Lec 5 Capsules Pharmaceutical Drug Dosage Forms PDF

Lecture (5) Introduction to Capsules Dosage Form Prepared by D. Basant A. Abou-Taleb, M.sc., PHD Lecturer of Pharmaceutics & Ph. Technology Department Pharos University of Alexandria (PUA) Dr. B...

Lecture (5) Introduction to Capsules Dosage Form Prepared by D. Basant A. Abou-Taleb, M.sc., PHD Lecturer of Pharmaceutics & Ph. Technology Department Pharos University of Alexandria (PUA) Dr. Basant Abou-Taleb 1 Contents of Lecture A. Introduction of Capsules 1 I Definition 2 Types of capsules 3 Advantages & disadvantages 4 Administration routes 5 Materials of capsules Factors affecting drug release 6 from capsules 7 Quality control Tests  Definition  Capsule is a word that is derived from a Latin word “Capsula” (small box)  Capsules are solid dosage forms in which one or more active ingredient & / or inert ingredients are enclosed in either a hard or soft shell  Capsules filled with drugs are unit dosage forms “single dose”  Types of Capsules Hard gelatin Soft gelatin capsules capsules “HGC” “SGC”  less flexible  more flexible  two pieces  one piece (body & cap) capsule shell  Advantages 1. Avoids many unit operations that are associated with the manufacture of tablets, e.g. Compression, granulation, drying 2. Increase the oral bioavailability of poorly soluble therapeutic agents. (Liquid-filled HGC or SGC) 3. Convenient method by which liquids may be orally administered to patients as a unit dosage form 4. Stability of therapeutic agents may be improved in a capsule formulation  Disadvantages 1. Specialized manufacturing equipment 2. Potential stability problems associated with capsules containing liquid fills 3. Problems regarding the homogeneity of fill weight & content  Administration Routes Oral Text Rectal Text Routes Text Inhalation Topical  I. Oral Route  Intact  Its content may be removed from the gelatin shell and be mixed with food for children or elderly unable to swallow  II. Rectal Route Rectocaps ™ e.g. OlfenTM Advantages:  Stable in the in tropical countries  Unlike ordinary suppositories made with hard fat, they retain their shape & action even at high ambient temperatures  III. Inhalation Route  Capsules contain powder for inhalation e.g. Foradile® Caps  Qualicaps® (gelatin) Quali V® (HPMC)  Used in dry powder inhalers (DPI’s)  IV. Topical Route  Soft gelatin capsules contain cosmetics  e.g. Anti-ageing collagen & vitamin C  Materials of Capsules Gelatin Text Materials Colorants Text Process Text aids  1. Gelatin  Gelatin is a mixture of proteins that is extracted from animal collagen derived from animal skins, by either partial acid or alkaline hydrolysis  Two types of gelatin are obtained; termed Type A & Type B  Gelatin Type A is obtained by an acid treatment of pig skin  Gelatin Type B is obtained using an alkaline treatment of demineralised bones  The difference in between is in the isoelectric points (IEP) resulting in differing solubility as a function of pH  Isoelectric point : pH at which amino acid carries both positive and negative charge  IEP of Gelatin Type A: 7-9  IEP of Gelatin Type B: 4.7- 5.3  The two types of gelatin are often used independently; mixtures of the two types are commercially available  Molecular weight range for gelatin is 15 000–250 000  Gelatin, being a protein, is digested by proteolytic enzyme  Solubility property of gelatin:  Insoluble in cold water, soften through the absorption of up to ten times its weight of water  Soluble in hot water and in warm gastric fluid  Parameters 1.Viscosity 3. Bloom 2. Thickness Strength 4. Gel rigidity Concept  Advantages of Gelatin  Non-toxic material  Soluble in biological fluids at room temperature (N.B. gelatin capsules do not dissolve but swell)  Excellent mechanical properties, exhibiting good film-forming  Advantages of Gelatin cont.  Excellent rheological properties at elevated temperatures.  At 50°C, gelatin acts as a mobile liquid (sol ) , thereby enabling the production of capsules.  Gelatin is converted to the rigid (gel) state by allowing warmed solutions of gelatin to cool.  