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Dosage - Chapter 8

Dosage - Chapter 8

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Published by Kim Manlangit

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Published by: Kim Manlangit on Aug 08, 2010
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1
 Name:Pharmaceutical DosageChapter 8: TabletsTablets
y
 
S
olid dosage forms prepared by compression with the aid of suitable pharmaceutical excipients
y
 
V
ary in: size, shape, weight, hardness, thickness, disintegrationand dissolution characteristics and in other aspects, depending ontheir intended use and method of manufacture
y
 
F
or oral administration of drugs, others sublingually, buccally or vaginally, with features mist applicable to the routes of administration
y
 
S
ome are scored allow to be easily broken into two or more partsCharacteristics of Ideal Tablets
y
 
F
ree of defects: chips, cracks, discoloration and contamination
y
 
S
trength to withstand mechanical stresses of production
y
 
S
table
y
 
elease medicinal agents in a predictable and reproducible manner Types of Tablets
y
 
Compressed tablets (CT)
 
 No special coating manufactured with tablet machinewith great pressure or compacting the powdered or granulated tableting material
 
Contain pharmaceutical adjuncts: diluents or filters, binders or adhesives, disintegrants, antidiarrheals, etc
y
 
M
ultiple compressed tablets (
M
CT)
 
Prepared by: subjecting the fill material to more than asingle compression
 
esult: multiple layer or a tablet within a tablet, inner tablet (core) and outer portion (shell)
y
 
S
ugarcoated tablets (
S
CT)
 
Compressed tablets with colored or uncoloured sugar layer:
o
 
Protects the enclosed drug from theenvironment
o
 
Provides a barrier to objectionable taste of odor 
o
 
E
nhances the appearance
o
 
Permits imprinting of identifyingmanufacturer¶s information
 
Disadvantages:
o
 
Time and expertise needed in the coating process
o
 
Increased shipping cost: 50% larger andheavier than uncoated
y
 
F
ilm-coated tablets (
F
CT)
 
A
re compressed tablets coated with a thin layer of  polymer (cellulose acetate phthalate) capable of forming a skin like film
 
A
dvantage: more durable, less bulky and less timeconsuming to apply than sugar-coating
y
 
G
elatin-coated tablets (
G
CT)
 
Innovation product: gelcap, a capsule shapedcompressed tablet
 
A
llows the coated product to be about 1/3 smaller thana capsule filled with an equivalent amount of powder 
 
M
ore case in swallowing and more tamper evident
y
 
E
nteric-coated tablets (
E
CT)
 
H
ave delayed release features
 
Pass unchanged through the stomach to the intestines(tablet disintegrate and allow drug dissolution andabsorption and/ or effect)
 
 Needed when drug substance:
 
Destroyed by gastric acid
 
Irritating to the gastric mucosa
 
B
y-pass the stomach enhances the drugabsorption in the intestines
y
 
Tablets used in the oral cavity:
 
B
uccal and sublingual tablets
 
F
lat oval tablets to be dissolved in the buccal pouch (buccal tablet) or beneath the tongue(sublingual tablet)
 
F
or oral absorption of drugs destroyed bygastric acid or poorly absorbed in the
G
IT
 
L
ozenges or troches
 
Disc-shaped solid forms in a hard candy or sugar base
 
Dissolved slowly for localized effect or systemic effect
y
 
Chewable tablets
 
Pleasant tasting have smooth, rapid disintegration(chewed or allowed to dissolve in the mouth)
 
H
ave a creamy base, specially flavoured and coloredmannitol
 
Prepared by compression or wet granulation
 
X
ylitol: may be used in the preparation of sugar-0freechewable tablets
y
 
E
ffervescent tablets
 
Prepared by compressing granular effervescent saltsthat release gas when in contact with water 
y
 
M
olded tablet triturate (
M
IT)
 
M
ay be prepared by molding rather than bycompression
 
esultant tablets are very soft and soluble and aredesigned for rapid dissolution
 
The mold is made of hard rubber, hard plastic or metal
 
H
as 2 parts: the upper part (die) and the mower part(flat punches)
 
B
ase is a mixture of finely powdered lactose with or without portion of powdered sucrose
y
 
Compressed tablet triturate (CTT)
 
S
mall, usually cylindrical, molded or compressedtablets (limited pressure) containing small amounts of usually potent drugs
 
S
ucrose and lactose are used for diluents
 
Declined its use
y
 
H
ypodermic tablets (
H.
T
.
)
 
U
sed by physicians for extemporaneous preparation of  parenteral solutions rendered sterile
 
Dissolved in suitable vehicle sterility attained, and theinjection performed
 
E
asily carried in the physician¶s medicine bag andinjections prepared to meet the needs of the individual patients
 
A
dvent of prefabricated injectable products anddisposable syringes, declined its use
y
 
Dispensing tablets (D
.
T
.
)
 
Compounding tablets
 
U
sed by the pharmacist to compound prescription andnot dispensed to patients
 
Contains large amount of potent substances enablingthe pharmacist to obtain pre-measured amounts
 
