Capsules (1- HGC) PDF Lecture 7

11/12/2024 *Are solid dosage forms *Intended for oral administration. *In which one or more drugs and excipients are enclosed in a small shell or container usually made of gelatin. * The medication may be powder, liquid or semisolid....

11/12/2024 *Are solid dosage forms *Intended for oral administration. *In which one or more drugs and excipients are enclosed in a small shell or container usually made of gelatin. * The medication may be powder, liquid or semisolid. 1  11/12/2024 Advantages of capsules: 1- Mask the unpleasant taste and odor of drugs. 2- Easily administered  they are slippery when moist so easy to swallow with water. 3- the shell is easily & quickly digested in GIT  Rapid onset of action. 4-The gelatin shells are physiologically inert  no interaction with drugs in the capsule. 5- Elegant appearance 6-Compared to tablets  less excipients are required more economical 7- Compared to powders and solutions  accurate dosing and easy to handle and carry. 8- The shells can be opacified (with titanium dioxide) or colored  give protection from light. Disadvantages of capsules: Capsules are not suitable for use with: 1. Drugs containing liquids that dissolve gelatin (water – hydroalcoholic solution). 2. Hygroscopic drugs  absorb water from the capsule shell  making it brittle (easily broken) 3. Drugs that interact with gelatin 4. Some medications that might cause gastric irritation rapid release in stomach  Gastric irritation (NSAIDs). 5. Very soluble salts (such as bromides or iodides) rapid release  cause gastric irritation. 2  11/12/2024 Types of Capsules Hard gelatin Soft gelatin Capsules Capsules Hard or 'two-piece‘: Soft or 'one-piece'. Consists of 2 pieces in the form of Usually enclose liquid or cylinders closed at one end: semisolid medications. Long  body shorter piece  cap The common between two types is the shell (gelatin capsule) Composition of Capsule shells 1- Shell material (mainly gelatin) + water 2- colorants 3- plasticizers mostly in soft capsules. 4- Optional excipients (processing aids). 3  11/12/2024 1- Shell material: Gelatin Gelatin is a translucent brittle solid substance, colourless or slightly yellow, nearly tasteless and odourless the major component of the capsule shell Gelatin possesses five basic properties: 1- Safe, non-toxic, non irritant and widely used in foodstuffs. 2- inert No interaction with drugs in the capsule. 3- It is a good film-forming material  produce strong flexible film. 4- Easily manufactured : A- Highly concentrated solutions (40%) when heated  are mobile when heated above 50 °C. B- When heated gelatin solution is slowly cooled  reversible change from a sol to a gel at temperatures only a few degrees above room temperature. 5- Readily soluble in biological fluids at body temperature Gelatin Prepared by hydrolysis of collagen (the main protein constituent of connective tissues) such as Animal skins and bones. There are two main types of gelatin: Type A Type B Produced by acid hydrolysis. Produced by basic hydrolysis. Used mainly for animal skins, Used mainly for animal bones because they require less pretreatment than do bones. The basic process takes about 10 The acid process takes about 7-10 times as long as acid process. days. 4  11/12/2024 Alternative material for Hard-shell capsules (materials can be used instead of gelatin):  Hypermellose = HPMC (Hydroxy Propyl Methyl Cellulose)  is a semisynthetic, inert, viscoelastic polymer  Used to make shells usually for vegetarian capsules. 2- colorants (coloring agents)  coloring agents are usually used to identify a product (capsule brand).  Capsules are colored by the addition of colorants to the gelatin solution during the manufacturing stage.  There are two types of colorants : I- water soluble dyes – e.g. erythrosine II- water-insoluble pigments – e.g. iron oxides (black, red and yellow) and titanium dioxide (white) more preferred because : a. make the capsule opaque to provide protection against light b. more protection against humidity 5  11/12/2024 3- plasticizer  PLASTICIZERS are low-molecular-weight polymers that change the mechanical properties of gelatin  they make the gelatin shell more elastic (flexible) and reduce the brittleness  Plasticizers are main constituents of GELATIN CAPSULE shells  (it is used in higher conc in soft gelatin capsule shells  they are what make the soft capsules SOFT)  E.g. polyols (glycerol, sorbitol , PG) 4- Process aids Those are materials added during capsule manufacture to aid in processing. First type of process aids: are added to the gelatin solution during capsule manufacture to aid in processing. A. Preservatives: To prevent microbiological contamination and microbial growth during manufacture as warm gelatin solutions are an ideal medium for bacterial growth. B. Surfactants: Act as wetting agent (to ensure that the gelatin solution will uniformly cover the lubricated metal moulds when dipped into it). (0.15 % w/w of sodium lauryl sulphate ) 6  11/12/2024 second type of process aids: added to help in capsule manufacturing and filling process C. Glidant : to enhance the flow properties of the powder mix during capsule filling D. Diluent / filler: to produce the proper capsule fill volume, especially in small dose drugs e.g. lactose, microcrystalline cellulose and starch Types of Capsules Hard gelatin Soft gelatin Capsules Capsules 7  11/12/2024 A- Hard gelatin Capsules (HGC) Cap Body Hard gelatin Capsule sizes Capsules are available in many sizes and shapes to provide dosing flexibility  The size selected for use is determined by the amount of material to be encapsulated. For human use, empty capsules ranging in size from 000 (the largest) to 5 (the smallest) larger capsules are available for veterinary use. 8  11/12/2024 Hard gelatin Capsules a) Shell b) Filling material A) The shells consist largely of : (Drug + excipients) Gelatin water. Might contain sugar (special cases) May also contain: plasticizers Preservatives Colors, and flavors. b) Filling material: Materials that can be filled into HARD gelatin capsules (HGC): Dry solids: powders, granules, pellets or mini-tablets Semisolids: semisolid suspensions or pastes Liquids: non-aqueous liquids ( in HGC Liquids cannot be used in their original liquid form they may be adsorbed onto inert carrier powders (sorbents) to form dry powders suitable for capsule filling.) 