Soft Gelatin Capsule

Overview of Soft Gelatin Capsule (Softgels)

1. Soft Gelatin Capsules BANGABANDHU SHEIKH MUJIBUR RAHMAN SCIENCE & TECHNOLOGY UNIVERSITY, GOPALGANJ WELCOME TO OUR PRESENTATION ON COURSE TITLE: PHARMACEUTICAL TECHNOLOGY-II COURSE CODE: PHR361

2. The first capsule prepared from gelatin was a one-piece capsule patented in France by Mothes and Du Blance in 1834 . Capsules are solid dosage forms in which the drug substances is enclosed within either a hard or soft soluble shell, usually formed from gelatin . Most capsules of are intended to shallowed whole ; however some soft gelatin capsules are intended for rectal or vaginal insertion as suppositions.

3. There are two types of capsule:

4. Soft gelatin capsules are one piece, hermetically sealed, soft gelatin shells containing a liquid , a suspension or a semisolid .

5. Types of soft gelatin capsule: According to different drug delivery systems: Used for pessaries or suppositories U sed as topical and inhalations or for oral dosing of pediatric product Highly flavored shell is chewed to release the drug liquid fill matrix Containing solutions of suspension. Highly flavored shell

6. According to shape- Round - (1-7)types Oval - (1-110)types. Oblong - (3-360)types. Tube - (5-480)types. Miscellaneous - (6-80)types.

7. Typical Softgel shells are made up of gelatin, plasticizer and materials that impart the desired appearance and some flavors. Gelatin: Most commonly alkali processed gelatin (type B) - 40% of the wet molten gel mass. Type A acid processed gelatin can also be used . Plasticizers: Plasticizers are used to make the Softgel shell elastic and pliable. They usually account for 20-30 % of the wet gel formulation. The most common plasticizer used in softgels is glycerol. Sorbitol and propylene glycol are also frequently used, often in combination with the glycerol. In soft gelatin capsule the amount of plasticizer and gelatin used is more. In soft gelatin capsule the amount of plasticizer and gelatin ratio is 0.8:1

8. Water Water usually accounts for 30-40% of the wet gel formulation. I ts presence is important to ensure proper processing during gel preparation and encapsulation . Colorants/ Opacifiers Colorants and Opacifiers are used in low concentrations in the wet gel formulation. Colorants are used to impart desired shell color for product identification Opacifiers are used to produce opaque shell.

9. Oxygen permeability The gelatin shell of a softgel provides a good barrier against the diffusion of oxygen into the contents of the product. Gelatin should be dry and formulated to contain about 30-40% glycerol. Residual water content Softgels contain a little residual water and compounds which are susceptible to hydrolysis are protected if dissolved or dispersed in an oily liquid fill material. Presence of iron Iron is always present in the raw gelatin. Soft gelatin capsules should not contain more than 15 ppm of iron. Bloom or gel strength bloom of softgels ranges from 150 to 250g.

10. Lipophilic liquids/oils: Triglyceride oils, such as soya bean oil are commonly used in soft gels. Active ingredients like hydroxycholecalciferol oestradiol can be formulated for softgel encapsulation. Hydrophilic liquids Polar liquids with a sufficiently higher molecular weight are commonly used such as Polyethylene glycol. Self-emulsifying oils : A combination of a pharmaceutical oil and a non-ionic surfactant such as polyoxyethylene sorbitan monooleate can provide an oily formulation which disperse readily in GI fluids. Microemulsion and nanoemulsion systems: In a m icroemulsion, the droplet size is in the submicron range. A nanoemulsion describes a similar system but droplet size is not in the 100 nm size. Both of them have advantage of a capacity to solubilize drug compounds and to retain the drug in the solution even after dilution in GI fluids. Suspensions: Drugs that are insoluble in softgel fill matrices are formulated as suspension. With the appropriate choice of excipients, softgel suspensions can have improved bioavailability .

11. Soft gelatin capsules are generally manufactured by two methods: In the plate process , a warmed sheet of plasticized gelatin is placed over a plate having a number of depressions or moulds, the sheet is drawn into these depressions by applying vacuum. A measured quantity of liquid medicament is poured over it, then another sheet of gelatin is placed on it.over this another plate of the mould is placed and the pressure is then applied to the combined plates. The capsules are then simultaneously shaped,filled,sealed and cut into individual units .