F
or compounding multiple dosage units
y
 
Immediate-release tablets (I
.R.
)
 
Disintegrate and release their medication with
 
 No special rate-controlling features, such as specialcoating and other techniques
y
 
Instant disintegrating or dissolving tablets
 
Disintegrate or dissolve in the mouth within 10 secondsto 1 minute
 
M
ethod of instant-release or disintegrating tablets
 
L
yophilized foam (lyophilization techniques)
o
 
Prepared by foaming a mixture of gelatin,sugar, drug and other components and pouring the foam into a mold
o
 
Z
ydis: 1
st
entry into the
TD field
 
2
 
o
 
Disadvantage: taste masking can be a problem since the drug is incorporatedduring the formation of the tablet
 
S
oft direct compression
o
 
U
sing standard tableting technology willenhance fluid uptake and tabletdisintegration and dissolution
o
 
E
xample product: Dimetapp: ND orallydisintegrating tablet
 
U
se of water-soluble excipients
o
 
Designed to ³wick´ water into thetablet for rapid disintegration
 
L
arge scale lyophilizers
o
 
W
ater is removed from temperaturesensitive or unstable product solutionsand transformed to stable dry productswith its original properties
y
 
E
xtended-release tablets (
E.R.
) or controlled release (C
.R.
) tablets
 
A
re designed to release their medication in a predetermined manner over an extended period
y
 
V
aginal tablets or inserts
 
U
ncoated bullet-shaped or ovoid tablets inserted intothe vagina for local effect
 
Contain antibacterials (against
H
emophilia vaginitis)and antifungals (against Candida albicans)Compressed Tablets
y
 
Physical features of compresses tablets are well known: oblong,round or unique in shape, thick or thin; large or small in diameter;flat or convex; unscored or scored in halves, thirds or quadrant
y
 
The less concave the punch the more flat the resulting tablets
y
 
Punches with raised impressions will have recessed impressions onthe tablets
y
 
Tablet diameters and shapes are determined by the die and punchesused in compressionTablet
W
eight and
U
S
P
W
eight
V
ariation Test
y
 
Q
uantity of ill in die of a tablet press determines the weight of thetabletContent
U
niformity
y
 
A
mount of active ingredient in each dosage unit lies within: 85%to 115% of the label claim is less than 6% standard deviationTablet Thickness
y
 
Determined by the diameter of the die, amount of fill permitted toenter the die, the compaction characteristics of the fill material, andthe force or pressure applied during compression
Q
uality
S
tandards and Compendial
equirements
y
 
Tablet thickness
 
The greater the pressure, the harder the tablet
 
H
ard enough to resist breaking (normal handling) andyet soft enough to disintegrate (after swallowing)
 
M
inimum requirement for a satisfactory tablet: force of 4 kg (hardness tester)
y
 
Tablet hardness and friability
 
A
tablet¶s durability or tendency to crumble: the use of a friabilator 
 
A
cceptable: maximum weight loss of not more than 1%of the weight of the tablets
y
 
Tablet disintegration
 
The basket rack assembly is raised and lowered in theimmersion fluid at 29-32 cycle per minute, the wirescreen always below the level of the fluid
y
 
Tablet dissolution
 
In vitro dissolution testing of solid dosage forms isimportant:
 
G
uides formulation and productdevelopment toward product optimization
 
M
anufacturing monitored: a component of the overall quality assurance program
 
E
nsures bioequivalence from batch to batch
 
A
requirement for regulatory approval of marketing for products registered with the
F
D
A
and regulatory agencies of other countries
F
actors
A
ffecting Tablet Disintegration and Dissolution
y
 
Particle size of the drug substance
y
 
S
olubility and hygroscopicity of the formulation
y
 
Type and concentration of the disintegrant, binder and lubricant
y
 
M
anufacturing, particularly the compactness of the granulation andcompression force used in tableting
A
 pparatus
A
ssembly
U
sed for Drug
elease and Dissolution Testing
y
 
U
S
P apparatus 1 and 2 consists of the following:
 
V
ariable: speed stirrer motor 
 
Cylindrical stainless steel basket on a stirrer shaft (
U
S
P
A
 pparatus 1) or a paddle as a stirring element (
U
S
P
A
 pparatus 2)
 
1
L
vessel of glass or other inert transparent materialfitted with a cover having a center port for the shaft of the stirrer and 3 additional ports, two for removal of samples and one for the thermometer 
 
W
ater bathPooled dissolution testing
y
 
The tablet must meet the stated monograph requirement for rate of dissolution
y
 
S
teps:
 
A
volume of the dissolution medium is placed in thevessel and allowed to come to 37
o
C + 0
.
5
o
C
 
S
tirrer rotated at the speed specified at stated intervalsamples of the medium are withdrawn for chemicalanalysis of the proportion of drug dissolved
S
uccessful in
V
ivo in
V
itro Correlation (I
V
I
V
C)
y
 
elates combination of drug¶s solubility (high or low) and itsintestinal permeability (high or low)
y
 
