Professional Documents
Culture Documents
PHARMACEUTICAL PRODUCTS
Reference:
Remington: Essentials of Pharmaceutics,
2013, Chapter 4, Stability of Pharmaceutical
Products
藥品安定性問題(實例一)
降脂妥膜衣錠10毫克
Atorin F.C. Tablet
10mg
回收分級 2
文號 105年12月2日 FDA藥字第1050050118號(食藥署藥品組)
發布日期 2016/12/15
發文日期 2016/12/02
產品 降脂妥膜衣錠10毫克 Atorin F.C. Tablet 10mg
許可證字號 衛署藥製字第049543號
批號 AEB011
許可證持有者 健O生物科技股份有限公司
原因
廠商主動通報,說明案內批號藥品於長期安定性試驗結果發現主成分含量低
於原核准規格下限
備註
主成分: ATORVASTATIN (CALCIUM)
適應症:高膽固醇血症、高三酸甘油脂血症。
藥品安定性問題(實例二)
"美O" 美胰持續性藥效錠
30公絲 MEZIDE MR
TABLETS 30MG
"LOTUS"
回收分級 2
文號 105年3月1日 FDA藥字第1050007040號(食藥署藥品組)
發布日期 2016/03/17
發文日期 2016/03/01
產品 "美O" 美胰持續性藥效錠30公絲 MEZIDE MR TABLETS 30MG "LOTUS"
許可證字號 衛署藥製字第046070號
批號 效期106年10月前所有批號
許可證持有者 美O化學製藥股份有限公司
原因 廠商主動通報,說明藥品因長期安定性試驗結果發現不純物含量超出原核准規格
備註 主成分:GLICLAZIDE MICRONIZED
適應症:經飲食及體重控制無法達到理想效果之成人非胰島素依賴型糖尿病 (TYPE
II)。
"
藥品安定性問題(實例三)
信O" 夜舒寧 膠囊 YES-
Z CAPSULES "SL"
回收分級 2
文號 105年12月13日 FDA藥字第1051413384號(食藥署藥品組)
發布日期 2016/12/22
發文日期 2016/12/13
產品 "信O" 夜舒寧 膠囊 YES-Z CAPSULES "SL"
許可證字號 衛署藥製字第047305號
批號 6160839
許可證持有者 信O藥品工業股份有限公司
原因
廠商主動通報,說明案內批號藥品於長期安定性試驗之溶離度試驗結果未符合原
核准規格
備註
主成分: DIPHENHYDRAMINE HCL
適應症:在成人短期使用以緩解入睡之困擾
Introduction
Definitions
e.g.:
Initiation Step
Propagation Step
(Chain Reaction)
Termination Step
Dehydroascorbic acid
Oil-Soluble antioxidants
a-Tocopherol (a form of Vit. E),
Butylated hydroxy toluene (BHT),
Propyl gallate, etc.
a-Tocopherol
Tocols:
R1 = R2 = R3 = H : Tocol
R1 = R2 = R3 = Me, known as a-tocopherol, is designated a-
tocopherol or 5,7,8-trimethyltocol.
propyl gallate
When minimum
reaction rate
constant
observed at the
acid side (pH < 7)
indicates that the
hydroxyl ion has
the stronger
catalytic effect
Hydrolysis of
acetylsalicylic
acid (Aspirin)
Methods to Prevent Hydrolysis
Ea
k A exp( ) (1)
RT
Ea: Arrhenius activation energy
(the difference between the average energy of reactive
molecules and the minimum energy required for reactants
to proceed to products)
Ea
exp( ) : the Boltzmann factor
RT
(which expresses the fraction of molecules having energies
greater than or equal to Ea )
k2 Ea T2 T1
ln ( ) (4)
k1 R T1T2
Plastic containers:
Polyethylene (PE), Polystyrene (PS),
Polyvinyl Chloride (PVC),
Polypropylene (PP), etc.
Blister packages
PVC, PVDC (Polyvinylidenechloride),
Aclar (Polychlorotrifluoroethylene,
PVC-CTFE)
Plastic composition, processing,
cleaning procedures, contacting media,
inks, adhesives, adsorption and
permeability affect the suitability of
plastic for pharmaceutical usage
Barrier Properties –
Moisture Vapor Transmission Rate (MVTR) in
g/m2/day @38°C/90%RH)
Cold Form Aluminium 0.00
Aclar ® 33C 0.08
Aclar ® UltRx2000 0.11 - 0.12
Aclar ® 22C 0.22
Aclar ® SupRx 900 0.23 - 0.26
Aclar ® 22A 0.31 - 0.34
PVC/80g PVDC 0.31
Aclar ® Rx160 0.39 - 0.42
Aclar ® 33C 0.42
PVC/60g PVDC 0.47 - 0.6
PVC/40g PVDC 0.7 - 0.75
PP 0.7 - 1.47
PVC 2.4 - 4
Aclar ® is a registered trade mark of Allied Signal
Metals
Q1A(R2)
Stability Test Conditions for Drug Substances of
General Case
*It is up to the applicant to decide whether long term stability studies are
performed at 25 ± 2°C/60% RH ± 5% RH or 30°C ± 2°C/65% RH ± 5% RH.
**If 30°C 2°C/65% RH 5% RH is the long-term condition, there is no
intermediate condition.
Stability Test Conditions for Drug substances
intended for storage in a refrigerator
*It is up to the applicant to decide whether long term stability studies are
performed at 25 ± 2°C/60% RH ± 5% RH or 30°C ± 2°C/65% RH ± 5%
RH.
**If 30°C 2°C/65% RH 5% RH is the long-term condition, there is no
intermediate condition.
Stability Test Conditions for Drug Products
intended for storage in a refrigerator
Stability
Sample Initiation
Testing Points Date
Study Storage Condition Storage
(months)
Positions
6.Particulate Matter
Shelf life Estimation with upper and lower acceptance criterion based on assay
at 5C/60%RH
115.00
110.00
105.00
Assay (%)
100.00
Regression line
95.00 Lower confidence limit
Upper confidence limit
90.00
85.00
80.00
0 5 10 15 20 25 30 35 40
Time point (months)
Example: Shelf-Life Prediction using
Degradation Test Result
4.50
Upper acceptance criterion
4.00
3.50
Imp E level (%)
3.00
2.00
Upper confidence limit
1.50
1.00
0.50
0.00
0 10 20 30 40 50 60
Time point (months)