capsules Lecturer: dr. Asmaa abdelaziz Mohamed Faculty of pharamcay Ibn hayyan University 1
Capsules Definition: capsules are solid dosage forms in which the medication contained within gelatin shells. Hard gelatin are rigid two-piece capsules made from gelatin, water and colourants. The capsules are produced as empty shells consisting of a cap and body. 2
Advantages 1-elegant in appearance 2- suitable for substances having bitter taste and unpleasant color 3- ready solubility of gelatin at gastric pH provides rapid release in stomach 4- minimum excipients required 5- as produced in large quantities it is economic , attractive and available in wide range of colors 6- little pressure required to compact the material 7. easy to store and transport 8-ease of swallowing due to to their elongated shape 3
disadvantages 1.The filling speeds of capsule machines are lower than the speeds of the fastest tablet presses 2. the cost of the capsule shells makes them a more expensive dosage form. 3-Certain materials are unsuitable for inclusion in capsule shells due to incompatibility with gelatin or liquids that dissolve gelatin 4-capsules are more prone to sticking in the oesophagus than tablets following swallowing. 5-capsules are often larger than corresponding tablets due to the reduced compression of the powder and incomplete filling of the shells 6-very soluble salts such bromides or iodides should not dispensed in capsules because its rapid release may cause gastric irritation 4
Basic components of hard gelatin cap Gelatinis a heterogeneous product prepared by the hydrolysis of collagen, the principal constituent of connective tissue. There are two basic types of gelatin TYPE A Produced by acid hydrolysis of animal skin mainly from pork skin. TYPE B Produced by basic hydrolysis mainly from bovine bone. Although capsules may be made from either type of gelatin, the usual practice is to use a mixture of both types 5
The suitability of gelatin for capsule manufacture due to the following properties: 1- It is commonly used in foods and has global regulatory acceptability. However, because it can be derived from a number of animal sources, not all gelatin is acceptable in all markets, and capsule manufacturers produce capsules from different animal sources to allow for local religious restrictions. 2-It is a good film former, producing a strong flexible film. 3-It is readily soluble in water and in GI fluids at body temperature, so will not retard the release of drugs. 4-It changes state at low temperatures enabling a homogeneous film to be formed at ambient temperature. 6
Cont. components of hard gelatin caps Colorants: Colorants may be added to gelatin to prepare cap shells with variety of colors. There are two types: Water soluble dyes such as erythrosine Pigments such as iron oxides, titanium dioxide (make opaque cap for protection from light) 7
Capsule size: • For human use, capsules ranging in size from 000 ( the largest ) to 5 (the smallest) are commercially available 8
Limitations in properties of materials for filling into capsules -Must not react with gelatin e,g, formaldhyde (make the cap insoluble ) -Must not contain high level of free moisture(can be absorbed by gelatin causing it to soften) • 3-Unique identification marking • 4-Organoleptic properties • 5-Weight variation • 6-Friability • 7-Hardness • 8-Disintegrationtime: • 9-Dissolution rate: • 10-Content Uniformity Test 9
Manufacture of hard gelatin capsules: Manufacturing consist of two parts, which are mirror images of each other : on one half the capsule cap is made and on the other the capsule body. The moulds “pins” are made of stainless steel and are mounted in sets on metal strip called bars The prepared gelatin solution is then transferred to a heated holding hopper on manufacturing machine Steps: 1.Dipping 2.Spinning 3.Drying 4.Stripping (separating from bars) 5.Trimming and Joining 6.Polishing Manufacturing of hard gelatin capsules • 3-Unique identification marking • 4-Organoleptic properties • 5-Weight variation • 6-Friability • 7-Hardness • 8-Disintegrationtime: • 9-Dissolution rate: • 10-Content Uniformity Test 10
steps 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 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. 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. 11
Cont. steps 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. Polishing by 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.
Methods of Filling a) Manual filling: the powder placed on a sheet of clean paper or glass or porcelin plate. The empty body is held between thumb and forfinger and the cap was filled with a spatula and the body repeatedy punched downward until it full. the cap is returned and the filled capsule is weighed using the empty capsule as zeroing weight
Cont. Methods of Filling b) Industrial filling: Filling equipment: • The capsules are delivered into perforated capsule filling ring. The ring is rotated on turntable and a vacuum pulls the bodies into the lower half of the ring leaving cap in the upper half of the ring • The top and bottom half of filling ring are separated and the cap half of the ring is set aside. The body half of the ring is rotated mechanically under powder hopper the hopper contains auger which feeds the powder into the bodies. When the body is filled the cap and body rings are rejoined.
