Beruflich Dokumente
Kultur Dokumente
Murat Kizaibek
Tablets are solid dosage forms consisting of active ingredient(s) and suitable pharmaceutical excipients. They may vary in size, shape, weight, hardness, thickness, disintegration and dissolution characteristics, and in other aspects. They may be classyfied, according to the method of manufacture, as compressed tablets or molded tablets.
Advantages
Production aspect Large scale production at lowest cost Easiest and cheapest to package and ship High stability User aspect (doctor, pharmacist, patient) Easy to handling Lightest and most compact Greatest dose precision & least content variability
Disadvantages
Some drugs resist compression into dense compacts Drugs with poor wetting, slow dissolution, intermediate to large dosages may be difficult or impossible to formulate and manufacture as a tablet that provide adequate or full drug bioavailability Bitter taste drugs, drugs with an objectionable odor, or sensitive to oxygen or moisture may require encapsulation or entrapment prior to compression or the tablets may require coating
Types of tablets
1)compressed tablets 2)sugar coated tablets 3)film coated tablets 4)enteric coated tablets 5)effervescent tablets 6)chewable tablets 7)dispersible tablets 8)sustained release tablets
9)multilayer tablets 10)sublingual tablets 11)toroches 12)buccal tablets 13)implant tablets 14)hypodermic tablets 15)solution tabletc 16)vaginal tablets
A. DILUENTS
Diluents increase the volume to a formulation to prepare tablets of the desired size. Widely used fillers are lactose, dextrin, microcrystalline cellulose starch, pregelatinized starch, powdered sucrose, and calcium phosphate.
The diluent is selected based on various factors, such as the experience of the manufacturer in the preparation of
the GI tract.
B.BINDERS
Binders promote the adhesion of particles of the formulation. Such adhesion enables preparation of granules and maintains the integrity of the final tablet. As listed in the Table, Commonly used binding agents include: starch, gelatin and sugars (sucrose, glucose, dextrose, and lactose).
Examples of Binders
Carboxymethylcellulose, sodium Karaya gum
Acacia gum
Agar Algin acid Guar gum
Gelatin
Dextrin Glucose Molasses
C. LUBRICANTS
Lubricant is a substance capable of reducing or preventing friction, heat, and wear when introduced as a film between solid surfaces. It works by coating on the surface of particles, and thus preventing adhesion of the tablet material to the dies and punches. Glycerylmonostearate(USP/NFCH2(OH)CH(OH)CH2O2 CC17H35) is one example of a lubricant. Lubricants play more than one role in the preparation of tablets as described below.
the die wall during the tablets ejection from the tablet
machine. 4. Lubricants give a sheen to the finished tablets.
Commonly used lubricants include: talc, magnesium stearat, calcium stearate ,stearic acid, hydrogenated vegetable oils and (PEG).
D. DISINTEGRATORS
The breakup of the tablets to smaller particles is important for dissolution of the drug and subsequent bioavailability. Disintegrators promote such breakup. To rupture or breakup of tablets, disintegrating agents must swell or expand on exposure to aqueous solution. Thus, the most effective disintegrating agents in most tablet systems are those with the highest wa-ter uptake property. In general, the more hydrophilic, the better disinte-
E. WETTING AGENTS
Water molecules attract each other equally in all directions. Water molecules on the surface, however, can only be pulled into the bulk
granulation
wet granulation
drug
sieving excipients
adhesive
prilling
mix
press
dry granulation
adhesive smash sieving mix press cake processing smash granule
drug
excipient
mix
press
powder compression
adhesive
smash excipients sieving mix mix press
drugs
crystal compression
drugs
smash
sieving mix
excipients
wet granulation
screening the damp mass into pellets or granules drying the granulation sizing the granulation by dry screening adding lubricant and disintegrant, and blending tableting by compression
External()
lower punch
upper punch
hopper feed-frame head: upper turret, lower turret, die table upper turret die table lower turret
A: upper punch B: die cavity C: die D: lower punch The compression is applied by both the upper punch and the lower punch.
