two types: 1. Hard gelatin capsules 2. Soft gelatin capsules

4. CAPSULE SIZE For human use, empty capsules ranging in size from 000 the largest to 5 the smallest. Generally, hard gelatin capsule are used to encapsulate between 65 mg to 1 gram.

5. ADVANTAGES Capsules are tasteless, odorless and can easily be administered. Combination of powders can be used. They are attractive in appearance. The drugs having un-pleasant odour and taste can be enclosed in a tasteless shell. They can be filled quickly and conveniently. They are economical. They are easy to handle and carry.

6. DISADVANTAGES Hygroscopic drugs are not suitable for filling into capsules, because they absorb water present in capsule shell makes shell very brittle and ultimately lead it to crumble into pieces. The concentrated solutions which require previous dilution are unsuitable for capsules because if administered as such lead to irritation into stomach.

7. Plasticizer and Gelatin ratio In soft gelatin capsule the amount of plasticizers used is more. In soft gelatin capsule the plasticizer and gelatin ratio is 0.8 : 1 In hard gelatin capsule the plasticizer and gelatin ratio is 0.4 : 1

8. HARD GELATIN CAPSULES

9. Hard gelatin capsules, are made of two parts, the body and the cap. This form of capsule holds dry ingredients in powder form. The body is first filled with the mix of active ingredients and any excipients used, and then closed with the cap using either a manual or automatic press machine. Once ingested, the hard capsules disintegrate within three minutes and quickly release the drug inside.

10. CAPSULE SHELL These capsules are made up of gelatin blends, small amount of certified dyes, opaquants , plasticizers and preservatives. Certified Dyes: Colour approved by D & C act. Opacifiers : Titanium dioxide. Plasticizers: Sorbitol , Glycerin. Preservatives: Propyl and Methyl Parabens

11. GELATIN Gelatin is heterogeneous product derived by hydrolytic extraction of animal's collagen. The sources of gelatin include animal bones, hide portions and frozen pork skin. TYPES OF GELATIN Type A Type B

12. PRODUCTION OF GELATIN On a commercial scale, gelatin is made from by-products of the meat and leather industry, mainly pork skins, pork and cattle bones, or split cattle hides. Contrary to popular belief, horns and hooves are not commonly used. The raw materials are prepared by different curing, acid, and alkali processes which are employed to extract the dried collagen hydrolysate . The entire process takes several weeks.

13. MANUFACTURING OF HARD GELATIN CAPSULES Dipping Spinning Drying Stripping Trimming and Joining Polishing

14. Dipping : Pairs of the stainless steel pins are dipped into the dipping solution to simultaneously form the caps and bodies. The dipping solution is maintained at a temperature of about 500°C in a heated, jacketed dipping pan. Spinning : The pins are rotated to distribute the gelatin over the pins uniformly and to avoid the formation of a bead at the capsule ends.

15. Drying : The gelatin is dried by a blast of cool air to form a hard shells. The pins are moved through a series of air drying kilns to remove water. Stripping : A series of bronze jaws strip the cap and body portions of the capsules from the pins.

16. Trimming and joining The stripped cap and body portions are trimmed to the required length by stationary knives. After trimming to the right length, the cap and body portion are joined and ejected from the machine.

17. Polishing Pan Polishing : Acela-cota pan is used to dust and polish. Cloth Dusting : Capsule are rubbed with cloth. Brushing : Capsule are feed under soft rotating brush.

18. Preparation of filled hard gelatin capsules: In large scale or small scale, preparations of filled hard gelatin capsules are divided into the following general steps: Developing and preparing formulation. Filling the capsule shell Capsule sealing Cleaning and polishing the filled capsules.

19. FILLING OF HARD GELATIN CAPSULES Hand Operated methods. ex: feton capsule filling machine Semi Automatic Capsules Devices. Automatic filling machine. ex: osaka capsule filling machine , macofar capsule filling machine

20. A hand operated gelatin capsule filling machine consists of the following parts: A bed with 200-300 holes. A capsule loading tray A powder tray A pin plate having 200 or 300 pins corresponding to the number of holes in the bed and capsule loading tray. A lever A handle A plate fitted with rubber top.

21. Working: The empty capsules are filled into the loading tray which is then placed over the bed. By opening the handle, the bodies of the capsules are locked and caps separated in the loading tray itself which is then removed by operating the liver. The weighed amount of the drug to be filled in the capsules is placed in powder tray already kept in position over the bed. Spread the powder with the help of a powder spreader so as to fill the bodies of the capsules uniformly.

22. Collect excess of the powder on the platform of the powder tray. Lower the pin plate and move it downward so as to press the powder in the bodies. Remove the powder tray and place the caps holding tray in position. Press the caps with the help of plate with rubber top and operate the lever to unlock the cap and body of the capsules. Remove the loading tray and collect the filled capsules in a tray. With 200 hole machine about 5000 capsules can be filled per hour and with 300 hole machine 7500 capsules can be filled per hour.

23. CAPSULE SEALING Tamper evident capsules are made by sealing the joint between the 2 capsule parts. Distinctive looking capsules by sealing them with colored band of gelatin ( Kapseals ). If removed, the band cannot be restored without expert sealing with gelatin . Through a heat welding process that fuses the capsule cap to the ring around the capsule where heat welded. Example: Weld’s gelatin seal

24. 4. Capsule may also be sealed through a heat welding process that fuse capsule cap to the body. 5. Lightly coating the inner surface of the cap with a warm gelatin solution immediately prior to placement on the filled capsule body.

