HYPROMELLOSE CAPSULES FOR PHARMACEUTICALS
A multi-functional two-piece hard shell capsule manufactured from hypromellose using patented technology. Hypromellose is derived from plants. USA: Drug Master File
No. 12900 No. 14765 Canada: No. 2002-068
for Japanese plant for European plant for Japanese plant
Quali-V® Features ●
Good dissolution at acid pH
Non-brittle ◗ ◗
At low relative humidities (RHs) At reduced moisture contents
Chemically stable ◗
No cross-linking after ICH accelerated storage testing
Quali-V® meets the pharmaceutical requirements for two-piece hard capsules ●
Quali-V® capsules are made from plant derived hypromellose. This has been used extensively in oral solid dosage forms for many years. It is chemically stable and is compatible with most pharmaceutical materials.
Quali-V® capsules does not undergo cross-linking reactions like gelatin and assures encapsulated products with good dissolution.
Quali-V® capsules have the required strength and dimensions that enable them to be filled and packaged on automatic high-speed machines.
Quali-V® capsules meet the exacting requirements for a pharmaceutical-grade hard two-piece capsule.
Quali-V® Composition Polymer base
USP, PhEur, JP
USNF, EEC, JPE
USP, PhEur, JP
Additional benefits of Quali-V® capsules ●
Filling performance comparable to gelatin two-piece capsules.
Patented composition and manufacturating process.
Registered DMF’s in USA & Canada.
Complies with requirements of JP, PhEur and USP/NF.
Available in a variety of sizes and colours.
Physical Stability Benefits Quali-V速 capsules have a lower moisture content, 4.0% to 6.0%, than gelatin capsules. They can be filled with many types of formulations: powders, pellets, tablets, semi-solids and non-aqueous liquids. Quali-V速 capsules maintain their physical stability when filled with hygroscopic materials or exposed to low humidity conditions. Quali-V速 capsules are particulary suited to use in dry powder inhalers because they can be cut and punctured cleanly without shedding particles. Moisture Content and Brittleness Brittleness Test (empty capsule)
Brittleness Test-Pressure Resistance Test (filled capsule)
Product Dissolution Quali-VÂŽ capsules have a patented formulation. Hypromellose solutions are converted into a gelling system by the addition of carrageenan and potassium chloride. They are manufactured by the same process as used for hard gelatin capsules. Carrageenan is soluble at low acid pHs giving good dissolution at a range of pH. Dissolution of acetaminophen in acid medium and water
Capsule fill formulation: Acetaminophen 50 mg Lactose 175 mg Croscarmellose 25 mg Fill weight: 250 mg (Size 1 capsule) Dissolution test method: Paddle at 50 rpm
Dissolution after ICH storage
Storage condition: 40 ÂşC, 75% RH, 6 months Capsule fill formulation: Acetaminophen 50 mg Lactose 175 mg Croscarmellose 25 mg Fill weight: 250 mg (Size 1 capsule) Dissolution test method: Paddle at 50 rpm
(Redrawn from data in S. Nagata et al., Poster, AAPS Annual Meeting, Denver, 2001)
Comparative Dissolution The composition of hypromellose capsules is dependent on the manufacturer: each has patented compositions. Quali-V® capsules are the only ones that use carrageenan. Carrageenan is the only gelling agent soluble at pH < 4. Quali-V® capsules made by our patented process have a solubility profile different to other manufacturers’ capsules. Hypromellose capsules from 3 different suppliers for the Japanese market were tested and the results are shown below. Dissolution of acetaminophen from hypromellose capsules in acid medium (pH 1.2)
Capsule fill formulation: Acetaminophen 60 mg Lactose 210 mg Croscarmellose 30 mg Fill weight: 300 mg (Size 0 capsule) Dissolution test method: Paddle at 50 rpm
Redrawn from data in Sakaeda, T., Nakamura, K., Tochio, S. and Nagata, S., Jpn J. Pharm. Health Care Sci., 28(6), 594-598 (2002)
In Vivo Performance In vivo studies have shown that Quali-V® and gelatin capsules have similar disintegration and release properties. The results showed that the two capsules have identical performances. Disintegration (Fasted state)1
Pharmacokinetic parameters (Fed state)2
Disintegration time (mean ± SD)
AUC 0-6h (µg/ml.h-1)
7 ± 4 min
6.0 ± 0.7
1.88 ± 0.49
9 ± 2 min
5.8 ± 2.4
2.25 ± 0.66
1) Tuleu et al, Poster AAPS meeting. Baltimore, 2004. 2) Tuleu et al, Poster AAPS meeting. Nashville, 2005.
Volunteers: 8 healthy males Capsules: size 0, filled with Acetaminophen 250 mg, Lactose 200 mg, Croscarmellose 50 mg
Property comparison with gelatin capsules Quali-V速
4 - 6%
13 - 16%
Lower than gelatin
Moisture content Water vapour permeability Cross linking Static charging Solubility in water at room temperature
Compatibility with liquid-fill excipients Excipients
Cotton seed oil
+ Compatible - Incompatible Redrawn from data in S. Nagata et al, CRS Annual Meeting, 485 (2002).
Qualicaps hard shell capsule products ●
Qualicaps® Gelatin capsules
Qualicaps® PEG/Gelatin capsules
Quali-V® hypromellose capsules
Quali-V®-I hypromellose capsules
Patents on Quali-V® Japan
JP Patents # 2.552.937
US Patents # 5.264.223
EP Patents # 0.592.130
JP Patents # 3.116.602
US Patents # 5.431.917
EP Patents # 0.714.656
JP Patents # 2.959.423
US Patents # 5.756.123
QUALICAPS GROUP Qualicaps Europe, S.A.
Qualicaps, Co., Ltd.
6505 Franz Warner Parkway Whitsett, NC 27377-9215 USA Tel.: +1 336 449 39 00 Fax: +1 336 449 33 33 e-mail: firstname.lastname@example.org
321-5, Ikezawacho Yamatokoriyama Nara 639-1032 Japan Tel.: +81 743 56 0651 Fax: +81 743 56 5113 e-mail: email@example.com
Calle de la Granja, 49 28108 Alcobendas, Madrid, Spain Tel.: +34 91 663 08 00 Fax: +34 91 663 08 30 e-mail: firstname.lastname@example.org
Quali-V. Hypromellose Capsules for Pharmaceuticals