Tabletting 3- Tablet evaluation and coating Flashcards
What is tablet evaluation and what is the general standards for tablets?
- Finished tablets need to meet a number of standards before they are considered suitable for marketing.
- B.P. (incorporating Ph. Eur. requirements) sets a number of standards and describes tests that must be conducted for quality assurance
- TGA (TGO 78) applies different requirements regarding dissolution, disintegration and uniformity of dosage units to listed (lower risk) and registered (higher risk) medicines
- Validate processes and maintain proper environment for manufacturing process.
- Manufacturers may conduct additional tests
General standards for tablets
- Strength and shock resistance to withstand handling
- Uniform weight and consent
- Drug content must be bioavailable
- Elegant appearance
- Maintanence of function (stability)
What are the two B.P. tests for Physical Stability
B.P. Test for Resistance to Crushing (hardness)
- B.P. sets no limits for this test, but mandates it and describes the method. 10 tablets from batch are tested using a device to determine resistance to crushing eg Monsanto hardness tester
B.P. Friability Test (App XVIIG)
- Testing tendency of tablets to become chipped or abraded during use.
- Test a sample of tablets weighing as close as possible to 6.5g (minimum of 10 tablets) in friabilator for 100 revolutions. Weight loss after test should be ≤1%.
What are the four B.P. tests for content?
B.P. Test for Content of Active Ingredient 20 tablets
- (or smaller allowable sample ≥5) are combined and assayed to determine the amount of drug present. Limits are given in the monograph for each tab (eg 90-110%)
B.P. Test for Uniformity of Content (App XIIC3)
Required for tablets which contain active ingredient less than 2mg or 2% of total mass.
- Sample of individual tablets are assayed for drug content to ensure each tablet has correct amount of drug.
- Effects of inadequate mixing are very significant if drug is only small proportion of mix.
B.P. Test for Uniformity of Dosage Units (APP XIIC4)
Test for consistency between dosage units and adherence to label claim
Content uniformity: can be applied to any tablet. Individual tablet assays used to determine % of label claim of each tablet
Mass variation: For uncoated and film coated tablets with ≥25mg of drug comprising ≥25% of tablet mass. Individual tablet masses and pooled assay used to estimate % of label claim
What are the two B.P. test for drug release?
B.P. Disintegration Test (App XIIA) – tests how long it takes 6 tablets to break down into particles small enough to pass through a mesh when agitated in water at 37oC (or other suitable medium). Limit is less than 15mins unless otherwise stated.
- Rapid disintegration does not necessarily imply rapid dissolution.
- Superseded by the Dissolution Test for many tablets.
- Remains an official test for some tablets and useful for comparing performance of batches.
- Not applicable for chewable tablets. NOTE: an in vitro test
B.P. Dissolution Test (App XIIB) -measures cumulative amount of drug released into water bath over time. Medium used is HCL, buffer or water
- 4different apparatus approved (paddle, basket apparatus)
- 6 tablets separately tested and 75% (70% for tablet formulations listed in BP before 2008) of stated dose must have dissolved by 45mins.
- n vitro test. Manufacturer may verify relationship with release of drug in vivo.
What are the different types of coatings?
- Sugar coating
- Press coating
- Film coating
- Enteric coating
What are some of the reasons for coating?
- Protect ingredients against the atmosphere
- Mask unpleasant taste and odour
- Improve the appearance
- Control the site of action and rate of release of the drug eg enteric coatings
- Separate incompatible ingredients by placing one in core and other in coating
What is sugar coating? What are the 6 stages of sugar coating proces (SSSCPP)?
- Sealing or undercoating
- Sufficient to seal the core tablet to prevent ingress of water from subsequent coats, also strengthens core.
- Water impervious resins
- May adversely affect tablet disintegration
- Dry overnight
2.Subcoating
- Achieves a rapid build-up & rounds off the edges (about 50% of weight of coating).
- Examples: Heavy syrups such as a hot solution of gelatin and sucrose
- As soon as tablets become tacky, sub-coating powder (sucrose and starch in chalk) is added
- Repeat layering process until edges of tablets are completely covered. Dry overnight.
- Smoothing
- Correct deficiencies of the sub-coating & to prepare a smooth hard surface for colouring.
- Increases tablet size to previously determined dimensions.
