Transcript Drugs

‫الرحيم‬
‫محن‬
‫الر‬
‫هللا‬
‫بسم‬
‫ّ‬
‫ّ‬
Rx
WHEN DO DRUGS BECOME A PART OF YOUR TREATMENT????
PAIN!!!!
INFECTION CONTROL
FEAR OR ANXIETY
ANTIVIRAL
ANTIFUNGAL
PRESCRIPTION VS
OVER THE COUNTER (OTC)
Definition and Format
A prescription is a
written, verbal, or
electronic order from a
practitioner or
designated agent to a
pharmacist for a
particular medication for
a specific patient.
Prescription Writing
 The prescription is one of the most important therapeutic
transactions between physician and patient.
 The art of prescription writing is an ancient inheritance.
 The ancients started their prescription with an appeal to
the gods for its success.
‫هوالشافی‬
 The ancient symbol, Rx, signifying the appeal, was
established centuries ago and has been carried down to the
present time.
11
Prescription Writing
 To avoid undesirable and/or serious effects on the
patient, both physician and pharmacist must render
the highest of professional services.
 Accurate diagnosis; proper selection of medication,
dosage form and route of administration; proper size
and timing of dose; precise dispensing; accurate
labeling; and correct packaging all must be provided.
12
Writing Prescriptions
Who can write a Rx?
 Practitioners
 Physicians,
veterinarians, dentists,
podiatrists
 Mid-level practitioners
 nurse practitioners,
physician assistants,
optometrists,
pharmacists
Definition and Format
Sample of Generic Hospital
Prescription
Sample of Physician Specific
Prescription
Contents of the Prescription
 All prescriptions should have the following essential elements:
 Date of the order
 Patient Name and Address
 If the drug is prescribed for an animal, the species of the






animal
Name of the drug
Strength of the drug
Quantity of the drug
Directions for use
Intended use of the drug, unless practitioner feels indication
is not in best interest of patient
Practitioner Name, Address, Telephone number
Parts of prescriptions
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







For Arthur H. Recipe
Take thou
Potassium Acetate of.............................one drachm.
Of Solution of Acetate of Ammonium........three and a half
drachms.
Of Spirits of Nitrous Ether...........................two drachms.
Of Infusion of Buchu (a quantity sufficient) up to four
ounces.........
Signa: -Mix. Let a mixture be made.
Label: -One drachm three times a day after meals.
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Parts of prescriptions
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Form of the Written Prescription
 A prescription consists of the superscription, the
inscription, the subscription, the signa, and the name
of the prescriber
1- Superscription
 The date when the prescription order is written; the
name, address and age of the patient; and the symbol
Rx (an abbreviation for "recipe," the Latin for "take")
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Form of the Written Prescription
2- Inscription
 The body of the prescription, containing the name and
amount or strength of each ingredient.
3- Subscription
 The directions to the pharmacist, usually consisting of
a short sentence such as: "make a solution," "mix and
place into 10 capsules," or "dispense 10 tablets."
20
Form of the Written Prescription
4- Signature
 From the Latin "signa," meaning "write," "make," or
"label," this sections contains the directions to the
patient.
 These should always be written in English; however,
physicians continue to insert Latin abbreviations, e.g. "1
cap t.i.d. pc," which the pharmacist translates into
English, "take one capsule three times daily after meals."
Since the pharmacist always writes the label in English,
the use of such abbreviations or symbols should be
discouraged.
21
Form of the Written Prescription
Follow: 4- Signature
 The instruction, "take as directed," is not satisfactory
and should be avoided.
 The directions to the patient should include a
reminder of the intended purpose of the medication
by including such phrases as "for pain," "for relief of
headache," or "to relieve itching"
22
Form of the Written Prescription
5- Labeling
 When the physician wants his patient to know the
name of the drug, the box on the prescription form
marked "label" should be checked.
6- Refills
 The physician should designate the number of refills
he wishes the patient to have.
23
Proprietary vs. Non-Proprietary
("Generic") Prescriptions
 In recent years, some hospitals and private physicians
are indicating on the prescription their willingness or
desire that the pharmacist dispense a non-proprietary
or "generic-named" preparation instead of the trade
name item written on the prescription. Some have a
box on the prescription designated "N.P.P." In this way,
the pharmacist can use a form of the drug which may
be less expensive to the patient.