Categories:
 
H
igh solubility and high permeability: dissolution rateis slower than the rate of gastric emptying
 
L
ow solubility and high permeability: dissolution may be rate-limiting step for absorption
 
H
igh solubility and low permeability: permeability isthe rate-controlling step, and only a limited I
V
I
V
C may be possible
 
L
ow solubility and low permeability: significant problems are likely for oral drug delivery
M
ethod of Compressed Tablet
M
anufacture
y
 
W
et
G
ranulation
 
W
idely employed method for production of compressedtablets
 
A
dvantages:
 
Traditional method for many drugs since itimparts compressibility
 
U
seful for fluffy powder (don¶t flow or mixwell)
 
Thermolabile compounds
 
3
 
 
Powders generating static change
 
W
ide range of available excipients
 
Disadvantages:
 
S
ome drugs are moisture sensate(esterhydrolysis) or heat sensitive
 
B
inder needed in the excipient mix
 
M
ultiple steps, lots of equipment- time,space, money, personnel, material loss
 
E
xpertise required
 
S
teps:
 
W
eighing and blending
o
 
Diluents or filler, anddisintegrating agent are mixed bymechanical powder blender or mixer until uniform
 
Preparing the damp mass
o
 
A
liquid blender is added to the powder mixture to facilitateadhesion of the powder particles
 
S
creening the damp mass into pellets or granules
o
 
The wet mass is pressed througha screen to prepare the granules
 
Drying the granulation
o
 
G
ranules may be dried in thethermostatically controlled ovensthat constantly record the time,temperature, and humidity
 
S
izing the granulation by drying screening
o
 
A
fter drying, the granules are passed through a screen of asmaller mesh than that used to prepare the original granulation
 
A
dding lubrication and blending
o
 
A
fter dry screening, a drylubricant is dusted over thespread-out granulation through amesh screen
 
W
et granulation pelletization
 
Two all-in-one granulation methods
 
F
luid bed granulator performs the followingsteps: (continuous operation)
o
 
Preblending the formulation powder 
o
 
G
ranulating the mixture byspraying onto the fluidized powder bed
o
 
Drying the granulated product tothe desired moisture content
y
 
Dry granulation
 
Powder mixture is compacted in large pieces or slugging and broken down or sized into granules
 
E
ither the active ingredient or the diluents must havecohesive properties
 
A
dvantages: for materials degraded by moisture or elevated temperature during drying
 
Types of dry granulation
 
S
lugging: after weighing or mixing theingredients, the powder mixture is slugged,or compressed into large flat tablets, or  pellets about 1 inch in diameter 
 
oller compaction: powder compactors(instead of slugging) used to increase thedensity of the powder by pressing it betweenroller at 1 ton to 6 tons of pressure
 
Property of granulation important in making tablets
 
Provides the powders free flowing
 
Increases material density (use of roller compaction) improving powder compressibility
 
Conditions at which materials are applicable for drygranulation
 
Possesses free flowing and cohesive properties
 
Thus, be compressed directly in a tabletmachine without the need of granulation
y
 
Direct compression tableting
 
Compressed directly into a tablet machine without needof granulation
 
G
ranular chemicals possess free flowing and cohesive properties (example: potassium chloride)
 
F
ree flowing property of a drug mixture is arequirement for the manufacture of tablets of thesemethods: wet granulation, dry granulation and directcompression
H
igh
S
hear 
G
ranulation
y
 
M
ixing and granulation
y
 
Combines the active powder with a binder solution using a highspeed mixing blade and chopper 
y
 
Capacity: from 36 to 1800
L
 Precision
G
ranulation
y
 
G
ranulate soluble and hygroscopic materials
y
 
G
ranulate fine particles
F
luid
B
ed Processor 
y
 
F
or granulation, coating and pelletization, and solution layeringThe
G
P
S
of 
F
luid
B
ed Process
y
 
Control real time process determination
M
icrowave
V
acuum Process
y
 
U
sing microwave
y
 
Powder mix is mixed, wetted, agglomerated and driedTablet Production Processing Problems
E
ncountered
y
 
esults from air entrapment and high speed production
 
Capping: partial or complete separation of the top or  bottom crowns of a tablet from the main body of thetablet and unclean punches and imperfectly smooth or  by granulation with too much fine
 
S
 plitting/laminations/horizontal striations: separation of the tablet into 2 or more distinct layers, aging tablets or improper storage
y
 
esults from excessive moisture or substances with low melting point temperatures in the formulation
 
Picking: removal of tablet¶s surface area
 
S
ticking: adhesion of tablet material to a die wall
y
 
esults from use of a drug with a color from that of the tabletexcipients or from a drug with a colored degradation products
y
 
M
ottling: unequal distribution on a tab with light or dark areas,standing out on an otherwise uniform surface
y
 
Tablet dedusting: removes traces of loose powder adhering totablets following compression, the tablets are conveyed directlyfrom the tableting machine to a deduster 

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