Capsules PDF

CAPSULES Prof Thiru Govender Discipline of Pharmaceutical Sciences  CAPSULES Definition: a dose of one or more medicinal substance/s enclosed in a hard or soft gelatin shell.  Advantages 1. Few formulation problems. 2. Better stability than tablets. 3...

CAPSULES Prof Thiru Govender Discipline of Pharmaceutical Sciences  CAPSULES Definition: a dose of one or more medicinal substance/s enclosed in a hard or soft gelatin shell.  Advantages 1. Few formulation problems. 2. Better stability than tablets. 3. Reproducible disintegration. 4. Fewer ingredients than tablets → therefore ↓ chance of interaction and ↓ interference with bioavailability. 5. Convenient dosage form for many solids and liquids.  Disadvantages 1. Fairly poor mass control. 2. The unit is not tamper proof. 3. High production cost. Raw Materials for Gelatin Capsules ž Raw materials used in manufacture of hard and soft gelatin capsules are similar. ž Both contain gelatin, water, colourants and optional materials e.g. preservatives. Soft gelatin capsules include plasticisers. ž Gelatin solution is prepared → add colourants, preservatives and process aids depending on the type of capsule required.  1. Gelatin ž Major component of capsules. ž Possesses 5 basic properties that make it suitable — Non-toxic → widely used. — Readily soluble in biological fluids at body temperature. — Good film forming material-forms strong flexible film. — Solutions of high concentrations, 40%w/v, are mobile at 50 degrees. — As a solution in H2O or a H2O-glycerol blend, it undergoes a reversible phase change from sol to gel at temps only a few degrees above ambient temperature to form a film. Substance of natural origin, but does not occur as such in nature. ž Prepared by hydrolysis of collagen which is the main protein constituent of connective tissue (animal bones and skins). 2. Plasticizers ž Soft gelatin capsules required to be flexible. ž Addition of plasticizers → ↑ flexibility. ž Proportion of plasticizers → affects characteristics of capsule e.g. glycerol, sorbitol, propylene glycol, acacia 3. Colourants ž Soluble dyes or insoluble pigments are two types of colourants. ž Mixtures of dyes and pigments can be mixed to provide different colours. ž Colourants for medicines are governed by legislation. 4. Preservatives ž Are used to prevent microbial contamination during manufacture. ž Finished capsules do not contain sufficient moisture to support microbial growth. ž Soft gelatin capsules may contain an antifungal to prevent growth on their surfaces when stored in non-protective package.  Manufacture Hard capsule shells are made by: 1) dipping moulds into gelatin solution 2) the resulting film on the mould is dried 3) the shell is cut to length and then stripped from the mould. 1 2 3 Sizes (see table) — Range of 8 sizes→ from size 000 (largest) to size 5 (smallest) — To determine the size of capsule to be used or the fill weight for a formulation, the following equation is used: Capsule fill weight = tapped bulk density x capsule volume — Eg. if powder has a fill weight of 500 mg and a tapped bulk density of 0.80 gml-1 — Capsule volume required = 0.5g 0.8g/ml = 0.63ml therefore use size 0 capsule (vol → 0.67ml) [size rounded up] Hard Gelatin Capsule Sizes and Fill Volumes Capsule Fill Volume Size No. (ml) 5 0.13 4 0.20 3 0.27 2 0.37 1 0.48 0 0.67 00 0.95 000 1.36 Filling ž All formulations for filling into capsules must possess two basic requirements. They must: — be able to be accurately dosed into the capsule shell. — release their active contents in a form which is available to the patient. ž Dry solids as well as semi-solids (e.g. paste and thixotropic mixtures) may be filled into hard gelatin capsules. Formulation Aspects ž Powders as well as non-powders (minitablets, granules/ pellets, semi-solids) may be used in capsules. ž Diluents may be required for low dose drugs → can improve flow by using free-flowing diluents e.g. maize starch or spray dried lactose. ž For high dose drugs → glidants (up to 5% w/w) may be used to improve flow e.g. colloidal silicon dioxide. ž Lubricants may be added to reduce powder to metal adhesion e.g. Mg stearate. ž Wetting agents can be used to ↑ release of drug. Bioavailability Aspects ž Absorption from capsule → generally more rapid than tablet → provided that gastric and intestinal fluids penetrate the contents after the shell has ruptured. ž Absorption is related to formulation components (e.g. drug particle size, hydrophobicity of glidants etc) and preparation. Soft Gelatin Capsules ž Cpnsists of a liquid or semisolid matrix inside a one piece outer gelatin shell. ž Drug is in solution or suspension in the capsule-fill matrix. ž Capsules are formed, filled and sealed in one operation. ž Available in different sizes & shapes.  Advantages 1. No compression is required → useful for poorly compressible drugs. 2. Drug is in form of solution-can be rapidly absorbed. 3. Drug is dissolved or dispersed in liquid, therefore dose content uniformity is optimized. 4. Drugs can be protected against hydrolysis and oxidation → can use as a solution or dispersion of drug in oil. 5. For a drug dissolved or dispersed in liquid → the break-up of the capsule → leads to drug dispersion of high surface area → leads to good bioavailability. Formulation of the Gelatin Capsule ž Softgel capsule shell consists of gelatin, water and plasticizers (e.g. glycerol). May be coloured or opaque. ž Other additives: preservatives, dyes, flavours. ž Can be coated with enteric resistant material. Formulation of the Capsule Contents ž Limitation for fill materials — Drugs or excipients containing high concentrations of H2O or other gelatin solvents cannot be incorporated. — Emulsions are not recommended (o/w or w/o) → unstable and will crack as the water is lost from the shell in the manufacturing process. — Extremes of pH must be avoided → below pH 2.5 and above pH 7.5 ž Liquid Vehicles — H2O-immiscible oils → include volatile and non- volatile oils → fixed and aromatic vegetable oils, hydrocarbons, liquid ethers and esters. — H2O-miscible liquids → e.g. PEG’s (400-600), alcohols, triacetin. ž Suspensions — Insoluble drugs → can be dispersed in the above vehicles and encapsulated. — Suspending agents (beeswax, ethylcellulose, PEG4000 and 6000) and surfactants (to promote wetting) are added. — Emulsions: drug formulated as an emulsion (water-in oil system)-high capacity to solubilize drug. Bioavailability Aspects ž Yield similar blood levels of drug to those produced by liquids. ž More rapid absorption than tablets. ž Drugs dissolved in oils or drugs that are oils and are emulsified → are absorbed from GIT into lymphatic systems → surface area of emulsified system is high therefore ↑ dissolution rate → enhanced bioavailability.  Testing of Capsules 1. Uniformity of fill weight 2. Disintegration test 3. Dissolution test 4. Content uniformity 5. Assay 6. Related substances (impurities). 7. Microbiological testing