- Thin grossing syrups or suspensions (eg titanium dioxide, sucrose and water) are used, with or without dusting powderColouring
- Colouring
- Soluble certified dye syrups. Colour intensity of syrup increased until desired shade attained.
- Multiple coats applied drying between each. Sugar coating is now dull & unattractive
- Polishing
- Tablets transferred to Polishing pans for 2-3 applications of beeswax or paraffin wax in petroleum ether or wax added in solid form.
- After drying, tablets dusted with a fine grade of talc, examined & packed.
-
Printing
* Logos or codes printed onto tablet surface
What is compression coating (press-coating)? What are its advantages
- Involves compression of coating granules around a tablet core > Requires special twin tablet press.
- Soft compressed core compressed on one side and transferred to coating press.
- Core is placed in a die on top of coating granules. More granules are added around and on top of core.
- Coating is compressed onto core
Advantages
- Completely anhydrous process (waterproofing unnecessary)
- Core does not need heavy compression
- Coating is uniform
- Time & labour-saving process
- Ability to separate incompatible ingredients
What is film coating?
Originally involving polymeric substances (large molecules) dissolved in in various organic solvents or polyethylene glycol 6000 in ethanol. Aqueous based coating solutions now frequently used.
- Most common type of tablet coating.
- Advances in coating pans and spray methods have made film coating rapid and allowed aqueous based coatings to be used.
- Flexible polymer coating is applied by spraying onto the compressed tablets.
- Film coating is very thin, so the tablets for coating must be almost perfect in appearance.
- Incorporation of plasticisers improves flexibility of coatings
- Pigments and lakes are used in the coatings for colouring.
What are the advantages of film coating
- Operation faster & less skilled operator can perform coating
- Coatings are durable & can be applied to any shaped tablets
- Little increase in disintegration time
- Improved resistance to chipping
- Minimal increase in weight (2-3%)
- Weight variation amongst finished tablets decreased
What are enteric coatings? What are the reasons for enteric coating? What are the requirements for enteric coating
Enteric coating protects tablet core while passing through acid secretions of stomach yet breaks down & allows tablet to disintegrate when in contact with intestinal fluid
Reasons for enteric coating
- Prevent gastric decomposition of drug. eg: erythromycin
- Prevent nausea & vomiting caused by drug or gastric irritation eg: KCl, sodium salicylate
- Prevent dilution of drug before reaching intestines eg: anthelmintics
- Give delayed (or prolonged) action eg: antihistamines
- Deliver drugs to intestine for optimal absorption in duodenum or jejunum
Requirements of enteric coating
- Non toxic
- Coating and its degradation products physiologically inactive
- Must not disintegrate in stomach within time expected
- Must dissolve or disintegrate in intestines
What are the principles behind enteric coatings and what are some of the factors that determine how enteric coating will disintegrate in the intestine?
Principles behind enteric coating
- Enteric coatings are almost insoluble in aqueous media at lower pH (the fasting pH of the stomach = pH 1.2 - 3.5).
- They exhibit a sharp, well defined increase in solubility/permeability at a specific higher pH.
- The pH of the intestine (3.6 - 7.9) increases from proximal to distal end.
- cellulose acetate phthalate that becomes soluble at pH 5.7, therefore the coating dissolves at the distal end of the intestines and absorption occurs here.
- cellulose acetate phthalate that becomes soluble at pH 5.7, therefore the coating dissolves at the distal end of the intestines and absorption occurs here.
The Disintegration of an Enteric Coating in the Intestine will depend on one or more of these Factors:
- Presence of acidic groups in enteric substance causing solubility in higher pH of intestine (pH 3.6 –> 7.9)
- Degree of ionisation of an acid depends on pH of solution and the pkA of the acid (pkA 5 is ideal)
What are the materials sued for enteric coatings and how do you apply enteric coatings?
The materials most commonly used are Hydroxypropylmethylcellulose Phthalate (grades HP 50 or HP 55), polyvinyl acetate phthalate or acrylic co-polymers.
HP 50: 5.0 pH for solubility
HP 55: 5.5 pH for solubility
Applying enteric coatings
- Usually dissolved in a mixed organic solvent system or as an aqueous dispersion
- Can be applied as film coating or as the sealing coat in a sugar coated tablet
- A granulation containing an enteric coating agent can be formulated or applicaiton by press-coating