9  11/12/2024 Manufacturing of hard gelatin capsules There are three main steps in manufacturing of hard gelatin Capsules: A- Preparation of the gelatin solution B- manufacturing of the EMPTY HARD GELATIN SHELLS C- capsule filling 10  11/12/2024 Capsules manufacturing steps A- manufacturing of the gelatin solution gelatin (35-40%) + Hot water (60-70° C) in a hot jacketed pressure vessel  Stirred until the gelatin is dissolved  Concentrated gelatin solution Required additives are added (coloring, sweetening, preservative,…etc). Vacuum is applied  remove any entrapped air bubbles The viscosity is measured and adjusted using hot water. Note: Viscosity is used to control the thickness of the capsule shells during production: the higher the viscosity the thicker the shell wall produced. B- manufacturing of the EMPTY gelatin shells 1- Metal moulds The metal pins 2- The gelatin gels to (pins) are dipped in form films on the the heated surface of each mould gelatin solution 4- Dried by passing 3- Moulds are slowly through a series of drying removed and rotated ovens during their transfer to form a film of uniform thickness.. 11  11/12/2024 5- The dried films are removed from the moulds  cut to the correct length 6- The two capsule parts joined together  the complete capsule delivered from the machine. B- manufacturing of the EMPTY gelatin shells 1- Metal moulds The metal pins 2- The gelatin gels to (pins) are dipped in form films on the the heated surface of each mould gelatin solution 4- Dried by passing through a 3- Moulds are slowly series of drying ovens removed and rotated during their transfer to form a film of 5- The dried films are uniform thickness. removed from the moulds.  cut to the correct length 6- The two capsule parts joined together  the complete capsule delivered from the machine. 12  11/12/2024 (4) (2-3) (5) (1) Capsules manufacturing steps: A- manufacturing of the gelatin solution B- manufacturing of the EMPTY hard gelatin shells C- capsule filling 13  11/12/2024 C- Capsule filling step 1- Manual filling 2- Automatic filling b. Fully b. Hand operated a. semi- a. Fully Manual automated filling machine automated 14  11/12/2024 1- Manual Capsule filling a. Fully manual Capsule filling Using a spatula  the powder The powder to be encapsulated is formed into a cake having a is placed on a sheet of clean depth of one fourth the length paper or a glass or porcelain of the capsule body. plate The empty capsule is weighed The cap is replaced and the  then the cap is removed and the filled capsule is re-weighed to empty capsule body is held between ensure the correct filling thumb and forefinger and material weight repeatedly punched downward until it is full. 15  11/12/2024 1- Manual Capsule filling b. Hand operated Capsule filling machine C- Capsule filling step 1- Manual filling a. Fully Manual b. Hand operated filling machine 2- Automatic filling (industrial filling ) a. Semi- automated b. Fully Automated filling machines 16  11/12/2024 2- Automatic Capsule filling (Industrial filling) A. semi-Automated filling 4 main steps: a. removal of caps b. filling of the bodies c. replacement of caps d. ejection of filled capsules. (1) (2) (3) (4) 17  11/12/2024 (3) Filling of (5) Ejection (1) feeding into the machine the capsules (2) Removal of the caps (4) Replacement of the caps 18  11/12/2024 b. Fully automated Capsule filling machines The same 4 main steps of : Removal of caps Filling of the bodies Replacement of caps Ejection of filled capsules Are done in the same machine in consecutive automated steps LOCKING AND SEALING OF CAPSULES: a - The capsule-sealing process of banding: The two capsule parts are sealed with a gelatin or polymer band at the joint of the cap and body. b- tamper-resistant seal: The contact areas of the cap and body are wetted with a mixture of water and ethanol  thermally sealed at 40-45 oC. 19  11/12/2024 c- self sealing designs: Hard gelatine capsules are made self locking by forming indentations or grooves on the inside of the cap and body portions When they are fully engaged, a positive interlock is created between the cap and body portions Spansules (Sustained drug release capsules)  Spansules are hard gelatine capsules containing part of the medication uncoated to produce immediate effect and another part coated with materials having slow dissolving rates (in the form of coated beads or pellets) so that the drug is delivered delayed after some time after the capsule is taken.  In general, the drug inside the capsule is delivered in two forms: 1- an immediate release portion. 2- a sustained release portion which gradually release medicament (coated beads or pellets) Sustained release capsules are suitable for antibiotics. Advantage:  Administration is more convenient, since a single dose provides all-day or all-night medication. 20 11/12/2024 21