Soft gelatin capsules, Capsules content, production,base adsorption,minim per gram factor, importance of minim

Soft gelatin capsules, Capsules content, production,base adsorption,minim per gram factor, importance of minim,5th semester, Bpharm, Capsules, softgel capsules, determination of base adsorption,press die process, rotary die press, reciprocating die process, accogel process, seamless process, bubble method industrial pharamcy, industrial pharamcy

1. SOFT GELATIN CAPSULES Nirupam Kumar Verma DELHI PHARMACEUTICAL SCIENCES AND RESEARCH UNIVERSITY

2. Contents Production of Softgel Capsules Plate press Rotary die process Reciprocating process Accogel process Bubble method Type of fill material Base adsorption Minim per gram factor Importance of minim per gram factor

3. PRODUCTION OF SOFT GELATIN CAPSULES

4. Plate press/process
Rotary die process
Reciprocating Die process
Accogel process
Seamless process/Bubble method Methods

5. Plate Press/Process Oldest Commercial Process Semi automatic process Equipment is no longer available Procedure Placing the upper half of a plasticize gelatin sheet over a die plate containing numerous die pockets Application of vacuum to draw the sheet into the die pockets Filling the pockets with liquid or paste Folding the lower half of the gelatin sheet back over the filled pockets And inserting the sandwich under a die press where the capsules are formed and cut out

6. Press plate Flat die surface Die surface with cavity

7. Use- This method is used for small scale preparation of soft gelatin capsules had one flat side. Drawbacks- Lack of dosage uniformity High manufacturing losses Labour-/cost-intensiveness(2-3 operators).

8. Rotary Die Press Most soft gelatin capsules are prepared by the rotary die process.
Developed and Perfected in 1933 by Robert P. Scherer. Improved uniformity and high standards of accuracy.

9. Rotary Die press Two plasticized gelatin ribbons (prepared in the rotary-die machine). Continuously and simultaneously fed with the liquid, semiliquid or paste fill between the rollers of the rotary die mechanism. The forced injection of the feed material between the two ribbons causes the gelatin to swell into the left- and right-hand die pockets which govern the size and shape of the softgels as they converge. As the die rolls rotate, the convergence of the matching dies pockets hermetically seals and cuts out the filled capsules.

10. Softgel capsules ----Drying station ------Dried on trays(in air or under vacuum)-----Infra red step(Removes 60-70%moisture+ to Speed up the process). Note- Lubrication oil is applied to increase efficiency of machine. The lubrication oil should, therefore, be a GRAS (generally recognized as safe) material. Immediately after manufacture, the formed capsules automatically undergo volatile solvent(naptha solvent unit) washing to remove any traces of lubricating oil from the exterior of the capsules. Rotary Die press Tumbler dryer Toward drying station Trays

11. Rotary die process reduces the loss of materials to a negligible level and reduces content variation to ± 3%. Production capacity of the machine is determined by the die size, the speed of the machine and the physical characteristics of the material to be encapsulated. For most capsules, the gelatine thickness is between 0.25-0.32 inches. Thicker shells are used on products requiring structural strength. The product cost is directly proportional to shell thickness. Rotary Die press

12. Product Quality Consideration The process involves careful control of three parameters:
• Temperature- this controls the heat available for capsule seal formation(37-40°)

• Timing- The timing of the dosing of unit quantities of liquid fill matrix into the softgel during its formation is critical.

• Pressure- the pressure exerted between the two rotary dies controls the softgel shape and the final cut-out from the gel ribbon. Rotary Die press

13. Reciprocating Die Process C ontinuous soft gelatin capsule processing technology Developed by Norton Company in 1949. S imilar to rotary die process It differs in the actual encapsulating process.  The gelatin ribbons are fed between a set of vertical dies that continually open and close to form rows of pockets in the gelatin ribbons. These pockets are filled with the medication and are sealed, shaped, and cut out of the film as they progress through the machinery. As the capsules are cut from the ribbons, they fall into a cooled solvent bath that prevents the capsules from adhering to one another.