24
Types of Drugs
 Legend Drugs: These drugs may not be dispensed by
a pharmacist without a prescription from a physician.
 Controlled Drugs: In addition to requiring a
prescription, these drugs require additional safeguards
for storage. Refills are also limited.
 Over-the-Counter (OTC) Drugs: These drugs do not
require a prescription.
25
Controlled Substances
 Schedules of Controlled Drugs: These drugs are divided
into five schedules.
 Drugs can be scheduled, unscheduled, or moved from one
schedule to another as the need arises.
Schedule I
 Drugs in this schedule have a high abuse potential
(narcotic and hallucination effects).
Examples are heroin, marijuana.
27
Controlled Substances
Schedule II
 Drugs in this schedule have a high abuse potential with
severe psychic or physical dependence liability. Included
are certain narcotic analgesics, stimulants, and depressant
drugs. Examples are opium, morphine, codeine,
hydromorphone, methadone, meperidine, oxycodone,
anileridine, cocaine, amphetamine, methamphetamine,
phenmetrazine, methylphenidate, amobarbital,
pentobarbital, secobarbital, methaqualone, and
phencyclidine.
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Controlled Substances
Schedule III
 Drugs in this schedule have an abuse potential less than
those in Schedules I and II and include compounds
containing limited quantities of certain narcotic analgesic
drugs, and other drugs such as barbiturates, glutethimide,
methyprylon, and chlorphentemine. Any suppository
dosage form containing amobarbital, secobarbital, or
pentobarbital is in this schedule.
29
Controlled Substances
Schedule IV
 Drugs in this schedule have an abuse potential less
than those listed in Schedule III and include such
drugs as barbital, phenobarbital, chloral hydrate,
ethchlorvynol, meprobabmate, chlordizepoxide,
diazepam, oxazepam, chloroazepate, flurazepam, etc.
30
Controlled Substances
Schedule V
 Drugs in this schedule have an abuse potential less
than those listed in Schedule IV and consist primarily
of preparations containing limited quantities of
certain narcotic analgesic drugs used for antitussive
and antidiarrheal purposes.
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Requirements for Prescriptions
Written for Controlled Substances
 Required Information on the Prescription
 Must be dated and signed on the day it is issued. Must
have the full name and address of the patient.
 Must have the name, address, and registration number
of the physician.
 May be prepared by the secretary, but must be signed
by the physician.
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Refilling Prescriptions for
Controlled Substances
 Refills for Schedule II drugs are not permitted.
 Refills for Schedule III, IV, and V drugs are permitted
if the number of refills is indicated on the
prescription. However, the prescription order may be
renewed only up to five times within six months after
the date of issue. After five renewals or after six
months a new prescription order is required.
33
Classification of pharmaceutical dosage forms according
to the route of administration
 for systemic administration






Peroral (p.o)
Sublingual (S.L) and buccal.
Rectal
Parenteral
Transdermal
Inhalation
34
Classification of pharmaceutical dosage forms according
to the route of administration
 for local administration



Topical (on the skin or mucosa)
Into/onto - the eye, nose, ear
- the oral cavity
- the vagina, rectum
- the brochi
- the skin
Local parenteral (viz Parenteral above)
Oral (local effect within GIT; antacids, adsorbents)
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% exhibiting
desired
effect
EFFECT OF ROUTE OF
ADMINISTRATION ON XENOBIOTIC
DISPOSITION AND ACTION
70
60
50
40
30
20
10
0
oral
im, thigh
im, buttock
20
40
60
90
Time (min)
Influence of route of administration on the clinical action of diazepam.
.
Data from Assaf et al. Anaesthesia 30:152-158, 1975
36
From: http://www.drugdeliverytech.com/cgi-bin/articles.cgi?idArticle=128
37
I. PARENTERAL
A. Intravenous
Advantages: •rapid achievement of concentration
•precise delivery of dosage
•easy to titrate dose
Disadvantages: •high initial concentration - toxicity
•invasive - risk of infection
•requires a certain level of skill
38
There are some preparations that, due to
poor solubility of the drug, contain
solvents that may produce rate-related
toxicity. For example, diazepam injection
USP contains 40% propylene glycol,
among other solvents. Injected rapidly,
diazepam may induce hypotension or
arrhythmias. For this reason, it is
recommended that IV injections of
diazepam be given no more rapidly than 1
mL/min.
