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{TANDF_FPP}CMO/CMO_A_365060(NEW).3d (CMO) [First Proof]
Current Medical Research and Opinion
C213
Volume 25, Number 2 2008
Table 1. Branded and generic bisphosphonate tablets.
Drug product Company Lot Number
Alendronate Sodium Tablets, 70mg Merck & Co., Inc., Whitehouse Station, NJ, USA A¼U7687
Alendronate Sodium Tablets, USP, 70mg Teva Pharmaceuticals USA, Sellersville, PA A¼28731
B¼28349
C¼28859
Alendronate Sodium Tablets, USP, 70mg Distributed by: Watson Pharma Inc., A¼U7577
Corona, CA, USA Manufactured by:
Merck & Co., Inc., Whitehouse
Station, NJ, USA
Alendronate Sodium Tablets, USP, 70mg Barr Laboratories, Inc., Pomona, NY, USA A¼700885
B¼306450
C¼306522
Table 2. Mean onset time and mean complete disintegration time for the bisphosphonate tablets.
Company Mean onset of disintegration Mean disintegration time Mean disintegration meets
(standard deviation) seconds (standard deviation) seconds ODT’s guidance of530s
Merck A 1 (0) 53 (9) No
Teva A 1 (0) 60 (24) No
Teva B 1 (0) 27 (3) Yes
Teva C 1 (0) 72 (6) No
Watson A 1 (0) 108 (42) No
Barr A 1 (0) 10 (2) Yes
Barr B 1 (0) 9 (1) Yes
Barr C 1 (0) 9 (2) Yes
30s which is considered rapid for a compressed tablet that Pharmacopeia (USP) disintegration test method or alterna-
is designed to be swallowed. tive
15
. Thus, the rapid disintegration of the three Barr lots
consistentlyshowedbehaviorthatismoresimilartothatof
an ODT rather than a tablet designed to be swallowed
intact. The disintegration time of one Teva lots had a
Discussion
disintegration time of 27s which is similar to that of the
Today, disintegration is typically conducted as an in-pro-
ODTs. The in vitro disintegration time of 9–10s for the
cess test during tablet manufacture and not as a finished
Barr lots was extremely rapid for a tablet designed to be
product release test. The European Pharmacopoeia
14
states
swallowed intact. We believe this should be taken into
that for uncoated tablets the disintegration time limit is
consideration (or merits further study) as a potentially
15min unless otherwise justified and authorized. There
serious safety concern, as the patient labeling of bispho-
was never a specification for the onset of disintegration,
sphonate tablets warns against dissolving the tablet in the
as the time to complete disintegration is important from a
mouth (e.g., the prescribing information states that these
drug absorption perspective. Disintegration is a limits test
tablets should not be sucked or chewed because of the
because from a drug absorption perspective the faster the
potential for oropharyngeal ulceration
16
).
dosage form disintegrates the longer the time for subse-
A limitation of the study is that there is no in vitro/
quent dissolution and drug absorption. However, for a
in vivo correlation and there is no direct proof that the
drug like alendronate sodium, premature tablet disintegra-
tablets with a very rapid in vitro disintegration time will
tion in the mouth or the esophagus may be important with
disintegrate upon swallowing.
respect to the potential for oral or esophageal exposure. It
should also be noted that there is not a disintegration
standard for generic alendronic acid tablets in the USP
Conclusion
monograph
11
.
In the FDA Guidance for Industry, Orally The disintegration time of the generic alendronate sodium
Disintegrating Tablets (ODTs) it states that ‘ODTs be tablets available in the United States at the time of this
considered solid oral preparations that disintegrate rapidly study shows that some of the generics have rapid disinte-
in the oral cavity, with an in vitro disintegration time of gration times which are similar to the disintegration stan-
approximately 30s or less, when based on the United States dards (530s) for orally disintegrating tablets. The rapid
!
2009 Informa UK Ltd
www.cmrojournal.com In vitro disintegration studies of weekly generic alendronate sodium Dansereau et al.
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