The compression cycle of a rotary tablet press
excipient
prilling processing granule
mix
mix
press
1Magnesium stearate
table 1 formula
adhesive
Hardness Kg
10% Starch
0.68
10%PVP water
0.83
10%CMC-Na
0.75
10%PVP (Ethanol)
particles deformed
table 2
formula fillers
5 starch
8
10%PVP ( Ethanol)
Hardnes sKg
0.68
3.55
1 2 3 4 5 6 7 8 9 K1 K2 K3
R6
0.2
table5
variance source total variance A B AB error SS 5.658 4.698 0.191 0.139 0.630
2 2 4 9
table
Comparison group
A1andA3
-1.1
0.1074
-10.241
4.34
6.33
<0.01
A1andA2
-1.0
0.1074
-9.310
3.46
5.24
<0.01
A2andA3
-0.1
0.1074
-9.310
3.46
5.24
>0.05
Tablet coating
The reasons for tablet coating
1) sugarcoating tablets
2) film-coating tablets 3) enteric coating 4) pan coating 5) fluid-bed or air suspension coating 6) compression coating
The sugarcoating of tablets may be divided into the following steps: 1) waterproofing and sealing (if needed)
2) subcoating
3) smoothing and final rounding 4) finishing and coloring (if desired) 5) polishing
film-coating machine
1) waterproofing and sealing (if needed) aim: to prevent the components from being adversely affected by moisture; one or more coats; shellac , zein ,
acacia, or PVP.
b) When the tablets are partially dry they are sprinkled with
a dusting powder, usually a mixture of powdered sugar and starch but sometimes talc, acacia, or precipitated chalk as well. c) Then drying the tablets. Repetition (15 to 18 times) the
3) smoothing and final rounding aim: to complete the rounding and smooth the coatings
5) imprinting
a) time-consuming
b) requiring the expertise of highly skilled technicians c) doubling the size and weight of the original uncoated tablets d) may vary in size from batch to batch and within a batch e) large tablets are not as easily swallowed as are small tablets.
2) The advantages of film-coating process a) coated tablets having essentially the same weight, shape, and size as the originally compressed tablet b) The coating is thin enough to reveal any identifying monograms. c) far more resistant to destruction by abrasion than are sugar-coated tablets d) the coating may be colored to make the tablets attractive and distinctive.
c) plasticizer: to render flexibility and elasticity to the coating e.g. castor oil
d) surfactant: to enhance spreadability of the film e.g. polyoxyethylene sorbitan derivatives e) opaquants and colorants: e.g. titanium dioxide, FD&C or D&C dyes f) sweeteners, flavors, and aromas: saccharin, vanillin g) glossant: beeswax h) volatile solvent: alcohol-acetone mixture
4) The components of a typical aqueous film-coating solutions: a) film-forming polymer (7-18%): e.g. cellulose ether
d) water
filling-in of the score-line or indented logo on the tablet by the film e) tablet erosion disfiguration of the core tablet
5) Some problems with aqueous film-coating a) picking and peeling b) orange peel effect c) mottling d) bridging filling-in of the score-line or indented logo on the tablet by the film e) tablet erosion disfiguration of the core tablet the appearance of small amounts or large roughness of the tablet surface due to failure of amounts of film fragments flaking from the tablet surface
5) unscored or scored in halves, thirds and quadrants 6) engraved or imprinted with an identifying symbol and/or code number 7) coated or uncoated 8)colored or uncolored 9) number of layer. The die and punches determine the physical features of compressed tablets.
tablet hardness
drug dissolution in-process controls
tablet disintegration
quality standards and compendial requirements tablet weight and Chp weight variation
Chp weight variation: sample amount 20 tablets Tablets should comply
5%
quality standards and compendial requirements tablet weight and Chp weight variation
The procedure of weight variation determination in Chp:
Weigh accurately 20 tablets and calculate the average weight, then weigh individually each of the 20 tablets. Compare the weight of each tablet with the labelled tablet (if no labelled weight is stated, compare the weight of each tablet with the average weight calculated). No more than 2 of the individual weights exceed the weight variation limit stated in the table above and none doubles the limit.
quality standards and compendial requirements tablet hardness and friability (continued)
Friability 1) It is used to determine a tablets durability 2) Method: allowing the tablets to roll and fall within the
a) to guide the formulation and product development process toward product optimization
2) The goal of in vitro dissolution is to provide a reasonable prediction of the products in vivo bioavailability. Basis: The combinations of a drugs solubility and its intestinal permeability are supposed as a basis for predicting the likelihood of achieving a
Considered are drugs determined to have: a) high solubility and high permeability (IVIVC may be expected.) b) low solubility and high permeability (IVIVC
may be expected.)
c) high solubility and low permeability d) low solubility and low permeability
4) Test method a) A volume of the dissolution medium is placed in the vessel and allowed to come to 370.5.
6) Inconsistencies in dissolution
occur not between dosage units from the same production batch, but rather between batches or between products from different manufacturers. Pooled dissolution testing has emerged. This process