39
While it is generally viewed that 100% of drug
administered intravenously is bioavailable,
prodrug administration via this route may result
in less than 100% bioavailability.
Drug
Chloramphenicol succinate
Dexamethasone phosphate
Dexamethasone sulfate
Prednisolone phosphate
Prednisolone phthalate
Bioavailability
~70%
~90%
~40%
~90%
~50%
Comparative bioavailability of IV chloramphenicol
succinate and oral chloramphencol palmitate
IV
PO
Mean C90-min (mg/L)
22.6
27.5
Mean AUC (mg/hr/L)
78
110
40
From: Kauffman R et al. J Pediatr 99:963, 1981.
I. PARENTERAL
A. Intravenous
B. Intra-arterial
C. Intramuscular
Injection sites for IM
administration
From: Fundamentals of Nursing, 4th edition,
Lippincoitt, Williams & Wilkins
41
Advantages: •less skill necessary for administration
•can be used to administer oily vehicles
•prompt absorption from aqueous sol’n
Disadvantages: •painful
•cannot be used in presence of
abnormal clotting time
•drug may ppt at the site of
administration
•variability in bioavailability
Z-track method for IM injections
42
Reproduced from: Rowland M, Tozer TN. Clinical Pharmacokinetics: Concepts and Applications, 3rd
edition, 1994, p. 39.
43
Blood concentration of chlordiazepoxide after oral () or intramuscular (o)
administration of 50 mg. Reproduced from Greenblatt DJ, et al. NEJM
29:1116-1118, 1974.
44
Plasma phenytoin concentrations in patients during
oral and IM administration
IM
oral
Phenytoin Concentration
(mcg/mL)
oral
20
40
60
Days
Redrawn from: Wilder et al. Clin Pharmacol Ther 16:507-513, 1974.
45
Deltoid
Vastus Lateralis
18
16
14
VEBs/min
12
10
8
6
4
2
0
0
2
4
6
TIME (hr)
Effect of administration site on lidocaine suppression
of arrhythmias after intramuscular injection. Data from:
Swartz et al. Clin Pharmacol Ther 14:77, 1974.
46
Peak plasma cephradine concentrations
(mcg/mL) after IM administration to
different sites in male and female subjects
Injection site
Males
deltoid
vastus lateralis
gluteus maximus
11.7
9.8
11.1
Females
10.2
9.4
4.3
Data from: Vukovich et al. Clin Pharmacol Ther 18:215, 1975.
47
Deltoid Fat Pad Thickness in Men and Women, and
Implications for Needles Length for Immunizations.
Data from: Poland et al JAMA 277:1709-1711, 1997.
Women
Deltoid fat pad thickness (mm) 11.7
Deltoid skin-fold thickness
34.7
Percent in whom a standard
16 mm needle would not reach
5 mm into muscle
48.4
Men
8.3
17.2
17.0
Needle length recommendation based on above data:
All men: 25 mm; women <60 kg: 16 mm; women 60-90 kg: 25 mm;
women >90 kg: 38 mm
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D. Subcutaneous
Sites for SC injection
Advantages:
•prompt absorption from aqueous solns
•little training necessary
•avoid harsh GI tract environment
•can be used for suspensions
Disadvantages:
•cannot be used for large volumes
•potential pain and tissue damage
•variability in absorption from various sites
49
Disappearance of I125-insulin from subcutaneous injection
at different sites. Data from Koivisto & Felig, Ann Intern Med 92:59, 1980.
110
% of initial counts
100
Abdomen
Arm
Leg
90
80
70
60
50
40
0
30
60
90
120
Time (minutes)
50
Postprandial rise in plasma glucose after insulin injection at
different sites. Data from: Koivisto & Felig, Ann Intern Med 92:59-61, 1980.
