22 July 2020 Tablets & Capsules
Enteric capsules manufactured with hydroxypro-
pyl methylcellulose acetate succinate (HPMCAS) and
HPMC can greatly simplify and accelerate prototype
development and rapid in vivo testing of products requir-
ing targeted delivery to the upper GI tract. Enteric cap-
sules eliminate the need to develop, scale-up, and validate
an enteric coating step; allow rapid screening and optimi-
zation of enteric performance; remove process variability
as a factor influencing enteric functionality; and obviate
the need for coating system preparation and application
steps during production.
A new era of functional development
Polymer science and engineering have opened a new
era of functional development that allows formulators to
select the optimal capsule for each API. HPMC capsules
not only offer mechanical stability for manufacturing,
they also offer excellent formulation stability that elimi-
nates compatibility issues and helps formulators acceler-
ate development timelines and provide both immediate-
and modified-release alternatives. T&C
References
1. https://www.kiplinger.com/slideshow/investing/
T027-S001-the-15-all-time-best-selling-prescription-
drugs/index.html
2. https://www.futuremarketinsights.com/reports/
oral-solid-dosage-pharmaceutical-formulation-market
3. https://www.pharmamanufacturing.com/articles/
2019/solid-dose-under-hyped-but-not-under-represented/
4. http://www.samedanltd.com/uploads/pdf/white_
paper/9908ae04a14145d662675ac2eb0e0e5c.pdf
5. https://www.contractpharma.com/issues/2018-
09-01/view_features/hpapi-market-trends/
6. https://www.ncbi.nlm.nih.gov/pubmed/21092714
7. https://www.ncbi.nlm.nih.gov/pubmed/21092714
8 . h t t p s : / / w w w . r e s e a r c h g a t e . n e t / p u b l i c a t i o n /
259578506_A_current_technology_for_modified_
release_drug_delivery_sytsem_Multiple-Unit_Pellet_
System_MUPS
9. https://www.researchgate.net/publication/30458
2250_Challenges_in_Protein_Formulation_Focused_on_
Extrusion-Spheronization_Process
10. https://www.researchgate.net/publication/31059
1360_Rationale_and_strategies_for_formulation_devel-
opment_of_oral_fixed_dose_combination_drug_products
11. https://www.ncbi.nlm.nih.gov/pubmed/19900518
12. https://www.biopharma-reporter.com/Article/
2019/03/18/Oral-delivery-of-biologics
Julien Lamps is product manager, capsules and health ingredi-
ents, at Lonza (201 316 9200, www.lonza.com). The company
manufactures Capsugel HPMC capsules, including Vcaps Plus
immediate-release capsules, which disintegrate and release their
contents independent of pH levels, and Vcaps Enteric capsules,
which offer an alternative to enteric coating as well as potential
product differentiation and life-cycle management.
tion techniques offer developers great utility and flexibil-
ity for delivering APIs in vivo and demonstrate more repro-
ducible pharmacokinetic (PK) and pharmacodynamic
(PD) behaviors—including for poorly soluble, potent
APIs—compared to traditional methods, resulting in
improved therapeutic performance in patients [8, 9, 10].
Manufacturers recognize hard capsules as one of the
best ways to deliver these pelletized API forms because of
their compatibility with the capsule shell, reduced formula-
tion times, and economical and efficient manufacturability.
HPMC for future formulations
Developers of both new and generic drug products
are increasingly interested in using HPMC capsules
because of their stability, versatility, and patient satisfac-
tion. Advancements in HPMC capsule technology are
leading to broader compatibility with the more complex
drug products currently in development and dissolu-
tion performance that is comparable to that of gelatin.
Early HPMC capsules included gelling agents that could
cause variability in the capsules' in vitro dissolution. New
HPMC capsule technologies eliminate the gelling agents
to provide ion- and pH-independent dissolution perfor-
mance in various dissolution media, as shown in Figure 1.
This feature addresses patient compliance concerns,
as it permits patients to take the medication under either
fasted or fed conditions. HPMC capsules have also been
optimized to stabilize formulation performance even in
low-humidity and low-moisture conditions. This offers
formulators greater flexibility and allows HPMC to be a
standard, reliable alternative to gelatin for the next gener-
ation of drug products [11].
Specific grades of HPMC are also ideal for targeting
API release in the gastrointestinal (GI) tract. Targeting
dispersion to occur along a specific point in the GI tract
is proving to be an effective delivery strategy for certain
therapeutics [12]. Depending on the capsule's film com-
position, this control can be relatively precise.
Figure 1
In vitro dissolution of caffeine in HPMC capsules
without gelling agent (Capsugel Vcaps Plus)
pH 1.2 USP
pH 6.8 USP
pH 6.8 JP2
Simulated milk fluid
PpH 1.2—2 g KCI/L
PpH 1.2—9 g KCI/L
Caffeine
dissolved
(%)
100
80
60
40
20
0
Time (minutes)
0 60 6 50 12 40 18 30 24
