Ghada M. El Zaafarany , PhD Associate Professor of Pharmaceutics and Industrial Pharmacy Faculty of Pharmacy Ain Shams University Pharmaceutical Technology II • Capsules are solid - dosage forms available in two types : hard (two - piece) & soft (one piece) • The major component of the capsule shell is gelatin • Other polymers have been investigated ( vegicaps ) e g starch , HPMC , PVA Capsules A) Hard Gelatin Capsules (HGCs) Are capsules composed of 2 pieces in the form of cylinders (hemispheres) closed at one end The shorter piece with larger diameter, the “ cap ” , fits over the open end of the longer piece, the “ body ” Shell composition : Gelatin ( 25 - 30 % ) + coloring agent + opacifier (optional) + wetting agent (low conc of SLS) ❖ Production of HGC shells (Dip - coating method) 1. Dip pin pairs (metal molds arranged in rows for bodies & caps) into hot gelatin solution ( 25 - 30 % ) at 50 - 60 ° C 2. Spin pins by rotation → distribute gelatin uniformly 3. Dry gelatin by a blast of cool air (when gelatin cools it forms a film) 4. Strip bodies & caps from pins by bronze jaws 5. Trim to the required length by stationary knives 6. Join caps and bodies 7. Eject from the machine Once raw materials have been received and released by Quality Control, the gelatin and hot demineralized water at 50 - 60 ° C are mixed under vacuum in Stainless Steel System Preparing hot gelatin solution in large tanks After mixing in stainless steel receiving tanks, the gelatin solution is transferred to stainless steel feed tanks Transferring gelatin solution to feed tanks Dyes and opacifants are added to the gelatin in the feed tanks The feed tanks are then used to gravity - feed gelatin into the Capsule Machine Add other ingredients to gelatin solution e.g. colorants & opacifiers From the feed tank, the gelatin is gravity fed to the Dipper section Here, the capsules are moulded onto stainless steel Pin Bars which are dipped into the gelatin solution The Pin Bars pass through the Capsule Machine Drying System Here gently moving air which is controlled for volume, temperature, and humidity, removes the exact amount of moisture from the capsule halves Dipping Drying In the Automatic section, capsule halves are individually stripped from the pins by bronze jaws The cap and body lengths are precisely trimmed to a ± 0.15 mm tolerance. Trimming with stationary knives Stripping The capsule bodies and caps are joined automatically in the joiner blocks. Finished capsules are pushed onto a conveyer belt which carries them out to a container. Joining body & cap Ejection of whole capsule shells Perfect capsules are imprinted with the logo on high - speed capsule printing machines. Capsule quality is monitored throughout the production process including size , moisture content , thickness and colour QC testing Printing logo Filling of HGCs ❖ Formulation fill types 1 Dry solids powder – granules – pellets – tablets – capsules 2 Semisolids - thixotropic mix - thermosoftening mix - pastes 3 Liquids Oily/non - aqeuous solution/suspension ❖ Limitations in HGC fill materials : 1. Must not react with gelatin e g formaldehyde cross - links with gelatin → makes the capsule insoluble 2. Must not interfere with the integrity of the shell : materials with high water content → absorbed by gelatin → softens & distorts 3. The unit dose volume must not exceed the available capsule size Powder filling of HGCs ► Bench scale ► Industrial scale Uniform particle size distribution of the components of the powder mix is important to ensure : homogeneous mixing + minimal segregation A) Bench - scale filling Is a manual method used for filling small quantities of capsules : 50 to 1000 caps They consist of sets of plastic plates with predrilled holes to take from 30 – 100 capsules of a specific size B) Industrial - scale filling Output ranges from 5 , 000 - 15 , 000 capsules/ hour Machines vary from semi - to fully automatic STEPS : rectification – separation – dosing – rejoining - ejection 1 Rectification Empty closed capsules are orientated so that they are all pointing in the same direction ( body downwards ) HOW ?? Capsules are passed (one at a time) through channels that allow passage of body but stop the cap (due to its larger diameter) → a blade pushes against the capsule causing it to flip over → all capsules become aligned with body downwards into the plate 2 Separation of caps from bodies The body is separated from the cap by suction HOW ?? Rectified capsules are delivered into the upper portion of split bushes → vacuum applied from below pulls the bodies down into the lower portion of the split bushes → the diameter of the cap is too large to allow it to follow the body → the split bushes are separated to expose the bodies for filling This step can be done manually by the operator pulling apart the 2 bushes (in case of semi - automatic machines) 3 Dosing of fill material into body The split bush containing the body is presented to a dosing system to transfer feed material into it 4 Rejoining of caps Cap & body bushing portions are rejoined → by pins (allow indentations on cap and body to engage correctly for self locking mechanism by indentations in cap & body ) 5 Ejection of filled capsules by pins or compressed air VIDEO The dosing systems in the industrial scale filling machines may be either : ➢ Dependent system : - the capsule body is used directly to measure the powder fill dose - uniformity of the fill weight is achieved by complete filling of the capsule ➢ Independent system : - the powder dose is measured independent of the body → a special measuring device is used to measure the powder dose - weight uniformity is not dependent on filling the body completely → the capsule can be partly filled