Pharmaceutics 2

Hard capsules
Lecturer: NGUYEN Phuoc-Vinh (NPV)
Ph.D; Pharm.D.

npvinh@medvnu.edu.vn
School of Medicine, VNU, March, 2024
Outline 1

I. Definition and classifications

II. Advantages and drawbacks

III. Preparation process

IV. Composition of hard capsules

V. Quality tests
 Pharmaceutical tablets 2
1. Hard capsules: an edible package made from gelatin or other materials and filled
with a drug to produce a unit dosage form
2. Routes of administration: P.O.; rectal or vaginal administration
3. Classification: Starch (hygroscopic, big size, hard to be swallowed) vs gelatin
hard capsules (the most widely used)
4. Size: 8 sizes (from 5 to 000) corresponding from 0.15 to 1.37 mL
 Advantages and drawbacks 3

✔ Taste masking X Not suitable for liquids

✔ Combination of powders X High concentrated drugs may irritate the

✔ Simplicity stomach (hard gelatin capsules are soluble in

✔ Cheaper gastric acid)

✔ Dose accuracy

✔ Attractive appearance

✔ Easy of administration
Preparation process of hard capsules 4

Storage:
Finished capsules normally contain an
equilibrium moisture content of 13-16%
To maintain a relative humidity ò 40-60%
when handling and storing capsules
 Preparation process of hard capsules 5

Excipients Granulation Powder/

APIs APIs+Excipients Granules Granules
Characterizat
Blending
ion

Filling

Quality tests Quality tests

Market Packaging

Diluent + Glidant + Wetting agent + Binder (if granulation is required)

 Selection of hard capsule size 6
1. According to the necessary amount of drug powder: Tapped density
determination 🡪 Volume of hard capsule (V = m/d) 🡪 Selection of hard capsule
size 🡪 Calculation of diluent volume (with determined tapped density) 🡪 Weight
of diluent necessary for the filling
2. Filling process: Open of the cap and the body 🡪 Drug filling into the body 🡪
Closure of the cap onto the body

Filling
Quality control of hard capsules 7
Definition: a set of steps/procedure taken during the
product manufacture to ensure that it meets
specific requirements and the manufacture is
reproducible, or to enhance the product quality

Process: Sampling 🡪 Testing 🡪 Documentation

Measurement of curent quality performance
Comparision with standards (indicated in
pharmacopea)
Finding out the cause of deviation (if exist)
Enhancement of product quality
Role:
✔ Ensure the safety, efficacy, stability,
patient acceptability and compliance
✔ Check whether a tablet satisfies
certain standards to be a quality
drug
 Kind of tests 8

✔ Weight variability test

✔ Drug content

✔ Disintegration test

✔ Dissolution test
 Weight variability test (VP.5 <PL.11.3>) 9
✔ Role: to ensure that a tablet contains the proper API quantity
✔ Apparatus: Analytical balance
✔ Procedure:
• Weigh 20 hard capsules selected at random 🡪 Take the drug inside🡪
Individual weights🡪 Average weight🡪 No more than 02 units are out of
limitation range and no unit is out of the double of the limitation
✔ For hard capsules >= 300 mg (limitation is 7.5%)
✔ For hard capsules < 300 mg (limitation is 10%)
 Content uniformity (VP.5 <PL.11.2>) 10
✔ Application: only for API with content less than 2 mg or 2% in tablet (w/w)
✔ Method: Determine the amount of API by the method described in
ASSAY (monograph)
✔ Procedure:
• 10 tablets selected at random 🡪 Assay 🡪 Individual content + average
content, there are 03 cases:
Pass: all individual contents are in range of 85-115%
Not-pass: more than 1 individual content out of 85-115% or 1
tablet out of 75-125%
1 individual content out of 85-115% 🡪 re-test on 20 other tablets:
o Pass: if no more than 1/30 tablets out of 85-105% and no
table is out of 75-125%
 Disintegration test (VP.5 <PL.11.6>) 11
✔ Definition: the time required for the tablet to break into particle in liquid medium at
specific conditions
✔ Complete disintegration: no aggregate/part of tablet on the mesh screen (except
insoluble film-coating) or if there is still some pellets (it needs to be in soft form)
✔ Apparatus: A (for tablet with diameter <= 18 mm) or B for big-size tablets
• 06 tablets selected at random 🡪 Test (37±2 0C, in water or in acid pH 1.2) for
specific time (determined by manufacturer, 30 min)🡪 Take out and observation:
Pass: all 06 tablets are completely disintegrated within 30 min
Not-pass: more than 02 not-completely disintegrated tablets
01 or 02 tablets are not disintegrated 🡪 re-test on 12 other tablets:
o Pass: if not less than 16/18 tablets are completely disintegrated
 Dissolution test (VP.5 <PL.11.4>) 12
✔ Definition: the amount of API transformed from solid state into solution/ unit of time
under standardized condition (solvent, pH, temperature)
✔ Role: dissolution kinetics can reveal the bioavailability of an API
✔ Apparatus: Basket type (Type 1), Paddle type (Type 2), Flow-through (Type 3)

Tablets, chewable, Capsules, chewable, HPMC, Poor soluble tablets

controlled-release tablets controlled-release tablets
 Dissolution test (VP.5 <PL.11.4>) 13
✔ Dissolution media: selected according to in-house standards, pH within ± 0.05 unit
of the chosen value
• Gastric fluid, simulated: Dissolve 2.0 g of sodium chloride and 3.2 g of pepsin in
7.0 mL of hydrochloric acid (~420 g/L) and sufficient water to produce 1000 mL.
This test solution has a pH of about 1.2.
• Mix 77.0 mL of sodium hydroxide (0.2 mol/L), 250.0 mL of a solution containing
6.8 g of potassium dihydrogen phosphate and 500 mL of water. Add 10.0 g
pancreatin, mix and adjust the pH with the buffer components to 6.8 ± 0.1.
Dilute to 1000 mL with water.
✔ Procedure: 06 tablets selected at random 🡪 Test (37±2 0C, pH= 1.2 or 6.8) for 45
min🡪 Sampling 🡪 Filtration (by a filter with poresize NMT 0.45 µm) 🡪 Assay
Pass: all 06 tablets have a dissolution rate NLT 70%
Not-pass: more than 01 with a dissolution rate < 70%
01 tablet with a dissolution rate < 70%🡪 re-test on 06 other tablets:
o Pass: if 11/12 tablets have a dissolution rate NLT 70%
Dissolution test (VP.5 <PL.11.4>) 14
Dissolution test (VP.5 <PL.11.4>) 15
Dissolution test (VP.5 <PL.11.4>) 16
Dissolution test (VP.5 <PL.11.4>) 17
Dissolution test (VP.5 <PL.11.4>) 18
Dissolution test (VP.5 <PL.11.4>) 19