12. In the rotary die process , the ribbon and the unit dose of liquid fill matrix are combined to form soft gel. The process involves careful control of three parameters: Temperature- this controls the heat available for capsule seal formation . 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. Manufacture of soft gelatin capsule (continued)

13. In short, these processes take place simultaneously, such that the machine feeds the gelatin ribbon as the wedge injects fill material. At the same time, the die system cuts and hermetically seals the two halves of the gelatin ribbons together. Manufacture of soft gelatin capsule (continued)

14. Ingredient specifications- All the ingredients of a Softgel dosage form are controlled and tested to ensure compliance with pharmacopoeial specifications. Additional specification tests may be added for certain excipients in order to ensure manufacture of a highly-quality soft gel product. For example, it is important to limit certain trace impurities such as aldehyde and peroxide that may be present in polyglycerol. In process testing- During this process four tests are carried out: The gel ribbon thickness. Softgel gel seal thickness at the time of encapsulation. Fill matrix weight and capsule shell weight. Softgel shell moisture level and Softgel hardness at the end of the drying stage.

15. Finished product testing- Finished softgels are subjected to a number of tests in accordance with compendial requirements for unit dose capsule products. These include capsule appearance, active ingredient assay, content uniformity , weight, microbiological and dissolution testing. Product quality consideration(continued)

16. The hard and soft gelatin capsules are should be subjected to following tests for standardization :

17. In official books the following quality control tests are recommended for capsules: Disintegration test For performing disintegration test on capsules the tablet disintegration test apparatus is used but guiding disc may not be used. The capsules pass the test if no residue of drug or other than fragments of shell remains on no.10 mesh screen of the tubes. Weight variation test 20 capsules are taken and weighed individually. Then average weight is calculated. The capsules pass the test if the weight of individual cap. Falls within 90-110 % of the average weight. Content uniformity test This test is applicable to all capsules which are meant for oral administration for this test a sample of the contents is assayed and compared with standard. Evaluation of capsule (continued)

18. Disa dvantages of soft gelatin capsule

19. Hard gelatin capsules   Soft gelatin capsules Cylindrical in shape   Round, oval and tube-like shapes.   Hard gelatin capsules shell consists of two parts namely a body and a cap . Soft gelatin capsules consists of only 1 piece   Plasticizer and gelatin in hard gelatin capsule (0.4: 1 ) The ratio of plasticizer and gelatin in a soft gelatin capsule (0.8 : 1)   Boundary wall firm and rigid   Boundary wall soft and flexible   Volatile drug substance is not suitable for filling.   Volatile drug substance is suitable for filling.   Preservative less than soft gelatin capsule Preservative more than hard gelatin capsule   Plasticizer less than soft gelatin capsule.   Plasticizer more than hard gelatin capsule  

20. Although the formulation of drugs into softgel capsules has been reported to solve many problem associated with tableting including Lack of content or weight uniformity. P owder flow or mixing problems. Poor differentiation or mismatching of gel material added to cross-linking with the drug If gelatin is not suitable, alternative polymers for capsule production may be exploited. The major challenge in the development of the softgel dosage form is that the system is very dynamic in terms of The physical migration of components between the shell and the fill and the shell and the external environment. The occurrence of physical and chemical interactions within and between the shell and fill component .

21. Problem Causes Remedies Loss of cap during transfer High vacuum Misalignment of cap and bush By adjusting the vacuum Check the alignment of cap and body bush Capsule non separation Incorrect vacuum pump Leakage through filters, Worn out bushes Loss of spring tension at top slide By adjusting the vacuum Cleaned and/or replace the filter Replacing the bushes with new one

22. Target weight not achieved Wrong selection of capsule size Incorrect slug formation due to incorrect setting parameter Insufficient binding Poor flow of product Formulation is stick Check the variation in physical parameters Proper selection of dosing disc Tamping block 1-5 are placed along the direction of rotation of dosing disc Improve the flow property Powder must be non- hygroscopic Length variation Excess joined length Improper setting of closing plate Damage rubber sheet of closing plate Checking the standard locking length The gap should be between 0.5-0.8 mm Replacing the rubber sheet with one Problem Causes Remedies

23. Unit dosage form of drugs like tablets and capsules are capsules are enclosed individually in strip or blister packs . In strip packing the unit drugs are hermetically sealed between strips of aluminum foil or plastic foil . The contents are removed by tearing or cutting the individual pocket. In blister packing the unit dosage forms are enclosed in between transparent blisters and suitable backing material, generally aluminum foil. The contents are removed simply by pushing the drug through the backing strip. Soft capsules are packed by blister packaging . Sometimes glass bottles are used.

24. More than 40% of new chemical entities (NCEs) coming out of the current drug discovery process have poor biopharmaceutical properties, such as low aqueous solubility and/or permeability. Development of soft gelatin capsule (softgel) dosage form is of growing interest for the oral delivery of poorly water soluble compounds. For this reason the softgel dosage forms are increasingly being preferred.