Abdomen
Arm
Leg
Rise in plasma glucose (mg/dl)
120
100
80
60
40
20
0
0
50
100
150
Time (min)
51
Effect of exposure to a sauna bath on insulin absorption after subcutaneous adminsitration.
From Koivisto VA. Br Med J 280:1411, 1980.
52
Aradigm Intraject®
NFI device in
protein delivery
Reproduced from: http://www.drugdeliverytech.com/cgibin/articles.cgi?idArticle=178
53
Reproduced from: http://www.drugdeliverytech.com/cgibin/articles.cgi?idArticle=178
54
Reproduced from: http://www.drugdeliverytech.com/cgibin/articles.cgi?idArticle=178
55
II. ENTERAL
Reproduced from: Rowland M, Tozer TN.
Clincal Pharmacokinetics – Concepts and
Applications, 3rd edition, Williams & Wilkins,
1995, p. 12.
56
A. ORAL
Advantages:
•Convenient (storage, portability, pre-measured dose)
•economical
•non-invasive, often safer route
•requires no special training
Disadvantages:
•drug delivery is often erratic and incomplete
•highly dependent upon patient compliance
•increased sources of drug-drug and drug-nutrient
interactions
•many drugs degrade in GI environment
•exposes drugs to first-pass effect
57
Effect of varying
volumes of water
on oral drug
absorption
From: Shargel L, Yu ABC.
Applied Biopharmaceutics
and Pharmacokinetics, 4th
edition, 1999, p. 119.
58
59
From: Benet LZ, Cummins CL. The drug-efflux-metabolism alliance: biochemical aspects. Adv Drug Deliv Rev 50:S3-S11, 2001.
60
B. Sublingual/Buccal
Advantages:
•rapid onset
•avoids first-pass effect
•ability to swallow is not required
Disadvantages:
•few drugs adequately absorbed
•patients must avoid swallowing
•compliance difficult
61
Isosorbide concentrations after a 5 mg oral or sublingual dose.
Isosorbide Conc (ng/ml)
Data from: Assinder et al. J Pharm Sci 66:775, 1977.
14
12
10
8
6
Sublingual
4
2
Oral
0
5
15
30
45
60
90
120
Time (min)
62
Effect of buffer pH on the buccal absorption of nicotine
% Absorbed
Adapted from: Svensson CK. Clin Pharmacokinet 12:30, 1987.
35
30
25
20
15
10
5
0
5
5.5
6
6.5
7
7.5
8
9
Buffer pH
63
http://www.novadel.com/
http://www.vitamist.com/
64
C. Rectal
Advantages:
•can be used when patients cannot take oral meds
•good option in pediatric population
•may avoid first-pass metabolism
Disadvantages:
•absorption from solid dosage forms erratic
•many patients have an aversion to rectal administration
65
66
From: Washington N, Washington C, Wilson CG. Physiological Pharmaceutics, 2nd edition, 2001, Taylor & Francis
Availability (%) of lidocaine after IV, oral and
rectal administration
Data from: de Boer et al. Clin Pharmacol Ther 26:701-709, 1979.
Subject
1
2
3
4
5
6
IV
Oral
Rectal
100
100
100
100
100
100
100
17
49
53
13
35
37
34
59
87
80
31
100
59
71
67
68
From: Washington N, Washington C, Wilson CG. Physiological Pharmaceutics, 2nd edition, 2001, Taylor & Francis
III. PULMONARY
Pharmacologic Agents Administered
via Inhalation
For Systemic Effects For Local Effect
pentamidine
halothane
ergotamine
methoxyflurane
enflurane
isoflurane
nitrous oxide
beclomethasone
terbutaline
cromolyn
metaproterenol
albuterol
pirbuterol
69
III. PULMONARY
Advantages:
•easy to titrate dose
•rapid onset
•for local effect, maximize benefit/minimize
side effects
Disadvantages:
•takes significant degree of coordination
•patients with lung disease may be able to
inhale adequately
•variability in delivery
70
Reproduced from: Pliss et al. Ann Emerg Med 10:353-355, 1981.