filling Various Filling Machine Available… •Eli-lily and Co •Farmatic
Farmatic -continuous motion with dosator type powder feeding units and fully closed for dust and noise -Dosatorsmeasure and deliver the powder to capsules as slug -Digital display the status of weight and compression -Adjustable vacuum for separating capsules after rectification -any unopened capsules are automatically rejected
•Hofliger and Karg Empty capsule storage hopper : holds the empty capules shell Faulty capsules are removed by a vacuum system Completely automatic and require only compressed air and powder for operation
Osaka - High capacity with continous motion -Only model R-180 -Follow vibratory filling principle
Finishing operations: General procedures applied : 1. Pan polishing: Accela cota coating pan is generally employed for this process. In order to eliminate the dust and to give shining, a cheese cloth liner is used. 2. Cloth dusting: The capsules after the filling operation are rubbed with cloth. This gives shine to the capsules along with elimination of the materials that are tough to remove. 3. Brushing: This is done with the help of brushes and generally vacuum is employed in order to remove the dust
polish equipment:The Erweka KEA dedusting and polishing machine Seidenader equipment, offers two units for inspection and brushing Storage: Finished capsules normally contain equilibrium moisture content of 13-16%. To maintain a relative humidity of 40-60% when handling and storing capsules
The most common problem in filling: 1- Demixing: The flow of powder should be adequate to deliver the sufficient powder per each cap in filling 2- Physical incomptabilities 3-Major general considerations: a)The powder to be filled must be free flowable b)Potential incompitabilities should be expected and reactions at elevated temperature and humdity should be studied
excipients Types of excipients used in powder-filled capsules • Diluents–bulking agents when the quantity of the active ingredient is insufficient to make up the required bulk eg. Lactose, maize starch, calcium sulfate etc. • Lubricants and Glidants– which reduce powder to metal adhesion and promote flow properties eg. Magnesium stearate, talc. • Wetting agents – which improve water penetration for poorly soluble drugs eg. Sodium lauryl sulfate • Disintegrants– which produce disruption of the powder mass crospovidone, sodium starch glycolate.
Special techniques 1- Imprinting on empty capsule or filled capsules but it is better to be done on empty because imprinting of filled capsules may lead to contamination, poor print quality and actual damage to imprinting machine 2-Special purpose capsules which are capsules treated to retard solubility or to have enteric properties By a)Formalin treatment due to crosslinking of gelatin b)Coatings include shellac, cellulose acetate phthalate
Cont. Special techniques 3-Separation of incompatible materials by use of two phase fill in the capsule. One phase consist of a soft cap, small hard cap or a pill which filled into each capsule and second phase in which a powder is filled as usual. 4-Filling hard gelatin capsules with semisolids by pipes or Semisolids are melted prior to filling if melting is satisfactory or If a material is too fluid to be worked as described, it may be necessary to add corn to yield a more firm consistency. it can be melted and poured into the capsule bases, cooled, and the caps replaced and machines for filling of semisolids are available from Bosch and Zanasi 5-Filling hard gelatin capsules with liquids.
Soft gelatin capsules also called softgel or soft elastic capsules consist of one piece hermetically sealed soft shells Manufacturing methods of soft gelatin cap: •Plate process •Rotary die process •Reciprocating die •Accogelmachine: uses a system of rotary dies but it is unique because can fill dry powder into the soft gelatin capsules
IMPORTANT SPECIFICATIONS OF GELATIN Bloom or gel strength: It is a measure of cohesive strength of cross-linkage and is proportion to the molecular weight of gelatin. Bloom is determined by measuring the weight in grams required to move a plastic plungerغطاس of 0.5 inches in diameter, 4mm into a 62/3% gelatin that has held at 10°C for 17 hrs. The unit of bloom is grams and it is between 150-250g
cont. IMPORTANT SPECIFICATIONS OF GELATIN Viscosity: Is determined on a 6 2/3% gelatin of water at 60°C and it is a measure of the molecular chain length. Standard used: 25-45 millpoise. Iron content:Iron is always present in raw gelatin, and its concentration usually depends on the iron content of the large quantities of water used in its manufacture . amount should not exceed 15ppm.
Components of caps Plasticizers: Such as glycerin and sorbitol Plasticizer and Gelatin ratio The ratio by weight of dry plasticizer to dry gelatin determines “the hardness” of soft gelatin capsules The ratio of dry plasticizer to dry gelatin can vary from 0.3-1 for very hard shell to 1-1.8 for very soft shell
The nature of the capsule content(fill formulation) Liquid Semisolids Suspensions Dry powders
Liquids i) water miscible liquids: PEG 400, POLYSORBATES, glycerin ii) water immiscible liquids: vegetable oils, esters, ethers aliphatic & aromatic chlorinated hydrocarbons iii) liquids which can not be incorporated - water exceed 5% of contents - Liquids with pH not between 2.5 and 7.5 - Aldehydes, in general, must be excluded (Cause cross-linking)
Suspensions Suspending agents For water miscible vehicles Solid glycol ester High molecular weight PEG For water immiscible vehicles Paraffin wax Bees wax Hydrogenated vegetable oils
Capsule manufacture and processing N.B. The temperature in the range of 20-22 C and humidity up to 40% in operating area and 30% in drying areas. a)Gelatin preparation 1-The gelatin powder is mixed with water and glycerin melted under vacuum 29.5 hg at 93 C 2-the mixing process requires 25 min for 270 kg. melting require 3 hrs. colorants are blended then at temp 57 C to 60 C before and during encapsulation. 3- if there are colours and flavors are added
CONT. Capsule manufacture and processing b)Material preparation: 1-In stainless steel all solids and liquid are mixed 2-the mixture is milled and homogenized c)dearation: of all mixtures d) samples are sent to Q.C. e) after, q.c release , the material is encapsulated through pump which which accurately meters Then the capsules filled, shaped, sealed and cut f) drying by dry air to remove moisture from outer surface of capsules • g)supplemental drying (curing ): capsules are placed on trays for final drying in drying room for period up to 48 hr.
quality control tests (evaluation tests) for capsules: Disintegration test Weight variation test Content uniformity test Assay: as the validated method of analysis and its limit or as monograph in pharmacopeia Dissolution rate : as for tab
APPLICATION OF SOFT GELATIN CAPSULE The pharmaceutical applications of soft gelatin capsules are: as an oral dosage form as a suppository dosage form as a specialty package in tube form, for human and veterinary use, single dose application for topical, ophthalmic, and rectal ointments.