25. Storage: Finished capsules normally contain an equilibrium moisture content of 13-16%. To maintain a relative humidity of 40-60% when handling and storing capsules.

26. SOFT GELATIN CAPSULES

27. Soft Gelatin capsules are one piece, hermetically sealed, soft gelatin shells containing a liquid, a suspension, or a semisolid. Soft gelatin is mainly composed of gelatin, plasticizers, preservative, colouring and opacifying agents, flavoring agents and sugars.

28. SHAPE OF CAPSULE The shape of soft gelatin capsule are round, oval, oblong, tube.

29. MANUFACTURING OF SOFT GELATIN CAPSULES 1.Composition of the shell : The basic component of soft gelatin shell is gelatin; however, the shell has been plasticize. The ratio of dry plasticizer to dry gelatin determines the “hardness” of the shell and can vary from 0.3-1.0. Up to 5% sugar may be included to give a “chewable” quality to the shell. The residual shell moisture content of finished capsules will be in the range of 6-10%.

30. Formulation : Formulation for soft gelatin capsules involves liquid, rather than powder technology. Materials are generally formulated to produce the smallest possible capsule consistent with maximum stability, therapeutic effectiveness and manufacture efficiency. The liquids are limited to those that do not have an adverse effect on gelatin walls. Emulsion can not be filled because water will be released that will affect the shell. The pH of the liquid can be between 2.5 and 7.5.

31. MANUFACTURE OF SOFT GELATIN CAPSULES Manufactured by four methods: 1)Plate process 2)Rotary die process 3)Reciprocating die 4) Accogel machine

32. PLATE PROCESS Place the gelatin sheet over a die plate containing numerous die pockets. Application of vacuum to draw the sheet in to the die pockets. Fill the pockets with liquid or paste. Place another gelatin sheet over the filled pockets, and sandwich under a die press where the capsules are formed and cut out.

33. ROTARY DIE PROCESS In this machine the soft gelatin capsules are prepared & then filled immediately with liquid medicaments it is having two hoppers & two rotating dies Liquid mixture is placed in one hopper & the liquid medicament in other Hopper. The two rotating dies rotate in opposite directions when the fluid gelatin mixture enters the machine from the hopper it produces two continuous ribbons . With these half shell of the capsule is formed.

34. At this stage the measured quantity of the medicament is filled in to it with the stroke of a pump with the subsequent movement of the dies the other half capsule is formed. The two halves' of the capsules are sealed together by the heat & pressure of the rotating dies. As the die rolls rotate, the convergence of the matching die pockets seals and cuts out the filled capsules

35. ACCOGEL MACHINE Accogel Capsule Machine Or Stern machine, uses a system of rotary dies but is unique in that it is the only machine that can successfully fill dry powder into a soft gelatin capsule.

36. EVALUTION OF CAPSULES 1. STABILITY TESTS. a) Shell integrity test b) Determination of shelf life 2.INVARIABILITY TESTS. a ) Weight variation b) Content uniformity 3. DISINTEGRATION TEST. 4. DISSOLUTION TEST. 5. MOISTURE PERMEATION TEST

37. 1.STABILITY TESTS Stability tests for capsules are performed to know the integrity of gelatin capsule shell (but not to know the stability of therapeutically active agent ) and for determining the shelf life of capsules. The tests helps in improving the quality of contents of capsule shell and for choosing the appropriate retail package.

38. SHELL INTEGRITY TEST : This test is performed to find out the integrity of capsule shell. The standard capsule shells kept at the room temperature 40 ⁰c and 80% RH becomes more soft ,sticky and swollen . b) DETERMINATION OF SHELF LIFE : Shelf life or the expiry date of packed capsules is determined under normal storage conditions.

39. 2. INVARIABILITY TESTS The invariabilty in the medicaments packed in the capsule shells can be determined by performing the following tests : a) Weight variation test b) Content uniformity test

40. Weight variation test: In which 20 capsules are individually weighed and standard deviation from mean weight was measured that should not be <90% or >110% . b) Content uniformity: The amount of active ingredient should be within the range of 85% to 115% of the label amount for 9 of 10 capsules, with no unit outside the range of 70% to 125% of label amount.

41. 3. DISINTEGRATION TEST Disintegration test is a method to evaluate the rate of disintegration of solid dosage forms . disintegration is defined as the breakdown of solid dosage form into small particles after it is ingested .

42. 4. DISSOLUTION TEST Dissolution test is an official method to determine the dissolution rate of a solid dosage form . Dissolution rate is defined as the rate at which the drug is released into the systemic circulation from the dosage from .

43. 5. MOISTURE PERMEATION TEST To assure the suitability of containers for packaging capsules . The moisture permeating feature of capsules packaged in: single unit containers – blister pack or strip pack unit dose containers – glass or plastic bottles Are to be determined .

44. REFERENCE The science and practice of pharmacy by Remington The theory and practice of industrial pharmacy by Leon Lachman ,Herbert A.Lieberman Pharmaceutics the design and manufacture of medicines by E. Aulton Practical pharmaceutics by Dr.G.D . Gupta , R.S . Gaud