14. 16 The rotary die process and reciprocating die process were capable of producing soft gelatin capsules containing oily liquids and pastes , but not for powders and granules. Lederle Laboratories in 1949 developed accogel process, a continuous process that produces soft gelatin capsules containing powders and granules. Accogel Process What was the need? Vaccum Vaccum Vaccum Rotary die press

15. 17 The process involves a measuring roll that holds the fill formulation in its cavities under the vacuum and rotates directly above the elasticized sheet of the gelatin ribbon. The ribbon is drawn into the capsule cavities of the capsule die roll by vacuum. The measuring rolls empty the fill material into the capsule-shaped gelatin cavities on the die roll. The die roll then converges with the rotating sealing roll covered with another sheet of elasticized gelatin. The convergence of two rotary rolls creates pressure to seal and cut the formed capsules

16. 18 The seamless technique produces one-piece soft gelatin capsules without the use of dies. Referred to as a bubble method that creates seamless, spherical soft gelatin capsules. Seamless process (Bubble Method)

17. 19 In this process, a molten gelatin stream flows though the outer nozzle of a concentric tube at a constant rate, and the medicated liquid formulation is dispensed through the inner orifice by means of a precision metering pump . The emerging stream is broken up into an intermittent but steady flow of uniform-sized by a pulsating mechanism, leading to the formation of droplets enveloped in molten gelatin. The formed capsules are quickly removed from the nozzle, slowly congealed(on cooling) , and automatically ejected from the system.

18. 20 Soft gelatin capsules may contain a single liquid, a combination of miscible liquids, a solution of a drug in a liquid, or a suspension of a drug in a liquid. All these are formulated to produce smallest calsules with maximum ingredients and physical stability, therapeutic effectiveness and production efficiency.(why not Gelatin shell filling?) The pH of the liquid can be between 2.5 and 7.5pH. Aqueous emulsions, water, alcohol (upto 5% as minor constituent) cannot be filled because inevitably water will be released, which will affect the shell(Hydrophillic)(_Gelucire44/14). Plasticizers like glycerine, propylene glycol(upto 10% with PEG) can’t act as major constituent as they will Show softening effect on shell. Types of Fill Material for Softgel capsules

19. 21 Combinations of miscible liquids(why)- To increase absorption of active ingredient (vitamin A and polysorbate 80); To produce desired physiochemical results, such as improved flow properties (dilution or partial substitution with a thinner liquid), To improved solubility (steroid with oil and benzyl alcohol). The most widely used liquids for human use are- Oily active ingredients(clofibrate) Veg. Oils(soyabean oils), mineral oils Non ionic surface active agents(polysorbate 80) PEG 400and 600 Fish oil used as solvent or suspending agent in vit. Capsules. Usually, a solution is more easily capsulated and exhibits better uniformity, stability, and biopharmaceutical properties than does a suspension. Types of Fill Material for Softgel capsules

20. 22 Base adsorption is defined as the number of grams of liquid base required to produce a capsulated mixture (medicament) when mixed with 1 gram of solid(API). Base adsorption = Weight of base/Weight of solid Solids that are not sufficiently soluble in liquids are capsulated as suspensions. Such materials should be 80 mesh or finer in particle size. Base Adsorption The base adsorption mixture is milled or homogenized, and deaerated (a desiccator under vacuum is suitable), and the specific gravity is taken.

21. 23 Base Adsorption (Solid~API) (Liquid Base) Capsulated mixture = 1gm =?

22. 24 When the mixture tend to stop flowing,note down the weight of liquid base

23. 25 Influenced by factors as – solid's particle size and shape, physical state (fibrous, amorphous, or crystalline), density, moisture content, and oleophilic or hydrophilic nature. In the determination of base adsorption solids must be completely wetted by the liquid base . For glycol and nonionic type bases, the addition of a wetting agent is required, but for vegetable oil bases, complete wetting of the solid(s) is not achieved without an additive. Soy lecithin , at a concentration of 2 to 3% by weight of the oil, serves excellently for this purpose. Base Adsorption

24. 26 Solid + liquid base(ex. PEG400)= Capsulated mixture - it can be used to determine minimum calsule size but Suspending agent (Ex.Liquid wax) or Gelucire 44/14 (prevent crystallization) is added to make the mixture stable, uniform, ⬆️ bioavailability and lubricity. Mostly used suspending agent for oily bases is wax mixture, and in nonoily bases, the polyethylene glycols 4000 and 6000. Minim per gram factor

25. 27 Minim per gram factor 1ml=16.23minim

26. 28 Importance

27. 29 References Lachman/Lieberman’s the Theory and Practice of Industrial Pharmacy Aulton’s Pharmaceutics: The Design and Manufacture of Medicines Gibson, M. (2009). Pharmaceutical Preformulation and Formulation: A Practical Guide from Candidate Drug Selection to Commercial Dosage Form. New York: Taylor & Francis Group. Allen L. and Ansel H. (2014). Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems. Philadelphia: Lipincott Williams and Wilkins. https://youtu.be/YvTXNHsoshk https://youtu.be/__GUEeh2oYQ