Manufacturing of medical capsules and microcapsules

1. Manufacturing of medical capsules and microcapsules

2. Plan • Characteristic of capsules as dosage forms. • Manufacturing of Hard Gelatin Shells (capsules). • Hard-Gelatin Capsule filling. • Soft-Gelatin Capsules. • Microcapsules.

3. Capsules are solid dosage forms with hard or soft shells. They are of various shapes and sizes, and contain a single dose of one or more active ingredients. They are intended for oral administration. • In capsules the drug is enclosed within hard or soft shell.

4. Capsule shells are made of gelatin or other substances, the consistency of which may be modified by the addition of substances such as glycerol or sorbitol. • The shell should disintegrate in the presence of digestive fluids so that the contents are released. • The contents should not cause deterioration of the shell.

5. Excipients for production of the Capsule shells : • diluents, • solvents, • surface-active substances, • opaque fillers, • antimicrobial agents, • sweeteners, • colouring matter, • flavouring substances, • disintegrating agents, • glidants, • lubricants, • substances capable of modifying the behaviour of the active ingredient(s) in the gastrointestinal tract.

6. Categories of capsules • hard capsules; • soft capsules (softgels); • modified-release capsules: • delayed-release capsules (gastroresistant / enteric capsules) • sustained-release capsules (extended-/prolonged release capsules).

7. Type of capsules depend on plasticizer content and technological principle 1. Hard-Shell Gelatin Capsules; 2. Soft- Gelatin Capsules (softgels);

8. Soft gelatin capsules (softgels) are hermetically sealed one-piece capsules containing a liquid or a semisolid fill.Soft capsules are usually formed, filled, and sealed in one operation.

9. Advantagesof soft-gelatin capsules • Improved bioavailability, as the drug is presented in a solubilized form. • Enhanced drug stability. • Consumer preference regarding ease of swallowing, convenience, and taste can improve compliance. • Offer opportunities for product differentiation via colour, shape, and size and product line extension. • The softgels can be enteric coated for delayed release. They are popular for pharmaceuticals, cosmetics, and nutritional products.

10. Hard capsules have shells consisting of two prefabricated cylindrical sections that fit together. • One end of each section is rounded and closed, and the other is open. The contents of hard capsules are usually in solid form (powder or granules).

11. In the manufacture of capsules, measures are taken to: • ensure that the active ingredient(s) when present in solid state form have appropriate solid-state properties such as particle-size distribution and polymorphic form; • ensure that mixing with excipients is carried out in a manner that ensures homogeneity; • minimize the degradation of the active ingredient(s); • minimize the risk of microbial contamination; • minimize the risk of cross contamination.

12. Preparing of gelatin solutions. Preparing of gelatin shells. Hard-gelatin capsule filling. Packing and labeling. Preparing of gelatin solutions. Preparing and filling of soft-gelatin capsules. Packing and labeling. Stage of capsules production:

14. HJ Series Gelatin Melting Tank

15. Obtaining of gelatin solutions with stage of swelling • Swelling of gelatin in cold water (15 - 18 °C, 1.5 - 2 hours). • Dissolving of gelatin. • Adding preservatives, plasticizers and others excipients. • Remove of air bubbles from the solution of the gelatin by the vacuum. • Stabilization of solution of the gelatin (45-60 °C).

16. Obtaining of gelatin solutions without stage of swelling • Heating of purified water (70-75 °C). • Dissolution of preservatives, plasticizers and others excipients in the water. • Dissolution of the gelatin. • Remove of air bubbles from the solution of the gelatin by a vacuum. • Stabilization of the solution of the gelatin (45-60 °C).

18. 1. Container with medicines substance 2. Hoper with medicines substance 3. Container with gelatin solution 4. Conical nozzle 5. Pulsater 6. Cooler 7. Container with Vaseline oil Droplet method

19. Characteristic of Droplet method It is based on formation of spherical gelatinous drop filled with a solution or suspension of medicinal substance at simultaneous drop dosage of medicinal substance solution followed by subsequent cooling of heated gelatinous mass in cool liquid petrolatum. As the result joinless spherical gelatious capsule with elastic shell is formed.