71
Forms of pulmonary delivery
• Metered dose inhaler
• Dry powder inhalers
• Nebulizer
72
Metered Dose Inhaler (MDI)
• Propellant based
• Most common delivery system in
tx of asthma
• Chlorofluorocarbons vs
hydrofluoroalkanes
• Products contain a surfactant or
dispersing agent (e.g., oleic
acid)
• Co-solvent (e.g., ethanol) –
especially needed with use of
HFA
• Flavoring agent (e.g., menthol)
typical MDI
73
Techniques for use of MDI devices:
Two finger width
from mouth
Patient must
coordinate
inhalation and
actuation of
device
Use of space or
holding chamber
Placement of
inhaler in mouth
(not for use with
steroids)
74
Dry Powder Inhalers (DPI)
• Breath activated
• Micronized drug particles
blended with an excipient
(e.g., glucose or lactose)
• Physical properties of drug
and excipient critical (i.e.,
particle size, shape, surface
morphology, etc)
75
Diskus
76
Nebulizer
• Device produces small droplets from a
suspension or solution through an air jet
or ultrasonic atomization (quieter, but
more expensive)
77
Factors that influence deposition
of particles in the lung
• Physicochemical properties
• Formulation
• Technique (depth of inspiration,
pause prior to exhalation,
coordination of inhalation)
• Pulmonary disease
78
79
From: Washington N, Washington C, Wilson CG. Physiological Pharmaceutics, 2nd edition, 2001, Taylor & Francis
80
From: Washington N, Washington C, Wilson CG. Physiological Pharmaceutics, 2nd edition, 2001, Taylor & Francis
IV. TOPICAL
A. Percutaneous
81
Advantages:
•when used for local effects, minimize
systemic side effects
•for systemic use, may mimic IV infusion (i.e.,
zero-order)
•avoid first-pass effect
Disadvantages:
•cosmetically unappealing
•may display erratic absorption
82
Reproduced from: Brown L, Langer R. Ann Rev Med 39:221-229, 1988.
83
Factors that influence
percutaneous absorption
•
•
•
•
•
Site of application
Condition of skin
Hydration of skin
Temperature
Vehicle
84
Change in Mean SBP (mmHg)
Effect of Nitroglycerin on Systolic Blood Pressure When
Adminisitered Percutaneously at Different Sites
5
0
-5 0
50
100
150
200
-10
Forehead
Chest
Ankle
-15
Adapted from: Hansen et al. Heart & Lung 8:716-720, 1979
85
Plasma Nicotine Concentration (ng/ml)
30
25
C o n tro l
S a u n a b a th
20
15
10
5
S a u n a b a th
0
0
1
T im e (h o u r s)
2
3
Plasma nicotine concentration in subjects wearing nicotine patches exposed
(squares) or not exposed (diamonds) to three 10 min sauna bath sessions
over 1 hr. Figure adapted from: Vanakoski et al Clin Pharmacol Ther 60:308-315, 1996.
86
B. Ocular
From: Fundamentals of Nursing, 4th edition, Lippincoitt, Williams & Wilkins
87
Types of Ophthalmic
Preparations
•
•
•
•
•
Solutions
Suspensions
Ointments
Inserts
Intraocular solutions
88
Factors that influence ocular drug
retention
• Technique of application
89
Factors that influence ocular drug
retention
•
•
•
•
Technique of application
Drop size (volume)
Formulation (tonicity, viscosity)
pH of solution
90
Pupillary diameter, mm
Effect of drop size on effect and systemic
availability of phenylephrine in infants
5
Systemic (plasma)
concentration range
(ng/mL)
4
3
8 uL: 0 – 1.8
2
30 uL: 0.6 – 3.2
1
0
8 uL
30 uL
Phenylephrine 2.5% drop size
From: Lynch et al. Arch Ophthamol 105:1364, 1987)
91
Timolol, ng/ml
Systemic Absorption of Timolol
1 hour after instillation
1.5
1
0.5
0
No NLO
NLO
Eyelid
Closure
Adapted from Zimmerman et al. Arch Opthamol 102:551, 1984.
92
Reproduced from: Ellis et al. J Pharm Sci 81:219-220, 1992.
