Capsule Technology.
- Capsules are solid dosage forms that are most commonly composed of gelatin and are designed to contain a drug-containing formulation.
- Two types of capsules are available – hard and soft gelatin capsules.
- These differ in both their mechanical properties and in capsule design.
- Hard gelatin capsules are less flexible and are composed of two pieces, termed the capsule and the body, whereas soft gelatin capsules are more flexible and are composed of a one-piece capsule shell.
- A wide range of formulation types may be included within the interior of the capsule.
- For example, powders, tablets, semisolids and nonaqueous liquids/gels may be filled into hard capsules, with powders being the most common formulation option.
- Soft gelatin capsules are usually filled with non-aqueous liquids containing the therapeutic agent either dispersed or dissolved within this carrier.
- Capsules offer the pharmaceutical scientist with an alternative method for the formulation of solid-dosage forms.
Advantages and disadvantages of capsule formulations
Advantages:
The formulation of capsules may be preferred for several reasons:■ The use of capsules avoids many unit operations that are associated with the manufacture of tablets, e.g. compression, granulation, drying.
■ Capsules (generally soft gelatin capsules) may be formulated to increase the oral bioavailability of poorly soluble therapeutic agents. This is particularly the case when formulated as a liquid-filled hard gelatin or soft gelatin capsule.
■ Capsules are a convenient method by which liquids may be orally administered to patients as a unit dosage form. ■ Capsules are difficult to counterfeit.
■ The stability of therapeutic agents may be improved in a capsule formulation.
■ Capsules are a convenient means of formulating substances of abuse, e.g. temazepam.
Disadvantages
The disadvantages of capsule formulations include:■ The requirement for specialized manufacturing equipment
■ Potential stability problems associated with capsules containing liquid fills
■ Problems regarding the homogeneity of fill weight and content may be associated with capsule formulations.
Materials and manufacture of capsules
- Capsules are primarily (but not exclusively) manufactured using gelatin; however, the suitability of other materials, e.g. hydroxypropylmethylcellulose and starch, has been investigated as suitable replacements.
- Gelatin is a mixture of proteins that is extracted from animal collagen (derived from animal skins, sinews and/or bovine bones) by either partial acid or partial alkaline hydrolysis.
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- From these processes, two types of gelatin are obtained, termed type A and type B.
- Type A is obtained by an acid treatment of pig skin (HCl, H2SO4, H2SO3 or H3PO4, pH 1–3 for approximately 1 day) whereas type B is obtained using an alkaline treatment of demineralised bones (immersion in a calcium hydroxide slurry for 1–3 months), following which gelatin is extracted using a series of hot-water washes (of successive increasing temperatures).
- The gelatin solutions are then cooled to form a gel; subsequent evaporation of water results in the production of dried gelatin.
- The isoelectric points of type A and type B gelatin differ (between 7 and 9 and between 4.7 and 5.3, respectively), resulting in differing solubilities as a function of pH.
- Typically the molecular weight range for gelatin is 15 000–250 000.
- Whilst the two types of gelatin are often used independently, mixtures of the two types are commercially available.
- The manufacture of the two types of gelatin is summarized as blow,
- The grade of gelatin is defined by the bloom strength, which is defined as the weight (in grams) required to depress a plunger (of defined diameter, 12.7 mm) to a defined depth (4 mm) within an aged gelatin gel (6.66% w/w in water).
- The use of gelatin as a capsule material is principally due to the excellent physicochemical and biological properties of this material, including on-toxic material, being used widely as a component of foods.
- More recently, the production of gelatin using bovine sources has received considerable attention due to the possible transmission of bovine spongiform encephalopathy (BSE).
- Therefore, if gelatin has been manufactured from bovine sources, it is important that this has been produced from countries in which the incidence of BSE is low – termed grades 1 (highly unlikely) or 2 (unlikely but not excluded)
- soluble in biological fluids at room temperature (note: gelatin capsules do not dissolve but swell when immersed in an aqueous solution at 30 C)
- ■ excellent mechanical properties, most notably exhibiting good film, and hence capsule-forming properties
- ■ excellent rheological properties at elevated temperatures. At 50 C, gelatin acts as a mobile liquid (termedasol), thereby enabling the production of capsules by dip processing
- ■ undergoes a sol–gel transition at relatively low temperatures. Therefore, gelatin is readily converted to the rigid (gel) state by allowing warmed solutions of this material to cool.