20. 1. Container with medicines substance 2. Hoper with medicines substance 3. Container with gelatin solution 4. Conical nozzle 5. Pulsater 6. Cooler 7. Container with Vaseline oil Droplet method

21. For volume-production, increase the utilization ration of gelatin skin; convey gelatin skin with a plane surface more steady running condition; oil saving; suitable for volume-production, continually for 24 hour. (Huizhou Pingfang pharmaceutical machinery co. ltd.) RG2-200 250 300 Series Soft Gelatin Encapsulation Machine

22. Preparing of an initial gelatinous tape, placing it into metal plates and rolls having deepening holes resembling half of the capsules. While heating gelatin fills this mould. Drug is fed into a hollow in a gelatinous tape, then this half of a capsule is joined with another one formed and filled in the same way. Obtained capsules have a horizontal weld. Pressing method

23. The glycerol – gelatin solution is heated and pumped onto two chilled drums-1 to form two separate ribbons-2, which form each half of the softgel. The ribbons are lubricated and fed into the filling machine, forcing the gelatin to adopt the contours of the die. The fill-4 is manufactured in a separate process and pumped in, and the softgels are sealed by the application of heat and pressure. Once cut from the ribbon (5), they are tumble - dried and conditioned at 20 % relative humidity. Pressing (rotate die) method

24. Hard capsules production • To manufacture the shells, pairs of molds, for the body and the cap, are dipped into an aqueous gelatin solution (25 – 30 % w/w), which is maintained at about 50 °C in a jacketed heating pan. • As the pins are withdrawn, they are rotated to distribute the gelatin evenly and blasted with cool air to set the film. • Drying is carried out by passing dry air over the shell as heating temperatures are limited due to the low melting point of gelatin. • The two parts are removed from the pins, trimmed, and joined using a prelock mechanism.

25. In this model of capsule making machine, dipping action, transfer along upper deck, transfer from upper to lower deck and transfer from lower deck to table are all performed by high precision programmable servo motors combined with precision ball screws SFR 901 FS6/7

26. Hard - Gelatin Capsule Filling Powders and granules are the most common filling materials for hard - shell gelatin capsules, although pellets, tablets, pastes, oily liquids, and nonaqueous solutions and suspensions have been used. • Filling machines are differentiated by the way they measure the dose of material and range in capacity from bench - top to high - output, industrial, fully automated machines.

27. Hard - Gelatin Capsule Filling Most automated machinery is of the independent type and compresses a controlled amount of powder using a low compression force (typically 50 – 200 N ) to form a plug. Most are piston - tamp fillers and are dosator or dosing disk machines. The powder is passed over a dosing plate containing cavities slightly smaller than the capsule diameter, and powder that falls into the holes is tamped by a pin to form a plug.

28. In the dosator method, the plug is formed within a tube with a movable piston that controls the dosing volume and applies the force to form the plug. • The dose is controlled by the dimensions of the dosator, the position of the dosator in the powder bed, and the height of the powder bed.

29. It comply with volume-produce. This machine adopts full sealed filling and turret parts and easy to clean, upper and lower die assemblies move in one-way, imported double-lip sealing ring made of polyurethane and have high performance, die assemble cleaning work station combine blowing and breathing to ensure no powder in die hole during high speed running, there is no absorb device in locking work station, lubricant be added timing in transmission work station. NJP-3000,3500 series automatic capsule filling machine

30. Modified-release capsules • They are hard or soft capsules in which the contents or the shell or both contain excipients or are prepared by special procedures such as microencapsulation which, separately or together, are designed to modify the rate, place or time of release of the active ingredient(s) in the gastrointestinal tract.

31. Sustained-release capsules (Extended- or Prolonged-release capsules)are designed to slow the rate of release of the active ingredient(s) in the gastrointestinal tract. • Delayed-release capsules (gastro-resistant/enteric capsules) are hard or soft capsules prepared in such a manner that either the shell or the contents resist the action of gastric fluid but release the active ingredient(s) in the presence of intestinal fluid.

32. Microcapsule is a small sphere with a uniform wall around it. • Micro-encapsulation is a process in which tiny particles or droplets are surrounded by a coating to give small capsules many useful properties. • The material inside the microcapsule is referred to as the core, internal phase, or fill, whereas the wall is sometimes called a shell, coating, or membrane. • Most microcapsules have diameters between a few micrometers and a few millimeters.

33. The reasons for microencapsulation • In some cases, the core must be isolated from its surroundings, as in isolating vitamins from the deteriorating effects of oxygen, • retarding evaporation of a volatile core, • improving the handling properties of a sticky material, or isolating a reactive core from chemical attack. • In other cases, the objective is not to isolate the core completely but to control the rate at which it leaves the microcapsule, as in the controlled release of drugs or pesticides. • The problem may be as simple as masking the taste or odor of the core, or as complex as increasing the selectivity of an adsorption or extraction process.