93
Change in pupillary diameter, mm
3
2.5
2
1.5
1
0.5
0
A
B
C
Treatments:
A – 25 mL pilocarpine
B – 25 mL pilocarpine followed 2-min later by saline drop
C – 25 mL pilocarpine followed 30-sec later by saline drop
94
From: Shell JW. Surv Ophthamol 26:207, 1982
Steroid Concentration (mg/ml)
Aqueous humor concentration of
fluorometholone following
various preparations
0.1
0.01
0.05 mL Saturated Solution
0.05 mL 0.1% suspension
50 mg dose of ointment
0.001
100
200
300
400
Time, min
From: Sieg JW, Robinson JR. J Pharm Sci 64:931, 1975
95
C. Nasal
•Historically utilized only for local effects
•Growing number of compounds
administered intranasally that are
intended for systemic effects
•For drugs that are destroyed in the GI
environment (or first-pass effect)
•As an alternative to intravenous
administration – better safety and patient
acceptance
Drugs include anticonvulsants (midazolam),
narcotic antagonists (naloxone), peptides
(calcitonin, insulin), and smoking cessation agents
96
(nicotine)
Intranasal naloxone
administration in
the field by
paramedics
Mucosal Atomizer Device
From: www.ofmaa.org
97
Nicotine Concentration (nmole/ml)
180
160
140
120
C ig a r e tte
100
N a s a l S o lu tio n
C h e w in g G u m
80
60
40
20
0
0
10
20
30
40
50
60
T im e (m in u te s )
N a s a l s o l'n
N ic o tin e g u m
C ig a r e tte
Comparison of nicotine concentrations after administration via smoking,
chewing gum, or use of a nasal solution. Redrawn from Russell et al. Br Med J 286:683, 1983
98
Factors that influence absorption
from the nasal mucosa
•
•
•
•
•
pH
Concentration
Molecular weight
Formulation
Condition of nasal mucosa
99
100
From: Washington N, Washington C, Wilson CG. Physiological Pharmaceutics, 2nd edition, 2001, Taylor & Francis
Reproduced from: Lunell E, et al. Eur J Clin Pharmacol 48:71, 1995.
101
Nasal to brain delivery of drugs
102
Figure from: http://www.drugdeliverytech.com/cgi-bin/articles.cgi?idArticle=61
$65.55
Which route is best?
$143.11
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$41.71
103
Route for administration
-Time until effect









intravenous
30-60 seconds
intraosseous
30-60 seconds
Endotracheal
2-3 minutes
inhalation
2-3 minutes
sublingual
3-5 minutes
intramuscular
10-20 minutes
subcutaneous
15-30 minutes
rectal
5-30 minutes
ingestion
30-90 minutes
transdermal (topical) variable (minutes to hours)
Comparison of parenteral
routes
Drug Product Performance
Parameters
Multiphasic Drug
Elimination
pentobarbital plasma concentration versus time illustrating
the multiphasic distribution pattern
Absorption and First-Pass
Effect
Extra absorption of salicylamide at higher doses.
The green dots represent results after a 1 g dose and the
red dots represent results after a 2 g dose
Absorption versus Particle
Size
plasma phenacetin versus time curve after oral
administration of 1.5 g in various suspension dosage forms
Absorption of Different Salt Forms
plasma penicillin concentration versus time curve after oral
administration of various salts. dependent on the solubility
Effect of Absorption Rate Constant
C
MTC
MEC
t
‘The Therapeutic Range’
Bioavailability




Bioavailability [Shargel and Yu, 1985] indicates
a measurement of the rate and extent (amount)
of therapeutically active drug which reaches the
general circulation.
Studies, which are carried out to evaluate
different dosage forms and might compare:
two (or more) dosage forms made by two (or
more) different manufacturers,
e.g. innovator versus generic.
Bioequivalence
 Bioequivalence study looking for similarity of F and ka
values between products.
 one type of dosage form with another, e.g. tablet versus
intravenous dosage form or regular tablet with
sustained release tablet.
CONCENTRATION
EFFECT
TIME
DOSE
D
PK
C
PD
E
New
source of
an
excipient
Types of variation?
New site of
manufacture
New
manufacturing
equipment
Extension
of shelf
life
Removal of
offensive
Change
of
container
material
New
batch
size
excipients