Undergoes a sol–gel transition at relatively low temperatures.  2. Colorants  Water soluble dyes : synthetic & subdivided into azo-dyes and non-azo dyes.  Most dyes used currently: non -azo dyes e.g. Erythrosine (E127), indigo carmine (E132) & quinoline yellow (E104)  Insoluble pigments: iron oxide (E172) adv: not absorbed on ingestion  Titanium dioxide (E171): white used as opacifying agent  3. Process aids Sodium Lauryl Sulphate Preservatives  Wetting agent : manufacture of Gelatin in dry form is stable shells with uniform thickness against microbial growth, if in Increase the wetting properties aqueous solution it is a good of the capsule shell following medium for microbial growth. contact with an aqueous Factories applying Good solution hence enhance the Manufacturing Practice “GMP” dissolution properties of the now don’t use preservatives formulation contained within during manufacture. the capsule. HARD GELATIN CAPSULES “HGC”  HARD GELATIN CAPSULES “HGC”  Used in most commercial medicated capsules.  Commonly employed in clinical drug trials.  Used in extemporaneous (topical ) compounding of prescriptions in community pharmacy.  Composition of HGC “BODY” & Mixture of Body is Same or “CAP”, smaller in Different gelatin, which fits diameter colors sugar & & firmly over water longer in the body of size than the capsule the cap Capsule cap & body have some indentations ‫اخدود او تضاريس‬ that fit together and lock the capsule preventing detachment of cap from the body Standard water content 13 - 16%, If capsules are plasticizer for stored in gelatin to ensure extremely dry mechanical atmosphere they properties of the tend to dry & If stored in become brittle capsule atmosphere with high humidity content, they may absorb moisture & soften  Capsule Sizes  Manufactured in various lengths, diameters & capacities  Size range from 000(largest) to 5 (smallest)  Encapsulate about 65 mg to 1 g of powdered material MANUFACTURE OF HGC “Dip-coating method”  Two sets of bars, each containing a series of pins (moulds) aligned in columnar formation that have been lubricated prior to use.  One set for the production of the cap and one for the body of the capsule.  Preparation of gelatin solution  A concentrated solution of gelatin is prepared (35–40% w/w) in demineralised hot water with stirring.  A vacuum is then applied to remove entrapped air.  Incorporation of other constituents of the capsule added within the heated gelatin solution e.g.: Colorants, wetting agents and lubricants  Stages of manufacture Dipping→ Spinning → Drying → Stripping→ Trimming→ Joining  Dipping Lubricated pairs of stainless steel pins, are dipped into gelatin solution to form caps & bodies simultaneously. Pins are at ambient temperature, 22° C.  Dipping solution is at 50° C in heated jacketed heating pan. Dipping time to cast‫صب‬the film is about 12 secs.  Spinning (Rotation ) The pins are withdrawn from the dipping solution, elevated and rotated until they are facing upward. This helps distribution of gelatin over the pins uniformly & avoid the formation of bead at the capsule ends After rotation they are given a blast of cool air to set the film   Four drying ovens Drying  Drying is done by dehumidification by passing large volumes of dry air over the pins.  Temperature elevation of few degrees are permissible to prevent film melting.  Drying also must be too rapid to prevent case hardening. Notes:  Under drying leave film sticky  Over drying could cause the films to split on the pins due to shrinkage or at least make them brittle for trimming (cutting) step.  Stripping (removing) A series of bronze jaws strip (remove) the cap and body portions of the capsules from the pins.  Trimming (Cutting)  Stripped caps & bodies are delivered to collects in which they are firmly held ‫ممسوكة بقوة‬.  As the collects rotate the knives are brought against the shells to trim them to the required length  Joining Cap & body portions are aligned concentrically in channels, and the two portions are slowly pushed together.  