Cápsulas / Capsules - Universidad de Navarra

Hard Gelatin vs Soft Gelatin "Softgels" Capsules
Criterion Soft gelatin
Hard Gelatin
Capsules
Capsules
Shell Plasticized (glycerin,
propylene glycol, sorbitol)
Not plasticized
Content Usually liquids or suspensions Usually dry solids (liquids/
(dry solids possible) semi-solid matrices possible)
Manufacture Formed/filled in one Shells made in one operation
operation
and filled in a separate
process
Closure Hermetically sealed Traditional friction-fit;
(inherent)
mechanical interlock,
banding and liquid sealing
possible
Sizes and
Shapes
Many Limited
Formulation
Technology
Liquids Solids
Fill Accuracy 1-3% 2-5% (with modern
automatic machines)
Farmacia y Tecnología Farmacéutica
Universidad de Navarra
2.1. Hard capsules: sizes and capacities
Size Volume Capacity
(mL) (mg)
000 1.37 1096
00 0.91 728
0 0.68 554
1 0.50 400
2 0.37 296
3 0.30 240
4 0.21 168
5 0.10 104
Capacity (mg) at packing density=0.8 g/mL
Specials “containers”
00el: 1.02 mL, 816 mg
0el: 0.78 mL, 624 mg
Farmacia y Tecnología Farmacéutica
Universidad de Navarra
Formas Sólidas Oral: cápsulas
Juan M. Irache
Formas Sólidas Oral: cápsulas
Juan M. Irache
2. Hard gelatin capsules
Advantages of Hard Gelatin Capsules
Rapid drug release possible
Flexibility of formulation
- Easily compounded
- No need to form a compact that must stand up to handling
- Unique mixed fills possible
- Role in drug development / Role in clinical tests
Sealed HGCs are good barriers to atmospheric oxygen.
Disadvantages of Hard Gelatin Capsules
Very bulky materials are a problem
Filling equipment slower than tableting
Generally more costly than tablets, but judge on a case-by-case basis
Concern over maintaining proper shell moisture content
- Shell should have moisture content of 13-15%
If too dry – become brittle/easily fractured
It to moist – become too soft and can get sticky
- Unprotected capsules are best stored at 45-65% RH
- Caution using strongly hygroscopic drugs
Cross-linking can affect soft/hard gelatin capsules, gelatin coated tablets
Farmacia y Tecnología Farmacéutica
Universidad de Navarra
2.2. Composition of Hard Gelatin Shells
Formas Sólidas Oral: cápsulas
Juan M. Irache
Composition hard capsules
a. Gelatin
Bone Gelatin (Type B, alcaline gelatin; pI: 4.7-5.1)
Skin Gelatin (Type A, acidic gelatin; pI: 7-9)
Bloom strength (Poder gelificante): a measure of relevance to cohesive
strength of gelatin film
The weight in g required to depress a plunger 12.7 mm diameter 4 mm into
a 6.67% gel held for 17 hours at 10 degrees (O.T. Bloom, 1925)
Typically for hard capsules: 200-260 "bloom-grams"
Viscosity: single most important factor controlling shell thickness
Capillary viscometer; 6.67% soln.
Typical range 25-45 millipoise.
b. Water
c. Dyes and other colorants:
http://www.capsugel.com/amer/color/catalog.php
d. Opaquing agent (TiO 2 )
e. Preservative:
no necessary if work under GMP conditions
water content of 13-16%: no possibility for microbial contamination
Farmacia y Tecnología Farmacéutica
Universidad de Navarra
Formas Sólidas Oral: cápsulas
Juan M. Irache