Stages of manufacture Dipping→ Spinning → Drying → Stripping→ Trimming→ Joining  Sorting ‫فرز‬  Capsules pass on a lighted moving conveyor & observed visually by inspector.  Any defective capsules spotted are thus manually removed.  Defects may cause serious problem : stoppage of a filling machine due to imperfect cuts, dented ‫انبعاج‬capsules, or capsule with holes  Painting Capsules are printed prior to filling as they are easy to handle. Available equipment can print axially along the length or radially around the circumference ‫ محيط الدايرة‬of capsules  Sealing and self locking closures HGC are made self locking by forming indentations ‫حز‬ or grooves on the inside of the cap & body portions, when they are fully engaged, a positive interlock is created between the cap & body portions. 1. Technique of banding ‫شريط‬: a film of gelatin, often colored, laid down around the seam ‫ وصلة‬of the cap & body. 2. Spot welding thermal method: two hot metal jaws are brought into contact with the area where the cap overlaps the filled body 3. Immersion of the capsules for a fraction of second in hydro alcoholic solvent, followed by rapid removal excess solvent, leaving traces in the overlapping area of cap & body and then capsules are dried with warm air. Preparation of filled hard gelatin capsules Developing & preparing formulation Selecting size of capsule Filling capsule shells Capsule sealing Cleansing & polishing filled capsules Hard Gelatin Capsules Filling types Powders or granules Pellets or beads Tablets Capsules Semisolids as paste Non-aqueous liquids  Criteria of Filling Material  It must not interact with gelatin.  It must not contain high level of free moisture.  It should have a volume not exceeding that of the shell. 1- Powders Homogeneity Good flow Compatibility  Powder Filling Glidants Drug Lubricants Excipients Powder Text Wetting agents Disintegrant TextText Starch is not used PLUGS cylinders of the powders prepared by compression at much lower pressure just enough to keep them intact  Small-scale filling plugs  Done manually by a spatula.  For large number of small scale filling a device that removes caps from many capsules at once may be used (as in hospitals)  Industrial-scale filling Automated machines that are divided into two main categories:  Dependent dosing system: depends on the size of capsule body for measuring the dose. Capsule body is filled completely with powder from a hopper.  Independent dosing system: automated machines that pre-compress the powder into “PLUGS” that will be filled into the capsule body.  2. Pellets & Granules Filling  Granules maybe prepared to increase flow of a powder.  Coated-pellets are used to control the release of a drug or for enteric coating.  3. Tablet filling  Tablet size with a diameter ≤ 3 mm.  Used for :  Incompatible ingredients.  Drug release at different sites of the GIT.  Treatment of concurrent diseases.  4. Semisolid filling Semisolid are filled as liquids by heating or strong stirring, then they solidify in the capsule on standing.  5. Liquid filling  Only non-aqueous liquids can be filled into capsules.  After filling capsule, body & cap should be sealed together to prevent leakage of the liquid. MARKETED FORMS OF HGC  Quali-V® / VCaps (Capsugel)  Multifunctional two-piece hard shell capsule derived from non-animal sources, which satisfy vegetarian and cultural needs.  Formulated with HPMC  Advantages:  chemical stability and low moisture content –  making it an attractive  alternative for hygroscopic formulations Licaps® Capsules: Two-piece gelatin capsules that been specially designed to be sealed for secure containment of liquids and semi-solids. Press-fit® and Xpress- fit® Gelcaps High-gloss gelatin coating that encases a caplet core (elongated medicine tablet)  Advantages: 1. Easy to swallow 2. Taste and odor free 3. Energize ‫بنشاط‬sales with a new brand image  PC caps™ Capsules  Very small size gelatin capsules that are ideal  for oral dosage to rodents in pre-clinical studies. Size 9 and are available in white opaque color.  DB caps® Capsules  Two-piece gelatin capsules that are designed for double-blind clinical trials. LOGO